CYP1A2 is responsible for metabolizing caffeine, and it competes with other drugs that are also metabolized by this enzyme. When caffeine is consumed excessively, it can deplete the CYP1A2, leaving none available to metabolize clozapine, resulting in increased levels of clozapine. However, this is not a common issue in clinical settings.

The Cytochrome P450 system is a group of enzymes that metabolize drugs by altering their functional groups. The system is located in the liver and small intestine and is involved in drug interactions through enzyme induction of inhibition. Notable inducers include smoking, alcohol, and St John’s Wort, while notable inhibitors include grapefruit juice and some SSRIs. CYP2D6 is important due to genetic polymorphism, and CYP3A4 is the most abundant subfamily and is commonly involved in interactions. Grapefruit juice inhibits both CYP1A2 and CYP3A4, while tobacco smoking induces CYP1A2. The table summarizes the main substrates, inhibitors, and inducers for each CYP enzyme.

Hardy-Weinberg Principle and Allele Frequency

Allele frequency refers to the proportion of a population that carries a specific variant at a particular gene locus. It can be calculated by dividing the number of individual alleles of a certain type by the total number of alleles in a population. The Hardy-Weinberg Principle states that both allele and genotype frequencies in a population remain constant from generation to generation unless specific disturbing influences are introduced. To remain in equilibrium, five conditions must be met, including no mutations, no gene flow, random mating, a sufficiently large population, and no natural selection. The Hardy-Weinberg Equation is used to predict the frequency of alleles in a population, and it can be used to estimate the carrier frequency of genetic diseases. For example, if the incidence of PKU is one in 10,000 babies, then the carrier frequency in the general population is 1/50. Couples with a previous child with PKU have a 25% chance of having another affected child.

Thought insertion is a symptom commonly experienced by individuals with schizophrenia, where they believe that their thoughts are not their own and have been placed in their head from an external source. This is one of the many first rank symptoms of schizophrenia, which also include delusional percept, audible thoughts, third person auditory hallucination, running commentary, thought withdrawal, thought broadcast, passivity of affect, passivity of impulses, passivity of volition, and somatic passivity. Third person auditory hallucinations involve hearing multiple voices discussing the patient as a third person. Thought broadcast is a passivity experience where the patient believes their thoughts are being widely broadcasted after being taken away from their head. Thought withdrawal is the belief that one’s thoughts are being taken away from their head against their will. Somatic passivity is a delusional belief that one’s body is being controlled from outside, which is different from haptic hallucination.

The biological response to a drug can only be triggered by the portion of the drug that is not bound.

Drug Distribution in the Body

After being absorbed, drugs can distribute to different parts of the body, such as fat, plasma, muscle, brain tissue, and glands like the thyroid. However, for a drug to have an effect, it must be present in the plasma in an unbound state. This means that the drug molecules are not attached to any other molecules and are free to interact with their target receptors. The concentration of unbound drug in the plasma is what determines the drug’s effectiveness and potential side effects. Therefore, understanding a drug’s distribution in the body is crucial for determining the appropriate dosage and monitoring its effects.

Cerebrovascular accidents (CVA), also known as strokes, are defined by the World Health Organization as a sudden onset of focal neurological symptoms lasting more than 24 hours and presumed to be of vascular origin. Strokes can be caused by either infarction of hemorrhage, with infarction being more common. Hemorrhagic strokes tend to be more severe. Intracranial hemorrhage can be primary, caused mainly by hypertension, of subarachnoid, caused by the rupture of an aneurysm of angioma. Primary intracranial hemorrhage is most common in individuals aged 60-80 and often occurs during exertion. Infarction can be caused by thrombosis of embolism, with thrombosis being more common. Atherosclerosis, often caused by hypertension, is the main cause of infarction. CT scanning is the preferred diagnostic tool during the first 48 hours after a stroke as it can distinguish between infarcts and hemorrhages. Recovery from embolism is generally quicker and more complete than from thrombosis due to the availability of collateral channels.

FGM is against the law in the UK, and arranging for a child to undergo the procedure abroad is also illegal. Those who are caught can face a prison sentence of up to 14 years and a hefty fine. Shockingly, it is estimated that 66,000 women in the UK have already undergone FGM, and over 20,000 girls under the age of 15 are at risk. Often, children are taken to have the procedure during the summer holidays so that they have time to heal before returning to school. There are four main types of FGM, including clitoridectomy, excision, infibulation, and other harmful procedures such as pricking, piercing, cutting, scraping, and burning the genital area. FGM is carried out for cultural, religious, and social reasons and is most prevalent in Africa, although it also occurs in Asia and the Middle East. The experience can be extremely traumatic, and those who have undergone FGM may require counseling in the future. Recently, medical professionals have faced criminal prosecution for allegedly performing the procedure, which is illegal in the UK.

Alzheimer’s disease is characterized by both macroscopic and microscopic changes in the brain. Macroscopic changes include cortical atrophy, ventricular dilation, and depigmentation of the locus coeruleus. Microscopic changes include the presence of senile plaques, neurofibrillary tangles, gliosis, degeneration of the nucleus of Meynert, and Hirano bodies. Senile plaques are extracellular deposits of beta amyloid in the gray matter of the brain, while neurofibrillary tangles are intracellular inclusion bodies that consist primarily of hyperphosphorylated tau. Gliosis is marked by increases in activated microglia and reactive astrocytes near the sites of amyloid plaques. The nucleus of Meynert degenerates in Alzheimer’s, resulting in a decrease in acetylcholine in the brain. Hirano bodies are actin-rich, eosinophilic intracytoplasmic inclusions which have a highly characteristic crystalloid fine structure and are regarded as a nonspecific manifestation of neuronal degeneration. These changes in the brain contribute to the cognitive decline and memory loss seen in Alzheimer’s disease.

Auditory Hallucinations: Running Commentary, Audible Thoughts, Thought Broadcast, and Thought Withdrawal

Running commentary is a type of auditory hallucination that is classified as a first rank symptom. Patients who experience running commentary hear voices that comment on their activities. The commentary may occur before, during, of after the patient’s actions.

Audible thoughts are another type of auditory hallucination where patients hear their own thoughts spoken aloud. They may hear people repeating their thoughts out loud just after they have thought them, answering their thoughts, of saying aloud what they are about to think. This can cause their thoughts to repeat the voices they hear.

Thought broadcast is a passivity experience where patients believe that their thoughts are being taken away from their heads and widely broadcast. This is also classified as a first rank symptom.

Thought withdrawal is another type of passivity experience where patients believe that their thoughts are being taken away from their heads against their will.

It is important to note that these symptoms are often associated with schizophrenia and other psychotic disorders. Proper diagnosis and treatment are crucial for managing these symptoms and improving the patient’s quality of life.

Phenomena of Memory

There are several phenomena related to memory that people may experience. Jamais vu is when someone cognitively knows they have experienced a situation, but it does not feel familiar to them. Confabulation is when someone falsifies a memory while in clear consciousness. Déjà vu is a feeling of familiarity for a new event that has not been experienced before. Derealisation is a feeling of unreality in perception and altered feelings towards perceived objects. Finally, panoramic recall is when a patient feels like they are rapidly re-enacting long periods of their life.

Knowing the half life of a drug is important in determining the steady state concentration, which occurs when absorption and elimination reach an equilibrium after repeated doses. This equilibrium depends on factors such as dose, time between doses, and the drug’s elimination half life. Typically, steady state is achieved after four to five half lives. The following are the half lives of some atypical antipsychotics: Aripiprazole – 90 hours, Clozapine – 16 hours, Olanzapine – 30 hours, Risperidone – 15 hours, and Quetiapine – 6 hours.

While weight gain is a known side effect of valproate, the most significant consideration when prescribing it to women of childbearing age is the significant risk of neural tube defects in the fetus if taken during pregnancy. Effective contraception should be carefully considered. Hair loss is usually transient and hypotension and Stevens-Johnson syndrome are not commonly associated with valproate.

Antidepressants can cause discontinuation symptoms when patients stop taking them, regardless of the type of antidepressant. These symptoms usually occur within 5 days of stopping the medication and can last up to 3 weeks. Symptoms include flu-like symptoms, dizziness, insomnia, vivid dreams, irritability, crying spells, and sensory symptoms. SSRIs and related drugs with short half-lives, such as paroxetine and venlafaxine, are particularly associated with discontinuation symptoms. Tapering antidepressants at the end of treatment is recommended to prevent these symptoms. TCAs and MAOIs are also associated with discontinuation symptoms, with amitriptyline and imipramine being the most common TCAs and all MAOIs being associated with prominent discontinuation symptoms. Patients at highest risk for discontinuation symptoms include those on antidepressants with shorter half-lives, those who have been taking antidepressants for 8 weeks of longer, those using higher doses, younger people, and those who have experienced discontinuation symptoms before. Agomelatine is not associated with any discontinuation syndrome. If a discontinuation reaction occurs, restarting the antidepressant of switching to an alternative with a longer half-life and tapering more slowly may be necessary. Explanation and reassurance are often sufficient for mild symptoms. These guidelines are based on the Maudsley Guidelines 14th Edition and a study by Tint (2008).

The concept of the sick role pertains to an implicit agreement between an individual who falls ill and the community they belong to.

The Sick Role and Illness Behavior

Mechanic and Volkart (1961) introduced the term illness behavior to describe how individuals perceive, evaluate, and respond to symptoms of physical dysfunction. Meanwhile, Talcott Parsons (1951) introduced the concept of the sick role as a temporary form of deviant behavior that is medically sanctioned.

According to Parsons, a sick person experiences conflicting desires to recover from the illness and to enjoy the secondary gains of attention and exemption from normal duties. The sick role is characterized by several rules, including the exemption of the sick person from their normal social roles, which is legitimized by society through the physician. The severity of the illness determines the strength of the exemption.

Additionally, sick persons are not held responsible for their illnesses, as they are beyond personal control. However, they have a duty to try to get well, as sickness is considered undesirable by society. Seeking competent technical help and cooperating with caregivers are also expected of sick persons.

In summary, the sick role and illness behavior are important concepts in understanding how individuals respond to physical dysfunction and how society legitimizes and responds to illness.

Professionalism and UK Regulation

Oaths and declarations are important in establishing trust and credibility for professions. The Hippocratic Oath, dating back to 425 BC, is a part of the Western medical tradition and emphasizes the teaching of medicine, patient’s best interests, confidentiality, and abstinence from harmful practices. However, it does not mention concepts such as autonomy of justice and forbids surgery. The Declaration of Geneva (1948) and the Declaration of Helsinki (1964) are modern-day versions of the Hippocratic Oath, emphasizing the patient’s health and interests over science and society. These declarations arose from the concern of the medical community’s complicity with the Nazi party during World War II.

In the UK, doctors must register with the General Medical Council (GMC), which sets professional standards and maintains a register of licensed doctors. It is illegal to practice medicine without a license in the UK. The GMC’s Good Medical Practice and the Good Medical Practice: Framework for Appraisal and Revalidation document emphasizes the duty of doctors to be honest and trustworthy, with dishonesty viewed harshly. Confidentiality is an important legal and ethical duty, but it is not absolute. Breaches of confidentiality may occur in emergencies, in the interests of others, when required by statute of the courts, of when required by the Driver and Vehicle Licensing Agency (DVLA). Sexualized relationships with current patients are prohibited, and accepting unsolicited gifts from patients is allowed but must not affect the way doctors prescribe, advise, treat, refer, of commission services.

