Diagnosis of Bulimia Nervosa

Bulimia nervosa is the likely diagnosis for the patient, given her recurrent binges and use of laxatives to compensate for them. The DSM-IV criteria for bulimia nervosa require that these features occur more than twice weekly for three months. Weight loss is not a diagnostic requirement. In both anorexia nervosa and bulimia nervosa, self-worth is judged largely of exclusively in terms of shape and weight, and obtaining a reliable dietary history from the patient is unlikely. A key feature of bulimia nervosa is a feeling of loss of control during binge eating episodes.

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Bulimia nervosa is the likely diagnosis for the patient, given her recurrent binges and use of laxatives to compensate for them. The DSM-IV criteria for bulimia nervosa require that these features occur more than twice weekly for three months. Weight loss is not a diagnostic requirement.

In both anorexia nervosa and bulimia nervosa, self-worth is judged largely of exclusively in terms of shape and weight, and obtaining a reliable dietary history from the patient is unlikely.

A key feature of bulimia nervosa is a feeling of loss of control during binge eating episodes.

Placebos that are inert can still cause negative effects.

Understanding the Placebo Effect

In general, a placebo is an inert substance that has no pharmacological activity but looks, smells, and tastes like the active drug it is compared to. The placebo effect is the observable improvement seen when a patient takes a placebo, which results from patient-related factors such as expectations rather than the placebo itself. Negative effects due to patient-related factors are termed the nocebo effect.

Active placebos are treatments with chemical activity that mimic the side effects of the drug being tested in a clinical trial. They are used to prevent unblinding of the drug versus the placebo control group. Placebos need not always be pharmacological and can be procedural, such as sham electroconvulsive therapy.

The placebo effect is influenced by factors such as the perceived strength of the treatment, the status of the treating professional, and the branding of the compound. The placebo response is greater in mild illness, and the response rate is increasing over time. Placebo response is usually short-lived, and repeated use can lead to a diminished effect, known as placebo sag.

It is difficult to separate placebo effects from spontaneous remission, and patients who enter clinical trials generally do so when acutely unwell, making it challenging to show treatment effects. Breaking the blind may influence the outcome, and the expectancy effect may explain why active placebos are more effective than inert placebos. Overall, understanding the placebo effect is crucial in clinical trials and personalized medicine.

Narrow Therapeutic Index Drugs

Narrow therapeutic index (NTI) drugs are medications that have a small difference between the amount that causes a therapeutic effect and the amount that causes toxicity. In other words, the therapeutic index (TI) of these drugs is narrow. The TI is a ratio that compares the blood concentration at which a drug causes a therapeutic effect to the amount that causes death of toxicity.

In clinical practice, the TI is the range of doses at which a medication appeared to be effective in clinical trials for a median of participants without unacceptable adverse effects. For most drugs, this range is wide enough, and the maximum plasma concentration of the drug achieved when the recommended doses of a drug are prescribed lie sufficiently above the minimum therapeutic concentration and sufficiently below the toxic concentration.

However, some drugs have a narrow therapeutic index, which means that even small changes in dose of blood concentration can lead to serious adverse effects. The US Food and Drug Administration (FDA) defines a drug product as having an NTI when there is less than a twofold difference in the minimum toxic concentrations and minimum effective concentrations in the blood and safe and effective use of the drug requires careful titration and patient monitoring.

Examples of drugs with a narrow therapeutic index include carbamazepine, lithium, phenytoin, warfarin, digoxin, and gentamicin. These drugs require close monitoring to ensure that the blood concentration remains within the therapeutic range and does not reach toxic levels.

Undoing and sublimation are two psychological concepts that are often mistaken for each other. While both involve a person’s attempt to deal with negative thoughts of emotions, there is a key difference between the two.

In undoing, a person tries to undo of neutralize their own unacceptable thoughts, emotions, of behaviors. This is often driven by feelings of guilt or remorse over something they have done of felt. The goal is to make amends and alleviate the negative feelings associated with their actions.

On the other hand, sublimation involves turning negative emotions into positive ones. However, unlike undoing, the person does not necessarily feel guilty of remorseful about their emotions. Instead, they may see their emotions as justified and seek to channel them into more positive outlets.

Therefore, while both undoing and sublimation involve coping with negative emotions, the key difference lies in the underlying motivation and feelings associated with the process.

Intermediate Mechanism: Rationalisation

Rationalisation is a defense mechanism commonly used by individuals to create false but credible justifications for their behavior of actions. It involves the use of logical reasoning to explain away of justify unacceptable behavior of feelings. The individual may not be aware that they are using this mechanism, and it can be difficult to identify in oneself.

