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.

Both ADHD and ASD are believed to have a strong genetic component, although only one of them is classified as a developmental disorder.

Heritability: Understanding the Concept

Heritability is a concept that is often misunderstood. It is not a measure of the extent to which genes cause a condition in an individual. Rather, it is the proportion of phenotypic variance attributable to genetic variance. In other words, it tells us how much of the variation in a condition seen in a population is due to genetic factors. Heritability is calculated using statistical techniques and can range from 0.0 to 1.0. For human behavior, most estimates of heritability fall in the moderate range of .30 to .60.

The quantity (1.0 – heritability) gives the environment ability of the trait. This is the proportion of phenotypic variance attributable to environmental variance. The following table provides estimates of heritability for major conditions:

Condition Heritability estimate (approx)
ADHD 85%
Autism 70%
Schizophrenia 55%
Bipolar 55%
Anorexia 35%
Alcohol dependence 35%
Major depression 30%
OCD 25%

It is important to note that heritability tells us nothing about individuals. It is a population-level measure that helps us understand the relative contributions of genetic and environmental factors to a particular condition.

Neuroimaging techniques can be divided into structural and functional types, although this distinction is becoming less clear as new techniques emerge. Structural techniques include computed tomography (CT) and magnetic resonance imaging (MRI), which use x-rays and magnetic fields, respectively, to produce images of the brain’s structure. Functional techniques, on the other hand, measure brain activity by detecting changes in blood flow of oxygen consumption. These include functional MRI (fMRI), emission tomography (PET and SPECT), perfusion MRI (pMRI), and magnetic resonance spectroscopy (MRS). Some techniques, such as diffusion tensor imaging (DTI), combine both structural and functional information to provide a more complete picture of the brain’s anatomy and function. DTI, for example, uses MRI to estimate the paths that water takes as it diffuses through white matter, allowing researchers to visualize white matter tracts.

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)

Trephination, the act of creating a hole in a living person’s skull, is believed to be the earliest form of surgery. It was likely used to treat various ailments such as convulsions, headaches, infections, and fractures, of to allow the exit of entrance of spirits thought to cause illness. The practice was also used in ancient Egypt, where skull scrapings were used to create medicinal potions. Trephination was written about by both Hippocrates and Galen and continued to be performed throughout the Middle Ages and into the Renaissance. Evidence of successful operations can be seen in skulls that show bone regrowth, suggesting that many people survived the treatment.

While antipsychotics can cause secondary amenorrhoea by increasing prolactin levels, it is important to first rule out pregnancy as it is the most common cause of this condition.

Ventricular enlargement is a common finding in individuals with schizophrenia.

Schizophrenia is a pathology that is characterized by a number of structural and functional brain alterations. Structural alterations include enlargement of the ventricles, reductions in total brain and gray matter volume, and regional reductions in the amygdala, parahippocampal gyrus, and temporal lobes. Antipsychotic treatment may be associated with gray matter loss over time, and even drug-naïve patients show volume reductions. Cerebral asymmetry is also reduced in affected individuals and healthy relatives. Functional alterations include diminished activation of frontal regions during cognitive tasks and increased activation of temporal regions during hallucinations. These findings suggest that schizophrenia is associated with both macroscopic and functional changes in the brain.

The frontal lobe is located at the front of the cerebrum and is responsible for managing executive functions and working memory. The hippocampus plays a role in spatial navigation and the consolidation of short term memory to long term memory, but is often the first region of the brain to suffer damage in Alzheimer’s disease. The corpus callosum is a bundle of nerve fibers that connects the left and right cerebral hemispheres, facilitating communication between them. The thalamus is a symmetrical midline structure that relays sensory and motor signals to the cerebral cortex, while also regulating consciousness, alertness, and sleep. Broca’s area, which is typically located in the inferior frontal gyrus, is a key region involved in language production.

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.

Deceitfulness is the core diagnostic criterion, while the other options are considered associated features that may be present but are not essential for diagnosis.

Personality Disorder (Antisocial / Dissocial)

Antisocial personality disorder is characterized by impulsive, irresponsible, and often criminal behavior. The criteria for this disorder differ somewhat between the ICD-11 and DSM-5. The ICD-11 abolished all categories of personality disorder except for a general description of personality disorder. This diagnosis can be further specified as “mild,” “moderate,” of “severe.” Patient behavior can be described using one of more of five personality trait domains; negative affectivity, dissociality, anankastic, detachment, and disinhibition. Clinicians may also specify a borderline pattern qualifier.

