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.

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 ascent of the National Socialist Party during the 1930s had a negative effect on psychiatry in Germany, which was previously a leading force in European psychiatry. As a result of the Second World War, numerous skilled scientists and psychiatrists fled Germany and sought refuge in the United States. Their contributions were instrumental in establishing the US as the dominant force in both academic and clinical psychiatry.

A case-control design is more suitable than a cohort study for studying sudden infant death syndrome due to its low incidence.

Types of Primary Research Studies and Their Advantages and Disadvantages

Primary research studies can be categorized into six types based on the research question they aim to address. The best type of study for each question type is listed in the table below. There are two main types of study design: experimental and observational. Experimental studies involve an intervention, while observational studies do not. The advantages and disadvantages of each study type are summarized in the table below.

Type of Question Best Type of Study

Therapy Randomized controlled trial (RCT), cohort, case control, case series
Diagnosis Cohort studies with comparison to gold standard test
Prognosis Cohort studies, case control, case series
Etiology/Harm RCT, cohort studies, case control, case series
Prevention RCT, cohort studies, case control, case series
Cost Economic analysis

Study Type Advantages Disadvantages

Randomized Controlled Trial – Unbiased distribution of confounders – Blinding more likely – Randomization facilitates statistical analysis – Expensive – Time-consuming – Volunteer bias – Ethically problematic at times
Cohort Study – Ethically safe – Subjects can be matched – Can establish timing and directionality of events – Eligibility criteria and outcome assessments can be standardized – Administratively easier and cheaper than RCT – Controls may be difficult to identify – Exposure may be linked to a hidden confounder – Blinding is difficult – Randomization not present – For rare disease, large sample sizes of long follow-up necessary
Case-Control Study – Quick and cheap – Only feasible method for very rare disorders of those with long lag between exposure and outcome – Fewer subjects needed than cross-sectional studies – Reliance on recall of records to determine exposure status – Confounders – Selection of control groups is difficult – Potential bias: recall, selection
Cross-Sectional Survey – Cheap and simple – Ethically safe – Establishes association at most, not causality – Recall bias susceptibility – Confounders may be unequally distributed – Neyman bias – Group sizes may be unequal
Ecological Study – Cheap and simple – Ethically safe – Ecological fallacy (when relationships which exist for groups are assumed to also be true for individuals)

In conclusion, the choice of study type depends on the research question being addressed. Each study type has its own advantages and disadvantages, and researchers should carefully consider these when designing their studies.

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.

Opioid Pharmacology and Treatment Medications

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

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

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

Prescribing in the Elderly: Iatrogenic Consequences

Many medications, both prescribed and over-the-counter, can have significant adverse effects in the elderly population. It is important to note that the lists provided below are not exhaustive, and only the most common and important examples are given.

Medications Linked to Delirium and Other Cognitive Disorders

Medications are the most common reversible cause of delirium and dementia in the elderly. Many medications can cause cognitive impairment, but the classes of drugs most strongly associated with the development of drug-induced dementia are opioids, benzodiazepines, and anticholinergics.

According to a systematic review done in 2011 (Clegg, 2011), long-acting benzodiazepines (e.g., diazepam) are more troublesome than those that are shorter-acting. Opioids are associated with an approximately 2-fold increased risk of delirium in medical and surgical patients (Clegg, 2011). Pethidine appears to have a higher risk of delirium compared with other members of the opioid class. This may be because pethidine can accumulate when renal function is impaired and is converted to a metabolite with anticholinergic properties.

Some antipsychotic drugs have considerable antimuscarinic (anticholinergic) activity (e.g., chlorpromazine and clozapine), which may cause of worsen delirium. Delirium is uncommon in newer antipsychotics (but has been reported).

Medications Linked to Mood Changes

The following medications are well known to precipitate mood changes:

– Centrally-acting antihypertensives (e.g., methyldopa, reserpine, and clonidine) can cause depressive symptoms.
– Interferon-a is capable of inducing depressive symptoms.
– Digoxin is capable of inducing depressive symptoms.
– Corticosteroids can cause depressive, manic, and mixed symptoms with of without psychosis.
– Antidepressants can precipitate mania.