There is limited evidence of effectiveness for fluoxetine, making it the only viable option. It is worth noting that the contents of ketamine injections have been used sublingually and have shown apparent efficacy.

Alternative Routes of Administration for Antidepressants

While most antidepressants are taken orally, there are a few alternative routes of administration available. However, it is important to note that these non-oral preparations should only be used when absolutely necessary, as they may not have a UK licence.

One effective alternative route is sublingual administration of fluoxetine liquid. Buccal administration of selegiline is also available. Crushed amitriptyline has been shown to be effective when administered via this route.

Intravenous administration is another option, with several antidepressants available in IV preparations, including citalopram, escitalopram, mirtazapine, amitriptyline, clomipramine, and allopregnanolone (which is licensed in the US for postpartum depression). Ketamine has also been shown to be effective when administered intravenously.

Intramuscular administration of flupentixol has been shown to have a mood elevating effect, but amitriptyline was discontinued as an IM preparation due to the high volumes required.

Transdermal administration of selegiline is available, and suppositories containing amitriptyline, clomipramine, imipramine, and trazodone have been manufactured by pharmacies, although there is no clear data on their effectiveness. Sertraline tablets and doxepin capsules have also been given rectally.

The use of HAART has led to a complete elimination of new cases of toxoplasmosis in individuals who are HIV positive. Studies conducted on the Edinburgh cohort have revealed a significant decrease in the occurrence of CMV by 50% during autopsy, a 68% reduction in HIVE, and complete eradication of toxoplasmosis. However, there has been a slight increase in the incidence of PML and lymphoma in this group and other samples.

The Sally-Anne Test and the Theory of Mind

The Sally-Anne test, conducted by Simon Baron-Cohen, led to the development of the theory of mind idea. The experiment involved several groups of children, including those with autism. During the test, a skit was performed where Sally put a marble in a basket and left the room. Anne then removed the marble from the basket and placed it in a box. When Sally returned, the children were asked where she would look for her marble.

The results showed that most non-autistic children correctly identified the basket, while most autistic children pointed to of named the box. This led the researchers to conclude that the autistic children who chose the box lacked the ability to understand that Sally did not know the marble was in the box. The Sally-Anne test thus became a crucial tool in understanding the theory of mind, which refers to the ability to attribute mental states to oneself and others.

History of Psychiatric Terms

In the exams, it is important to be familiar with the individuals associated with certain psychiatric terms. For example, Kraepelin is associated with dementia praecox and manic depression, while Bleuler is associated with schizophrenia. Other terms and their associated individuals include Hebephrenia (Hecker), Catatonia (Kahlbaum), Schizoaffective (Kasanin), Neurasthenia (Beard), Unipolar and bipolar (Kleist), Hypnosis (Braid), Group dynamics (Lewin), Group psychotherapy (Moreno), Psychopathic inferiority (Koch), Psychiatry (Reil), and Institutional Neurosis (Barton).

It should be noted that there is some debate over the origins of certain terms. While Kraepelin is often credited with coining the term dementia praecox, some sources suggest that it was first used in its Latin form by Arnold Pick in 1891. The original term demence precoce was first used by Morel in 1852. Despite this, the College appears to favor the Kraepelin attribution.

Porphyria: The Little Imitator

Porphyria is a medical condition that is often referred to as the little imitator because it can mimic various common psychiatric presentations. This condition can be triggered by the use of certain psychotropic drugs, including barbiturates, benzodiazepines, sulpiride, and some mood stabilizers.

Porphyria can manifest in different ways, and it is important to be aware of the symptoms. These may include abdominal pain, mental state changes, constipation, vomiting, and muscle weakness.

Broca’s and Wernicke’s are two types of expressive dysphasia, which is characterized by difficulty producing speech despite intact comprehension. Dysarthria is a type of expressive dysphasia caused by damage to the speech production apparatus, while Broca’s aphasia is caused by damage to the area of the brain responsible for speech production, specifically Broca’s area located in Brodmann areas 44 and 45. On the other hand, Wernicke’s aphasia is a type of receptive of fluent aphasia caused by damage to the comprehension of speech, while the actual production of speech remains normal. Wernicke’s area is located in the posterior part of the superior temporal gyrus in the dominant hemisphere, within Brodmann area 22.

Inheritance: Phenotype and Genotype

Phenotype refers to the observable traits of an individual, such as height, eye colour, and blood type. These traits are a result of the interaction between an individual’s genotype and the environment. The term ‘pheno’ comes from the same root as ‘phenomenon’ and simply means ‘observe’.

On the other hand, genotype refers to an individual’s collection of genes. These genes determine the traits that an individual will inherit from their parents. A haplotype, on the other hand, is a set of DNA variations of polymorphisms that tend to be inherited together.

Finally, a karyotype refers to an individual’s collection of chromosomes. These chromosomes contain the genetic information that determines an individual’s traits. By examining an individual’s karyotype, scientists can determine if there are any genetic abnormalities of disorders present.

The Sick Role and Illness Behavior

Mechanic and Volkart (1961) introduced the term illness behavior to describe how individuals perceive, evaluate, and respond to symptoms of physical dysfunction. Meanwhile, Talcott Parsons (1951) introduced the concept of the sick role as a temporary form of deviant behavior that is medically sanctioned.

According to Parsons, a sick person experiences conflicting desires to recover from the illness and to enjoy the secondary gains of attention and exemption from normal duties. The sick role is characterized by several rules, including the exemption of the sick person from their normal social roles, which is legitimized by society through the physician. The severity of the illness determines the strength of the exemption.

Additionally, sick persons are not held responsible for their illnesses, as they are beyond personal control. However, they have a duty to try to get well, as sickness is considered undesirable by society. Seeking competent technical help and cooperating with caregivers are also expected of sick persons.

In summary, the sick role and illness behavior are important concepts in understanding how individuals respond to physical dysfunction and how society legitimizes and responds to illness.

Inheritance Patterns and Examples

Autosomal Dominant:
Neurofibromatosis type 1 and 2, tuberous sclerosis, achondroplasia, Huntington disease, and Noonan’s syndrome are all examples of conditions that follow an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene is needed to cause the condition.

Autosomal Recessive:
Phenylketonuria, homocystinuria, Hurler’s syndrome, galactosaemia, Tay-Sach’s disease, Friedreich’s ataxia, Wilson’s disease, and cystic fibrosis are all examples of conditions that follow an autosomal recessive inheritance pattern. This means that two copies of the mutated gene are needed to cause the condition.

X-Linked Dominant:
Vitamin D resistant rickets and Rett syndrome are examples of conditions that follow an X-linked dominant inheritance pattern. This means that the mutated gene is located on the X chromosome and only one copy of the gene is needed to cause the condition.

X-Linked Recessive:
Cerebellar ataxia, Hunter’s syndrome, and Lesch-Nyhan are examples of conditions that follow an X-linked recessive inheritance pattern. This means that the mutated gene is located on the X chromosome and two copies of the gene are needed to cause the condition.

Mitochondrial:
Leber’s hereditary optic neuropathy and Kearns-Sayre syndrome are examples of conditions that follow a mitochondrial inheritance pattern. This means that the mutated gene is located in the mitochondria and is passed down from the mother to her offspring.

Combining clozapine with carbamazepine increases the risk of agranulocytosis, making it a hazardous drug combination. In the event of clozapine-induced seizures, sodium valproate is typically the preferred anticonvulsant.

Genomic Imprinting and its Role in Psychiatric Disorders

Genomic imprinting is a phenomenon where a piece of DNA behaves differently depending on whether it is inherited from the mother of the father. This is because DNA sequences are marked of imprinted in the ovaries and testes, which affects their expression. In psychiatry, two classic examples of genomic imprinting disorders are Prader-Willi and Angelman syndrome.

Prader-Willi syndrome is caused by a deletion of chromosome 15q when inherited from the father. This disorder is characterized by hypotonia, short stature, polyphagia, obesity, small gonads, and mild mental retardation. On the other hand, Angelman syndrome, also known as Happy Puppet syndrome, is caused by a deletion of 15q when inherited from the mother. This disorder is characterized by an unusually happy demeanor, developmental delay, seizures, sleep disturbance, and jerky hand movements.

Overall, genomic imprinting plays a crucial role in the development of psychiatric disorders. Understanding the mechanisms behind genomic imprinting can help in the diagnosis and treatment of these disorders.

DBS is primarily used to treat Parkinson’s disease by targeting the Globus pallidus interna and subthalamic nucleus. However, for treatment-resistant depression (TRD), the subcallosal cingulate was the first area investigated for DBS, while vagal nerve stimulation has also been used. Psychosurgical treatment for refractory OCD and TRD involves targeting the anterior limb of the internal capsule. Although the caudate nucleus is part of the basal ganglia and associated with Parkinson’s disease, it is not a primary target for DBS.

Unlike forms of automatic obedience like mitmachen and mitgehen, where the limb will move even after the force is removed, cerea flexibilitas results in the limb staying in place once the force is no longer applied.

– Catatonia is a psychiatric syndrome characterized by disturbed motor functions, mood, and thought.
– Key behaviors associated with catatonia include stupor, posturing, waxy flexibility, negativism, automatic obedience, mitmachen, mitgehen, ambitendency, psychological pillow, forced grasping, obstruction, echopraxia, aversion, mannerisms, stereotypies, motor perseveration, echolalia, and logorrhoea.
– These behaviors are often tested in exam questions.
– Karl Ludwig Kahlbaum is credited with the original clinical description of catatonia.

Prader-Willi Syndrome: A Genetic Disorder with Unique Characteristics

Prader-Willi Syndrome is a genetic disorder that occurs when there is a deletion of genetic material from the paternal chromosome 15. This condition is a classic example of imprinting, where the expression of certain genes is dependent on whether they are inherited from the mother of father. The syndrome is characterized by several unique features, including hyperphagia (excessive eating) and obesity, short stature, delayed puberty, hypogonadism, infertility, learning difficulties, and compulsive behavior such as skin picking.

Drug-Induced Mania: Evidence and Precipitating Drugs

There is strong evidence that mania can be triggered by certain drugs, according to Peet (1995). These drugs include levodopa, corticosteroids, anabolic-androgenic steroids, and certain classes of antidepressants such as tricyclic and monoamine oxidase inhibitors.

Additionally, Peet (2012) suggests that there is weaker evidence that mania can be induced by dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine, and phencyclidine.

It is important for healthcare professionals to be aware of the potential for drug-induced mania and to monitor patients closely for any signs of symptoms. Patients should also be informed of the risks associated with these medications and advised to report any unusual changes in mood of behavior.

Cerebellar signs are evident in cases of lithium toxicity, which can manifest as slurred speech, a broad-based gait, and an intention tremor. The latter is characterized by a coarse appearance and a frequency of 2-3Hz (equivalent to 2 waves per second).

Types of Tremor

Essential Tremor

Otherwise known as benign essential tremor, this is the most common type of tremor. It is not associated with any underlying pathology. It usually begins in the 40’s, affects mainly the hands, and is slowly progressive. It tends to worsen with heightened emotion. It usually presents with unilateral upper limb involvement then progresses to both limbs.

Parkinsonian Tremor

This tremor is associated with Parkinson’s disease. It is classically described as ‘pill rolling’ due to the characteristic appearance of the fingers.

