Psychiatry NBME

disorders, pathophysiology, clinical features, genetics, treatment (mechanism, adverse effects)

Schizophrenia

• Pathophysiology: ↑Dopamine in mesolimbic pathway (positive symptoms), ↓dopamine in mesocortical pathway (negative symptoms), glutamate and GABA imbalance.

• Clinical Features:

  • Delusions, hallucinations, disorganized speech/thought, negative symptoms (flat affect, anhedonia, alogia).

  • ≥6 months of positive (hallucinations, delusions), negative (flat affect, alogia) and cognitive symptoms.

• Genetics: High heritability. Genes: DISC1, COMT, neuregulin.

• Treatment: Typical and atypical antipsychotics.(risperidone, olanzapine)

  • Mechanism: D2 antagonism (typicals); D2 + 5-HT2A antagonism (atypicals).

  • Adverse Effects: EPS, tardive dyskinesia, hyperprolactinemia, sedation, metabolic syndrome, agranulocytosis (clozapine).

Bipolar I Disorder

• Pathophysiology: ↑Catecholamines (dopamine, norepinephrine), limbic dysregulation.

• Clinical Features: ≥1 manic episode ± depressive episodes; mania includes grandiosity, decreased sleep, racing thoughts.

• Genetics: Strong familial risk; genes CACNA1C, ANK3.

• Treatment: Lithium, valproate, carbamazepine, atypical antipsychotics.

  • Mechanism: Lithium inhibits inositol monophosphatase; valproate ↑GABA.

  • Adverse Effects: Lithium: nephrotoxicity, tremor; valproate: hepatotoxicity, teratogenic.

Bipolar II Disorder

• Pathophysiology: Like Bipolar I but with hypomania, not full mania.

• Clinical Features: ≥1 hypomanic + ≥1 major depressive episode.

• Genetics: Similar to Bipolar I; CACNA1C, ANK3.

• Treatment: Lithium, lamotrigine, psychotherapy.

  • Mechanism: Lamotrigine blocks glutamate release; Lithium: inhibits inositol metabolism.

  • Adverse Effects: Lamotrigine: rash, SJS; lithium: hypothyroidism, nephrotoxicity, tremor.

Major Depressive Disorder (MDD)

• Pathophysiology: ↓Serotonin (from raphe nuclei), ↑Cortisol, ↓REM latency; monoamine deficiency.

• Clinical Features: ≥2 weeks with ≥5 of the following: Sleep disturbance, loss of Interest, Guilt, low Energy, poor Concentration, Appetite changes, Psychomotor changes, Suicidal thoughts (SIGECAPS).

• Genetics: Associated with serotonin transporter polymorphism (5-HTTLPR).

• Treatment: SSRIs, SNRIs, psychotherapy (CBT); always rule out mania first.

  • Mechanism: SSRIs inhibit serotonin reuptake.

  • Adverse Effects: Sexual dysfunction, GI upset, insomnia, serotonin syndrome if combined with serotonergic drugs.

Generalized Anxiety Disorder (GAD)

• Pathophysiology: ↓GABA, serotonin; ↑amygdala activatio, CNS hyperarousal.

• Clinical Features: Excessive worry >6 months + ≥3: restlessness, fatigue, muscle tension, irritability, sleep disturbance, difficulty concentrating.

• Genetics: Moderate heritability.

• Treatment: First-line = SSRIs; also buspirone, CBT.

  • Mechanism: SSRIs: ↑serotonin; Buspirone: partial 5-HT1A agonist; BZDs enhance GABA-A.

  • Adverse Effects: BZDs: sedation, dependence.; SSRIs → GI upset, sexual dysfunction; Buspirone → delayed onset, dizziness.

Obsessive-Compulsive Disorder (OCD)

• Pathophysiology: Dysfunction in CSTC loop; low serotonin.

• Clinical Features: Obsessions + compulsions causing distress.

• Genetics: Moderate; SLC1A1 gene.

• Treatment: High-dose SSRIs, clomipramine, CBT.

  • Mechanism: ↑Serotonin via reuptake inhibition.

  • Adverse Effects: Clomipramine: anticholinergic effects.

Post-Traumatic Stress Disorder (PTSD)

• Pathophysiology: ↑Amygdala, ↓hippocampus volume, HPA dysregulation.

• Clinical Features: Flashbacks, nightmares, hyperarousal, avoidance.

• Genetics: Interaction with trauma; moderate heritability.

• Treatment: SSRIs, prazosin, CBT.

  • Mechanism: Prazosin blocks α1-adrenergic receptors.

  • Adverse Effects: Prazosin: orthostatic hypotension.

Panic Disorder

• Pathophysiology: Autonomic overactivity, serotonin/GABA imbalance.

• Clinical Features: Recurrent, unexpected panic attacks + ≥4 symptoms (palpitations, chest pain, derealization, fear of dying) + concern about future attacks or avoidance.

• Genetics: Moderate heritability.

• Treatment: SSRIs/SNRIs (first-line), CBT, benzodiazepines for acute relief.

  • Mechanism: SSRIs increase serotonin; BZDs enhance GABA-A.

  • Adverse Effects: SSRIs: anxiety, GI upset; BZDs: sedation, dependence.

Specific Phobia

• Pathophysiology: Amygdala overactivation, learned fear.

• Clinical Features: Intense fear of object/situation, avoids exposure.

• Genetics: Environmental learning; possible genetic predisposition.

• Treatment: Exposure therapy; SSRIs if severe.

  • Mechanism: Desensitization of fear circuitry via exposure. SSRIs increase serotonin.

  • Adverse Effects: Anxiety, nausea, insomnia.

Social Anxiety Disorder

• Pathophysiology: Overactive amygdala to social threats.

• Clinical Features: Fear of judgment, avoidance of social interaction.