Rationalisation is considered an intermediate mechanism, as it is common in healthy individuals from ages three to ninety, as well as in neurotic disorders and in mastering acute adult stress. It can be dramatically changed by conventional psychotherapeutic interpretation.

Examples of rationalisation include a student who fails an exam and blames the teacher for not teaching the material well enough, of a person who cheats on their partner and justifies it by saying their partner was neglectful of unaffectionate. It allows the individual to avoid taking responsibility for their actions and to maintain a positive self-image.

Overall, rationalisation can be a useful defense mechanism in certain situations, but it can also be harmful if it leads to a lack of accountability and an inability to learn from mistakes.

The term paramnesia refers to memory disorders where fantasy and reality are confused. There are various types of paramnesias, including déjà vu, jamais vu, confabulation, reduplicative paramnesia, retrospective falsification, and cryptomnesia. Reduplicative paramnesia is a subset of delusional misidentification syndromes, which include Capgras delusion, the Fregoli delusion, and others. A review of reduplicative paramnesia was conducted by Politis in 2012.

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

Genetics plays a role in the development of Alzheimer’s disease, with different genes being associated with early onset and late onset cases. Early onset Alzheimer’s, which is rare, is linked to three genes: amyloid precursor protein (APP), presenilin one (PSEN-1), and presenilin two (PSEN-2). The APP gene, located on chromosome 21, produces a protein that is a precursor to amyloid. The presenilins are enzymes that cleave APP to produce amyloid beta fragments, and alterations in the ratios of these fragments can lead to plaque formation. Late onset Alzheimer’s is associated with the apolipoprotein E (APOE) gene on chromosome 19, with the E4 variant increasing the risk of developing the disease. People with Down’s syndrome are also at high risk of developing Alzheimer’s due to inheriting an extra copy of the APP gene.

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

APOE3 is considered to have a neutral effect on the risk of developing certain health conditions.

Genetics plays a role in the development of Alzheimer’s disease, with different genes being associated with early onset and late onset cases. Early onset Alzheimer’s, which is rare, is linked to three genes: amyloid precursor protein (APP), presenilin one (PSEN-1), and presenilin two (PSEN-2). The APP gene, located on chromosome 21, produces a protein that is a precursor to amyloid. The presenilins are enzymes that cleave APP to produce amyloid beta fragments, and alterations in the ratios of these fragments can lead to plaque formation. Late onset Alzheimer’s is associated with the apolipoprotein E (APOE) gene on chromosome 19, with the E4 variant increasing the risk of developing the disease. People with Down’s syndrome are also at high risk of developing Alzheimer’s due to inheriting an extra copy of the APP gene.

Senile plaques and neurofibrillary tangles contain accumulations of hyperphosphorylated tau, while Hirano bodies are primarily composed of actin. The cytoskeleton is made up of microtubules (composed of tubulin), actin filaments, and intermediate filaments. Lewy bodies are characterized by the presence of insoluble aggregates of α-Synuclein, a protein that plays a role in regulating synaptic vesicle trafficking and neurotransmitter release.

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.

Cerebellar signs are evident in cases of lithium toxicity, which can manifest as slurred speech, a broad-based gait, and an intention tremor. The latter is characterized by a coarse appearance and a frequency of 2-3Hz (equivalent to 2 waves per second).

Types of Tremor

Essential Tremor

Otherwise known as benign essential tremor, this is the most common type of tremor. It is not associated with any underlying pathology. It usually begins in the 40’s, affects mainly the hands, and is slowly progressive. It tends to worsen with heightened emotion. It usually presents with unilateral upper limb involvement then progresses to both limbs.

Parkinsonian Tremor

This tremor is associated with Parkinson’s disease. It is classically described as ‘pill rolling’ due to the characteristic appearance of the fingers.

Cerebellar Tremor

Otherwise known as an intention tremor. This is a slow, coarse tremor which gets worse with purposeful movement. This is seen in lithium toxicity (note that the tremor seen as a side effect of long term lithium is fine and classed as physiological).

Psychogenic Tremor

Also known as a hysterical tremor. This type of tremor tends to appear and disappear suddenly and is hard to characterise due to its changeable nature. It tends to improve with distraction.

Physiologic Tremor

This is a very-low-amplitude fine tremor that is barely visible to the naked eye. It is present in every normal person while maintaining a posture of movement. It becomes enhanced and visible in many conditions such as anxiety, hyperthyroidism, alcohol withdrawal, and as drug induced side effects.

It is useful to have a basic idea about the frequencies of different types of tremor.

