Neurosciences and Psychopharmacology Practice Flashcards
Clinical Prefrontal Lobe Syndromes
The prefrontal cortex is divided into distinct functional regions, each associated with specific clinical syndromes when damaged. The Medial Prefrontal Syndrome, also identified as the ventromedial or apathetic/pseudodepressive type, is clinically characterized by a significant paucity of spontaneous behaviors and poverty of speech. Patients often exhibit a sparse verbal output, reduced social knowledge, and an impaired judgment regarding harmful intent. In contrast, the Orbitofrontal Syndrome, known as the disinhibited or pseudopsychopathic type, manifests through poor impulse control, explosive outbursts, and inappropriate social behavior. This syndrome reflects a loss of inhibitory control over emotional and social responses. The Dorsolateral Prefrontal Syndrome, or the dysexecutive/disorganized type, is characterized by executive dysfunction, diminished planning abilities, cognitive dysfunction, and poor insight. Clinically, these patients are often described as being concrete and inflexible in nature.
Neuropsychological Assessment and Specialized Testing
Neuropsychological tests are designed to localize brain dysfunction by evaluating specific cognitive domains. The Cognitive Estimation Test assesses frontal lobe function by asking factual questions that require abstract reasoning rather than rote memory, such as, "How many camels are there in England?" The National Adult Reading Test (NART) is employed to estimate premorbid intelligence by requiring the subject to correctly pronounce complex, phonetically irregular words like DRACHM, SUPERFLUOUS, and PLACEBO. The Trail Making Test is divided into two parts: Part A requires the subject to connect numbers in a sequence (1-2-3 etc.), while Trail Making Test B involves connecting an alternating sequence of numbers and letters ( etc.) to assess mental flexibility and divided attention. Other recognized frontal lobe tests include the Wisconsin Card Sorting Test, the Stroop Test, and the Tower of London. Some tests, such as the California Verbal Learning Test (CVLT), are used primarily to assess verbal memory; while they may be impacted by frontal lesions, they are not specific to the frontal lobe.
Cardiovascular Risks and Medication Management
Psychiatric medications carry significant risks for cardiac conduction abnormalities, particularly the prolongation of the QTc interval. Amitriptyline, a tricyclic antidepressant, is known for causing dry mouth and QTc prolongation, which can lead to severe ventricular arrhythmias, collapse, and death in overdose scenarios. Prolongation of the QTc interval is also a common side effect of antipsychotic medications and methadone. The upper normal value of QTc in males is defined as and in females as . Mounting clinical evidence suggests that QTc values exceeding correlate with a clearly increased risk of arrhythmia. Torsades de Pointes is a specific risk associated with high-dose antidepressant use. Clozapine treatment is linked to unique cardiac complications, including clozapine-induced pericarditis, myocarditis, and cardiomyopathy. Myocarditis typically occurs within the first 6 to 8 weeks of treatment (median: 3 weeks), presenting with fever, tachycardia, and dyspnea. Monitoring protocols suggest obtaining baseline troponin I/T and C-reactive protein (CRP), with follow-up tests on days 7, 14, 21, and 28. Cardiomyopathy usually develops later in treatment, with a median onset of 9 months. If clozapine-induced myocarditis is suspected due to symptoms like shortness of breath or tachycardia, requesting an urgent troponin level is essential.
Medical Sequelae of Eating Disorders
Specific physical complications arise from disordered eating behaviors such as purging and laxative misuse. Parotitis, presenting as painless facial swelling, is associated with bulimia nervosa and frequently occurs approximately two days after an individual ceases self-induced vomiting. This condition usually resolves spontaneously, though sialagogues may be used. Long-term laxative misuse leading to overstimulation of the colon can result in a significant decrease in intestinal motility and abdominal swelling once the laxatives are discontinued. Gradual withdrawal is the preferred management strategy. Acute pancreatitis should be suspected in patients presenting with sharp epigastric pain radiating to the back that worsens with eating. The onset of pancreatitis in the absence of heavy alcohol use or biliary disorders should prompt an immediate inquiry into purging behaviors.