Cerebellar Tremor

Otherwise known as an intention tremor. This is a slow, coarse tremor which gets worse with purposeful movement. This is seen in lithium toxicity (note that the tremor seen as a side effect of long term lithium is fine and classed as physiological).

Psychogenic Tremor

Also known as a hysterical tremor. This type of tremor tends to appear and disappear suddenly and is hard to characterise due to its changeable nature. It tends to improve with distraction.

Physiologic Tremor

This is a very-low-amplitude fine tremor that is barely visible to the naked eye. It is present in every normal person while maintaining a posture of movement. It becomes enhanced and visible in many conditions such as anxiety, hyperthyroidism, alcohol withdrawal, and as drug induced side effects.

It is useful to have a basic idea about the frequencies of different types of tremor.

Type of Tremor Frequency

Intention 2-3Hz

Parkinsonian 5Hz

Essential 7Hz

Physiological 10Hz

Psychogenic variable

Lisinopril is a medication that belongs to the class of ACE inhibitors and is commonly prescribed to treat hypertension and heart failure.

Hyponatremia in Psychiatric Patients

Hyponatremia, of low serum sodium, can occur in psychiatric patients due to the disorder itself, its treatment, of other medical conditions. Symptoms include nausea, confusion, seizures, and muscular cramps. Drug-induced hyponatremia is known as the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), which results from excessive secretion of ADH and fluid overload. Diagnosis is based on clinically euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality. SSRIs, SNRIs, and tricyclics are the most common drugs that can cause SIADH. Risk factors for SIADH include starting a new drug, and treatment usually involves fluid restriction and sometimes demeclocycline.

Alternative splicing is a crucial process in post-transcriptional processing that has significant implications. It allows a single gene to produce multiple mRNAs that encode different polypeptides by modifying the splicing pattern. However, mutations in the gene sequence can lead to either a lack of splicing of excessive splicing, resulting in diseases.

Early onset Alzheimer’s disease is primarily caused by mutations in the Presenilin genes, while late onset Alzheimer’s disease is linked to Apolipoprotein and Neuronal Sortilin related receptors (SORL1).

Genetics plays a role in the development of Alzheimer’s disease, with different genes being associated with early onset and late onset cases. Early onset Alzheimer’s, which is rare, is linked to three genes: amyloid precursor protein (APP), presenilin one (PSEN-1), and presenilin two (PSEN-2). The APP gene, located on chromosome 21, produces a protein that is a precursor to amyloid. The presenilins are enzymes that cleave APP to produce amyloid beta fragments, and alterations in the ratios of these fragments can lead to plaque formation. Late onset Alzheimer’s is associated with the apolipoprotein E (APOE) gene on chromosome 19, with the E4 variant increasing the risk of developing the disease. People with Down’s syndrome are also at high risk of developing Alzheimer’s due to inheriting an extra copy of the APP gene.

Multiple Sclerosis: An Overview

Multiple sclerosis is a neurological disorder that is classified into three categories: primary progressive, relapsing-remitting, and secondary progressive. Primary progressive multiple sclerosis affects 5-10% of patients and is characterized by a steady progression with no remissions. Relapsing-remitting multiple sclerosis affects 20-30% of patients and presents with a relapsing-remitting course but does not lead to serious disability. Secondary progressive multiple sclerosis affects 60% of patients and initially presents with a relapsing-remitting course but is then followed by a phase of progressive deterioration.

The disorder typically begins between the ages of 20 and 40 and is characterized by multiple demyelinating lesions that have a preference for the optic nerves, cerebellum, brainstem, and spinal cord. Patients with multiple sclerosis present with a variety of neurological signs that reflect the presence and distribution of plaques. Ocular features of multiple sclerosis include optic neuritis, internuclear ophthalmoplegia, and ocular motor cranial neuropathy.

Multiple sclerosis is more common in women than in men and is seen with increasing frequency as the distance from the equator increases. It is believed to be caused by a combination of genetic and environmental factors, with monozygotic concordance at 25%. Overall, multiple sclerosis is a predominantly white matter disease that can have a significant impact on a patient’s quality of life.

Individuals with constructional apraxia are unable to replicate drawings of arrange objects to create patterns of designs.

Clock Drawing Test: A Screening Tool for Cognitive Dysfunction

The clock drawing test is a widely used screening tool for cognitive dysfunction. It involves asking the patient to draw a clock on a piece of paper, placing the numbers on the clock face and drawing the hands to indicate 10 minutes past 11. This simple task assesses a range of cognitive functions, including visuospatial ability, motor function, attention, and comprehension.

The test is quick and easy to administer, making it a useful tool for healthcare professionals to identify potential cognitive impairment in patients. The clock drawing test has been shown to be effective in detecting cognitive dysfunction in a variety of conditions, including Alzheimer’s and Parkinson’s disease.

The image below illustrates examples of clocks drawn correctly by healthy controls and those drawn by patients with Alzheimer’s and Parkinson’s disease. By comparing the drawings, healthcare professionals can quickly identify potential cognitive dysfunction and take appropriate action.

Excitatory neurotransmitters include glutamate, histamine, acetylcholine, and noradrenaline, as they increase ion flow and the likelihood of action potential in neurons. However, GABA functions as an inhibitory neurotransmitter, reducing ion flow and decreasing the probability of action potential.

Electroencephalography

Electroencephalography (EEG) is a clinical test that records the brain’s spontaneous electrical activity over a short period of time using multiple electrodes placed on the scalp. It is mainly used to rule out organic conditions and can help differentiate dementia from other disorders such as metabolic encephalopathies, CJD, herpes encephalitis, and non-convulsive status epilepticus. EEG can also distinguish possible psychotic episodes and acute confusional states from non-convulsive status epilepticus.

Not all abnormal EEGs represent an underlying condition, and psychotropic medications can affect EEG findings. EEG abnormalities can also be triggered purposely by activation procedures such as hyperventilation, photic stimulation, certain drugs, and sleep deprivation.

Specific waveforms are seen in an EEG, including delta, theta, alpha, sigma, beta, and gamma waves. Delta waves are found frontally in adults and posteriorly in children during slow wave sleep, and excessive amounts when awake may indicate pathology. Theta waves are generally seen in young children, drowsy and sleeping adults, and during meditation. Alpha waves are seen posteriorly when relaxed and when the eyes are closed, and are also seen in meditation. Sigma waves are bursts of oscillatory activity that occur in stage 2 sleep. Beta waves are seen frontally when busy of concentrating, and gamma waves are seen in advanced/very experienced meditators.

Certain conditions are associated with specific EEG changes, such as nonspecific slowing in early CJD, low voltage EEG in Huntington’s, diffuse slowing in encephalopathy, and reduced alpha and beta with increased delta and theta in Alzheimer’s.

Common epileptiform patterns include spikes, spike/sharp waves, and spike-waves. Medications can have important effects on EEG findings, with clozapine decreasing alpha and increasing delta and theta, lithium increasing all waveforms, lamotrigine decreasing all waveforms, and valproate having inconclusive effects on delta and theta and increasing beta.

Overall, EEG is a useful tool in clinical contexts for ruling out organic conditions and differentiating between various disorders.

Types of Tremor

Essential Tremor

Otherwise known as benign essential tremor, this is the most common type of tremor. It is not associated with any underlying pathology. It usually begins in the 40’s, affects mainly the hands, and is slowly progressive. It tends to worsen with heightened emotion. It usually presents with unilateral upper limb involvement then progresses to both limbs.

Parkinsonian Tremor

This tremor is associated with Parkinson’s disease. It is classically described as ‘pill rolling’ due to the characteristic appearance of the fingers.

Cerebellar Tremor

Otherwise known as an intention tremor. This is a slow, coarse tremor which gets worse with purposeful movement. This is seen in lithium toxicity (note that the tremor seen as a side effect of long term lithium is fine and classed as physiological).

Psychogenic Tremor

Also known as a hysterical tremor. This type of tremor tends to appear and disappear suddenly and is hard to characterise due to its changeable nature. It tends to improve with distraction.

Physiologic Tremor

This is a very-low-amplitude fine tremor that is barely visible to the naked eye. It is present in every normal person while maintaining a posture of movement. It becomes enhanced and visible in many conditions such as anxiety, hyperthyroidism, alcohol withdrawal, and as drug induced side effects.

It is useful to have a basic idea about the frequencies of different types of tremor.

Type of Tremor Frequency

Intention 2-3Hz

Parkinsonian 5Hz

Essential 7Hz

Physiological 10Hz

Psychogenic variable

Anankastic personality disorder, previously known as obsessive-compulsive personality disorder in DSM-IV, is a condition where individuals are excessively focused on schedules, rules, and details. Their perfectionism can hinder their ability to meet the criteria outlined in ICD-10, which characterizes the disorder as one marked by doubt, excessive conscientiousness, preoccupation with details, checking, stubbornness, caution, and rigidity. People with this disorder may experience persistent and unwanted thoughts of impulses that do not reach the level of an obsessive-compulsive disorder. They may also struggle to function effectively at work due to difficulty completing tasks.

Citalopram can moderately prolong QTc (>10 msec), while aripiprazole and paliperidone have no effect. Haloperidol and pimozide have a high effect, and quetiapine and amisulpride have a moderate effect. Clozapine, risperidone, and olanzapine have a low effect (<10 msec prolongation). Lamotrigine, mirtazapine, and SSRIs (excluding citalopram) do not have an effect on QTc interval.

Agreeableness pertains to an individual’s prioritization of social harmony, often demonstrated through traits such as generosity, consideration, trust, and helpfulness. Conscientiousness refers to an individual’s level of self-discipline. Extraversion pertains to an individual’s engagement with the external world. Neuroticism describes an individual’s emotional stability, rather than the Freudian concept of neuroticism. Openness to experience pertains to an individual’s inclination towards intellectual curiosity.

Naloxone hydrochloride is a morphine derivative that acts as a specific opioid antagonist by competitively binding to opioid receptors. It has a strong affinity for these receptor sites and can displace both opioid agonists and partial antagonists. Despite being administered at high doses (up to 10 times the usual therapeutic dose), naloxone does not produce significant analgesia, respiratory depression, psychotomimetic effects, circulatory changes, of miosis. In the absence of opioids of other agonistic effects of opioid antagonists, naloxone has no pharmacologic activity. It is a competitive antagonist at the mu, kappa, and delta receptors, with a high affinity for the mu receptor but lacking any mu receptor efficacy.

Opioid Pharmacology and Treatment Medications

Opioids work by binding to opioid receptors in the brain, specifically the µ, k, and δ receptors. The µ receptor is the main target for opioids and mediates euphoria, respiratory depression, and dependence. Dopaminergic cells in the ventral tegmental area produce dopamine, which is released into the nucleus accumbens upon stimulation of µ receptors, leading to the reward and euphoria that drives repeated use. However, with repeated exposure, µ receptors become less responsive, leading to dysphoria and drug craving.

There are several medications used in opioid treatment. Methadone is a full agonist targeting µ receptors, with some action against k and δ receptors, and has a half-life of 15-22 hours. However, it carries a risk of respiratory depression, especially when used with hypnotics and alcohol. Buprenorphine is a partial agonist targeting µ receptors, as well as a partial k agonist of functional antagonist and a weak δ antagonist. It has a high affinity for µ receptors and a longer half-life of 24-42 hours, making it safer than methadone. Naloxone is an antagonist targeting all opioid receptors and is used to reverse opioid overdose, with a half-life of 30-120 minutes. However, it can cause noncardiogenic pulmonary edema in some cases. Naltrexone is a reversible competitive antagonist at µ and ĸ receptors, with a half-life of 4-6 hours, and is used as an adjunctive prophylactic treatment for detoxified formerly opioid-dependent people.

