Grapefruit juice has been found to inhibit the activity of CYP3A4, an enzyme that plays a crucial role in the metabolism of various important drugs including aripiprazole, quetiapine, and tertiary amines like amitriptyline and imipramine. As a result, consumption of grapefruit juice can lead to increased levels of these drugs in the body. On the other hand, other drugs that induce the activity of CYP3A4 can decrease the levels of these drugs.

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.

Antipsychotics are commonly used to treat various mental health conditions. Most atypical antipsychotics require twice daily administration due to their short half-lives, except for olanzapine, aripiprazole, and risperidone. These medications have longer half-lives and can be administered once daily. A recent randomized controlled trial compared once versus twice daily dosing of risperidone and olanzapine and found no significant difference in effectiveness and efficacy outcomes. However, the study suggests that once-daily dosing may be preferable due to lower mean dose and better side effect profile, especially for olanzapine.

The term PrPSc originated from scrapie, a prion disease that affects sheep. In humans, the normal isoform of prion protein is PrPC, while the abnormal form is known as PrPres (protease-resistant) of PrPSc. Scrapie has been observed in sheep for over 300 years, while BSE in cattle was only identified in the 1980s. Feline spongiform encephalopathy (FSE) is a prion disease that affects cats, and Chronic wasting disease (CWD) is a similar condition that affects deer.

Sleep Stages

Sleep is divided into two distinct states called rapid eye movement (REM) and non-rapid eye movement (NREM). NREM is subdivided into four stages.

Sleep stage
Approx % of time spent in stage
EEG findings
Comment

I
5%
Theta waves (4-7 Hz)
The dozing off stage. Characterized by hypnic jerks: spontaneous myoclonic contractions associated with a sensation of twitching of falling.

II
45%
Theta waves, K complexes and sleep spindles (short bursts of 12-14 Hz activity)
Body enters a more subdued state including a drop in temperature, relaxed muscles, and slowed breathing and heart rate. At the same time, brain waves show a new pattern and eye movement stops.

III
15%
Delta waves (0-4 Hz)
Deepest stage of sleep (high waking threshold). The length of stage 3 decreases over the course of the night.

IV
15%
Mixed, predominantly beta
High dream activity.

The percentage of REM sleep decreases with age.

It takes the average person 15-20 minutes to fall asleep, this is called sleep latency (characterised by the onset of stage I sleep). Once asleep one descends through stages I-II and then III-IV (deep stages). After about 90 minutes of sleep one enters REM. The rest of the sleep comprises of cycles through the stages. As the sleep progresses the periods of REM become greater and the periods of NREM become less. During an average night’s sleep one spends 25% of the sleep in REM and 75% in NREM.

REM sleep has certain characteristics that separate it from NREM

Characteristics of REM sleep

– Autonomic instability (variability in heart rate, respiratory rate, and BP)
– Loss of muscle tone
– Dreaming
– Rapid eye movements
– Penile erection

Deafness:

(No information provided on deafness in relation to sleep stages)

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.

Assessment Tools:

Luria’s Test:
Luria’s test is a motor task designed by Alexander Luria, a Russian neuropsychologist. The test was developed based on his observation that individuals with significant frontal lobe damage were unable to modify their responses to a programmed motor task when the order of actions in the task was changed.

Geriatric Depression Scale:
The Geriatric Depression Scale is a screening tool used to identify depression in older adults. It is not designed to assess cognitive impairment.

Mini-Mental State Examination:
The Mini-Mental State Examination is a brief, 30-question screening tool used to assess cognitive impairment. It does not evaluate frontal lobe functions.

National Adult Reading Test:
The National Adult Reading Test is used to assess the premorbid level of intelligence in English-speaking patients.

Wechsler Adult Intelligence Scale:
The Wechsler Adult Intelligence Scale is a comprehensive assessment tool used to measure intelligence in adults and older adolescents.

While EMDR can be beneficial for various disorders, its effectiveness does not hold any diagnostic significance for PTSD. The presence of flashbacks of distressing reliving experiences is the primary requirement for diagnosing PTSD, and other symptoms such as autonomic disturbance, avoidance of work, and increased sensitivity to noise are not necessary for diagnosis.

