A Historical Note on the Development of Zimelidine, the First Selective Serotonin Reuptake Inhibitor

In 1960s, evidence began to emerge suggesting a significant role of serotonin in depression. This led to the development of zimelidine, the first selective serotonin reuptake inhibitor (SSRI). Zimelidine was derived from pheniramine and was marketed in Europe in 1982. However, it was removed from the market in 1983 due to severe side effects such as hypersensitivity reactions and Guillain-Barre syndrome.

Despite its short-lived availability, zimelidine paved the way for the development of other SSRIs such as fluoxetine, which was approved by the FDA in 1987 and launched in the US market in 1988 under the trade name Prozac. The development of SSRIs revolutionized the treatment of depression and other mood disorders, providing a safer and more effective alternative to earlier antidepressants such as the tricyclics and MAO inhibitors.

Prions are responsible for causing Creutzfeldt-Jakob disease (CJD), a fatal and uncommon condition that leads to progressive neurodegeneration. The disease is characterized by swiftly advancing dementia as one of its primary symptoms.

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%.

Catecholamines are a group of chemical compounds that have a distinct structure consisting of a benzene ring with two hydroxyl groups, an intermediate ethyl chain, and a terminal amine group. These compounds play an important role in the body and are involved in various physiological processes. The three main catecholamines found in the body are dopamine, adrenaline, and noradrenaline. All of these compounds are derived from the amino acid tyrosine. Overall, catecholamines are essential for maintaining proper bodily functions and are involved in a wide range of physiological processes.

The behavior described is an example of sublimation, where unconscious impulses are redirected into socially acceptable outlets for immediate gratification. The other options listed are all examples of mature defense mechanisms, including altruism, which involves finding satisfaction in helping others; anticipation, which involves mentally preparing for potential threats; humor, which allows for the expression of difficult emotions without personal discomfort; and suppression, which involves consciously delaying the processing of uncomfortable issues.

The pituitary gland is situated in the sella turcica, while the suprachiasmatic nucleus regulates circadian rhythms. Serotonin release in the brain is primarily sourced from the neurons of the raphe nuclei, which are located along the midline of the brainstem. The choroid plexus produces cerebrospinal fluid, and enterochromaffin cells in the gut contain the majority of the body’s serotonin.

The recommended treatment for emotionally unstable personality disorder (borderline type) does not involve a single psychological therapy of drug treatment as a first line of defense. However, for women who prioritize reducing self-harm, DBT is recommended. Drug treatments may be considered for comorbid conditions. According to NICE guidelines on Borderline personality disorder (BPD) (CG78), a comprehensive dialectical behaviour therapy programme should be considered for women with borderline personality disorder who prioritize reducing recurrent self-harm. Brief psychological interventions of less than 3 months’ duration should not be used specifically for borderline personality disorder of for the individual symptoms of the disorder. Drug treatment should not be used specifically for borderline personality disorder of for the individual symptoms of behavior associated with the disorder, such as repeated self-harm, marked emotional instability, risk-taking behavior, and transient psychotic symptoms. If sedatives are used for crisis intervention in a patient with EUPD, they should be prescribed for a maximum period of one week.

Assessment tools are commonly used in clinical research to diagnose and evaluate various conditions. The abnormal involuntary movement scale (AIMS) is one such tool that assesses the range of extrapyramidal side effects caused by neuroleptic medication. Another tool, Conors, is used to diagnose ADHD in children, while DIVA is used for the same purpose in adults. DISCO, on the other hand, is an assessment tool used to diagnose ASD at any age. Finally, the Hamilton depression rating scale, also known as HAM D-17, is used to evaluate the severity of depression in patients. Proper use of these assessment tools can aid in accurate diagnosis and effective treatment of various conditions.

Goffman coined the term ‘total institution’ in relation to asylums, which were responsible for fulfilling all the patients’ requirements, thereby hindering their rehabilitation.

D.W. Winnicott – Good enough mother, transitional object: Winnicott believed that a good enough mother is one who provides a secure and nurturing environment for her child, allowing them to develop a sense of self and independence. He also introduced the concept of the transitional object, such as a teddy bear of blanket, which helps a child transition from the mother’s care to the outside world.

Carl Jung – Collective unconscious, archetype, anima, animus: Jung believed in the existence of a collective unconscious, a shared pool of knowledge and experience that all humans possess. He also introduced the concept of archetypes, universal symbols and patterns that are present in the collective unconscious. The anima and animus are archetypes representing the feminine and masculine aspects of the psyche.