Medications Linked to Psychosis

The following medications are well known to precipitate psychosis:

– Anti-Parkinson’s Medications (e.g., bromocriptine, amantadine, selegiline, anticholinergics (e.g., trihexyphenidyl, benztropine, benzhexol), and levodopa).
– Corticosteroids

Medications Linked to Anxiety

The following medications are well known to precipitate anxiety:

– Stimulants
– β adrenergic inhalers

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

The temporal lobe is separated from the frontal and parietal lobes by the Sylvian fissure.

The Cerebral Cortex and Neocortex

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

Holmes and Rahe (1967) developed the social readjustment rating scale, which consisted of 43 life events of different levels of severity that appeared to occur before the onset of patients’ illnesses. The researchers analyzed 5000 patient records and found that the death of a spouse was the most serious life event, while a minor violation of the law was the least serious. Although this measure aimed to measure the impact of life events, it has received numerous criticisms, such as its failure to consider individual circumstances and its incomplete list of life events.

Antipsychotics and Sudden Death: Thioridazine and QTc Prolongation

Antipsychotic medications are known to carry a risk of sudden death, particularly due to their effects on cardiac function. Thioridazine, in particular, has been found to have pronounced effects on potassium channels and significantly prolongs the QTc interval, which is a measure of the time it takes for the heart to repolarize after each beat. This prolongation can lead to a potentially fatal arrhythmia known as torsades de pointes. As a result, thioridazine is most strongly associated with sudden death among antipsychotics.

However, all antipsychotics carry some degree of risk for QTc prolongation and should be closely monitored for changes in this interval. This is especially important for patients with preexisting cardiac conditions of other risk factors for arrhythmias. Regular electrocardiogram (ECG) monitoring may be necessary to detect any changes in QTc interval and adjust medication accordingly. By carefully monitoring patients and taking appropriate precautions, healthcare providers can help minimize the risk of sudden death associated with antipsychotic use.

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)

The list includes various psychiatric rating scales, with the Beck depression inventory (BDI) being the only self-report tool. It consists of 21 items that evaluate symptoms such as fatigue, irritability, and interest in others, and is designed to measure the severity of depression. On the other hand, the BAS is a clinician-administered scale that assesses medication-induced akathisia, while the BPRS evaluates depression, anxiety, and psychotic symptoms. The HAM-A is a clinician-administered questionnaire that measures the severity of anxiety, and the PANSS is a clinician-administered tool that assesses both positive (hallucinations and delusions) and negative symptoms (social and emotional withdrawal, disordered thinking) in patients with schizophrenia.

Antipsychotics and Sexual Dysfunction: Causes, Risks, and Management

Sexual dysfunction is a common side effect of antipsychotic medication, with the highest risk associated with risperidone and haloperidol due to their effect on prolactin levels. Clozapine, olanzapine, quetiapine, aripiprazole, asenapine, and lurasidone are associated with lower rates of sexual dysfunction. The Arizona Sexual Experiences Scale (ASEX) can be used to measure sexual dysfunction before and during treatment. Management options include excluding other causes, watchful waiting, dose reduction, switching to a lower risk agent, adding aripiprazole, considering an antidote medication, of using sildenafil for erectile dysfunction. It is important to address sexual dysfunction to improve quality of life and medication adherence.

Genetic Terms

Recombination Fraction

The recombination fraction is a measure of the distance between loci on a chromosome. If two loci are on different chromosomes, they will segregate independently. However, if they are on the same chromosome, they would always segregate together were it not for the process of crossing over. The closer two loci are on a chromosome, the less likely they are to be separated by crossing over. Blocks of alleles on a chromosome tend to be transmitted as a block through pedigree, and are known as a haplotype. The recombination fraction can vary from 0% if they are extremely close and 50% if they are on different chromosomes.

Gene Mapping

Mapping the genome is done in two ways: genetic mapping and physical mapping. Genetic mapping uses techniques such as pedigree analysis, while physical mapping is a technique used to find the order and physical distance between DNA base pairs by DNA markers. Physical maps can be divided into three general types: chromosomal of cytogenetic maps, radiation hybrid (RH) maps, and sequence maps. The different types of maps vary in their degree of resolution. Both maps are a collection of genetic markers and gene loci. While the physical map could be a more ‘accurate’ representation of the genome, genetic maps often offer insights into the nature of different regions of the chromosome.