Alpha2 adrenergic agonists, such as clonidine and lofexidine, can ameliorate opioid withdrawal symptoms associated with the noradrenaline system, including sweating, shivering, and runny nose and eyes. The locus coeruleus, a nucleus in the pons with a high density of noradrenergic neurons possessing µ-opioid receptors, is involved in wakefulness, blood pressure, breathing, and overall alertness. Exposure to opioids results in heightened neuronal activity of the nucleus cells, and if opioids are not present to suppress this activity, increased amounts of norepinephrine are released, leading to withdrawal symptoms. Clonidine was originally developed as an antihypertensive, but its antihypertensive effects are problematic in detox, so lofexidine was developed as an alternative with less hypotensive effects.

Neo-Freudians were therapists who developed their own theories while still retaining core Freudian components. Some important neo-Freudians include Alfred Adler, Carl Jung, Erik Erickson, Harry Stack Sullivan, Wilfred Bion, John Bowlby, Anna Freud, Otto Kernberg, Margaret Mahler, and Donald Winnicott. Each of these individuals contributed unique ideas to the field of psychology. For example, Carl Jung introduced the concept of the persona and differentiated between the personal and collective unconscious, while Erik Erickson is known for his stages of psychosocial development. Margaret Mahler developed theories on child development, including the three main phases of autistic, symbiotic, and separation-individuation. Donald Winnicott introduced the concept of the transitional object and the good enough mother. Overall, neo-Freudians expanded upon Freud’s ideas and helped to shape modern psychotherapy.

Varenicline for Smoking Cessation: Safety and Efficacy

Varenicline is a medication used to aid smoking cessation by reducing cravings and pleasurable effects of tobacco products. It has a high affinity for the alpha 4 beta 2 nicotinic receptor and is recommended by NICE for smoking cessation. Varenicline is safe to use in cases of liver dysfunction as it undergoes very little hepatic metabolism. It has been found to be nearly 80% more effective than bupropion and more effective than 24-hour nicotine replacement therapy in two large randomized controlled trials. The initial course of treatment could last 12 weeks, with an additional 12 weeks offered to those who have successfully quit smoking. However, varenicline has been observed to exacerbate underlying psychiatric illness, including depression, and is associated with changes in behavior of thinking, anxiety, psychosis, mood swings, aggressive behavior, suicidal ideation, and behavior. Patients with a psychiatric history should be closely monitored while taking varenicline. One randomized controlled trial has challenged this concern. The FDA has issued a safety announcement that varenicline may be associated with a small, increased risk of certain cardiovascular adverse events in patients with cardiovascular disease. The very common side effects of varenicline include nasopharyngitis, abnormal dreams, insomnia, headache, and nausea.

Olanzapine was found to have the highest duration of treatment before discontinuation due to inadequate efficacy, the longest period of successful treatment, and the lowest number of hospitalizations caused by worsening of schizophrenia among the patients.

CATIE Study: Comparing Antipsychotic Medications for Schizophrenia Treatment

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study, funded by the National Institute of Mental Health (NIMH), was a nationwide clinical trial that aimed to compare the effectiveness of older and newer antipsychotic medications used to treat schizophrenia. It is the largest, longest, and most comprehensive independent trial ever conducted to examine existing therapies for schizophrenia. The study consisted of two phases.

Phase I of CATIE compared four newer antipsychotic medications to one another and an older medication. Participants were followed for 18 months to evaluate longer-term patient outcomes. The study involved over 1400 participants and was conducted at various treatment sites, representative of real-life settings where patients receive care. The results from CATIE are applicable to a wide range of people with schizophrenia in the United States.

The medications were comparably effective, but high rates of discontinuation were observed due to intolerable side-effects of failure to adequately control symptoms. Olanzapine was slightly better than the other drugs but was associated with significant weight gain as a side-effect. Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications. Movement side effects primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs.

Phase II of CATIE sought to provide guidance on which antipsychotic to try next if the first failed due to ineffectiveness of intolerability. Participants who discontinued their first antipsychotic medication because of inadequate management of symptoms were encouraged to enter the efficacy (clozapine) pathway, while those who discontinued their first treatment because of intolerable side effects were encouraged to enter the tolerability (ziprasidone) pathway. Clozapine was remarkably effective and was substantially better than all the other atypical medications.

The CATIE study also looked at the risk of metabolic syndrome (MS) using the US National Cholesterol Education Program Adult Treatment Panel criteria. The prevalence of MS at baseline in the CATIE group was 40.9%, with female patients being three times as likely to have MS compared to matched controls and male patients being twice as likely.

Understanding Behavioural Activation Therapy for Depression

Behavioural activation therapy is a formal treatment for depression that emphasizes activity scheduling to encourage patients to approach activities they are avoiding. Unlike traditional cognitive therapy, it involves less cognitive therapy and is easier to train staff in its use. The therapy was introduced by Martell in 2001 and has two primary focuses: the use of avoided activities as a guide for activity scheduling and functional analysis of cognitive processes that involve avoidance.

Behavioural activation theory suggests that when people become depressed, many of their activities function as avoidance and escape from aversive thoughts, feelings, of external situations. As a result, someone with depression engages less frequently in pleasant of satisfying activities and obtains less positive reinforcement than someone without depression. To address this, the patient is encouraged to identify activities and problems that they avoid and to establish valued directions to be followed. These are set out on planned timetables (activity schedules).

In behavioural activation therapy, therapists do not engage in the content of the patient’s thinking. Instead, they use functional analysis to focus on the context and process of the individual’s response. The most common cognitive responses are rumination, fusion, and self-attack. A typical session has a structured agenda to review homework and progress towards goals, discuss feedback on the previous session, and focus on one of two specific issues. The number of sessions required to treat depression is typically between 12 and 24.

Neurotransmitters are substances used by neurons to communicate with each other and with target tissues. They are synthesized and released from nerve endings into the synaptic cleft, where they bind to receptor proteins in the cellular membrane of the target tissue. Neurotransmitters can be classified into different types, including small molecules (such as acetylcholine, dopamine, norepinephrine, serotonin, and GABA) and large molecules (such as neuropeptides). They can also be classified as excitatory or inhibitory. Receptors can be ionotropic or metabotropic, and the effects of neurotransmitters can be fast of slow. Some important neurotransmitters include acetylcholine, dopamine, GABA, norepinephrine, and serotonin. Each neurotransmitter has a specific synthesis, breakdown, and receptor type. Understanding neurotransmitters is important for understanding the function of the nervous system and for developing treatments for neurological and psychiatric disorders.

Serotonin (5-hydroxytryptamine, 5-HT) receptors are primarily G protein receptors, except for 5-HT3, which is a ligand-gated receptor. It is important to remember that 5-HT3 is most commonly associated with nausea. Additionally, 5-HT7 is linked to circadian rhythms. The stimulation of 5-HT2 receptors is believed to be responsible for the side effects of insomnia, agitation, and sexual dysfunction that are associated with the use of selective serotonin reuptake inhibitors (SSRIs).

Enzymes known as RNA polymerases are responsible for transcribing RNA from DNA. The role of RNA is crucial in the process of protein synthesis. Messenger RNA, a specific type of RNA, carries genetic information from DNA to ribosomes. Ribosomes are composed of ribosomal RNAs and proteins, and they function as a molecular apparatus that can interpret messenger RNAs and convert the information they contain into proteins.

Genomics: Understanding DNA, RNA, Transcription, and Translation

Deoxyribonucleic acid (DNA) is a molecule composed of two chains that coil around each other to form a double helix. DNA is organised into chromosomes, and each chromosome is made up of DNA coiled around proteins called histones. RNA, on the other hand, is made from a long chain of nucleotide units and is usually single-stranded. RNA is transcribed from DNA by enzymes called RNA polymerases and is central to protein synthesis.

Transcription is the synthesis of RNA from a DNA template, and it consists of three main steps: initiation, elongation, and termination. RNA polymerase binds at a sequence of DNA called the promoter, and the transcriptome is the collection of RNA molecules that results from transcription. Translation, on the other hand, refers to the synthesis of polypeptides (proteins) from mRNA. Translation takes place on ribosomes in the cell cytoplasm, where mRNA is read and translated into the string of amino acid chains that make up the synthesized protein.

The process of translation involves messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). Transfer RNAs, of tRNAs, connect mRNA codons to the amino acids they encode, while ribosomes are the structures where polypeptides (proteins) are built. Like transcription, translation also consists of three stages: initiation, elongation, and termination. In initiation, the ribosome assembles around the mRNA to be read and the first tRNA carrying the amino acid methionine. In elongation, the amino acid chain gets longer, and in termination, the finished polypeptide chain is released.

The prevention of a disease can be divided into three levels: primary, secondary, and tertiary. Tertiary prevention focuses on minimizing the effects of an existing disease and helping individuals achieve their optimal level of functioning. Primary prevention involves implementing broad changes to decrease the overall risk of a disease in a population, such as promoting healthy nutrition, positive parenting, and smoking cessation. Secondary prevention involves early detection and intervention through screening programs.

The First Pass Effect in Psychiatric Drugs

The first-pass effect is a process in drug metabolism that significantly reduces the concentration of a drug before it reaches the systemic circulation. This phenomenon is related to the liver and gut wall, which absorb and metabolize the drug before it can enter the bloodstream. Psychiatric drugs are not exempt from this effect, and some undergo a significant reduction in concentration before reaching their target site. Examples of psychiatric drugs that undergo a significant first-pass effect include imipramine, fluphenazine, morphine, diazepam, and buprenorphine. On the other hand, some drugs undergo little to no first-pass effect, such as lithium and pregabalin.

Orally administered drugs are the most affected by the first-pass effect. However, there are other routes of administration that can avoid of partly avoid this effect. These include sublingual, rectal (partly avoids first pass), intravenous, intramuscular, transdermal, and inhalation. Understanding the first-pass effect is crucial in drug development and administration, especially in psychiatric drugs, where the concentration of the drug can significantly affect its efficacy and safety.

Kohlberg’s moral development theory identifies stages 5 and 6 as post-conventional morality, which only 15% of individuals reach. This stage involves the capacity to discern conflicting moral standards and comprehend the variations in moral standards across different societies. Nazma’s reasoning demonstrates her ability to do so. In contrast, at the conventional morality stage, she may have given the same response but relied on someone else’s judgment regarding whether property of life takes precedence. The ultimate stage of Kohlberg’s moral development is universal principles, which refers to the ability to evaluate the correctness of our society’s regulations and assess their fairness from the standpoint of social justice.

The types of fear that arise during childhood and adolescence vary depending on the age of the individual. Fear of new things, like strangers, is common at 6 months and peaks at 2 years old. Fear of heights typically starts at 6 to 8 months and intensifies when the child begins to walk. From 3 to 5 years old, children often fear animals, the dark, and monsters. Between 6 and 11 years old, fear of embarrassing social situations, such as being made fun of, may develop. During adolescence, fear of death, failure, social events like parties, and even nuclear war may become more prevalent.

