Agomelatine (Valdoxan) is a novel antidepressant that functions as an agonist at both MT1 and MT2 receptors, while also acting as a 5HT2C antagonist. Unlike most other antidepressants, it does not affect monoamine uptake.
First-generation antipsychotics work by antagonizing D2 receptors.
Benzodiazepines exert their effects by potentiating GABA.
Noradrenaline reuptake inhibition is a common mechanism of action for many antidepressants, including SNRIs and tricyclics.
SSRI (and other) antidepressants function by inhibiting the reuptake of serotonin.

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

There are several types of perceptual experiences that fall under the category of hallucinations of synaesthesia. Functional hallucinations occur when a normal perception leads to a hallucinatory perception of the same modality, such as hearing music when a tap is running. Delusional perception, on the other hand, is a primary delusional experience that starts with a normal perception and is not an hallucination. Gedankenlautwerden is the experience of hearing one’s thoughts spoken aloud as they are thought, while reflex hallucination occurs when a stimulus in one sensory modality leads to an hallucination in another modality. Finally, synaesthesia is the automatic and involuntary experience of a stimulus in one sensory of cognitive pathway in a second pathway, such as experiencing letters of numbers as inherently coloured.

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.

The symptoms exhibited by the patient are consistent with Koro, a culture-specific disorder observed primarily in males (and occasionally in females) in China and Thailand. For more information, please refer to Edwards JW’s article Indigenous Koro, a genital retraction syndrome of insular Southeast Asia: a critical review published in Cult Med Psychiatry in 1984.

Genetic Conditions and Their Features

Genetic conditions are disorders caused by abnormalities in an individual’s DNA. These conditions can affect various aspects of a person’s health, including physical and intellectual development. Some of the most common genetic conditions and their features are:

– Downs (trisomy 21): Short stature, almond-shaped eyes, low muscle tone, and intellectual disability.
– Angelman syndrome (Happy puppet syndrome): Flapping hand movements, ataxia, severe learning disability, seizures, and sleep problems.
– Prader-Willi: Hyperphagia, excessive weight gain, short stature, and mild learning disability.
– Cri du chat: Characteristic cry, hypotonia, down-turned mouth, and microcephaly.
– Velocardiofacial syndrome (DiGeorge syndrome): Cleft palate, cardiac problems, and learning disabilities.
– Edwards syndrome (trisomy 18): Severe intellectual disability, kidney malformations, and physical abnormalities.
– Lesch-Nyhan syndrome: Self-mutilation, dystonia, and writhing movements.
– Smith-Magenis syndrome: Pronounced self-injurious behavior, self-hugging, and a hoarse voice.
– Fragile X: Elongated face, large ears, hand flapping, and shyness.
– Wolf Hirschhorn syndrome: Mild to severe intellectual disability, seizures, and physical abnormalities.
– Patau syndrome (trisomy 13): Severe intellectual disability, congenital heart malformations, and physical abnormalities.
– Rett syndrome: Regression and loss of skills, hand-wringing movements, and profound learning disability.
– Tuberous sclerosis: Hamartomatous tumors, epilepsy, and behavioral issues.
– Williams syndrome: Elfin-like features, social disinhibition, and advanced verbal skills.
– Rubinstein-Taybi syndrome: Short stature, friendly disposition, and moderate learning disability.
– Klinefelter syndrome: Extra X chromosome, low testosterone, and speech and language issues.
– Jakob’s syndrome: Extra Y chromosome, tall stature, and lower mean intelligence.
– Coffin-Lowry syndrome: Short stature, slanting eyes, and severe learning difficulty.
– Turner syndrome: Short stature, webbed neck, and absent periods.
– Niemann Pick disease (types A and B): Abdominal swelling, cherry red spot, and feeding difficulties.

It is important to note that these features may vary widely among individuals with the same genetic condition. Early diagnosis and intervention can help individuals with genetic conditions reach their full potential and improve their quality of life.

The WAIS-III provides results for verbal IQ, performance IQ, and full scale IQ, which are compared to the average scores of the population. The average IQ for adults is 100, with a standard deviation of 15 points. However, the Wisconsin card sorting test, which is used to evaluate frontal lobe impairment, is not included in the WAIS-III.

Flumazenil acts as an antagonist for GABA-A receptors and is known to reverse the effects of benzodiazepines. While there is some speculation that it may also have an effect on alcohol, this has not been definitively proven.