Acute stress disorder is a brief yet intense condition triggered by a highly distressing event that can cause a range of symptoms. Although the symptoms can appear quickly, they typically subside within a few days. These symptoms may include psychological effects like feeling disconnected of confused, as well as physical symptoms such as sweating, trembling, heart palpitations, and difficulty sleeping. In some cases, individuals may progress to develop post-traumatic stress disorder.

Dementia Pugilistica: A Neurodegenerative Condition Resulting from Neurotrauma

Dementia pugilistica, also known as chronic traumatic encephalopathy (CTE), is a neurodegenerative condition that results from neurotrauma. It is commonly seen in boxers and NFL players, but can also occur in anyone with neurotrauma. The condition is characterized by symptoms such as gait ataxia, slurred speech, impaired hearing, tremors, disequilibrium, neurobehavioral disturbances, and progressive cognitive decline.

Most cases of dementia pugilistica present with early onset cognitive deficits, and behavioral signs exhibited by patients include aggression, suspiciousness, paranoia, childishness, hypersexuality, depression, and restlessness. The progression of the condition leads to more prominent behavioral symptoms such as difficulty with impulse control, irritability, inappropriateness, and explosive outbursts of aggression.

Neuropathological abnormalities have been identified in CTE, with the most unique feature being the abnormal accumulation of tau in neurons and glia in an irregular, focal, perivascular distribution and at the depths of cortical sulci. Abnormalities of the septum pellucidum, such as cavum and fenestration, are also a common feature.

While the condition has become increasingly rare due to the progressive improvement in sports safety, it is important to recognize the potential long-term consequences of repeated head injuries and take steps to prevent them.

While schizotypal personality disorder is included in the DSM, it is not listed as a separate diagnosis in the ICD-10. Instead, it is classified under the umbrella of schizophrenia. However, all of the other personality disorders mentioned are recognized in both the ICD-10 and DSM.

According to Bowlby’s (1980) model of grief, there are four stages: Numbing, Yearning and searching, Disorganisation and despair, and Reorganisation. Other models of grief may include Shock, Anger (Kubler-Ross, 1969), Awareness of loss, and Conservation-Withdrawal (Sanders, 1989).

Antipsychotic drugs are known to cause weight gain, but some more than others. The reason for this is not due to a direct metabolic effect, but rather an increase in appetite and a decrease in activity levels. The risk of weight gain appears to be linked to clinical response. There are several suggested mechanisms for this, including antagonism of certain receptors and hormones that stimulate appetite. The risk of weight gain varies among different antipsychotics, with clozapine and olanzapine having the highest risk. Management strategies for antipsychotic-induced weight gain include calorie restriction, low glycemic index diet, exercise, and switching to an alternative antipsychotic. Aripiprazole, ziprasidone, and lurasidone are recommended as alternative options. Other options include aripiprazole augmentation, metformin, orlistat, liraglutide, and topiramate.

Ganser syndrome is characterized by approximate answers, clouding of consciousness, somatic conversion features, and pseudohallucinations. It is controversially classified as a reactive psychosis, with stressful life events as a possible trigger. Pseudologia fantastica, of pathological lying, involves grandiose and extreme untruthful statements that may be believed by the individual, often associated with personality disorders such as histrionic of dissocial and precipitated by major life crises. Cryptomnesia involves falsely recalling an idea, thought, of song as new and original. Confabulation is the falsification of memory in clear consciousness, often used to cover up memory gaps. Dissociative fugue state involves narrowing of consciousness, wandering away from normal surroundings, and subsequent amnesia, with the individual appearing to be in good contact with their environment and maintaining basic self-care.

The only X-linked condition among the 5 options is Duchenne muscular dystrophy.

Modes of Inheritance

Genetic disorders can be passed down from one generation to the next in various ways. There are four main modes of inheritance: autosomal dominant, autosomal recessive, X-linked (sex-linked), and multifactorial.