The core feature of dissociality is a disregard for the rights and feelings of others, encompassing both self-centeredness and lack of empathy. Common manifestations of Dissociality include self-centeredness and lack of empathy. The DSM-5 defines antisocial personality disorder as a pervasive pattern of disregard for and violation of the rights of others, occurring since age 15, as indicated by three (of more) of the following: failure to conform to social norms with respect to lawful behaviors, deceitfulness, impulsivity of failure to plan ahead, irritability and aggressiveness, reckless disregard for safety of self of others, consistent irresponsibility, and lack of remorse.

Prevalence estimates are between 1%-6% in men and between 0.2-0.8% in women. Antisocial behaviors typically have their onset before age 8 years. Nearly 80% of people with ASPD developed their first symptom by age 11 years. Boys develop symptoms earlier than girls, who may not develop symptoms until puberty. An estimated 25% of girls and 40% of boys with Conduct Disorder will later meet criteria for ASPD.

The 2009 NICE Guidelines essentially make two recommendations on treatment: consider offering group-based cognitive and behavioral interventions and pharmacological interventions should not be routinely used for the treatment of antisocial personality disorder of associated behaviors of aggression, anger, and impulsivity. A Cochrane review found that there is not enough good quality evidence to recommend of reject any psychological treatment for people with a diagnosis of AsPD.

The term psychopathy has varied meanings. Some use the term synonymously with APD and consider it to represent the severe end of the spectrum of APD. Others maintain a clear distinction between psychopathy and APD. Psychopathy has been said to be a richer (broader) concept than APD. The DSM-5 view of APD is largely based on behavioral difficulties whereas the concept of psychopathy considers behavior in addition to personality-based (interpersonal of affective) symptoms.

The midbrain contains a section called the pars compacta, which is made up of neurons that produce dopamine and is situated next to the pars reticulata. Parkinson’s disease is identified by the loss of these dopamine-producing neurons in this area.

Parkinson’s Disease Pathology

Parkinson’s disease is a neurodegenerative disorder that affects the central nervous system. The pathology of Parkinson’s disease is very similar to that of Lewy body dementia. The macroscopic features of Parkinson’s disease include pallor of the substantia nigra (midbrain) and locus coeruleus (pons). The microscopic changes include the presence of Lewy bodies, which are intracellular aggregates of alpha-synuclein. Additionally, there is a loss of dopaminergic cells from the substantia nigra pars compacta. These changes contribute to the motor symptoms of Parkinson’s disease, such as tremors, rigidity, and bradykinesia. Understanding the pathology of Parkinson’s disease is crucial for developing effective treatments and improving the quality of life for those affected by this condition.

The retina and optic nerves originate from protrusions of the diencephalon known as eye vesicles during development.

Neurodevelopment: Understanding Brain Development

The development of the central nervous system begins with the neuroectoderm, a specialized region of ectoderm. The embryonic brain is divided into three areas: the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon). The prosencephalon further divides into the telencephalon and diencephalon, while the hindbrain subdivides into the metencephalon and myelencephalon.

The telencephalon, of cerebrum, consists of the cerebral cortex, underlying white matter, and the basal ganglia. The diencephalon includes the prethalamus, thalamus, hypothalamus, subthalamus, epithalamus, and pretectum. The mesencephalon comprises the tectum, tegmentum, ventricular mesocoelia, cerebral peduncles, and several nuclei and fasciculi.

The rhombencephalon includes the medulla, pons, and cerebellum, which can be subdivided into a variable number of transversal swellings called rhombomeres. In humans, eight rhombomeres can be distinguished, from caudal to rostral: Rh7-Rh1 and the isthmus. Rhombomeres Rh7-Rh4 form the myelencephalon, while Rh3-Rh1 form the metencephalon.

Understanding neurodevelopment is crucial in comprehending brain development and its complexities. By studying the different areas of the embryonic brain, we can gain insight into the formation of the central nervous system and its functions.

Redintegration pertains to the recollection of information from long term memory triggered by a cue, like a scent of noise. Recall entails actively searching memory stores for information. Recognition refers to the ability to identify an answer to a question from a list of options, without spontaneously recalling it. Reconstructive memory is the process of transferring information from one person to another. Relearning involves learning something again that was previously learned and forgotten, with faster learning occurring on subsequent attempts.

Personality assessment can be approached in two ways: objective and projective. Objective assessment involves structured, standardized measurement tools that typically require self-reporting. This approach uses direct questions to gather information about a person’s opinion of themselves. In contrast, projective assessment involves unstructured and often ambiguous stimuli to elicit responses that reveal information about a person’s personality. The Holtzman inkblot technique (HIT) is an example of a projective measure, while the Eysenck personality questionnaire (EPQ), Personality Assessment Inventory (PAI), and Millon Clinical Multiaxial Inventory (MCMI) are all examples of objective measures. The EPQ, PAI, and MCMI all use a true of false self-reporting format to gather information about a person’s personality.