Mechanisms of Action of Different Drugs

Understanding the mechanisms of action of different drugs is crucial for medical professionals. It is a common topic in exams and can earn easy marks if studied well. This article provides a list of drugs and their mechanisms of action in different categories such as antidepressants, anti dementia drugs, mood stabilizers, anxiolytic/hypnotic drugs, antipsychotics, drugs of abuse, and other drugs. For example, mirtazapine is a noradrenaline and serotonin specific antidepressant that works as a 5HT2 antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, and moderate muscarinic antagonist. Similarly, donepezil is a reversible acetylcholinesterase inhibitor used as an anti dementia drug, while valproate is a GABA agonist and NMDA antagonist used as a mood stabilizer. The article also explains the mechanisms of action of drugs such as ketamine, phencyclidine, buprenorphine, naloxone, atomoxetine, varenicline, disulfiram, acamprosate, and sildenafil.

The Corpus Callosum and Circle of Willis: Important Structures in the Brain

The corpus callosum is a thick bundle of fibers that connects the two cerebral hemispheres. When this structure is divided, communication between the hemispheres is disrupted, resulting in observable effects through experimental techniques. For instance, if an object is presented to the left visual field only (and therefore processed by the right visual cortex only), a subject may be unable to name the object out loud due to the speech center typically being located in the left hemisphere.

On the other hand, the Circle of Willis is a crucial part of the cerebral circulation. If the optic chiasm is divided, it can lead to specific visual problems known as chiasmal syndrome. These structures play important roles in brain function and can have significant consequences when damaged of disrupted.

Modafinil: A Psychostimulant for Wakefulness and Attention Enhancement

Modafinil is a type of psychostimulant that is known to improve wakefulness, attention, and vigilance. Although it is similar to amphetamines, it does not produce the same euphoric effects and is not associated with dependence of tolerance. Additionally, it does not seem to cause psychosis. Modafinil is approved for the treatment of narcolepsy, obstructive sleep apnea, and chronic shift work. It is also suggested as an adjunctive treatment for depression by the Maudsley. Recently, it has gained popularity as a smart drug due to its potential to enhance cognitive functioning in healthy individuals.

Medial temporal lobe atrophy (MTA) is prevalent in 80% to 90% of individuals diagnosed with Alzheimer’s dementia, and can also be present in other forms of dementia, albeit less frequently and severely. MTA is an early and relatively reliable indicator of Alzheimer’s disease, although it is not exclusive to this condition.

Legal Principles in Healthcare

In the case of Tarasoff vs. the Regents of the University of California, it was established that patient confidentiality can be breached if there is a threat of harm to another person. Practitioners have a duty to take reasonable steps to protect the threatened individual, which may include notifying the police of warning the intended victim.

Another important legal principle in healthcare is the Bolam test. This principle states that a practitioner’s care is not considered negligent if a responsible body of similar professionals supports the practice, even if it is not the standard care. These legal principles help to ensure that healthcare professionals are held accountable for their actions and that patients receive appropriate care.

Both MZ and DZ twins can be analyzed using pairwise and probandwise rates, but probandwise rates are more beneficial in genetic counseling scenarios as they provide information specific to individuals.

Concordance rates are used in twin studies to investigate the genetic contribution to a trait of condition. Concordance refers to the presence of the same trait of condition in both members of a twin pair. There are two main methods of calculating twin concordance rates: pairwise and probandwise. These methods produce different results and are calculated differently. The probandwise method is generally preferred as it provides more meaningful information in a genetic counseling setting.

The table below shows an example of a population of 100,000 MZ twin pairs, and the pairwise and probandwise concordance rates calculated from this population. Pairwise concordance is the probability that both twins in a pair are affected by the trait of condition. Probandwise concordance is the probability that a twin is affected given that their co-twin is affected. Both methods are conditional probabilities, but pairwise applies to twin pairs, while probandwise applies to individual twins. This is why probandwise is preferred, as it helps predict the risk at the individual level.

Extracampine hallucinations refer to hallucinations that occur beyond one’s sensory range, such as outside the visual of auditory field. Functional hallucinations require an external stimulus to trigger them, but the individual experiences both the normal perception of the stimulus and the hallucination simultaneously. Reflex hallucinations occur when a stimulus in one modality leads to a hallucination in another modality. Hypnagogic hallucinations occur during the process of falling asleep, while autoscopic hallucinations involve abnormal visual perception of oneself.

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

Discontinuation symptoms are less likely with bupropion, clomipramine, and fluvoxamine as their half life is around 21 hours, whereas venlafaxine has a relatively short half life of approximately five hours, leading to a higher rate of discontinuation symptoms. Mirtazapine has a half life of approximately 20-40 hours.

Lyonization: The Process of X-Inactivation

The X chromosome is crucial for proper development and cell viability, containing over 1,000 essential genes. However, females carry two copies of the X chromosome, which can result in a potentially toxic double dose of X-linked genes. To address this imbalance, females undergo a process called Lyonization, of X-inactivation, where one of their two X chromosomes is transcriptionally silenced. The silenced X chromosome then condenses into a compact structure known as a Barr body, which remains in a silent state.