Melanie Klein – Paranoid-schizoid position, depressive position, splitting: Klein introduced the concept of the paranoid-schizoid position, a stage of development in which a child experiences intense anxiety and fear of persecution. She also introduced the depressive position, a stage in which the child learns to integrate positive and negative feelings towards others. Splitting is the defense mechanism in which a person sees things as either all good of all bad.

Sigmund Freud – Free association, transference, ego, super-ego, id, eros, thanatos, defense mechanisms, oedipus Complex, the unconscious: Freud is known for his theories on the unconscious mind, including the id, ego, and super-ego. He also introduced the concepts of eros (the life instinct) and thanatos (the death instinct), as well as defense mechanisms such as repression and denial. The Oedipus complex is a theory about a child’s sexual desire for their opposite-sex parent.

Wilfred Bion – Basic assumption group: Bion introduced the concept of the basic assumption group, a group that forms around a shared fantasy of assumption. He believed that these groups can be helpful of harmful, depending on the assumptions they are based on.

Karen Horney – Womb envy: Horney believed that men experience womb envy, a feeling of inferiority and jealousy towards women due to their inability to bear children. She also introduced the concept of neurotic needs, such as the need for affection and the need for power.

Erving Goffman – Total institution: Goffman introduced the concept of the total institution, a place where people are completely cut off from the outside world and subjected to strict rules and regulations. Examples include prisons and mental hospitals.

Siegfried Foulkes – Foundation matrix: Foulkes introduced the concept of the foundation matrix, a group’s shared history and experiences that shape their current dynamics and interactions.

The DSM-III previously utilized the term passive-aggressive 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%.

Nissl substance is composed of rough endoplasmic reticulum with free ribosomes and is responsible for synthesizing proteins. The Golgi apparatus modifies, organizes, and packages macromolecules for either secretion of internal use. Mitochondria are involved in producing energy for the cell. Microfilaments and microtubules provide structural support and aid in transportation within the cell. Lysosomes are spherical structures that contain digestive enzymes, which break down cellular waste and protect against threats such as viruses.

The Function of Proteasomes in Protein Degradation

Proteasomes play a crucial role in breaking down proteins that are produced within the cell. These cylindrical complexes are present in both the nucleus and cytoplasm of the cell. The process of protein degradation involves the tagging of proteins with a small protein called ubiquitin. The proteasome consists of a core structure made up of four stacked rings surrounding a central pore. Each ring is composed of seven individual proteins. This structure allows for the efficient degradation of proteins, ensuring that the cell can maintain proper protein levels and function.

Valproate can pass through the placenta, increasing the likelihood of birth defects. The extent of risk during pregnancy is not fully understood, but it is believed to be influenced by the dosage. Children who were exposed to valproate in the womb may have a lower IQ, with those aged 6 showing an average decrease of 7-10 points compared to those exposed to other antiepileptic medications.

Valproate: Forms, Doses, and Adverse Effects

Valproate comes in three forms: semi-sodium valproate, valproic acid, and sodium valproate. Semi-sodium valproate is a mix of sodium valproate and valproic acid and is licensed for acute mania associated with bipolar disorder. Valproic acid is also licensed for acute mania, but this is not consistent with the Maudsley Guidelines. Sodium valproate is licensed for epilepsy. It is important to note that doses of sodium valproate and semi-sodium valproate are not the same, with a slightly higher dose required for sodium valproate.

Valproate is associated with many adverse effects, including nausea, tremor, liver injury, vomiting/diarrhea, gingival hyperplasia, memory impairment/confusional state, somnolence, weight gain, anaemia/thrombocytopenia, alopecia (with curly regrowth), severe liver damage, and pancreatitis. Increased liver enzymes are common, particularly at the beginning of therapy, and tend to be transient. Vomiting and diarrhea tend to occur at the start of treatment and remit after a few days. Severe liver damage is most likely to occur in the first six months of therapy, with the maximum risk being between two and twelve weeks. The risk also declines with advancing age.

Valproate is a teratogen and should not be initiated in women of childbearing potential. Approximately 10% of children exposed to valproate monotherapy during pregnancy suffer from congenital malformations, with the risk being dose-dependent. The most common malformations are neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, cardiac, renal and urogenital defects, and limb defects. There is also a dose-dependent relationship between valproate and developmental delay, with approximately 30-40% of children exposed in utero experiencing delay in their early development, such as talking and walking later, lower intellectual abilities, poor language skills, and memory problems. There is also a thought to be a 3-fold increase of autism in children exposed in utero.