• Genetics: Familial risk common.

• Treatment: SSRIs, propranolol (for performance), CBT.

  • Mechanism: SSRIs inhibit serotonin reuptake; propranolol blocks β-adrenergic.

  • Adverse Effects: Propranolol: bradycardia, fatigue

Persistent Depressive Disorder (Dysthymia)

• Pathophysiology: Chronic monoamine deficiency.

• Clinical Features: Depressed mood ≥2 years + ≥2: low energy, appetite/sleep changes, low self-esteem, poor concentration, hopelessness.

• Genetics: Moderate genetic contribution.

• Treatment: SSRIs, CBT.

  • Mechanism: SSRI → ↑serotonin tone.

  • Adverse Effects: Nausea, sexual dysfunction, agitation.

Psychosis (Syndrome)

• Pathophysiology: ↑Dopamine in mesolimbic; ↓glutamate activity.

• Clinical Features: Hallucinations (no stimulus), delusions (distorted perception of real stimuli), disorganized thoughts/speech.

• Genetics: Seen in schizophrenia, bipolar I, drug-induced.

• Treatment: Depends on cause; antipsychotics are mainstay.

  • Mechanism: D2 antagonism (typicals), D2 + 5-HT2A (atypicals).

  • Adverse Effects: EPS, sedation, metabolic issues.

Brief Psychotic Disorder

• Pathophysiology: Acute stress → dopamine dysregulation.

• Clinical Features: Psychotic symptoms ≥1 day but <1 month; full return to baseline.

• Genetics: Rare; often stress-induced.

• Treatment: Short-term antipsychotics; supportive care.

  • Mechanism: D2 blockade.

  • Adverse Effects: Mild sedation, reversible EPS.

Schizophreniform Disorder

• Pathophysiology: Intermediate stage of schizophrenia spectrum.

• Clinical Features: Same symptoms as schizophrenia, duration 1–6 months, no functional decline needed.

• Genetics: Similar to schizophrenia.

• Treatment: Antipsychotics.

  • Mechanism: D2 antagonism.

  • Adverse Effects: EPS, weight gain.

Schizoaffective Disorder

• Pathophysiology: Mood dysregulation + psychosis.

• Clinical Features: ≥2 weeks of delusions/hallucinations without mood symptoms + concurrent mood episode.

• Genetics: Shared with schizophrenia and bipolar.

  Treatment: Antipsychotics + mood stabilizers.

  • Mechanism: D2 + 5-HT2A blockade; mood modulators.

  • Adverse Effects: Multiple based on drug regimen.

Delusional Disorder

• Pathophysiology: Localized delusional thinking; normal function otherwise.

• Clinical Features: ≥1 delusion for ≥1 month; no other psychotic features.

• Genetics: Less understood; rare.

• Treatment: Psychotherapy; antipsychotics if needed.

  • Mechanism: D2 receptor modulation.

  • Adverse Effects: Minimal unless on meds.

Acute Stress Disorder

• Pathophysiology: Acute overactivation of the stress response system following trauma; ↑NE, cortisol, and amygdala activity.

• Clinical Features: Exposure to trauma + symptoms (e.g., intrusive memories, nightmares, dissociation, hyperarousal) lasting ≥3 days but <1 month.

• Genetics: Related to trauma sensitivity; no direct inheritance.

• Treatment: Trauma-focused CBT is first-line.

  • Mechanism: CBT promotes cognitive restructuring; avoids chronic PTSD.

  • Adverse Effects: None from CBT; avoid benzodiazepines if possible.

Adjustment Disorder

• Pathophysiology: Maladaptive emotional response to identifiable stressor within 3 months.

• Clinical Features: Depression, anxiety, outbursts in response to a stressor; symptoms ≤6 months once stressor resolves.

• Genetics: -.

• Treatment: CBT is first-line; SSRIs or anxiolytics if persistent/severe.

  • Mechanism: CBT improves stress coping; SSRIs enhance serotonin.

  • Adverse Effects: SSRIs → nausea, fatigue, sexual side effects.

Cluster A Personality Disorders

• Includes: Paranoid, Schizoid, Schizotypal.

• Pathophysiology: Social detachment, odd or eccentric thinking.

• Clinical Features:

  • Paranoid: Suspicious, humorless.

  • Schizoid: Loner, emotionally detached.

  • Schizotypal: Magical thinking, social anxiety, odd beliefs.

• Genetics: Related to schizophrenia spectrum.

• Treatment: Psychotherapy; antipsychotics for severe cases.

• Adverse Effects: EPS and sedation if medicated.

Cluster B Personality Disorders

• Includes: Borderline, Histrionic, Narcissistic, Antisocial.

• Pathophysiology: Emotional dysregulation, impulsivity.

• Clinical Features:

  • Borderline: Self-harm, unstable relationships.

  • Histrionic: Attention-seeking, dramatic.

  • Narcissistic: Grandiose, lacks empathy.

  • Antisocial: Lawbreaking, lack of remorse.

• Genetics: Strong with childhood trauma (especially in borderline and antisocial).

• Treatment: DBT for borderline; CBT for others.

• Adverse Effects: Medication only for comorbidities.

Cluster C Personality Disorders

• Includes: Avoidant, Dependent, Obsessive-Compulsive Personality Disorder (OCPD).

• Pathophysiology: Anxiety-driven behavior and interpersonal insecurity.

• Clinical Features:

  • Avoidant: Social inhibition, fears rejection.

  • Dependent: Clingy, indecisive.

  • OCPD: Perfectionistic, rigid, preoccupied with order.

• Genetics: Linked to anxiety traits.

• Treatment: CBT is first-line; SSRIs if comorbid anxiety.

• Adverse Effects: SSRIs → GI upset, sexual dysfunction.