Inhibited Mania

Inhibited mania is one of the six mixed affective states identified by Kraepelin. It is characterized by symptoms of both mania and depression, but with a predominance of depressive features. Patients with inhibited mania may experience feelings of sadness, guilt, and worthlessness, as well as decreased energy and motivation. At the same time, they may also exhibit symptoms of mania, such as increased activity, impulsivity, and irritability.

Inhibited mania is considered an autonomous mixed episode, meaning that the patient consistently experiences symptoms of both mania and depression. This type of mixed state is associated with a poorer prognosis compared to those occurring between transitions from one mood state to another.

Treatment for inhibited mania typically involves a combination of mood stabilizers, antidepressants, and psychotherapy. It is important for clinicians to carefully monitor patients with inhibited mania, as they may be at increased risk for suicide and other adverse outcomes.

René Spitz’s Study on Anaclitic Depression in Children

René Spitz conducted a study on children who were deprived of their primary caregiver and found that they experienced a type of depression known as anaclitic depression. This type of depression is characterized by a lack of interest in the environment, a decrease in physical activity, and a failure to thrive. Spitz’s study highlights the importance of a primary caregiver in a child’s development and the negative effects of deprivation on their emotional and physical well-being. The study emphasizes the need for children to form secure attachments with their caregivers to promote healthy development.

The process at play in this situation can be fully described as splitting. While the young woman may experience idealisation and denigration towards staff, these terms do not fully capture the impact on the team. Splitting can lead to a division within the staff team, with those who are idealised wanting to rescue the patient and those who are denigrated wanting to punish of remove them. This process likely involves both transference and projective identification. It is important to note that the concept of black and white thinking, commonly used in cognitive-behavioral therapy, is related but not the most accurate description of this phenomenon.

Antipsychotic medications have been associated with an increased risk of seizures, with second generation antipsychotics (SGAs) being more likely to cause seizures than first generation antipsychotics (FGAs). Among SGAs, clozapine has the highest risk of inducing seizures, while olanzapine and quetiapine also carry a relatively high risk. On the other hand, risperidone, haloperidol, and aripiprazole are considered to be relatively low risk in terms of inducing seizures. It is important for healthcare providers to be aware of these risks and monitor patients accordingly.

Formal Thought Disorders

In formal thought disorders, changes in the speed, coherence, and cogency of thought can be observed from a patient’s speech. These disorders can also be self-reported and may be accompanied by enhanced use of nonverbal language. One possible indication is a lack of an adequate connection between two consecutive thoughts, which is called ‘asyndesis’.

There are several types of formal thought disorders, including inhibited thinking, retarded thinking, circumstantial thinking, restricted thinking, perseverative thinking, rumination, pressured thinking, flight of ideas, tangential thinking, thought blocking, disruption of thought, incoherence/derailment, and neologisms.

Inhibited thinking is about the subjective experience of the patient, who may feel that their thinking process is slowed down of blocked by an inner wall of resistance. Retarded thinking, on the other hand, is about the observed quality of thought as inferred through speech, where the flow of thought processes is slowed down and sluggish.

Circumstantial thinking refers to an inability to separate the essential from the unessential during a conversation without rendering the conversation incoherent. Restricted thinking involves a limited range of thought content, fixation on one particular topic of a small number of topics only, and a stereotyped pattern of thinking.

Perseverative thinking is characterized by the persistent repetition of previously used words, phrases, of details to the point where they become meaningless in the context of the current stage of the interview. Rumination is the endless mental preoccupation with, of excessive concern over, mostly unpleasant thoughts.

Pressured thinking, also known as crowding of thought, is when the patient feels helplessly exposed to the pressures of floods of different ideas of thoughts. Flight of ideas involves an increasing multitude of thoughts and ideas which are no longer firmly guided by clear goal-directed thinking.

Tangential thinking occurs when the patient appears to understand the contents of the questions addressed to them but provides answers which are completely out of context. Thought blocking of disruption of thought refers to sudden disruption of an otherwise normal flow of thought of speech for no obvious reason.

Incoherence of derailment is when the interviewer is unable to establish sensible connections between the patient’s thinking and verbal output, which is sometimes also called derailment. Neologisms involve the formation of new words of usage of words which disregard normal conventions and are generally not easily understandable.

Dhat is a syndrome that is specific to Indian culture and affects men. Those who suffer from it experience anxiety about the presence of semen in their urine, which they believe leads to a loss of energy.

Creutzfeldt-Jakob Disease: Differences between vCJD and CJD

Creutzfeldt-Jakob Disease (CJD) is a prion disease that includes scrapie, BSE, and Kuru. However, there are important differences between sporadic (also known as classic) CJD and variant CJD. The table below summarizes these differences.

vCJD:
– Longer duration from onset of symptoms to death (a year of more)
– Presents with psychiatric and behavioral symptoms before neurological symptoms
– MRI shows pulvinar sign
– EEG shows generalized slowing
– Originates from infected meat products
– Affects younger people (age 25-30)

CJD:
– Shorter duration from onset of symptoms to death (a few months)
– Presents with neurological symptoms
– MRI shows bilateral anterior basal ganglia high signal
– EEG shows biphasic and triphasic waves 1-2 per second
– Originates from genetic mutation (bad luck)
– Affects older people (age 55-65)

Overall, understanding the differences between vCJD and CJD is important for diagnosis and treatment.

Fatal familial insomnia (FFI) is characterized by minimal spongiform change, but notable thalamic atrophy and astrogliosis. Diagnosis of FFI relies heavily on immunohistochemistry and genotyping. In contrast, spongiform change is a hallmark of CJD and Kuru. The majority of CJD cases (85%) are sporadic, while only a small percentage are caused by consuming contaminated food (variant CJD of vCJD).

Diogenes syndrome is a condition where elderly reclusive individuals, often wealthy and intelligent, exhibit gross self-neglect without necessarily having a psychiatric illness. It is named after an ancient Greek philosopher known for his simple lifestyle. Briquet’s syndrome, now called somatisation syndrome, is a chronic condition where individuals have multiple physical complaints across various systems without any physical cause found. Cotard’s syndrome is a type of psychotic depression in the elderly, characterized by nihilistic and hypochondriacal delusions, along with a depressed mood and either retardation of agitation. Munchausen’s syndrome is a factitious disorder where individuals repeatedly seek medical treatment for false symptoms and history, seemingly motivated by assuming the role of a patient and receiving care.

Prosopagnosia is a condition where individuals are unable to recognize familiar faces, which can be caused by damage to the fusiform area of be congenital. Achromatopsia, on the other hand, is color blindness that can result from thalamus damage. Parietal lobe lesions can cause agraphesthesia, which is the inability to recognize numbers of letters traced on the palm, and astereognosis, which is the inability to recognize an item by touch. Lastly, phonagnosia is the inability to recognize familiar voices and is the auditory equivalent of prosopagnosia, although it is not as well-researched.

Perseveration: The Clinical Symptoms in Chronic Schizophrenia and Organic Dementia

Perseveration is a common behavior observed in patients with organic brain involvement. It is characterized by the conscious continuation of an act of an idea. This behavior is frequently seen in patients with delirium, epilepsy, dementia, schizophrenia, and normal individuals under extreme fatigue of drug-induced states.

In chronic schizophrenia and organic dementia, perseveration is a prominent symptom. Patients with these conditions tend to repeat the same words, phrases, of actions over and over again, even when it is no longer appropriate of relevant to the situation. This behavior can be frustrating for caregivers and family members, and it can also interfere with the patient’s ability to communicate effectively.

In schizophrenia, perseveration is often associated with disorganized thinking and speech. Patients may jump from one topic to another without any logical connection, and they may repeat the same words of phrases in an attempt to express their thoughts. In organic dementia, perseveration is a sign of cognitive decline and memory impairment. Patients may repeat the same stories of questions, forgetting that they have already asked of answered them.

Overall, perseveration is a common symptom in patients with organic brain involvement, and it can have a significant impact on their daily functioning and quality of life. Understanding this behavior is essential for effective management and treatment of these conditions.

Projective identification is a multifaceted mechanism that involves elements of transference, countertransference, and projection. It occurs when a patient’s mistaken belief leads them to behave in a manner that causes the other person in the interaction to adopt the attitudes that the patient wrongly attributed to them.

For instance, a person at an airport who is overly anxious about being perceived as a terrorist may draw the attention of security guards. In a similar vein, a patient’s assumption that a doctor holds them in contempt may prompt them to act in a manner that elicits disrespectful feelings from the doctor.

Clozapine is an atypical antipsychotic drug that acts as an antagonist at various receptors, including dopamine, histamine, serotonin, adrenergic, and cholinergic receptors. It is mainly metabolized by CYP1A2, and its plasma levels can be affected by inducers and inhibitors of this enzyme. Clozapine is associated with several side effects, including drowsiness, constipation, weight gain, and hypersalivation. Hypersalivation is a paradoxical side effect, and its mechanism is not fully understood, but it may involve clozapine agonist activity at the muscarinic M4 receptor and antagonist activity at the alpha-2 adrenoceptor. Clozapine is also associated with several potentially dangerous adverse events, including agranulocytosis, myocarditis, seizures, severe orthostatic hypotension, increased mortality in elderly patients with dementia-related psychosis, colitis, pancreatitis, thrombocytopenia, thromboembolism, and insulin resistance and diabetes mellitus. The BNF advises caution in using clozapine in patients with prostatic hypertrophy, susceptibility to angle-closure glaucoma, and adults over 60 years. Valproate should be considered when using high doses of clozapine, plasma levels > 0.5 mg/l, of when the patient experiences seizures. Myocarditis is a rare but potentially fatal adverse event associated with clozapine use, and its diagnosis is based on biomarkers and clinical features. The mortality rate of clozapine-induced myocarditis is high, and subsequent use of clozapine in such cases leads to recurrence of myocarditis in most cases.

Piaget’s Stages of Development and Key Concepts

Piaget developed four stages of development that describe how children think and acquire knowledge. The first stage is the Sensorimotor stage, which occurs from birth to 18-24 months. In this stage, infants learn through sensory observation and gain control of their motor functions through activity, exploration, and manipulation of the environment.

The second stage is the Preoperational stage, which occurs from 2 to 7 years. During this stage, children use symbols and language more extensively, but they are unable to think logically of deductively. They also use a type of magical thinking and animistic thinking.

The third stage is the Concrete Operational stage, which occurs from 7 to 11 years. In this stage, egocentric thought is replaced by operational thought, which involves dealing with a wide array of information outside the child. Children in this stage begin to use limited logical thought and can serialise, order, and group things into classes on the basis of common characteristics.

The fourth and final stage is the Formal Operations stage, which occurs from 11 through the end of adolescence. This stage is characterized by the ability to think abstractly, to reason deductively, to define concepts, and also by the emergence of skills for dealing with permutations and combinations.

Piaget also developed key concepts, including schema, assimilation, and accommodation. A schema is a category of knowledge and the process of obtaining that knowledge. Assimilation is the process of taking new information into an existing schema, while accommodation involves altering a schema in view of additional information.

Overall, Piaget’s stages of development and key concepts provide a framework for understanding how children learn and acquire knowledge.

Understanding the Volume of Distribution in Pharmacology

The volume of distribution (Vd) is a crucial concept in pharmacology that helps determine how a drug distributes in the body. It is also known as the apparent volume of distribution, as it is an abstract volume. The Vd indicates whether a drug concentrates in the plasma of spreads out in the body. Drugs that are highly polar tend to stay in central compartments such as the plasma, resulting in a low Vd. Conversely, drugs that are more lipid-soluble are distributed widely, such as in fat, resulting in a high Vd.