LOD Score

The LOD score (logarithm of the odds) is a method used to ascertain if there is evidence for linkage between two genes. When genes are very near to each other on a chromosome, they are unlikely to be separated during crossing over in meiosis, and such genes are said to be linked. The relative distance between two genes can be calculated by using the offspring of an organism showing two strongly linked traits, and finding the percentage of offspring where the traits do not run together. By convention, a LOD score of >3 is considered evidence for linkage, and a LOD score of <-2 excludes linkage. Epigenetic Epigenetics involves genetic control by factors other than an individual’s DNA sequence. Epigenetic changes can switch genes on of off and determine which proteins are transcribed. Penetrance Penetrance is the probability of a gene of genetic trait being expressed. ‘Complete penetrance’ means the gene of genes for a trait are expressed in all the population who have the genes. ‘Incomplete penetrance’ means the genetic trait is expressed in only part of the population. Heritability Heritability is the proportion of phenotypic variance attributable to genetic variance. Anticipation Anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation.

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

Patients who do not experience any improvement from antidepressant medication may be recommended to undergo ECT. This is particularly relevant for elderly individuals who commonly experience relapse of depressive symptoms and may also have underlying medical conditions such as Alzheimer’s disease. Additionally, suicide risk in the elderly should be taken seriously and depression should be properly diagnosed and treated.

Side effects of sildenafil (viagra) that occur frequently (affecting more than 1 in 10 people) include:

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.

Non-Mendelian inheritance patterns include mitochondrial inheritance, trinucleotide expansion, mosaicism, and genomic imprinting. These patterns do not follow the typical Mendelian principles. Examples of non-Mendelian mitochondrial inheritance include Leber’s hereditary optic neuropathy and MELAS syndrome, which is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent stroke.

On the other hand, Mendelian genetic inheritance patterns include autosomal dominant, autosomal recessive, and sex-linked disorders such as X-linked dominant and X-linked recessive.

Mitochondrial DNA abnormalities can lead to various diseases, including MELAS syndrome. Mitochondrial DNA is inherited solely from the mother’s ovum, and the embryo’s mitochondria are entirely maternally derived. Most mitochondrial diseases manifest as myopathies and neuropathies.

Charpentier synthesised Chlorpromazine in 1950, and it was subsequently introduced into clinical practice in the 1950s.

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.

Deletion of genetic material on chromosome 7 is the underlying cause of William’s syndrome.

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.

Both lithium carbonate and citrate are used for the treatment and prevention of various mental health conditions, including mania, bipolar disorder, recurrent depression, and aggressive of self-harming behavior. Lithium carbonate is available in tablet form, while lithium citrate is a liquid medication.

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.

Voyeuristic disorder is typically observed in adult males who develop a sexual interest in secretly observing individuals without their knowledge. While this interest may first arise during adolescence, a diagnosis of voyeuristic disorder is only made after the age of 18 due to challenges in distinguishing it from normal sexual curiosity during puberty. The DSM-5 identifies voyeuristic behavior as a disorder when it causes harm, which can manifest as either personal distress of engaging in non-consensual acts.

Paraphilias are intense and persistent sexual interests other than sexual interest in genital stimulation of preparatory fondling with phenotypically normal, physically mature, consenting human partners. They are divided into those relating to erotic activity and those relating to erotic target. In order to become a disorder, paraphilias must be associated with distress of impairment to the individual of with harm to others. The DSM-5 lists 8 recognised paraphilic disorder but acknowledges that there are many more. Treatment modalities for the paraphilias have limited scientific evidence to support their use. Psychological therapy (especially CBT) is often used (with extremely variable results). Pharmacological options include SSRI, Naltrexone, Antipsychotics, GnRH agonists, and Anti-androgens and progestational drugs (e.g. cyproterone acetate).

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.

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

Hyperphagia and hypersomnia are the defining features of Kleine-Levin syndrome.

