Harry Harlow conducted controversial experiments with rhesus macaque monkeys and surrogate ‘mothers’ made of inanimate objects, revealing that the infants preferred comfort and warmth over food.
Mary Ainsworth created the Strange Situation classification to categorize infants’ attachment behaviors.
John Bowlby coined the term ‘attachment’ to describe a child’s bond with their mother.
Konrad Lorenz studied imprinting in geese that were hatched in incubators.
Mary Main played a role in the development of the Adult Attachment Interview, which evaluates an individual’s early attachment experiences.

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.

Neuroleptic malignant syndrome is a condition caused by the blockade of dopamine receptors.

MAOIs: A Guide to Mechanism of Action, Adverse Effects, and Dietary Restrictions

First introduced in the 1950s, MAOIs were the first antidepressants introduced. However, they are not the first choice in treating mental health disorders due to several dietary restrictions and safety concerns. They are only a treatment option when all other medications are unsuccessful. MAOIs may be particularly useful in atypical depression (over eating / over sleeping, mood reactivity).

MAOIs block the monoamine oxidase enzyme, which breaks down different types of neurotransmitters from the brain: norepinephrine, serotonin, dopamine, as well as tyramine. There are two types of monoamine oxidase, A and B. The MOA A are mostly distributed in the placenta, gut, and liver, but MOA B is present in the brain, liver, and platelets. Selegiline and rasagiline are irreversible and selective inhibitors of MAO type B, but safinamide is a reversible and selective MAO B inhibitor.

The most common adverse effects of MAOIs occurring early in treatment are orthostatic hypotension, daytime sleepiness, insomnia, and nausea; later common effects include weight gain, muscle pain, myoclonus, paraesthesia, and sexual dysfunction.

Pharmacodynamic interactions with MAOIs can cause two types of problem: serotonin syndrome (mainly due to SSRIs) and elevated blood pressure (caused by indirectly acting sympathomimetic amines releasers, like pseudoephedrine and phenylephrine). The combination of MAOIs and some TCAs appears safe. Only those TCAs with significant serotonin reuptake inhibition (clomipramine and imipramine) are likely to increase the risk of serotonin syndrome.

Tyramine is a monoamine found in various foods, and is an indirect sympathomimetic that can cause a hypertensive reaction in patients receiving MAOI therapy. For this reason, dietary restrictions are required for patients receiving MAOIs. These restrictions include avoiding matured/aged cheese, fermented sausage, improperly stored meat, fava of broad bean pods, and certain drinks such as on-tap beer. Allowed foods include fresh cottage cheese, processed cheese slices, fresh packaged of processed meat, and other alcohol (no more than two bottled or canned beers of two standard glasses of wine, per day).

Amantadine and QTc Prolongation

Amantadine is a medication used to treat Parkinson’s disease and influenza. It has been associated with QTc prolongation, which can increase the risk of Torsades de points. Therefore, caution should be exercised when prescribing amantadine to patients with risk factors for QT prolongation. If a patient is already taking amantadine and develops a prolonged QTc interval, the medication should be discontinued and an alternative treatment considered. It is important to monitor the QTc interval in patients taking amantadine, especially those with risk factors for QT prolongation.

Which of the following is NOT true regarding the equation Vd = amount in body / plasma concentration?

Understanding the Volume of Distribution in Pharmacology

The volume of distribution (Vd) is a crucial concept in pharmacology that helps determine how a drug distributes in the body. It is also known as the apparent volume of distribution, as it is an abstract volume. The Vd indicates whether a drug concentrates in the plasma of spreads out in the body. Drugs that are highly polar tend to stay in central compartments such as the plasma, resulting in a low Vd. Conversely, drugs that are more lipid-soluble are distributed widely, such as in fat, resulting in a high Vd.

The Vd is calculated by dividing the amount of drug in the body by the concentration in the plasma. Clinically, the Vd is used to determine the loading dose of a drug required for a desired blood concentration and to estimate blood concentration in the treatment of overdose. The units of Vd are in volume.

The apparent volume of distribution is dependent on the drug’s lipid of water solubility, plasma protein binding, and tissue binding. Plasma protein binding affects the Vd, as drugs that bind to plasma proteins like albumin have a smaller apparent volume of distribution. This is because they are extracted from plasma and included in drug concentration measurements, which can give a misleading impression of their volume of distribution. Understanding the Vd is essential in pharmacology to ensure the safe and effective use of drugs.

Loop diuretics and potassium sparing diuretics have been found to have no significant impact on lithium levels, unlike other diuretics. While acetazolamide can decrease lithium levels by increasing excretion, loop diuretics may initially increase excretion followed by a rebound phase of enhanced reabsorption, resulting in no significant effect on lithium levels over a 24-hour period.

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.