Movement Disorders, Apraxias, and Agnosias
Motor planning and perception deficits are often localized to specific cortical regions. Ideomotor apraxia involves a deficit in the ability to plan or complete motor actions that rely on semantic memory, representing an inability to convert an idea into action. Patients can often perform an action unconsciously (e.g., picking up a ringing phone) but fail when asked to do so on command. This is usually caused by a dominant frontal or parietal lobe lesion. Ideational apraxia is the inability to conceptualize a task leading to an impaired ability to complete multi-step actions, such as putting on shoes before socks or buttering bread before it is toasted. Visuospatial agnosia refers to the loss of the sense of "whereness," affecting the relationship between the individual and their environment or objects to each other. Tardive dyskinesia, an adverse effect of neuroleptic medication, is primarily assessed using the Abnormal Involuntary Movement Scale (AIMS). Neuroleptic Malignant Syndrome (NMS) is a life-threatening reaction to antipsychotics characterized by hyperthermia, rigidity, tachycardia, and raised Creatine Phosphokinase (CPK) levels; importantly, persistent bradycardia is NOT a feature of NMS.
Genetics of Neuropsychiatric Disorders
Familial cases of neurodegenerative diseases are often linked to specific genetic mutations on identified chromosomes. Parkinson's disease is associated with mutations in the alpha-synuclein (SNCA) gene on the long arm of chromosome 4 and the parkin (PRKN) gene on the long arm of chromosome 6. Fronto-temporal Dementia (FTD) is linked to three primary genes: C9ORF72 at position 9p21.2 (also associated with Amyotrophic Lateral Sclerosis), the MAPT gene (encoding tau protein) at position 17q21.31, and the GRN gene (encoding progranulin) also at 17q21.31. Huntington disease is caused by CAG trinucleotide repeats in the HTT gene, located on the short arm of chromosome 4 at position 4p16.3. The presence of ubiquitin inclusions in post-mortem examinations of patients with progressive non-amnesic cognitive impairment and disinhibition specifically points toward mutations in the Progranulin gene in the context of FTD.
Functional Neuroanatomy and Pathophysiology
Various psychiatric and neurological presentations are mapped to specific brain structures. Korsakoff's syndrome, resulting from thiamine () deficiency often due to alcohol dependence, causes damage to the mammillary bodies and the medial thalamus. Thiamine is a vital co-factor for alpha-ketoglutarate dehydrogenase and its deficiency impairs oxidative metabolism; once Korsakoff's memory deficits are established, they are typically irreversible. The Raphe nuclei represent the principal source of serotonin (5-HT) release in the brain. The hypothalamus is involved in several regulatory functions: the pre-optic area is responsible for thermoregulation, while the secretion of Neuropeptide Y by the hypothalamus potently induces food intake. Kleine-Levin syndrome is a rare condition (1-5 per million) characterized by recurrent hypersomnia, hyperphagia, and hypersexuality; it is associated with hypothalamic and asymmetric thalamic hypoperfusion. Autism spectrum disorder features like poor social interaction and stereotypical behavior are linked to hypoplasia of the cerebellar vermis and a lower Purkinje cell count. Akinetic mutism, a state of profound apathy and lack of movement/speech, can result from bilateral infarcts of the anterior cerebral artery.
Pediatric Development and Growth Milestones
Child development follows a predictable chronological sequence of motor, social, and language milestones. In fine motor development, children can typically stack 2 blocks by 15 months, 3 blocks by 18 months, 6 to 7 blocks by 2 years, and 9 to 10 blocks by age 3. Gross motor milestones include crawling between 6 and 9 months, with walking following by 9 to 12 months. Graphic skills develop from copying a circle at age 3, a square at age 4, and a triangle by age 5 to 6. Language acquisition involves saying simple words like "mama" or "dada" correctly by 12 months, using approximately 50 words and word pairings by age 2, and utilizing simple sentences by the age of 3. In educational interventions for intellectual disability, "chaining" is a technique where complex behaviors are broken into steps, with each step serving as a cue for the next. Severe learning disability is categorized by an IQ of 20-34, while moderate disability is defined by an IQ of 35-49.
Pharmacology of Dementia and Antidepressants
Dementia medications utilize various mechanisms of action regarding neurotransmitter levels. Donepezil is a selective and reversible acetylcholinesterase (AChE) inhibitor. Galantamine acts as both a selective/reversible AChE inhibitor and a nicotinic receptor modulator. Rivastigmine is a pseudo-irreversible AChE inhibitor and a butyrylcholinesterase inhibitor; notably, it undergoes breakdown by cholinesterase itself without hepatic involvement. Memantine is a non-competitive NMDA receptor antagonist and a 5-HT3 receptor antagonist. When switching antidepressants, safe transition periods and methods are required: switching from Phenelzine to Sertraline requires a 2-week washout, while switching from Fluoxetine to Tranylcypromine requires 5 to 6 weeks. A switch from Trazodone to Mirtazapine is managed via a cautious cross-taper. Hyponatraemia induced by SSRIs is a risk factor particularly in patients with low body mass, the elderly, and females. Weight gain is most associated with Mirtazapine among common antidepressants, likely due to its effects on 5-HT2C and H1 receptors.