Type of Tremor Frequency

Intention 2-3Hz

Parkinsonian 5Hz

Essential 7Hz

Physiological 10Hz

Psychogenic variable

The Durham rule states that an individual cannot be held criminally responsible if their unlawful actions were a result of a mental disease of defect. The M’Naghten rule, on the other hand, states that a person is not guilty by reason of insanity if they were unaware of the nature and quality of their actions due to a mental disease, of if they knew their actions were wrong. Additionally, the common law principle of necessity allows for reasonable force and necessary treatment to be used on individuals who lack capacity.

The origin of the term dementia praecox is a topic of controversy. While some sources credit Kraepelin with popularizing the term, others argue that it was first used in its Latin form by Arnold Pick in 1891. The original term demence precoce was coined by Morel in 1852. Despite this, the College has chosen to attribute the term to Kraepelin. Therefore, if the question refers to demence precoce, the answer should be Morel, and if it refers to dementia praecox, Kraepelin should be selected.

History of Psychiatric Terms

In the exams, it is important to be familiar with the individuals associated with certain psychiatric terms. For example, Kraepelin is associated with dementia praecox and manic depression, while Bleuler is associated with schizophrenia. Other terms and their associated individuals include Hebephrenia (Hecker), Catatonia (Kahlbaum), Schizoaffective (Kasanin), Neurasthenia (Beard), Unipolar and bipolar (Kleist), Hypnosis (Braid), Group dynamics (Lewin), Group psychotherapy (Moreno), Psychopathic inferiority (Koch), Psychiatry (Reil), and Institutional Neurosis (Barton).

It should be noted that there is some debate over the origins of certain terms. While Kraepelin is often credited with coining the term dementia praecox, some sources suggest that it was first used in its Latin form by Arnold Pick in 1891. The original term demence precoce was first used by Morel in 1852. Despite this, the College appears to favor the Kraepelin attribution.

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.

Engrossment refers to the emotional connection that a father develops with his child. This term was coined by Greenberg and Morris in their 1974 study, which explored the impact of newborns on fathers. In contrast, Bowlby used the term ‘attachment’ to describe the bond that develops between a child and their mother. Bonding, on the other hand, refers to the process by which a mother develops a strong emotional connection with her child. Imprinting is a phenomenon observed in some animal species, where newborns acquire certain behavioral characteristics from their parents shortly after birth. Finally, sociability is a crucial aspect of attachment, as it involves the pursuit of social contact and connection with others.

Historical Classification of Schizophrenia

The classification of schizophrenia has evolved over time, with various individuals contributing to its development. In 1801, Phillippe Pinel used the term ‘demencé’ to describe the loss of mental abilities in chronically ill patients. Benedict Morel coined the term ‘demencé precocé’ in 1852 to describe young patients with premature dementia. Kahlbaum was the first to describe ‘paraphrenia hebetica’ in the 1860s, which was later elaborated as ‘hebephrenia’ by Hecker in 1871.

In 1893, Emil Kraepelin used the term dementia praecox to describe the condition, emphasizing the importance of delusions, hallucinations, impaired attention, thought incoherence, stereotyped movements and expressions, deterioration of emotional life, and a loss of drive as key symptoms. In 1908, Eugen Bleuler coined the term ‘schizophrenia’ to replace dementia praecox, denoting ‘a splitting of the psychic functions.’ Bleuler expanded the concept to include presentations that did not include a ‘terminal state.’

Bleuler introduced a distinction between basic and accessory symptoms and primary and secondary symptoms. Basic symptoms are necessarily present in any case of schizophrenia, while accessory symptoms may of may not occur. The fundamental features of schizophrenia were loosening of associations, disturbances of affectivity, ambivalence, and autism. The alteration of associations is the only symptom that Bleuler regarded as both basic and primary, and can thus be described as the core disturbance in the Bleulerian conception of schizophrenia.

In 1939, Langfeldt introduced the term ‘schizophreniform psychosis’ to describe patients with Bleulerian schizophrenia who did not follow a progressively deteriorating course. In the 1960s, Rado/Meehl introduced the term ‘schizotypy’ to recognize the concept of a continuum of spectrum of schizophrenia-related phenotypes. In the 1980s, Crow proposed a subclassification of schizophrenia, dividing patients into types I and II. Type I patients present with positive symptoms such as delusions and hallucinations, while type II patients present with negative symptoms such as affective flattening and poverty of speech.