Autosomal Dominant Inheritance

Autosomal dominant inheritance occurs when one faulty gene causes a problem despite the presence of a normal one. This type of inheritance shows vertical transmission, meaning it is based on the appearance of the family pedigree. If only one parent is affected, there is a 50% chance of each child expressing the condition. Autosomal dominant conditions often show pleiotropy, where a single gene influences several characteristics.

Autosomal Recessive Inheritance

In autosomal recessive conditions, a person requires two faulty copies of a gene to manifest a disease. A person with one healthy and one faulty gene will generally not manifest a disease and is labelled a carrier. Autosomal recessive conditions demonstrate horizontal transmission.

X-linked (Sex-linked) Inheritance

In X-linked conditions, the problem gene lies on the X chromosome. This means that all males are affected. Like autosomal conditions, they can be dominant of recessive. Affected males are unable to pass the condition on to their sons. In X-linked recessive conditions, the inheritance pattern is characterised by transmission from affected males to male grandchildren via affected carrier daughters.

Multifactorial Inheritance

Multifactorial conditions result from the interaction between genes from both parents and the environment.

The M phase is where cell division takes place through mitosis.

Cytokinesis: The Final Stage of Cell Division

Cytokinesis is the final stage of cell division, where the cell splits into two daughter cells, each with a nucleus. This process is essential for the growth and repair of tissues in multicellular organisms. In mitosis, cytokinesis occurs after telophase, while in meiosis, it occurs after telophase I and telophase II.

During cytokinesis, a contractile ring made of actin and myosin filaments forms around the cell’s equator, constricting it like a belt. This ring gradually tightens, pulling the cell membrane inward and creating a furrow that deepens until it reaches the center of the cell. Eventually, the furrow meets in the middle, dividing the cell into two daughter cells.

In animal cells, cytokinesis is achieved by the formation of a cleavage furrow, while in plant cells, a cell plate forms between the two daughter nuclei, which eventually develops into a new cell wall. The timing and mechanism of cytokinesis are tightly regulated by a complex network of proteins and signaling pathways, ensuring that each daughter cell receives the correct amount of cytoplasm and organelles.

Overall, cytokinesis is a crucial step in the cell cycle, ensuring that genetic material is equally distributed between daughter cells and allowing for the growth and development of multicellular organisms.

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.

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.

According to a recent study by Ran (2019), lithium carbonate has been found to have a neuroprotective effect in individuals who have experienced a stroke. The study conducted exploratory analyses of neuroanatomical and cognitive outcomes in a poststroke population. It is interesting to note that while lithium is contraindicated in individuals with Addison’s disease, it is only cautioned in individuals with QT prolongation. Hypothyroidism (untreated) is also a contraindication for lithium. Addison’s disease is a condition characterized by inadequate production of cortisol and aldosterone by the adrenal cortex, leading to symptoms such as fatigue, gastrointestinal abnormalities, changes in skin pigmentation, and mood changes. In some cases, acute adrenal failure can occur, which is a serious condition that develops rapidly. The cause of Addison’s disease is often due to the body’s immune system mistakenly attacking the adrenal glands, causing progressive damage to the adrenal cortex.

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.

First Rank Symptoms: Their Significance in Identifying Schizophrenia

First rank symptoms were introduced by Kurt Schneider in 1938 as a practical tool for non-psychiatrists to identify schizophrenia. While they are highly suggestive of schizophrenia, they are not pathognomonic and can also be seen in affective and personality disorders. Additionally, there is no evidence to support their prognostic significance.

A systematic review in 2015 found that first rank symptoms differentiated schizophrenia from nonpsychotic mental health disorders with a sensitivity of 61.8% and a specificity of 94.1%. They also differentiated schizophrenia from other types of psychosis with a sensitivity of 58% and a specificity of 74.7%.

The first rank symptoms include running commentary, thought echo, voices heard arguing, thought insertion, thought withdrawal, thought broadcast, delusional perception, somatic passivity, made affect, and made volition. While they can be helpful in identifying schizophrenia, they should not be relied upon as the sole diagnostic criteria.