The Vd is calculated by dividing the amount of drug in the body by the concentration in the plasma. Clinically, the Vd is used to determine the loading dose of a drug required for a desired blood concentration and to estimate blood concentration in the treatment of overdose. The units of Vd are in volume.

The apparent volume of distribution is dependent on the drug’s lipid of water solubility, plasma protein binding, and tissue binding. Plasma protein binding affects the Vd, as drugs that bind to plasma proteins like albumin have a smaller apparent volume of distribution. This is because they are extracted from plasma and included in drug concentration measurements, which can give a misleading impression of their volume of distribution. Understanding the Vd is essential in pharmacology to ensure the safe and effective use of drugs.

Altered Perceptual Experiences

Disorders of perception can be categorized into sensory distortions and sensory deceptions. Sensory distortions involve changes in the intensity, spatial form, of quality of a perception. Examples include hyperaesthesia, hyperacusis, and micropsia. Sensory deceptions, on the other hand, involve new perceptions that are not based on any external stimulus. These include illusions and hallucinations.

Illusions are altered perceptions of a stimulus, while hallucinations are perceptions in the absence of a stimulus. Completion illusions, affect illusions, and pareidolic illusions are examples of illusions. Auditory, visual, gustatory, olfactory, and tactile hallucinations are different types of hallucinations. Pseudohallucinations are involuntary and vivid sensory experiences that are interpreted in a non-morbid way. They are different from true hallucinations in that the individual is able to recognize that the experience is an internally generated event.

Understanding the different types of altered perceptual experiences is important in the diagnosis and treatment of various mental health conditions.

The fundamental attribution error pertains to our tendency to make biased judgments about the behavior of others, rather than our own.

Attribution Theory: Understanding How We Explain Events

Attribution theory provides a framework for understanding how individuals explain events in their environment. It examines how people use information to arrive at causal explanations for events and what factors influence their judgments. Fritz Heider first proposed a theory of attribution in 1958.

However, attribution is prone to biases such as the Fundamental Attribution Error (FAE), which overemphasizes dispositional factors over situational causes when making attributions about others’ behavior. The Actor-Observer Bias, on the other hand, undervalues dispositional explanations and overvalued situational explanations of our own behavior. Correspondence bias is the tendency to draw inferences about a person’s unique and enduring dispositions from behaviors that can be entirely explained by the situations in which they occur. Self-serving bias refers to people’s tendency to attribute their successes to internal factors but attribute their failures to external factors. Hostile Attribution Bias (HAB) is an interpretive bias where individuals interpret ambiguous behavior as hostile, leading to aggression. Finally, the False Consensus Effect is the tendency for people to project their way of thinking onto others, assuming that everyone else thinks the same way they do.

Overall, attribution theory helps us understand how people make sense of events in their environment, but it is important to be aware of the biases that can influence our judgments.

The movements observed in chorea are characterized as both jerky and flowing, often described as resembling a dance. It is important to distinguish chorea from athetosis, which is less abrupt and more akin to the movements of a worm. Sydenham’s chorea, which typically affects children following an infection with Group A beta-haemolytic Streptococcus, was historically known as St Vitus’ dance.

Movement Disorders: Key Features

Movement disorders refer to a range of conditions that affect voluntary muscle movements. These disorders can be caused by various factors, including neurological conditions, medication side effects, and metabolic imbalances. The following table outlines some of the key features of common movement disorders:

Akinesia: Absence of loss of control of voluntary muscle movements, often seen in severe Parkinson’s disease.

Bradykinesia: Slowness of voluntary movement, a core symptom of Parkinson’s disease.

Akathisia: Subjective feeling of inner restlessness, often caused by antipsychotic medication use.

Athetosis: Continuous stream of slow, flowing, writhing involuntary movements, often seen in cerebral palsy, stroke, and Huntington’s disease.

Chorea: Brief, quasi-purposeful, irregular contractions that appear to flow from one muscle to the next, often seen in Huntington’s disease and Wilson’s disease.

Dystonia: Involuntary sustained of intermittent muscle contractions that cause twisting and repetitive movements, abnormal postures, of both.

Dyskinesia: General term referring to problems with voluntary movements and the presence of involuntary movements, often drug-induced.

Myoclonus: A sequence of repeated, often non-rhythmic, brief shock-like jerks due to sudden involuntary contraction of relaxation of one of more muscles.

Parkinsonism: Syndrome characterized by tremor, rigidity, and bradykinesia.

Tic: Sudden, repetitive, non-rhythmic, stereotyped motor movement of vocalization involving discrete muscle groups, often seen in Tourette’s syndrome.

Tremor: Involuntary, rhythmic, alternating movement of one of more body parts, often seen in essential tremor, Parkinson’s disease, and alcohol withdrawal.

Hemiballismus: Repetitive, but constantly varying, large amplitude involuntary movements of the proximal parts of the limbs, often seen in stroke and traumatic brain injury.

Stereotypies: Repetitive, simple movements that can be voluntarily suppressed, often seen in autism and intellectual disability.

It is important to consider the underlying conditions and factors that may contribute to movement disorders in order to properly diagnose and treat these conditions.

Overview of Cranial Nerves and Their Functions

The cranial nerves are a complex system of nerves that originate from the brain and control various functions of the head and neck. There are twelve cranial nerves, each with a specific function and origin. The following table provides a simplified overview of the cranial nerves, including their origin, skull exit, modality, and functions.

The first cranial nerve, the olfactory nerve, originates from the telencephalon and exits through the cribriform plate. It is a sensory nerve that controls the sense of smell. The second cranial nerve, the optic nerve, originates from the diencephalon and exits through the optic foramen. It is a sensory nerve that controls vision.

The third cranial nerve, the oculomotor nerve, originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement, pupillary constriction, and lens accommodation. The fourth cranial nerve, the trochlear nerve, also originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement.

The fifth cranial nerve, the trigeminal nerve, originates from the pons and exits through different foramina depending on the division. It is a mixed nerve that controls chewing and sensation of the anterior 2/3 of the scalp. It also tenses the tympanic membrane to dampen loud noises.

The sixth cranial nerve, the abducens nerve, originates from the pons and exits through the superior orbital fissure. It is a motor nerve that controls eye movement. The seventh cranial nerve, the facial nerve, also originates from the pons and exits through the internal auditory canal. It is a mixed nerve that controls facial expression, taste of the anterior 2/3 of the tongue, and tension on the stapes to dampen loud noises.

The eighth cranial nerve, the vestibulocochlear nerve, originates from the pons and exits through the internal auditory canal. It is a sensory nerve that controls hearing. The ninth cranial nerve, the glossopharyngeal nerve, originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls taste of the posterior 1/3 of the tongue, elevation of the larynx and pharynx, and swallowing.

The tenth cranial nerve, the vagus nerve, also originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls swallowing, voice production, and parasympathetic supply to nearly all thoracic and abdominal viscera. The eleventh cranial nerve, the accessory nerve, originates from the medulla and exits through the jugular foramen. It is a motor nerve that controls shoulder shrugging and head turning.

The twelfth cranial nerve, the hypoglossal nerve, originates from the medulla and exits through the hypoglossal canal. It is a motor nerve that controls tongue movement. Overall, the cranial nerves play a crucial role in controlling various functions of the head and neck, and any damage of dysfunction can have significant consequences.

The working memory is overseen by the central executive, which manages all its functions. Although the exact location of the central executive is not fully comprehended, it is believed to involve various regions of the brain.

Memory Forms

Memory is the ability to store, retain, and retrieve information. There are different forms of memory, including sensory memory, short-term/working memory, and long-term memory.

Sensory memory is the capacity for briefly retaining the large amounts of information that people encounter daily. It includes echoic memory (gathered through auditory stimuli), iconic memory (gathered through sight), and haptic memory (acquired through touch).

Short-term memory is the ability to keep a small amount of information available for a short period of time. Atkinson and Shiffrin’s multistore model (1968) suggests the existence of a short-term storehouse with limited capacity. Baddeley and Hitch (1974) further developed the concept of short-term memory, which eventually became known as Baddeley’s multi-storehouse model (2000). This model includes the central executive, visuospatial sketchpad, phonological buffer/loop, and episodic buffer.

Long-term memory includes declarative (of explicit) memories, which can be consciously retrieved, and nondeclarative (of implicit) memories, which cannot. Declarative memory includes episodic memory (stores personal experiences) and semantic memory (stores information about facts and concepts). Non-declarative memory includes procedural memory (recalls motor and executive skills), associative memory (storage and retrieval of information through association with other information), and non-associative memory (refers to newly learned behavior through repeated exposure to an isolated stimulus).

Overall, memory is a complex and essential cognitive function that plays a crucial role in learning, reasoning, and understanding.

Patients who are not informed about the potential side effects of a medication may initially agree to treatment, but are less likely to follow through if they experience adverse effects. To improve adherence, healthcare providers can implement various strategies. These include educating patients about the treatment, discussing the benefits and drawbacks of different options, and promoting insight into the importance of prophylactic treatment. Encouraging patients to be open about any side effects they experience, even if they are embarrassing, can also help. Regular reviews of the medication plan, including discussions about side effects and the possibility of stopping medication if necessary, can further improve adherence. Simplifying the medication regimen and choosing medications with tolerable side effect profiles can also be helpful. Communication between the patient and their GP should be clear and in writing. Finally, the use of depot antipsychotics may be considered as an option.

Electroencephalography

Electroencephalography (EEG) is a clinical test that records the brain’s spontaneous electrical activity over a short period of time using multiple electrodes placed on the scalp. It is mainly used to rule out organic conditions and can help differentiate dementia from other disorders such as metabolic encephalopathies, CJD, herpes encephalitis, and non-convulsive status epilepticus. EEG can also distinguish possible psychotic episodes and acute confusional states from non-convulsive status epilepticus.

Not all abnormal EEGs represent an underlying condition, and psychotropic medications can affect EEG findings. EEG abnormalities can also be triggered purposely by activation procedures such as hyperventilation, photic stimulation, certain drugs, and sleep deprivation.

Specific waveforms are seen in an EEG, including delta, theta, alpha, sigma, beta, and gamma waves. Delta waves are found frontally in adults and posteriorly in children during slow wave sleep, and excessive amounts when awake may indicate pathology. Theta waves are generally seen in young children, drowsy and sleeping adults, and during meditation. Alpha waves are seen posteriorly when relaxed and when the eyes are closed, and are also seen in meditation. Sigma waves are bursts of oscillatory activity that occur in stage 2 sleep. Beta waves are seen frontally when busy of concentrating, and gamma waves are seen in advanced/very experienced meditators.

Certain conditions are associated with specific EEG changes, such as nonspecific slowing in early CJD, low voltage EEG in Huntington’s, diffuse slowing in encephalopathy, and reduced alpha and beta with increased delta and theta in Alzheimer’s.

Common epileptiform patterns include spikes, spike/sharp waves, and spike-waves. Medications can have important effects on EEG findings, with clozapine decreasing alpha and increasing delta and theta, lithium increasing all waveforms, lamotrigine decreasing all waveforms, and valproate having inconclusive effects on delta and theta and increasing beta.