FTDP-17 is a type of frontotemporal dementia that results from a mutation in the MAPT gene found on chromosome 17. The MAPT gene is responsible for producing Tau protein.

Genes Associated with Dementia

Dementia is a complex disorder that can be caused by various genetic and environmental factors. Several genes have been implicated in different forms of dementia. For instance, familial Alzheimer’s disease, which represents less than 1-6% of all Alzheimer’s cases, is associated with mutations in PSEN1, PSEN2, APP, and ApoE genes. These mutations are inherited in an autosomal dominant pattern. On the other hand, late-onset Alzheimer’s disease is a genetic risk factor associated with the ApoE gene, particularly the APOE4 allele. However, inheriting this allele does not necessarily mean that a person will develop Alzheimer’s.

Other forms of dementia, such as familial frontotemporal dementia, Huntington’s disease, CADASIL, and dementia with Lewy bodies, are also associated with specific genes. For example, C9orf72 is the most common mutation associated with familial frontotemporal dementia, while Huntington’s disease is caused by mutations in the HTT gene. CADASIL is associated with mutations in the Notch3 gene, while dementia with Lewy bodies is associated with the APOE, GBA, and SNCA genes.

In summary, understanding the genetic basis of dementia is crucial for developing effective treatments and preventive measures. However, it is important to note that genetics is only one of the many factors that contribute to the development of dementia. Environmental factors, lifestyle choices, and other health conditions also play a significant role.

Important Figures in the Development of Therapeutic Communities

Therapeutic communities have been an important approach to treating mental health and addiction issues for decades. Robert Rapoport introduced the four principles of therapeutic communities in his 1960 book Community as Doctor: New Perspectives on Therapeutic Community. These principles include reality confrontation, permissiveness, democracy, and communalism. In the late 1990s, Rex Haigh updated Rapoport’s four themes and added a fifth principle, attachment.

Wilfred Bion led some of the earliest experiments in the 1940s into therapeutic communities in the UK. The Northfield experiments were an attempt to rehabilitate soldiers into the army. However, at the time, these experiments were viewed as unsuccessful and were stopped after six weeks.

Tom Main is credited with coining the term ‘therapeutic community’ in his 1946 paper The hospital as a therapeutic institution. It is important to note that Donald Winnicott, who coined the term a good enough mother, is not directly related to the development of therapeutic communities.

These figures have played a significant role in the development and evolution of therapeutic communities, which continue to be an important approach to mental health and addiction treatment.

Antipsychotic use can lead to high levels of prolactin, which can cause amenorrhea. To address hyperprolactinemia, aripiprazole, quetiapine, and olanzapine are recommended. However, clozapine typically does not impact prolactin release.

Hyperprolactinemia is a potential side effect of antipsychotic medication, but it is rare with antidepressants. Dopamine inhibits prolactin, so dopamine antagonists, such as antipsychotics, can increase prolactin levels. The degree of prolactin elevation is dose-related, and some antipsychotics cause more significant increases than others. Hyperprolactinemia can cause symptoms such as galactorrhea, menstrual difficulties, gynecomastia, hypogonadism, and sexual dysfunction. Long-standing hyperprolactinemia in psychiatric patients can increase the risk of osteoporosis and breast cancer, although there is no conclusive evidence that antipsychotic medication increases the risk of breast malignancy and mortality. Some antipsychotics, such as clozapine and aripiprazole, have a low risk of causing hyperprolactinemia, while typical antipsychotics and risperidone have a high risk. Monitoring of prolactin levels is recommended before starting antipsychotic therapy and at three months and annually thereafter. Antidepressants rarely cause hyperprolactinemia, and routine monitoring is not recommended. Symptomatic hyperprolactinemia has been reported with most antidepressants, except for a few, such as mirtazapine, agomelatine, bupropion, and vortioxetine.

Melatonin: The Hormone of Darkness

Melatonin is a hormone that is produced in the pineal gland from serotonin. This hormone is known to be released in higher amounts during the night, especially in dark environments. Melatonin plays a crucial role in regulating the sleep-wake cycle and is often referred to as the hormone of darkness.

The production of melatonin is influenced by the amount of light that enters the eyes. When it is dark, the pineal gland releases more melatonin, which helps to promote sleep. On the other hand, when it is light, the production of melatonin is suppressed, which helps to keep us awake and alert.

Melatonin is also known to have antioxidant properties and may help to protect the body against oxidative stress. It has been suggested that melatonin may have a role in the prevention of certain diseases, such as cancer and neurodegenerative disorders.