Bion, a psychoanalyst, was fascinated by group dynamics and believed that groups had a collective unconscious that functioned similarly to that of an individual. He argued that this unconsciousness protected the group from the pain of reality. Bion identified two types of groups: the ‘working group’ that functioned well and achieved its goals, and the ‘basic assumption group’ that acted out primitive fantasies and prevented progress. Bion then described different types of basic assumption groups, including ‘dependency,’ where the group turns to a leader to alleviate anxiety, ‘fight-flight,’ where the group perceives an enemy and either attacks of avoids them, and ‘pairing,’ where the group believes that the solution lies in the pairing of two members. These dynamics can be observed in various settings, such as when strangers come together for the first time of when doctors in different specialties criticize one another.

The concept of recovery in mental disorder goes beyond symptom resolution and focuses on developing a rewarding and meaningful life while accepting the impact of mental distress on the self. Clinical remission, on the other hand, refers to the cessation of symptoms and is often measured through clinical outcome scales. Chronic psychosis is the ongoing experience of psychotic symptoms. Recovery in mental disorder is a rephrasing of the conventional medical definition of remission and recognizes the need for a holistic approach to treatment while still involving clinicians and allied professionals. For further reading, Anthony’s Recovery From Mental Illness and Davidson and Roe’s Recovery from versus recovery in serious mental illness offer valuable insights.

SNRIs include duloxetine and venlafaxine.

Mechanisms of Action of Different Drugs

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

The 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.

When a patient experiences new onset agitation and restlessness, it can be caused by various factors such as exacerbation of their underlying condition, akathisia, serotonin syndrome, neuroleptic malignant syndrome, of confusional states due to drug-induced hyponatremia. It is crucial to conduct a thorough assessment to rule out the most severe causes. Akathisia is a type of extrapyramidal symptom that involves increased motor activity and a distressing feeling of restlessness. It is typically caused by antipsychotics, but SSRIs can also produce similar symptoms. Akathisia may increase the risk of aggression and suicide. Oxazepam, a short-acting benzodiazepine, is only prescribed at night and would have worn off by the time the patient was evaluated. Serotonin syndrome is a medical emergency caused by serotonergic medication and presents with symptoms such as sweating, confusion, increased reflexes, and myoclonus. Although it remains a possibility in an agitated patient with recent changes in serotonergic drugs, these symptoms were absent. Neuroleptic malignant syndrome is a medical emergency caused by dopamine antagonists and presents with symptoms such as fever, increased muscle tone, sweating, fluctuating consciousness, and fluctuating blood pressure. These symptoms were not present in this patient. While antidepressant-induced hypomania/mania is rare, this patient did not exhibit an increased rate of speech of any other symptoms of mania except for over-activity.

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.

Dementia pugilistica, also known as CTE, is categorized as a tauopathy, which is a type of neurodegenerative disease that involves the accumulation of tau protein into NFTs of gliofibrillary tangles in the brain. While it commonly occurs due to repeated brain injuries, it can also develop from a single traumatic event, as reported by Smith in 2013.

Dementia Pugilistica: A Neurodegenerative Condition Resulting from Neurotrauma

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

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

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

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

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.

The defining feature of Lewy body dementia is the presence of alpha-synuclein protein clumps known as Lewy bodies.

Tau and Tauopathies

Tau proteins are essential for maintaining the stability of microtubules in neurons. Microtubules provide structural support to the cell and facilitate the transport of molecules within the cell. Tau proteins are predominantly found in the axons of neurons and are absent in dendrites. The gene that codes for tau protein is located on chromosome 17.

When tau proteins become hyperphosphorylated, they clump together, forming neurofibrillary tangles. This process leads to the disintegration of cells, which is a hallmark of several neurodegenerative disorders collectively known as tauopathies.

The major tauopathies include Alzheimer’s disease, Pick’s disease (frontotemporal dementia), progressive supranuclear palsy, and corticobasal degeneration. These disorders are characterized by the accumulation of tau protein in the brain, leading to the degeneration of neurons and cognitive decline. Understanding the role of tau proteins in these disorders is crucial for developing effective treatments for these devastating diseases.

The observed symptoms in the patient are indicative of simultanagnosia, a condition that arises due to dysfunction in the parieto occipital lobes on both sides of the brain.

Parietal Lobe Dysfunction: Types and Symptoms

The parietal lobe is a part of the brain that plays a crucial role in processing sensory information and integrating it with other cognitive functions. Dysfunction in this area can lead to various symptoms, depending on the location and extent of the damage.

Dominant parietal lobe dysfunction, often caused by a stroke, can result in Gerstmann’s syndrome, which includes finger agnosia, dyscalculia, dysgraphia, and right-left disorientation. Non-dominant parietal lobe dysfunction, on the other hand, can cause anosognosia, dressing apraxia, spatial neglect, and constructional apraxia.