Overall, EEG is a useful tool in clinical contexts for ruling out organic conditions and differentiating between various disorders.

Electroencephalography

Electroencephalography (EEG) is a clinical test that records the brain’s spontaneous electrical activity over a short period of time using multiple electrodes placed on the scalp. It is mainly used to rule out organic conditions and can help differentiate dementia from other disorders such as metabolic encephalopathies, CJD, herpes encephalitis, and non-convulsive status epilepticus. EEG can also distinguish possible psychotic episodes and acute confusional states from non-convulsive status epilepticus.

Not all abnormal EEGs represent an underlying condition, and psychotropic medications can affect EEG findings. EEG abnormalities can also be triggered purposely by activation procedures such as hyperventilation, photic stimulation, certain drugs, and sleep deprivation.

Specific waveforms are seen in an EEG, including delta, theta, alpha, sigma, beta, and gamma waves. Delta waves are found frontally in adults and posteriorly in children during slow wave sleep, and excessive amounts when awake may indicate pathology. Theta waves are generally seen in young children, drowsy and sleeping adults, and during meditation. Alpha waves are seen posteriorly when relaxed and when the eyes are closed, and are also seen in meditation. Sigma waves are bursts of oscillatory activity that occur in stage 2 sleep. Beta waves are seen frontally when busy of concentrating, and gamma waves are seen in advanced/very experienced meditators.

Certain conditions are associated with specific EEG changes, such as nonspecific slowing in early CJD, low voltage EEG in Huntington’s, diffuse slowing in encephalopathy, and reduced alpha and beta with increased delta and theta in Alzheimer’s.

Common epileptiform patterns include spikes, spike/sharp waves, and spike-waves. Medications can have important effects on EEG findings, with clozapine decreasing alpha and increasing delta and theta, lithium increasing all waveforms, lamotrigine decreasing all waveforms, and valproate having inconclusive effects on delta and theta and increasing beta.

Overall, EEG is a useful tool in clinical contexts for ruling out organic conditions and differentiating between various disorders.

Cannabis attaches to cannabinoid receptors, while heroin acts as an opioid agonist and alters the function of dopamine.

Serotonin: Synthesis and Breakdown

Serotonin, also known as 5-Hydroxytryptamine (5-HT), is synthesized in the central nervous system (CNS) in the raphe nuclei located in the brainstem, as well as in the gastrointestinal (GI) tract in enterochromaffin cells. The amino acid L-tryptophan, obtained from the diet, is used to synthesize serotonin. L-tryptophan can cross the blood-brain barrier, but serotonin cannot.

The transformation of L-tryptophan into serotonin involves two steps. First, hydroxylation to 5-hydroxytryptophan is catalyzed by tryptophan hydroxylase. Second, decarboxylation of 5-hydroxytryptophan to serotonin (5-hydroxytryptamine) is catalyzed by L-aromatic amino acid decarboxylase.

Serotonin is taken up from the synapse by a monoamine transporter (SERT). Substances that block this transporter include MDMA, amphetamine, cocaine, TCAs, and SSRIs. Serotonin is broken down by monoamine oxidase (MAO) and then by aldehyde dehydrogenase to 5-Hydroxyindoleacetic acid (5-HIAA).

The correct answer is the Lazarus theory, which proposes that emotions are the result of cognitive appraisal of a situation. According to this theory, the thought I’m being burgled triggers a cognitive appraisal of the situation, which in turn leads to the emotional response of fear. This is in contrast to the Singer-Schachter theory, which suggests that emotions are the result of a combination of physiological arousal and cognitive interpretation of that arousal.

Theories of Emotion

In membership exams, four main theories of emotion are commonly discussed: James-Lange theory, Cannon-Bard theory, Singer-Schachter theory, and Lazarus theory. The key to understanding the differences between these theories is to identify where the stimulus for the emotion arises.

According to the James-Lange theory, emotions occur as a result of bodily sensations. For instance, if you see a big dog, your heart races, and you feel afraid. This theory proposes that certain external stimuli stimulate specific sensory organs, leading to a particular emotion. The sequence of events suggested by this theory is as follows: event – arousal – interpretation – emotion. In other words, the stimulus for emotion arises from physical sensations.

The Cannon-Bard theory, also known as the thalami theory, proposes that when an event occurs, one experiences an emotion at the same time as physiological changes. The stimulus for emotion arises simultaneously in the body and the mind.

The Singer-Schachter theory, also known as the two-factor theory, suggests that emotions result from both physiological changes and the context. For example, if your heart is racing, and you are about to have an exam, you label yourself as afraid. However, if your heart is racing, and you are about to kiss your partner, you label your emotional state as excited. The stimulus for emotion arises via a combination of physical sensations and the mind’s appraisal of them.

Finally, the Lazarus theory proposes that a thought is required before an emotion occurs. For instance, if you see a big dog, you think it is going to bite you, and you feel afraid. The stimulus for emotion arises from the mind.

In summary, these theories offer different perspectives on the relationship between physical sensations, cognitive processes, and emotions.

Norepinephrine: Synthesis, Release, and Breakdown

Norepinephrine is synthesized from tyrosine through a series of enzymatic reactions. The first step involves the conversion of tyrosine to L-DOPA by tyrosine hydroxylase. L-DOPA is then converted to dopamine by DOPA decarboxylase. Dopamine is further converted to norepinephrine by dopamine beta-hydroxylase. Finally, norepinephrine is converted to epinephrine by phenylethanolamine-N-methyltransferase.

The primary site of norepinephrine release is the locus coeruleus, also known as the blue spot, which is located in the pons. Once released, norepinephrine is broken down by two enzymes: catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). These enzymes play a crucial role in regulating the levels of norepinephrine in the body.

Automatic obedience is a term used to describe the act of obeying without conscious thought. Mitgehen is a related term that describes an exaggerated form of automatic obedience. It is important to be aware of other German terms such as Gedankenlautwerden, which refers to the experience of hearing one’s own thoughts out loud, Gegenhalten, which is when a patient resists passive movements with equal force, and Schnauzkrampf, a facial grimace often seen in catatonic patients. Another term to be aware of is Vorbeigehen/vorbeireden, which is observed in Ganser syndrome and refers to giving approximate answers to questions. For example, a patient may answer 14 when asked how many fingers a man has.

– Catatonia is a psychiatric syndrome characterized by disturbed motor functions, mood, and thought.
– Key behaviors associated with catatonia include stupor, posturing, waxy flexibility, negativism, automatic obedience, mitmachen, mitgehen, ambitendency, psychological pillow, forced grasping, obstruction, echopraxia, aversion, mannerisms, stereotypies, motor perseveration, echolalia, and logorrhoea.
– These behaviors are often tested in exam questions.
– Karl Ludwig Kahlbaum is credited with the original clinical description of catatonia.

The Dopamine Hypothesis is a theory that suggests that dopamine and dopaminergic mechanisms are central to schizophrenia. This hypothesis was developed based on observations that antipsychotic drugs provide at least some degree of D2-type dopamine receptor blockade and that it is possible to induce a psychotic episode in healthy subjects with pharmacological dopamine agonists. The hypothesis was further strengthened by the finding that antipsychotic drugs’ clinical effectiveness was directly related to their affinity for dopamine receptors. Initially, the belief was that the problem related to an excess of dopamine in the brain. However, later studies showed that the relationship between hypofrontality and low cerebrospinal fluid (CSF) dopamine metabolite levels indicates low frontal dopamine levels. Thus, there was a move from a one-sided dopamine hypothesis explaining all facets of schizophrenia to a regionally specific prefrontal hypodopaminergia and a subcortical hyperdopaminergia. In summary, psychosis appears to result from excessive dopamine activity in the striatum, while the negative symptoms seen in schizophrenia appear to result from too little dopamine activity in the frontal lobe. Antipsychotic medications appear to help by countering the effects of increased dopamine by blocking postsynaptic D2 receptors in the striatum.

Inheritance: Phenotype and Genotype

Phenotype refers to the observable traits of an individual, such as height, eye colour, and blood type. These traits are a result of the interaction between an individual’s genotype and the environment. The term ‘pheno’ comes from the same root as ‘phenomenon’ and simply means ‘observe’.

On the other hand, genotype refers to an individual’s collection of genes. These genes determine the traits that an individual will inherit from their parents. A haplotype, on the other hand, is a set of DNA variations of polymorphisms that tend to be inherited together.

Finally, a karyotype refers to an individual’s collection of chromosomes. These chromosomes contain the genetic information that determines an individual’s traits. By examining an individual’s karyotype, scientists can determine if there are any genetic abnormalities of disorders present.

Clock Drawing Test: A Screening Tool for Cognitive Dysfunction

The clock drawing test is a widely used screening tool for cognitive dysfunction. It involves asking the patient to draw a clock on a piece of paper, placing the numbers on the clock face and drawing the hands to indicate 10 minutes past 11. This simple task assesses a range of cognitive functions, including visuospatial ability, motor function, attention, and comprehension.

The test is quick and easy to administer, making it a useful tool for healthcare professionals to identify potential cognitive impairment in patients. The clock drawing test has been shown to be effective in detecting cognitive dysfunction in a variety of conditions, including Alzheimer’s and Parkinson’s disease.

The image below illustrates examples of clocks drawn correctly by healthy controls and those drawn by patients with Alzheimer’s and Parkinson’s disease. By comparing the drawings, healthcare professionals can quickly identify potential cognitive dysfunction and take appropriate action.

Thurstone’s Theory of Intelligence

Louis Leon Thurstone believed that intelligence could not be reduced to a single factor. Instead, he proposed that intelligence is composed of seven distinct abilities, which he called the primary abilities. These abilities include word fluency, verbal comprehension, spatial visualization, number facility, associative memory, reasoning, and perceptual speed. According to Thurstone, each of these abilities is independent of the others and contributes to an individual’s overall intelligence. This theory challenged the prevailing view of intelligence at the time, which held that intelligence could be measured by a single factor known as the g factor. Thurstone’s theory has had a lasting impact on the field of psychology and has influenced the development of modern intelligence tests.

Nucleotides: The Building Blocks of DNA and RNA

Nucleotides are the fundamental units of DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Each nucleotide consists of three components: a sugar molecule (deoxyribose in DNA and ribose in RNA), a phosphate group, and a nitrogenous base. The nitrogenous bases can be classified into two categories: purines and pyrimidines. The purine bases include adenine and guanine, while the pyrimidine bases are cytosine, thymine (in DNA), and uracil (in RNA).

The arrangement of nucleotides in DNA and RNA determines the genetic information that is passed from one generation to the next. The sequence of nitrogenous bases in DNA forms the genetic code that determines the traits of an organism. RNA, on the other hand, plays a crucial role in protein synthesis by carrying the genetic information from DNA to the ribosomes, where proteins are synthesized.

Understanding the structure and function of nucleotides is essential for understanding the molecular basis of life. The discovery of the structure of DNA and the role of nucleotides in genetic information has revolutionized the field of biology and has led to many breakthroughs in medicine, biotechnology, and genetics.

Lewy body dementia is a neurodegenerative disorder that is characterized by both macroscopic and microscopic changes in the brain. Macroscopically, there is cerebral atrophy, but it is less marked than in Alzheimer’s disease, and the brain weight is usually in the normal range. There is also pallor of the substantia nigra and the locus coeruleus, which are regions of the brain that produce dopamine and norepinephrine, respectively.