Myelination: The Insulation of Neurons

Myelin is a fatty material that insulates the axon of a neuron, allowing messages to be sent quickly and without interference. Glial cells, such as oligodendrocytes and Schwann cells, produce myelin in the central and peripheral nervous systems, respectively. Myelination begins in the developing foetus and continues through childhood and adolescence into early adulthood, with the frontal lobes being the last area to myelinate. Myelinated axons appear white, hence the term ‘white matter’ of the brain. Myelination progresses from central to peripheral, caudal to rostral, and dorsal to ventral, with sensory myelination preceding motor myelination.

Initially used to treat tuberculosis, iproniazid was found to have a positive impact on patients’ moods. Kline’s publication provided the first evidence supporting its effectiveness in treating depression.

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.

Dissociative seizures, also known as pseudoseizures of functional seizures, are abnormal paroxysmal manifestations that resemble epileptic seizures but are not related to abnormal epileptiform discharges. They can be caused by physical factors such as hypoglycemia of cardiac dysfunction, but more commonly result from mental of emotional processes. Dissociative seizures are more common in females and tend to have an onset in late adolescence. Distinguishing between true seizures and pseudoseizures can be challenging, but a rise in serum prolactin levels after a seizure is a helpful diagnostic tool. Treatment options for psychogenic nonepileptic seizures are limited, with cognitive-behavioral therapy being the most studied and effective intervention.

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.

Abnormal Motor Behaviours Associated with Utilization Behaviour

Utilization behaviour (UB) is a condition where patients exhibit exaggerated and inappropriate motor responses to environmental cues and objects. This behaviour is automatic and instrumentally correct, but not contextually appropriate. For instance, a patient may start brushing their teeth when presented with a toothbrush, even in a setting where it is not expected. UB is caused by frontal lobe lesions that result in a loss of inhibitory control.

Other motor abnormalities associated with UB include imitation behaviour, where patients tend to imitate the examiner’s behaviour, and the alien hand sign, where patients experience bizarre hand movements that they cannot control. Manual groping behaviour is also observed, where patients automatically manipulate objects placed in front of them. The grasp reflex, which is normal in infants, should not be present in children and adults. It is an automatic tendency to grip objects of stimuli, such as the examiner’s hand.

Environmental Dependency Syndrome is another condition associated with UB. It describes deficits in personal control of action and an overreliance on social and physical environmental stimuli to guide behaviour in a social context. For example, a patient may start commenting on pictures in an examiner’s office, believing it to be an art gallery.

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.

For the long-term management of mania, NICE (CG185) recommends offering a psychological intervention designed for bipolar disorder to prevent relapse. Additionally, lithium should be offered as the first-line, long-term pharmacological treatment. If lithium is not effective, valproate may be considered as an alternative. If lithium is not well-tolerated of not suitable due to reasons such as the person not agreeing to routine blood monitoring, olanzapine or quetiapine may be considered instead, with quetiapine being a viable option if it has been effective during an episode of mania of bipolar depression. It is important to note that valproate would be the next best option if lithium is contraindicated due to severe renal impairment.

Renal Impairment and Psychotropic Drugs

The following table provides recommendations for drug treatment in patients with renal impairment, based on the Maudsley 14th guidelines. When a new drug treatment is required, the suggestions below should be followed.

Drug Group Recommendation

Antipsychotics: It is recommended to avoid sulpiride and amisulpride. Otherwise, no agent is clearly preferable to another. For first-generation antipsychotics, haloperidol (2-6 mg/day) is the best choice. For second-generation antipsychotics, olanzapine (5mg/day) is the best choice.

Antidepressants: No agent is clearly preferable to another. Reasonable choices include sertraline (although there is poor efficacy data in renal disease), citalopram (with care over QTc prolongation), and fluoxetine (with care over long half-life).

Mood stabilizers: Lithium is nephrotoxic and contraindicated in severe renal impairment. Otherwise, no agent is clearly preferable to another. Valproate of lamotrigine are suggested.

Anxiolytics: No agent is clearly preferable to another. Lorazepam and zopiclone are suggested.

Anti-dementia drugs: No agent is clearly preferable to another. Rivastigmine is suggested.

Out of these options, only the cytotoxic reaction is immunologic and specifically mediated by antibodies.

Adverse Drug Reactions (ADRs) refer to the harmful effects associated with the use of a medication at a normal dose. These reactions are classified into two types: Type A and Type B. Type A reactions can be predicted from the pharmacology of the drug and are dose-dependent, meaning they can be reversed by withdrawing the drug. On the other hand, Type B reactions cannot be predicted from the known pharmacology of the drug and include allergic reactions.

Type A reactions account for up to 80% of all ADRs, while Type B reactions are less common. Allergic reactions are a type of Type B reaction and are further subdivided by Gell and Coombs into four types: Type I (IgE-mediated) reactions, Type II (cytotoxic) reactions, Type III (immune complex) reactions, and Type IV (cell-mediated) reactions. Proper identification and management of ADRs are crucial in ensuring patient safety and optimizing treatment outcomes.