Bilateral damage to the parieto-occipital lobes, a rare condition, can lead to Balint’s syndrome, which is characterized by oculomotor apraxia, optic ataxia, and simultanagnosia. These symptoms can affect a person’s ability to shift gaze, interact with objects, and perceive multiple objects at once.

In summary, parietal lobe dysfunction can manifest in various ways, and understanding the specific symptoms can help diagnose and treat the underlying condition.

Migraine

Migraine is a common condition that affects 5-10% of the population, with a higher prevalence in women than men (2-3:1). It typically starts in childhood of adolescence and has a strong familial association, with 2/3 of cases reporting a family history of migraine.

The most prominent symptom of migraine is headache, which is usually unilateral but can occur on both sides. Other symptoms include anorexia, nausea and vomiting, photophobia, and intolerance of noise.

In about 1/3 of cases, migraines are preceded by a visual aura (known as classic migraine). The most common form of visual aura is the ‘fortification spectra’ (semicircle of zigzag lights), but other disturbances such as micropsia, macropsia, zoom vision, mosaic vision, scotomas, and even hallucinations can occur.

Basilar migraines are a subtype of migraine where headache and aura are accompanied by difficulty speaking, vertigo, ringing in ears, of other brainstem-related symptoms, but not motor weakness.

Migraine can be triggered by various factors, including alcohol, cheese, chocolate, skipping meals, missing sleep, and oral contraceptives. Stress is also a common precipitant of migraine.

When under stress, the paraventricular nucleus of the hypothalamus releases two hormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP).

HPA Axis Dysfunction in Mood Disorders

The HPA axis, which includes regulatory neural inputs and a feedback loop involving the hypothalamus, pituitary, and adrenal glands, plays a central role in the stress response. Excessive secretion of cortisol, a glucocorticoid hormone, can lead to disruptions in cellular functioning and widespread physiologic dysfunction. Dysregulation of the HPA axis is implicated in mood disorders such as depression and bipolar affective disorder.

In depressed patients, cortisol levels often do not decrease as expected in response to the administration of dexamethasone, a synthetic corticosteroid. This abnormality in the dexamethasone suppression test is thought to be linked to genetic of acquired defects of glucocorticoid receptors. Tricyclic antidepressants have been shown to increase expression of glucocorticoid receptors, whereas this is not the case for SSRIs.

Early adverse experiences can produce long standing changes in HPA axis regulation, indicating a possible neurobiological mechanism whereby childhood trauma could be translated into increased vulnerability to mood disorder. In major depression, there is hypersecretion of cortisol, corticotropin-releasing factor (CRF), and ACTH, and associated adrenocortical enlargement. HPA abnormalities have also been found in other psychiatric disorders including Alzheimer’s and PTSD.

In bipolar disorder, dysregulation of ACTH and cortisol response after CRH stimulation have been reported. Abnormal DST results are found more often during depressive episodes in the course of bipolar disorder than in unipolar disorder. Reduced pituitary volume secondary to LHPA stimulation, resulting in pituitary hypoactivity, has been observed in bipolar patients.

Overall, HPA axis dysfunction is implicated in mood disorders, and understanding the underlying mechanisms may lead to new opportunities for treatments.

Parietal Lobe Dysfunction: Types and Symptoms

The parietal lobe is a part of the brain that plays a crucial role in processing sensory information and integrating it with other cognitive functions. Dysfunction in this area can lead to various symptoms, depending on the location and extent of the damage.

Dominant parietal lobe dysfunction, often caused by a stroke, can result in Gerstmann’s syndrome, which includes finger agnosia, dyscalculia, dysgraphia, and right-left disorientation. Non-dominant parietal lobe dysfunction, on the other hand, can cause anosognosia, dressing apraxia, spatial neglect, and constructional apraxia.

Bilateral damage to the parieto-occipital lobes, a rare condition, can lead to Balint’s syndrome, which is characterized by oculomotor apraxia, optic ataxia, and simultanagnosia. These symptoms can affect a person’s ability to shift gaze, interact with objects, and perceive multiple objects at once.

In summary, parietal lobe dysfunction can manifest in various ways, and understanding the specific symptoms can help diagnose and treat the underlying condition.

Between 2007 and 2011, there was a significant increase in the suicide rate among males aged 45 to 59, with 22.2 deaths per 100,000 population in 2011. The highest suicide rate overall was observed in males aged 30 to 44, with 23.5 deaths per 100,000 population in 2011. For females, the highest suicide rate was seen in the 45- to 59-year-old age group, with 7.3 deaths per 100,000 population in 2011. In 2011, there were 4,552 male suicides (a rate of 18.2 suicides per 100,000 population) and 1,493 female suicides (5.6 per 100,000 population).