Sedatives and Liver Disease

Sedatives are commonly used for their calming effects, but many of them are metabolized in the liver. Therefore, caution must be taken when administering sedatives to patients with liver disease. The Maudsley Guidelines recommend using low doses of the following sedatives in patients with hepatic impairment: lorazepam, oxazepam, temazepam, and zopiclone. It is important to note that zopiclone should also be used with caution and at low doses in this population. Proper management of sedative use in patients with liver disease can help prevent further damage to the liver and improve overall patient outcomes.

Neuroimaging studies have shown that Alzheimer’s dementia is linked to a gradual increase in ventricular size, while schizophrenia is associated with non-progressive enlargement of the lateral and third ventricles. Although some studies have reported increased ventricular size in individuals with affective disorders, the findings are not consistent. Additionally, individuals with antisocial personality disorder may have reduced prefrontal gray matter volume.

Delusions that originate within the mind without any external influence are known as autochthonous. This term, derived from the Greek word for from the soil, emphasizes that the idea is self-generated rather than being triggered by a sensory experience of other external factor.

The DSM-5 employs the label ‘borderline personality disorder’, while the previous ICD utilized the term ’emotionally unstable personality disorder’, which was not included in the ICD-11. The ICD-11 now allows for the use of a borderline qualifier when providing a broad diagnosis of personality disorder.

Personality Disorder Classification

A personality disorder is a persistent pattern of behavior and inner experience that deviates significantly from cultural expectations, is inflexible and pervasive, and causes distress of impairment. The DSM-5 and ICD-11 have different approaches to classifying personality disorders. DSM-5 divides them into 10 categories, grouped into clusters A, B, and C, while ICD-11 has a general category with six trait domains that can be added. To diagnose a personality disorder, the general diagnostic threshold must be met before determining the subtype(s) present. The criteria for diagnosis include inflexibility and pervasiveness of the pattern, onset in adolescence of early adulthood, stability over time, and significant distress of impairment. The disturbance must not be better explained by another mental disorder, substance misuse, of medical condition.

Course

Borderline and antisocial personality disorders tend to become less evident of remit with age, while others, particularly obsessive-compulsive and schizotypal, may persist.

Classification

The DSM-5 divides personality disorders into separate clusters A, B, and C, with additional groups for medical conditions and unspecified disorders. The ICD-11 dropped the separate categories and instead lists six trait domains that can be added to the general diagnosis.

UK Epidemiology

The prevalence of personality disorders in Great Britain, according to the British National Survey of Psychiatric Morbidity, is 4.4%, with cluster C being the most common at 2.6%, followed by cluster A at 1.6% and cluster B at 1.2%. The most prevalent specific personality disorder is obsessive-compulsive (anankastic) at 1.9%.

Creutzfeldt-Jakob disease is characterized by a slow background rhythm accompanied by paroxysmal sharp waves on EEG, while the remaining options are typical EEG features of the aging process.

History of major works in psychiatry
Michel Foucault – Madness and civilization
Sigmund Freud – The interpretation of dreams, Beyond the Pleasure Principle, The Psychopathology of everyday life
Thomas Szasz – The myth of mental illness
Erving Goffman – Asylums, The Presentation of Self in Everyday Life
Ronald Laing – The divided self
Emile Durkheim – Le suicide. Durkheim proposed social causes for suicide. Until his work was published, suicide had been thought of as an individual act only.
Tom Main – The Ailment
Jerome Frank – Persuasion and Healing
George Brown and Tirril Harris – Social origins of depression

Post-traumatic stress disorder (PTSD) is a condition that develops in response to an exceptionally threatening of catastrophic event of situation, such as the one described above. It is only diagnosed if symptoms arise within six months of the traumatic event. The symptoms of PTSD can be categorized into three groups: re-experiencing the traumatic event (such as through nightmares of vivid thoughts), persistent avoidance of stimuli associated with the trauma, and persistent symptoms of increased arousal (such as difficulty sleeping of concentrating).

Agoraphobia is a fear of being in situations of places from which escape is difficult, leading to avoidance of many situations and confinement to the home. This fear is typically triggered by situations such as crowds, public places, of traveling alone of away from home.

Generalized anxiety disorder is characterized by persistent anxiety that is not limited to any specific environmental circumstance. To receive this diagnosis, a patient must experience symptoms of anxiety on most days for several weeks of months, with evidence of impairment in important areas of functioning. However, this diagnosis is not appropriate for the scenario described above, as the anxiety is related to a specific event of trigger.