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.

The mental state examination involves evaluating and documenting characteristics of mental illness in order to diagnose a clinical syndrome. It includes observing and describing the significant aspects of a person’s mental state at a specific moment in time. This assessment can be conducted before obtaining a patient’s medical history.

Psychogenic polydipsia is a condition where there is excessive consumption of fluids leading to polyuria, and it is commonly seen in psychiatric conditions such as schizophrenia and developmental disorders. The exact mechanism is unknown, but it is thought to be due to a defect in thirst and a dysfunction in AVP regulation. Patients with psychogenic polydipsia rarely complain of thirst but instead provide delusional explanations for their excessive drinking of state that drinking reduces their anxiety and makes them feel better. If fluid intake exceeds the capacity for excretion, then the resultant hyponatremia may produce signs of water intoxication. It is best managed by fluid restriction. Differential diagnosis should be done to rule out other causes of polyuria and polydipsia. Investigations such as fluid balance charts, urine dipstick, serum U&E and calcium, and urine and plasma osmolality should be arranged. Primary polydipsia can be subclassified into psychogenic and dipsogenic types.

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).

The MMSE does not evaluate verbal fluency as it is a measure of the frontal lobe function, which is assessed through the ACE-R.

Mini Mental State Exam (MMSE)

The Mini Mental State Exam (MMSE) was developed in 1975 by Folstein et al. Its original purpose was to differentiate between organic and functional disorders, but it is now mainly used to detect and track the progression of cognitive impairment. The exam is scored out of 30 and is divided into seven categories: orientation to place and time, registration, attention and concentration, recall, language, visual construction, and attention to written command. Each category has a possible score, and the total score can indicate the severity of cognitive impairment. A score equal to or greater than 27 indicates normal cognition, while scores below this can indicate severe, moderate, of mild cognitive impairment. The MMSE is a useful tool for detecting and tracking cognitive impairment.

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.

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.

Attachment Theory and Harlow’s Monkeys

Attachment theory, developed by John Bowlby, suggests that children have an innate tendency to form relationships with people around them to increase their chance of survival. This attachment is different from bonding, which concerns the mother’s feelings for her infant. Children typically single out a primary caregiver, referred to as the principle attachment figure, from about 1-3 months. The quality of a person’s early attachments is associated with their adult behavior, with poor attachments leading to withdrawn individuals who struggle to form relationships and good attachments leading to socially competent adults who can form healthy relationships.

Bowlby’s attachment model has four stages: preattachment, attachment in the making, clear-cut attachment, and formation of reciprocal attachment. The time from 6 months to 36 months is known as the critical period, during which a child is most vulnerable to interruptions in its attachment. Attachments are divided into secure and insecure types, with insecure types further divided into avoidant and ambivalent types.

Harlow’s experiment with young rhesus monkeys demonstrated the importance of the need for closeness over food. The experiment involved giving the monkeys a choice between two different mothers, one made of soft terry cloth but provided no food and the other made of wire but provided food from an attached baby bottle. The baby monkeys spent significantly more time with their cloth mother than with their wire mother, showing the importance of attachment and closeness in early development.

Lisinopril is a medication that belongs to the class of ACE inhibitors and is commonly prescribed to treat hypertension and heart failure.

Hyponatremia in Psychiatric Patients

Hyponatremia, of low serum sodium, can occur in psychiatric patients due to the disorder itself, its treatment, of other medical conditions. Symptoms include nausea, confusion, seizures, and muscular cramps. Drug-induced hyponatremia is known as the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), which results from excessive secretion of ADH and fluid overload. Diagnosis is based on clinically euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality. SSRIs, SNRIs, and tricyclics are the most common drugs that can cause SIADH. Risk factors for SIADH include starting a new drug, and treatment usually involves fluid restriction and sometimes demeclocycline.

The SASQ is a screening questionnaire that consists of a single question asking about the last time an individual had more than a certain number of alcoholic drinks in one day (8 for men and 6 for women). If the response indicates that this occurred within the past 3 months, it suggests that the individual may be engaging in harmful of hazardous drinking.

Alcohol screening tools are available to assist in the diagnosis of alcohol problems. One such tool is the AUDIT (Alcohol Use Disorders Identification Test), which consists of 10 questions and covers harmful use, hazardous use, and dependence. Another tool is the FAST (Fast Alcohol Screening Test), which has just 4 questions and was developed for use in a busy medical setting. The CAGE is a well-known 4 question screening tool, but recent research has questioned its value. Other tools include SASQ (Single alcohol screening questionnaire), PAT (Paddington Alcohol Test), MAST (Michigan Alcoholism Screening Test), and RAPS4 (Rapid Alcohol Problem Screen 4). These tools can help identify hazardous of harmful alcohol consumption and alcohol dependence.