Neurophysiology and Action Potentials
Neuronal firing is regulated by ion gradients and membrane potentials. The resting membrane potential is approximately , maintained by the sodium pump which concentrates potassium () inside the cell and sodium () outside. Consequently, there is an increased concentration of potassium in the axon terminal prior to depolarization. An action potential is initiated when synaptic signals raise the intracellular potential from to the threshold potential of . Sodium channels then open, causing an influx and reversing the potential to . Subsequent repolarization occurs as sodium channels close and voltage-gated potassium channels open, allowing to exit. Presynaptic regulation of serotonin release is managed by 5-HT1A receptors, which act as somatodendritic autoreceptors in the raphe nuclei.
Teratogenicity and Pregnancy in Psychiatry
The use of mood stabilizers and other psychotropics during pregnancy requires careful risk assessment. Valproate is the most teratogenic mood stabilizer, carrying a 10% risk for major malformations, including neural tube defects, skeletal malformations, and orofacial clefts. Topiramate is also associated with orofacial clefts. Lithium use during the first trimester is classically associated with Ebstein’s anomaly, a congenital heart defect where tricuspid valves are displaced toward the apex of the right ventricle. Lamotrigine is generally considered safer than carbamazepine or valproate during pregnancy.
Psychology, Social Dynamics, and Theory of Mind
Psychological development and social behavior are studied through specific tests and theories. The Sally Anne Test evaluates "Theory of Mind" in children, usually passed by age 4, requiring the child to understand that others can hold false beliefs. Attachment styles, as studied by Bowlby and Ainsworth, include "Avoidant Attachment," characterized by emotional distance and a lack of distress when a caregiver leaves. Social psychology concepts include the Hawthorne Effect (performance increase when observed), the Risky Shift (groups making more dangerous decisions than individuals), and Diffusion of Responsibility (decreased likelihood of action when others are present). High Expressed Emotion in families is a known predictor of relapse in schizophrenia, with no proven difference in the rate of relapse between males and females exposed to such environments. In terms of cultural psychiatry, "Bouffée délirante" is a syndrome in West Africa involving sudden paranoid delusions, while "Latah" is a Southeast Asian syndrome involving mimicry and abnormal behavior after a shock.
Psychoanalytic Concepts and Defense Mechanisms
Defense mechanisms are unconscious processes used to navigate anxiety and conflict. Repression is termed the "Primary Defence" because it prevents impulses from entering consciousness. Mature defenses include Suppression (consciously delaying attention to an emotion). Narcissistic or primitive defenses often seen in anorexia nervosa include denial, rationalization, and intellectualization. Intellectualization involves focusing on the intellectual components of a situation to distance oneself from emotion. "Undoing" is a mechanism where an individual tries to symbolically nullify a threatening thought by performing an opposite action (e.g., cleaning a room after an argument). Freud's dual instinct theory posits Eros (life) and Thanatos (death) as primary drivers, with Thanatos being the primal instinct underlying human psychology.
Questions & Discussion
Q: Which medication is used for symptomatic hyperprolactinaemia in schizophrenia?
A: For patients on prolactin-elevating drugs like risperidone, the first choice is switching to a non-elevating drug. If that is not possible, adding aripiprazole is the best add-on treatment, as it promptly improves hyperprolactinaemia symptoms.
Q: What is the significance of REM latency in depression?
A: Shortened REM latency is not a specific marker for depression, as it occurs in mania and schizophrenia as well. However, depression is characterized by sleep-EEG changes including shortened REM latency, sleep-onset REM periods, and increased REM density. Most antidepressants suppress REM sleep and increase REM latency.
Q: What is the vascular origin of sudden onset akinetic mutism?
A: It is associated with bilateral infarction of the anterior cerebral artery, which produces quadriparesis (legs weaker than arms) and ventromedial/cingulate syndromes.
Q: What genes are associated with familial Frontotemporal Dementia (FTD)?
A: The three primary genes are C9ORF72 (Chromosome 9), MAPT (Chromosome 17), and GRN (Chromosome 17, Progranulin). Mutations in these lead to the clinical presentation of disinhibition and non-amnesic cognitive decline.
Q: What are the symptoms of Kleine-Levin syndrome?
A: It presents with a classic triad of hypersomnia (sleeping 12-21 hours), hyperphagia, and hypersexuality, though only 45% of patients show all three. It is associated with thalamic hypoperfusion during symptomatic periods.