Kleine-Levin Syndrome: A Mysterious Condition

Kleine-Levin syndrome is a peculiar disorder that typically affects adolescent boys. It is characterized by an excessive need for sleep and an insatiable appetite when awake. The condition is also associated with emotional and behavioral issues such as irritability and aggression.

The onset of symptoms is sudden and can last for several days to weeks before disappearing. This is followed by a period of normalcy, only to be followed by another episode. This pattern can continue for years, but the severity of symptoms tends to decrease over time. During the periods between episodes, those affected appear to be perfectly healthy with no signs of physical of behavioral dysfunction. The media has dubbed this condition as Sleeping Beauty syndrome.

Despite extensive research, the cause of Kleine-Levin syndrome remains unknown. However, the prognosis is generally positive, with most individuals making a full recovery.

Inheritance Patterns and Examples

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

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

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

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

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

Paranoid Schizophrenia Diagnosis

This patient’s symptoms include hearing hallucinatory voices that command him to do things of non-verbal forms such as humming of laughing. He also experiences delusions with a persecutory of jealousy theme, as well as hallucinations of smell, changes in weight, and neglect of personal hygiene. These symptoms are consistent with a diagnosis of paranoid schizophrenia.

The patient’s clinical picture is dominated by fixed delusions, with less emphasis on mood changes, making diagnoses of psychotic depression and bipolar disease less likely. There is no evidence of epileptic-form activity of altered awareness during episodes of delusions or hallucinations.

It is important to differentiate paranoid schizophrenia from other disorders, such as schizoid personality disorder, which is characterized by emotional coldness, detachment, limited capacity to express emotion, and subsequently, few friends of close relationships.

Functional polymorphisms in two alcohol dehydrogenase genes (ADHIB and ADH1C on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) have been linked to lower rates of alcohol dependence. The strongest association is with the ALDH2*2 allele, which is almost exclusively found in Asian populations. Other alleles, such as ADH1B*2, ADH1B*3, and ADHlC*i, found in varying prevalence in different ethnic groups, have also been associated with lower rates of alcohol dependence.

The proposed mechanism for these associations is that the isoenzymes encoded by these alleles lead to an accumulation of acetaldehyde during alcohol metabolism. ALDH2*2 theoretically leads to a slower removal of acetaldehyde than ALDH2*1, while ADH1B*2 and ADH1B*3 lead to a more rapid production of acetaldehyde than ADHIB*I. It is believed that higher levels of acetaldehyde cause more intense reactions to alcohol and lead to lower levels of alcohol intake.

Genetics and Alcoholism

Alcoholism tends to run in families, and several studies confirm that biological children of alcoholics are more likely to develop alcoholism even when adopted by parents without the condition. Monozygotic twins have a greater concordance rate for alcoholism than dizygotic twins. Heritability estimates range from 45 to 65 percent for both men and women. While genetic differences affect risk, there is no “gene for alcoholism,” and both environmental and social factors weigh heavily on the outcome.

The genes with the clearest contribution to the risk for alcoholism and alcohol consumption are alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2). The first step in ethanol metabolism is oxidation to acetaldehyde, by ADHs. The second step is metabolism of the acetaldehyde to acetate by ALDHs. Individuals carrying even a single copy of the ALDH2*504K display the “Asian flushing reaction” when they consume even small amounts of alcohol. There is one significant genetic polymorphism of the ALDH2 gene, resulting in allelic variants ALDH2*1 and ALDH2*2, which is virtually inactive. ALDH2*2 is present in about 50 percent of the Taiwanese, Han Chinese, and Japanese populations. It is extremely rare outside Asia. Nearly no individuals of European of African descent carry this allele. ALDH2*504K has repeatedly been demonstrated to have a protective effect against alcohol use disorders.

The three different class I gene loci, ADH1A (alpha), ADH1B (beta), and ADH1C (gamma) are situated close to each other in the region 4q2123. The alleles ADH1C*1 and ADH1B*2 code for fast metabolism of alcohol. The ADH1B*1 slow allele is very common among Caucasians, with approximately 95 percent having the homozygous ADH1B*1/1 genotype and 5 percent having the heterozygous ADH1B*1/2 genotype. The ADH1B*2 allele is the most common allele in Asian populations. In African populations, the ADH1B*1 allele is the most common.

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