Panic disorder involves sudden onset of severe anxiety, with at least three panic attacks experienced over a three-week period. Symptoms may include sweating, palpitations, shortness of breath, nausea, trembling, chest pain of discomfort, dizziness of lightheadedness, chills of hot flushes, fear of losing control of dying, paraesthesia, feeling of choking, and derealization or depersonalization.

Social phobia is characterized by a marked fear of social situations in which embarrassment may occur, leading to avoidance of these situations.

Understanding Action Potentials in Neurons and Muscle Cells

The membrane potential is a crucial aspect of cell physiology, and it exists across the plasma membrane of most cells. However, in neurons and muscle cells, this membrane potential can change over time. When a cell is not stimulated, it is in a resting state, and the inside of the cell is negatively charged compared to the outside. This resting membrane potential is typically around -70mV, and it is maintained by the Na/K pump, which maintains a high concentration of Na outside and K inside the cell.

To trigger an action potential, the membrane potential must be raised to around -55mV. This can occur when a neurotransmitter binds to the postsynaptic neuron and opens some ion channels. Once the membrane potential reaches -55mV, a cascade of events is initiated, leading to the opening of a large number of Na channels and causing the cell to depolarize. As the membrane potential reaches around +40 mV, the Na channels close, and the K gates open, allowing K to flood out of the cell and causing the membrane potential to fall back down. This process is irreversible and is critical for the transmission of signals in neurons and the contraction of muscle cells.

Huntington’s Disease: Genetics and Pathology

Huntington’s disease is a genetic disorder that follows an autosomal dominant pattern of inheritance. It is caused by a mutation in the Huntington gene, which is located on chromosome 4. The mutation involves an abnormal expansion of a trinucleotide repeat sequence (CAG), which leads to the production of a toxic protein that damages brain cells.

The severity of the disease and the age of onset are related to the number of CAG repeats. Normally, the CAG sequence is repeated less than 27 times, but in Huntington’s disease, it is repeated many more times. The disease shows anticipation, meaning that it tends to worsen with each successive generation.

The symptoms of Huntington’s disease typically begin in the third of fourth decade of life, but in rare cases, they can appear in childhood of adolescence. The most common symptoms include involuntary movements (chorea), cognitive decline, and psychiatric disturbances.

The pathological hallmark of Huntington’s disease is the gross bilateral atrophy of the head of the caudate and putamen, which are regions of the brain involved in movement control. The EEG of patients with Huntington’s disease shows a flattened trace, indicating a loss of brain activity.

Macroscopic pathological findings include frontal atrophy, marked atrophy of the caudate and putamen, and enlarged ventricles. Microscopic findings include neuronal loss and gliosis in the cortex, neuronal loss in the striatum, and the presence of inclusion bodies in the neurons of the cortex and striatum.

In conclusion, Huntington’s disease is a devastating genetic disorder that affects the brain and causes a range of motor, cognitive, and psychiatric symptoms. The disease is caused by a mutation in the Huntington gene, which leads to the production of a toxic protein that damages brain cells. The pathological changes in the brain include atrophy of the caudate and putamen, neuronal loss, and the presence of inclusion bodies.

Delayed Seizures in Metrazol-Induced Convulsions

During the early development of electroconvulsive therapy (ECT), chemical convulsions using Metrazol were commonly used. However, this method was associated with a high risk of fractures due to the violent seizures induced. To address this issue, various forms of muscle relaxation were introduced, leading to the replacement of chemical convulsions with ECT.

Despite the risks associated with Metrazol-induced convulsions, they were noted to be effective for severe depression. However, delayed seizures were a common occurrence with this method.

Emil Kraepelin is credited with establishing modern scientific psychiatry and coining the term dementia praecox, while Aaron Beck is known as the pioneer of cognitive therapy. Carl Jung founded analytical psychotherapy, and Eugen Bleuler is recognized for introducing the term schizophrenia to replace dementia praecox. Additionally, Karl Jaspers was a psychiatrist and existential philosopher.