Drug-induced dystonias typically manifest within a few days of initiating antipsychotic medication (of following a significant dosage increase). While they can affect any muscle group, they most frequently occur in the head and neck region.

Movement Disorders: Key Features

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Antidepressants: Mechanism of Action

Antidepressants are a class of drugs used to treat depression and other mood disorders. The mechanism of action of antidepressants varies depending on the specific drug. Here are some examples:

Mirtazapine is a noradrenaline and serotonin specific antidepressant (NaSSa). It works by blocking certain receptors in the brain, including 5HT-1, 5HT-2, 5HT-3, and H1 receptors. It also acts as a presynaptic alpha 2 antagonist, which stimulates the release of noradrenaline and serotonin.

Venlafaxine and duloxetine are both serotonin and noradrenaline reuptake inhibitors (SNRIs). They work by blocking the reuptake of these neurotransmitters, which increases their availability in the brain.

Reboxetine is a noradrenaline reuptake inhibitor (NRI). It works by blocking the reuptake of noradrenaline, which increases its availability in the brain.

Bupropion is a noradrenaline and dopamine reuptake inhibitor (NDRI). It works by blocking the reuptake of these neurotransmitters, which increases their availability in the brain.

Trazodone is a weak serotonin reuptake inhibitor (SRI) and 5HT agonist. It works by increasing the availability of serotonin in the brain.

St John’s Wort is a natural supplement that has been used to treat depression. It has a weak monoamine oxidase inhibitor (MAOI) effect and a weak SNRI effect.

In summary, antidepressants work by increasing the availability of certain neurotransmitters in the brain, such as serotonin, noradrenaline, and dopamine. The specific mechanism of action varies depending on the drug.

Disease frequency can be measured using incidence, which counts the number of new cases of a disease in a specific population during a specified time period. Period prevalence refers to the number of existing cases during a given time period, while point prevalence refers to the number of existing cases at a specific point in time. The total disease burden within a population, of crude rate, is determined by the total number of people with the disease in that population. It is important to note that the number of newly diagnosed cases alone cannot determine the incidence rate, as it lacks a denominator.

Assessing Executive Function with the Hayling and Brixton Tests

The Hayling and Brixton tests are two assessments designed to evaluate executive function. The Hayling Sentence Completion Test consists of two sets of 15 sentences, with the last word missing. In the first section, participants complete the sentences, providing a measure of response initiation speed. The second part, the Hayling, requires participants to complete a sentence with a nonsense ending word, suppressing a sensible one. This provides measures of response suppression ability and thinking time. Performance on such tests has been linked to frontal lobe dysfunction and dysexecutive symptoms in everyday life.

The Brixton Test is a rule detection and rule following task. Impairments on such tasks are commonly demonstrated in individuals with dysexecutive problems. Overall, these tests provide valuable insights into executive function and can help identify areas of weakness that may require intervention.

Dopamine receptors are classified as metabotropic receptors rather than ionotropic receptors.

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.

Clinical Trials: Phases and Objectives

Clinical trials are conducted in four phases to evaluate the safety and efficacy of drugs of treatments. In Phase I, a small group of healthy individuals (15-20) is given the drug to determine its safety, dosage range, and side effects. Phase II involves a larger group (100-300) to assess the drug’s effectiveness and safety. In Phase III, the drug is given to a larger population (1,000-3,000) to confirm its efficacy, compare it with existing treatments, and collect data for safe use. Phase IV, also known as post-marketing trials, is conducted after the drug is licensed to gather additional information on safety and potential uses. These trials are crucial in determining the safety and efficacy of drugs and treatments before they are made available to the public.

Glutamate is the precursor for the synthesis of GABA.

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.

Functions of the Hypothalamus

The hypothalamus is a vital part of the brain that plays a crucial role in regulating various bodily functions. It receives and integrates sensory information about the internal environment and directs actions to control internal homeostasis. The hypothalamus contains several nuclei and fiber tracts, each with specific functions.

The suprachiasmatic nucleus (SCN) is responsible for regulating circadian rhythms. Neurons in the SCN have an intrinsic rhythm of discharge activity and receive input from the retina. The SCN is considered the body’s master clock, but it has multiple connections with other hypothalamic nuclei.

Body temperature control is mainly under the control of the preoptic, anterior, and posterior nuclei, which have temperature-sensitive neurons. As the temperature goes above 37ºC, warm-sensitive neurons are activated, triggering parasympathetic activity to promote heat loss. As the temperature goes below 37ºC, cold-sensitive neurons are activated, triggering sympathetic activity to promote conservation of heat.