In 1951, Charpentier in France synthesised Chlorpromazine with the aim of creating a centrally acting antihistamine to assist with general anaesthesia. Later, studies conducted by Delay and Deniker provided evidence for its effectiveness in treating schizophrenia.

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.

Multiple Sclerosis: An Overview

Multiple sclerosis is a neurological disorder that is classified into three categories: primary progressive, relapsing-remitting, and secondary progressive. Primary progressive multiple sclerosis affects 5-10% of patients and is characterized by a steady progression with no remissions. Relapsing-remitting multiple sclerosis affects 20-30% of patients and presents with a relapsing-remitting course but does not lead to serious disability. Secondary progressive multiple sclerosis affects 60% of patients and initially presents with a relapsing-remitting course but is then followed by a phase of progressive deterioration.

The disorder typically begins between the ages of 20 and 40 and is characterized by multiple demyelinating lesions that have a preference for the optic nerves, cerebellum, brainstem, and spinal cord. Patients with multiple sclerosis present with a variety of neurological signs that reflect the presence and distribution of plaques. Ocular features of multiple sclerosis include optic neuritis, internuclear ophthalmoplegia, and ocular motor cranial neuropathy.

Multiple sclerosis is more common in women than in men and is seen with increasing frequency as the distance from the equator increases. It is believed to be caused by a combination of genetic and environmental factors, with monozygotic concordance at 25%. Overall, multiple sclerosis is a predominantly white matter disease that can have a significant impact on a patient’s quality of life.

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

Inheritance Patterns:

Autosomal Dominant Conditions:
– Can be transmitted from one generation to the next (vertical transmission) through all forms of transmission observed (male to male, male to female, female to female).
– Males and females are affected in equal proportions.
– Usually, one parent is an affected heterozygote and the other is an unaffected homozygote.
– If only one parent is affected, there is a 50% chance that a child will inherit the mutated gene.

Autosomal Recessive Conditions:
– Males and females are affected in equal proportions.
– Two copies of the gene must be mutated for a person to be affected.
– Both parents are usually unaffected heterozygotes.
– Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder.

X-linked Dominant Conditions:
– Males and females are both affected, with males typically being more severely affected than females.
– The sons of a man with an X-linked dominant disorder will all be unaffected.
– A woman with an X-linked dominant disorder has a 50% chance of having an affected fetus.

X-linked Recessive Conditions:
– Males are more frequently affected than females.
– Transmitted through carrier females to their sons (knights move pattern).
– Affected males cannot pass the condition onto their sons.
– A woman who is a carrier of an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers.

Y-linked Conditions:
– Every son of an affected father will be affected.
– Female offspring of affected fathers are never affected.

Mitochondrial Inheritance:
– Mitochondria are inherited only in the maternal ova and not in sperm.
– Males and females are affected, but always being maternally inherited.
– An affected male does not pass on his mitochondria to his children, so all his children will be unaffected.

Schizophrenia Risk According to Gottesman

Irving I. Gottesman conducted family and twin studies in European populations between 1920 and 1987 to determine the risk of developing schizophrenia for relatives of those with the disorder. The following table displays Gottesman’s findings, which show the average lifetime risk for each relationship:

General population: 1%
First cousin: 2%
Uncle/aunt: 2%
Nephew/niece: 4%
Grandchildren: 5%
Parents: 6%
Half sibling: 6%
Full sibling: 9%
Children: 13%
Fraternal twins: 17%
Offspring of dual matings (both parents had schizophrenia): 46%
Identical twins: 48%

The Amygdala: A Key Player in Emotional Processing

The amygdala is a small, almond-shaped structure located in the anterior temporal lobe of the brain. As a core component of the limbic system, it plays a crucial role in emotional processing and regulation.

To better understand its function, we can use the metaphor of a car being driven on the road. The frontal lobe of the brain acts as the driver, making decisions and navigating the environment. The amygdala, on the other hand, serves as the dashboard, providing the driver with important information about the car’s status, such as temperature and fuel levels. In this way, the amygdala gives emotional meaning to sensory input, allowing us to respond appropriately to potential threats of opportunities.

One of the amygdala’s primary functions is to activate the fight or flight response in response to perceived danger. It does this by sending signals to the hypothalamus, which in turn triggers the release of stress hormones like adrenaline and cortisol. This prepares the body to either confront the threat of flee from it.

In addition to its role in the fight or flight response, the amygdala also plays a role in regulating appetite and eating behavior. Studies have shown that damage to the amygdala can lead to overeating and obesity, suggesting that it may be involved in the hypothalamic control of feeding behavior.

Overall, the amygdala is a key player in emotional processing and regulation, helping us to respond appropriately to the world around us.