Overall, melatonin is an important hormone that plays a crucial role in regulating our sleep-wake cycle and may have other health benefits as well.

Gerstmann’s Syndrome: Symptoms and Brain Lesions

Gerstmann’s syndrome is a condition that is characterized by several symptoms, including dyscalculia, dysgraphia, finger agnosia, and right-left disorientation. Patients with this syndrome have been found to have lesions in areas such as the left frontal posterior, left parietal, temporal, and occipital lobes. The left angular gyrus, which is located at the junction of the temporal, occipital, and parietal lobes, seems to be the main area of overlap. Although the function of the angular gyrus is not well understood, it is believed to be involved in various functions such as calculation, spatial reasoning, understanding of ordinal concepts, and comprehension of metaphors.

A Historical Note on the Development of Zimelidine, the First Selective Serotonin Reuptake Inhibitor

In 1960s, evidence began to emerge suggesting a significant role of serotonin in depression. This led to the development of zimelidine, the first selective serotonin reuptake inhibitor (SSRI). Zimelidine was derived from pheniramine and was marketed in Europe in 1982. However, it was removed from the market in 1983 due to severe side effects such as hypersensitivity reactions and Guillain-Barre syndrome.

Despite its short-lived availability, zimelidine paved the way for the development of other SSRIs such as fluoxetine, which was approved by the FDA in 1987 and launched in the US market in 1988 under the trade name Prozac. The development of SSRIs revolutionized the treatment of depression and other mood disorders, providing a safer and more effective alternative to earlier antidepressants such as the tricyclics and MAO inhibitors.

Hyperprolactinemia is frequently without symptoms, and determining whether treatment is necessary involves weighing the present symptoms, potential long-term risks, and perceived advantages of maintaining the antipsychotic. It is frequently discovered by chance and does not typically necessitate altering the medication regimen.

Hyperprolactinemia is a potential side effect of antipsychotic medication, but it is rare with antidepressants. Dopamine inhibits prolactin, so dopamine antagonists, such as antipsychotics, can increase prolactin levels. The degree of prolactin elevation is dose-related, and some antipsychotics cause more significant increases than others. Hyperprolactinemia can cause symptoms such as galactorrhea, menstrual difficulties, gynecomastia, hypogonadism, and sexual dysfunction. Long-standing hyperprolactinemia in psychiatric patients can increase the risk of osteoporosis and breast cancer, although there is no conclusive evidence that antipsychotic medication increases the risk of breast malignancy and mortality. Some antipsychotics, such as clozapine and aripiprazole, have a low risk of causing hyperprolactinemia, while typical antipsychotics and risperidone have a high risk. Monitoring of prolactin levels is recommended before starting antipsychotic therapy and at three months and annually thereafter. Antidepressants rarely cause hyperprolactinemia, and routine monitoring is not recommended. Symptomatic hyperprolactinemia has been reported with most antidepressants, except for a few, such as mirtazapine, agomelatine, bupropion, and vortioxetine.

Children typically take their first steps between 9 and 12 months of age, and are typically able to walk independently by around 15 months. At the age of two, children are expected to be able to build a tower of six cubes. Sorting objects into categories is a skill that typically develops around the age of three.

The Emergence of Social Smiling in Infants

Wormann (2014) discusses the emergence of social smiling in infants, which is usually interpreted as the first positive expression directed towards a cause. This occurs when an infant with an initially expressionless face examines the face of another person, and their face and eyes light up while the corners of their mouth pull upward. The age of the first appearance of the social smile varies across cultures, ranging from the fifth to seventh week. Additionally, there are differences in its duration and frequency between the second and seventh month of life. Understanding these milestones is important for a basic understanding of normal child development.

Child Development Milestones:
4 weeks Responds to noise (either by crying, of quieting), follows an object moved in front of eyes
6 weeks Begins social smiling*
3 months Holds head steady on sitting
6 months Rolls from stomach to back, starts babbling
7 months Transfers objects from hand to hand, looks for dropped object
9 months Sits unsupported, begins to crawl
12 months Cruising (walking by holding furniture)
18 months Walks without assistance, speaks about 10-20 words
2 years Runs, climbs up and down stairs alone, makes 2-3 word sentences
3 years Dresses self except for buttons and laces, counts to 10, feeds themself well
4 years Hops on one foot, copies a cross
5 years Copies a triangle, skips

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.

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.

The medial temporal lobe, comprising the hippocampus and parahippocampal gyrus, exhibits the earliest neuropathological alterations.