Microscopically, Lewy body dementia is characterized by the presence of intracellular protein accumulations called Lewy bodies. The major component of a Lewy body is alpha synuclein, and as they grow, they start to draw in other proteins such as ubiquitin. Lewy bodies are also found in Alzheimer’s disease, but they tend to be in the amygdala. They can also be found in healthy individuals, although it has been suggested that these may be pre-clinical cases of dementia with Lewy bodies. Lewy bodies are also found in other neurodegenerative disorders such as progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy.

In Lewy body dementia, Lewy bodies are mainly found within the brainstem, but they are also found in non-brainstem regions such as the amygdaloid nucleus, parahippocampal gyrus, cingulate cortex, and cerebral neocortex. Classic brainstem Lewy bodies are spherical intraneuronal cytoplasmic inclusions, characterized by hyaline eosinophilic cores, concentric lamellar bands, narrow pale halos, and immunoreactivity for alpha synuclein and ubiquitin. In contrast, cortical Lewy bodies typically lack a halo.

Most brains with Lewy body dementia also show some plaques and tangles, although in most instances, the lesions are not nearly as severe as in Alzheimer’s disease. Neuronal loss and gliosis are usually restricted to brainstem regions, particularly the substantia nigra and locus ceruleus.

Genomic Imprinting and its Role in Psychiatric Disorders

Genomic imprinting is a phenomenon where a piece of DNA behaves differently depending on whether it is inherited from the mother of the father. This is because DNA sequences are marked of imprinted in the ovaries and testes, which affects their expression. In psychiatry, two classic examples of genomic imprinting disorders are Prader-Willi and Angelman syndrome.

Prader-Willi syndrome is caused by a deletion of chromosome 15q when inherited from the father. This disorder is characterized by hypotonia, short stature, polyphagia, obesity, small gonads, and mild mental retardation. On the other hand, Angelman syndrome, also known as Happy Puppet syndrome, is caused by a deletion of 15q when inherited from the mother. This disorder is characterized by an unusually happy demeanor, developmental delay, seizures, sleep disturbance, and jerky hand movements.

Overall, genomic imprinting plays a crucial role in the development of psychiatric disorders. Understanding the mechanisms behind genomic imprinting can help in the diagnosis and treatment of these disorders.

Attachment (Ainsworth)

Psychologist Mary Ainsworth developed the ‘Strange Situation procedure’ to study and categorize attachment in children aged 12 to 18 months. The procedure involves seven steps, including two separations and two reunions, and takes place in one room. The child’s attachment is classified into one of three styles: secure, anxious-resistant, and anxious-avoidant. A fourth category, disorganized, is sometimes observed. Ainsworth suggested that the child’s attachment style is determined by the primary caregiver’s behavior.

Mary Main later developed the Adult Attachment Interview and identified four categories of attachment in adults that correspond to those observed in the strange situation. The distribution of adult attachment styles correlates with those of the strange situation, with 70% of children and adults having secure attachment. Attachment styles also seem to be passed on to subsequent generations.

Maslow’s Hierarchy of Needs is a theory of motivation introduced by Abraham Maslow. The hierarchy consists of five levels, with the most basic needs at the bottom and the most advanced needs at the top. Maslow proposed that a person would only become concerned with the needs of a particular level when all the needs of the lower levels had been satisfied. The levels include physiological needs, safety needs, social needs, esteem needs, and self-actualization needs. Maslow also made a distinction between D-needs (deficiency needs) and B-needs (being needs), with B-needs allowing us to reach our full potential but only after D-needs have been satisfied. Later in life, Maslow expanded upon the model and included cognitive, aesthetic, and transcendence needs, resulting in an eight-staged model. The cognitive needs include knowledge and understanding, while aesthetic needs involve appreciation and search for beauty. Transcendence needs are motivated by values that transcend beyond the personal self.

Prescribing medication for elderly individuals requires consideration of their unique pharmacokinetics and pharmacodynamics. As the body ages, changes in distribution, metabolism, and excretion can affect how medication is absorbed and processed. For example, reduced gastric acid secretion and motility can impact drug absorption, while a relative reduction of body water to body fat can alter the distribution of lipid soluble drugs. Additionally, hepatic metabolism of drugs decreases with age, and the kidneys become less effective, leading to potential accumulation of certain drugs.

In terms of pharmacodynamics, receptor sensitivity tends to increase during old age, meaning smaller doses may be needed. However, older individuals may also take longer to respond to treatment and have an increased incidence of side-effects. It is important to start with a lower dose and monitor closely when prescribing medication for elderly patients, especially considering the potential for interactions with other medications they may be taking.

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

Oxazepam is a significant metabolite found in various benzodiazepines, but it does not produce any significant metabolites of its own. It is occasionally prescribed to individuals with liver impairment because it does not necessitate hepatic oxidation and is instead metabolized through glucuronidation (which is often preserved even in severe liver disease).

The Significance of Active Metabolites in Drug Discovery and Development

Certain drugs are classified as prodrugs, which means that they are inactive when administered and require metabolism to become active. These drugs are converted into an active form, which is referred to as an active metabolite. Some drugs have important active metabolites, such as diazepam, dothiepin, fluoxetine, imipramine, risperidone, amitriptyline, and codeine, which are desmethyldiazepam, dothiepin sulfoxide, norfluoxetine, desipramine, 9-hydroxyrisperidone, nortriptyline, and morphine, respectively.

The role of pharmacologically active metabolites in drug discovery and development is significant. Understanding the active metabolites of a drug can help in the development of more effective and safer drugs. Active metabolites can also provide insights into the pharmacokinetics and pharmacodynamics of a drug, which can aid in the optimization of dosing regimens. Additionally, active metabolites can have different pharmacological properties than the parent drug, which can lead to the discovery of new therapeutic uses for a drug. Therefore, the study of active metabolites is an important aspect of drug discovery and development.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

Drug Clearance: Understanding the Rate of Drug Removal from the Body

Drug clearance refers to the efficiency of drug removal from the plasma, and is measured as the volume of plasma cleared of a drug over a specific time period. The unit of measurement for drug clearance is volume per time. Clearance of a drug involves both metabolism and excretion. When drug intake equals clearance, it is referred to as a steady state, which is usually achieved by 4.5 half-lives. The time taken to reach steady state depends on the half-life of the drug.

There are two main types of clearance: hepatic and renal. Hepatic clearance involves the conversion of the parent drug into a different chemical entity by the liver enzymes, while renal clearance involves the removal of the drug from the plasma into the urine. The clearance of a drug can take one of two forms: zero and first-order kinetics. In zero-order reactions, the clearance of a drug is constant and not related to the concentration of the drug in the plasma. This type of reaction is typically found when the material needed for the reaction to proceed (e.g. enzyme) is saturated. Ethanol and Phenytoin are good examples of this.

Most drugs tend to follow first-order reactions, where the clearance is related to the concentration of the drug in the plasma. The half-life of a drug is the time taken for its concentration to fall by half. In first-order reactions, this is constant. In zero-order reactions, it gets progressively shorter.

It is important to note that elimination and clearance are not the same. Elimination is the irreversible removal of the drug from the body, while clearance is a theoretical volume of blood that is cleared of the drug per unit of time, which is independent of the drug dose of concentration. Understanding drug clearance is crucial in determining the appropriate dosing regimen for a drug.

Classification of Intellectual Disability

Intellectual disability affects approximately 2% of the general population, with an estimated 828,000 adults aged 18 of older affected in England alone. Those with an IQ below 70 are considered to have an intellectual disability, with the average IQ being 100. The severity of intellectual disability is categorized based on IQ scores, with mild intellectual disability being the most common (85% of cases) and profound intellectual disability being the least common (1-2% of cases). People with intellectual disability may require varying levels of support in their daily lives, depending on their individual needs. It is important to use the preferred term ‘people with intellectual disability’ when referring to individuals with this condition.

Promethazine is utilized for its sedative properties in cases of agitation due to the fact that first generation H1 antihistamines easily penetrate the BBB and induce drowsiness.

Antihistamines: Types and Uses

Antihistamines are drugs that block the effects of histamine, a neurotransmitter that regulates physiological function in the gut and potentiates the inflammatory and immune responses of the body. There are two types of antihistamines: H1 receptor blockers and H2 receptor blockers. H1 blockers are mainly used for allergic conditions and sedation, while H2 blockers are used for excess stomach acid.

There are also first and second generation antihistamines. First generation antihistamines, such as diphenhydramine and promethazine, have uses in psychiatry due to their ability to cross the blood brain barrier and their anticholinergic properties. They tend to be sedating and are useful for managing extrapyramidal side effects. Second generation antihistamines, such as loratadine and cetirizine, show limited penetration of the blood brain barrier and are less sedating.

It is important to note that there are contraindications to first-generation antihistamines, including benign prostatic hyperplasia, angle-closure glaucoma, and pyloric stenosis in infants. These do not apply to second-generation antihistamines.

Understanding the Blood Brain Barrier

The blood brain barrier (BBB) is a crucial component of the brain’s defense system against harmful chemicals and ion imbalances. It is a semi-permeable membrane formed by tight junctions of endothelial cells in the brain’s capillaries, which separates the blood from the cerebrospinal fluid. However, certain areas of the BBB, known as circumventricular organs, are fenestrated to allow neurosecretory products to enter the blood.

When it comes to MRCPsych questions, the focus is on the following aspects of the BBB: the tight junctions between endothelial cells, the ease with which lipid-soluble molecules pass through compared to water-soluble ones, the difficulty large and highly charged molecules face in passing through, the increased permeability of the BBB during inflammation, and the theoretical ability of nasally administered drugs to bypass the BBB.

It is important to remember the specific circumventricular organs where the BBB is fenestrated, including the posterior pituitary and the area postrema. Understanding the BBB’s function and characteristics is essential for medical professionals to diagnose and treat neurological disorders effectively.

Individuals from higher social classes are more likely to be diagnosed with bipolar affective disorder and eating disorders, while those from lower social classes are more commonly diagnosed with alcohol dependence, depression, schizophrenia, and substance misuse disorders.

Intellectualisation involves disregarding the emotional aspect of a situation, such as a daughter’s severe illness, by concentrating solely on factual information and particulars. This behaviour is classified as a neurotic defence mechanism.

Delusions are false beliefs that are fixed and can be categorized as primary of secondary. Primary delusions include delusional intuition, delusional perception, delusional atmosphere, and delusional memory. Delusional atmosphere refers to a feeling that something is not right in the world around the patient, without any change in perception. Delusional intuition arises suddenly and occurs in a single stage, while delusional perception is a two-stage phenomenon where the patient misinterprets a normal perception with a delusional meaning. Delusional memory involves remembering past events with a delusional meaning. An example of delusional perception is when a patient misinterprets the marks of freckles and believes that water is being taken out of their body.

The Cerebral Cortex and Neocortex

The cerebral cortex is the outermost layer of the cerebral hemispheres and is composed of three parts: the archicortex, paleocortex, and neocortex. The neocortex accounts for 90% of the cortex and is involved in higher functions such as thought and language. It is divided into 6-7 layers, with two main cell types: pyramidal cells and nonpyramidal cells. The surface of the neocortex is divided into separate areas, each given a number by Brodmann (e.g. Brodmann’s area 17 is the primary visual cortex). The surface is folded to increase surface area, with grooves called sulci and ridges called gyri. The neocortex is responsible for higher cognitive functions and is essential for human consciousness.