The hypothalamus also plays a role in regulating prolactin secretion. Dopamine is tonically secreted by dopaminergic neurons that project from the arcuate nucleus of the hypothalamus into the anterior pituitary gland via the tuberoinfundibular pathway. The dopamine that is released acts on lactotrophic cells through D2-receptors, inhibiting prolactin synthesis. In the absence of pregnancy of lactation, prolactin is constitutively inhibited by dopamine. Dopamine antagonists result in hyperprolactinemia, while dopamine agonists inhibit prolactin secretion.

In summary, the hypothalamus is a complex structure that regulates various bodily functions, including circadian rhythms, body temperature, and prolactin secretion. Dysfunction of the hypothalamus can lead to various disorders, such as sleep-rhythm disorder, diabetes insipidus, hyperprolactinemia, and obesity.

The other conditions listed require careful consideration when using selective serotonin reuptake inhibitors (SSRIs), while acute mania is an absolute contraindication.

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.

Antipsychotics can be classified in different ways, with the most common being typical (first generation) and atypical (second generation) types. Typical antipsychotics block dopamine (D2) receptors and have varying degrees of M1, Alpha-1, and H1 receptor blockade. Atypical antipsychotics have a lower propensity for extrapyramidal side-effects and are attributed to the combination of relatively lower D2 antagonism with 5HT2A antagonism. They are also classified by structure, with examples including phenothiazines, butyrophenones, thioxanthenes, diphenylbutylpiperidine, dibenzodiazepines, benzoxazoles, thienobenzodiazepine, substituted benzamides, and arylpiperidylindole (quinolone). Studies have found little evidence to support the superiority of atypicals over typicals in terms of efficacy, discontinuation rates, of adherence, with the main difference being the side-effect profile. The Royal College also favors classification by structure.

Patients may feel that they have lost control over their thoughts, which can manifest as passivity of thought. This refers to the belief that an external agency is controlling one’s thoughts. Passivity can take different forms, such as thought withdrawal, thought insertion, and thought broadcasting.

Ego (Boundary) Disturbances

Ego (boundary) disturbances refer to experiences where there is a disturbance in the perception of self as distinct from the environment of the integrity of self. It also includes instances where bodily processes, personal thought processes, feelings, and actions are experienced as being externally directed. These phenomena are referred to as passivity phenomena, and some of the symptom characteristics are classified as bizarre delusional phenomena in the DSM.

Derealization is when a patient experiences their surroundings of time as if they are unreal and changed, losing all feelings of familiarity and trust in the environment. People, objects, and surroundings appear unreal, unfamiliar, of spatially altered. The sensations may be intense of weak in nature.

Depersonalization is when a patient perceives themselves as alien, unreal, changed, of as a stranger. The disturbances of depersonalization may be of a transient nature only of become more persistent over a longer period of time. It is generally felt to be both strange and unpleasant.

Thought broadcasting is when a patient’s personal thoughts are experienced as no longer belonging to the patient alone but accessible by others who will know what the patient is thinking (mind reading). Thought withdrawal is when a patient’s thoughts are being removed of stripped from them. Thought insertion is when patients experience their thoughts and ideas as being externally influenced, made externally, controlled, directed, entered/ of externally imposed.

Other feelings of alien influence refer to feelings, intentions, behavior, of bodily functions that are experienced as externally controlled of made by others (passivity phenomena). The patient feels externally compelled to say something specific, to scream, to act of behave in a particular way, to attack someone, to throw a tantrum, etc.

Tuberous Sclerosis: A Neurocutaneous Syndrome with Psychiatric Comorbidity

Tuberous sclerosis is a genetic disorder that affects multiple organs, including the brain, and is associated with significant psychiatric comorbidity. This neurocutaneous syndrome is inherited in an autosomal dominant pattern with a high penetrance rate of 95%, but its expression can vary widely. The hallmark of this disorder is the growth of multiple non-cancerous tumors in vital organs, including the brain. These tumors result from mutations in one of two tumor suppressor genes, TSC1 and TSC2. The psychiatric comorbidities associated with tuberous sclerosis include autism, ADHD, depression, anxiety, and even psychosis.

Topiramate is a medication used for epilepsy and bipolar affective disorder. It works by inhibiting voltage gated sodium channels and increasing GABA levels. Unlike most psychotropic drugs, it is associated with weight loss.

Macrocytic anaemia is the type that is commonly associated with valproate.

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.

Anticholinergic side effects, such as dry mouth, urinary retention, and dry skin, are commonly associated with Amitriptyline and other tricyclic antidepressants.