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.

John’s behavior is causing distress and impairment in his ability to participate in family therapy and may have contributed to his child’s depression. His behavior is consistent with histrionic personality disorder, which is only found in the ICD-10. This disorder is characterized by self-dramatization, exaggerated emotions, suggestibility, a shallow and unstable emotional state, a constant need for attention and excitement, inappropriate seductive behavior, and an excessive concern with physical appearance. Other associated features may include egocentricity, self-indulgence, a constant desire for appreciation, easily hurt feelings, and manipulative behavior to meet personal needs.

Alpha-synuclein is the main component of Lewy bodies, which are inclusion bodies found in the cytoplasm of neurons and appear eosinophilic.

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.

Erving Goffman was a prominent sociologist who made significant contributions to the field. He is well-known for his works such as The Presentation of Self in Everyday Life, Asylums, and Stigma. In fact, he is credited with introducing the term stigma into the sociological lexicon. Goffman’s ideas and theories have had a lasting impact on the study of sociology and continue to be studied and applied today.

Mechanisms of action for illicit drugs can be classified based on their effects on ionotropic receptors of ion channels, G coupled receptors, of monoamine transporters. Cocaine and amphetamine both increase dopamine levels in the synaptic cleft, but through different mechanisms. Cocaine directly blocks the dopamine transporter, while amphetamine binds to the transporter and increases dopamine efflux through various mechanisms, including inhibition of vesicular monoamine transporter 2 and monoamine oxidase, and stimulation of the intracellular receptor TAAR1. These mechanisms result in increased dopamine levels in the synaptic cleft and reuptake inhibition.

The inhibition of sexual behavior is caused by the activation of 5-HT2 receptors. However, this effect can be reversed by using 5-HT2 antagonists like cyproheptadine and 5-HT1a agonists like buspirone. These drugs are effective in treating sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs).

Antidepressants can cause sexual dysfunction as a side-effect, although the rates vary. The impact on sexual desire, arousal, and orgasm can differ depending on the type of antidepressant. It is important to rule out other causes and consider non-pharmacological strategies such as reducing the dosage of taking drug holidays. If necessary, switching to a lower risk antidepressant of using pharmacological options such as phosphodiesterase inhibitors of mirtazapine augmentation can be considered. The Maudsley Guidelines 14th Edition provides a helpful table outlining the risk of sexual dysfunction for different antidepressants.

Trinucleotide Repeat Disorders: Understanding the Genetic Basis

Trinucleotide repeat disorders are genetic conditions that arise due to the abnormal presence of an expanded sequence of trinucleotide repeats. These disorders are characterized by the phenomenon of anticipation, which refers to the amplification of the number of repeats over successive generations. This leads to an earlier onset and often a more severe form of the disease.

The table below lists the trinucleotide repeat disorders and the specific repeat sequences involved in each condition:

Condition Repeat Sequence Involved
Fragile X Syndrome CGG
Myotonic Dystrophy CTG
Huntington’s Disease CAG
Friedreich’s Ataxia GAA
Spinocerebellar Ataxia CAG

The mutations responsible for trinucleotide repeat disorders are referred to as ‘dynamic’ mutations. This is because the number of repeats can change over time, leading to a range of clinical presentations. Understanding the genetic basis of these disorders is crucial for accurate diagnosis, genetic counseling, and the development of effective treatments.

The parahippocampal gyrus is located surrounding the hippocampus and is involved in memory processing. Asymmetry in this area has also been observed in individuals with schizophrenia.

Aphasia is a language impairment that affects the production of comprehension of speech, as well as the ability to read of write. The areas involved in language are situated around the Sylvian fissure, referred to as the ‘perisylvian language area’. For repetition, the primary auditory cortex, Wernicke, Broca via the Arcuate fasciculus (AF), Broca recodes into articulatory plan, primary motor cortex, and pyramidal system to cranial nerves are involved. For oral reading, the visual cortex to Wernicke and the same processes as for repetition follows. For writing, Wernicke via AF to premotor cortex for arm and hand, movement planned, sent to motor cortex. The classification of aphasia is complex and imprecise, with the Boston Group classification and Luria’s aphasia interpretation being the most influential. The important subtypes of aphasia include global aphasia, Broca’s aphasia, Wernicke’s aphasia, conduction aphasia, anomic aphasia, transcortical motor aphasia, and transcortical sensory aphasia. Additional syndromes include alexia without agraphia, alexia with agraphia, and pure word deafness.