X-inactivation occurs randomly, with no preference for the paternal or maternal X chromosome. It takes place early in embryogenesis, soon after fertilization when the dividing conceptus is about 16-32 cells big. This process occurs in all somatic cells of women, but not in germ cells involved in forming gametes. X-inactivation affects most, but not all, genes on the X chromosome. If a cell has more than two X chromosomes, the extra Xs are also inactivated.

Assimilation refers to the process in which immigrants adopt the practices and values of their new culture while abandoning their own cultural heritage. Marginalization, on the other hand, occurs when immigrants neither adopt the new culture nor retain their own cultural values, resulting in social exclusion and isolation. These two outcomes are on opposite ends of the spectrum in terms of the degree of adoption and retention of cultural values.

Although many drugs are metabolized by CYP1A2, grapefruit juice does not have a significant effect on the metabolism of lithium, as the majority of lithium is excreted without undergoing significant metabolic changes.

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.

Bowlby’s attachment theory suggests that social relationships are formed based on the biological and psychological needs of both the mother and the infant. During the first year of life, attachment development is crucial, and infants begin to form selective attachments to individuals, typically starting with the mother. The interaction between the mother and infant is essential in promoting social relationships. In 1945, Rene Spitz coined the term hospitalism to describe the negative effects of institutionalization and maternal deprivation on young children’s development. These children failed to thrive, despite receiving adequate nutrition and healthcare, and experienced high mortality, morbidity, and severe psychopathology. Bowlby also identified separation anxiety as the fear infants exhibit when separated from their caregiver. Margaret Mahler’s separation-individuation theory explains the process by which individuals emerge as separate entities, both intrapsychically and interpersonally.

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.

The concept of ‘goodness of fit’ was introduced by Thomas and Chess, which refers to the interdependent relationship between a child’s temperament and their environment that impacts their development. The strange situation procedure is linked to Ainsworth, while Bowlby is known for his research on attachment and maternal deprivation. Main is recognized for developing the adult attachment interview. Winnicott coined the term ‘good-enough mother’.

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.

Aneuploidy: Abnormal Chromosome Numbers

Aneuploidy refers to the presence of an abnormal number of chromosomes, which can result from errors during meiosis. Typically, human cells have 23 pairs of chromosomes, but aneuploidy can lead to extra of missing chromosomes. Trisomies, which involve the presence of an additional chromosome, are the most common aneuploidies in humans. However, most trisomies are not compatible with life, and only trisomy 21 (Down’s syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) survive to birth. Aneuploidy can result in imbalances in gene expression, which can lead to a range of symptoms and developmental issues.

Compared to autosomal trisomies, humans are more able to tolerate extra sex chromosomes. Klinefelter’s syndrome, which involves the presence of an extra X chromosome, is the most common sex chromosome aneuploidy. Individuals with Klinefelter’s and XYY often remain undiagnosed, but they may experience reduced sexual development and fertility. Monosomies, which involve the loss of a chromosome, are rare in humans. The only viable human monosomy involves the X chromosome and results in Turner’s syndrome. Turner’s females display a wide range of symptoms, including infertility and impaired sexual development.

The frequency and severity of aneuploidies vary widely. Down’s syndrome is the most common viable autosomal trisomy, affecting 1 in 800 births. Klinefelter’s syndrome affects 1-2 in 1000 male births, while XYY syndrome affects 1 in 1000 male births and Triple X syndrome affects 1 in 1000 births. Turner syndrome is less common, affecting 1 in 5000 female births. Edwards syndrome and Patau syndrome are rare, affecting 1 in 6000 and 1 in 10,000 births, respectively. Understanding the genetic basis and consequences of aneuploidy is important for diagnosis, treatment, and genetic counseling.

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.

Lithium is well-known for causing various thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis.

Paraschemazia is a type of body image distortion that involves a feeling that certain body parts are twisted, distorted, of separated from the rest of the body. This can be caused by various factors, including hallucinogenic drug use, epileptic aura, and migraine. Body image distortions can be caused by both organic and psychiatric conditions. Organic causes may include Brown-Séquard paralysis, epileptic aura, and migraine, while psychiatric causes may include anorexia nervosa, hypochondriasis, depersonalization, and conversion disorders. Hemiasomatognosia is a specific type of body image distortion where the person feels that one half of their body is missing, and it can occur in epileptic aura and migraine. Other types of body image distortions include hyperschemazia, where parts of the body feel magnified in size, and hyposchemazia, where parts of the body feel diminished in size.

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.

Brugada syndrome typically appears in males during adulthood, usually around age 40, and sudden death may be the initial symptom. This genetic disorder is inherited in an autosomal dominant pattern. This information is sourced from the National Organization for Rare Disorders (NORD).

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.

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.