Psychosis: Schizophrenia, Manic-Depressive Psychosis, and Involutional Psychosis

1. OVERVIEW: WHAT IS PSYCHOSIS?

• Schizophrenia (and its subtypes, including paranoid)
• Manic-depressive psychosis (bipolar disorder with psychosis)
• Involutional psychosis (late-onset psychosis)
• Brief psychotic disorder, schizoaffective disorder, delusional disorder

2. SCHIZOPHRENIA

Definition and Epidemiology

• Lifetime prevalence: slightly less than 1%
• Peak onset: late adolescence to young adulthood (slightly younger in males)
• Annual incidence: approximately 15 per 100,000
• Slightly more common in males than females
• Average life expectancy is shortened by 10-15 years

Four Sub-Types (Classical Classification)

Pathobiology

• Pathogenesis remains unknown; multifactorial
• Genetic factors account for up to 50% of risk; multiple gene loci involved
• Highly heterogeneous genetically - many severe ultrarare mutations related to synaptic plasticity
• Postmortem brains show nongliotic neuropathology with subtle disruptions of cortical cytoarchitecture
• Dopamine hypothesis: DA hyperfunction in subcortical regions (especially striatum) produces positive symptoms; DA hypofunction in the prefrontal cortex (PFC) is associated with negative/cognitive symptoms
• Glutamatergic systems are also important
• Psychosocial stressors can precipitate exacerbations

DSM-5 Diagnostic Criteria (Table 362-11)

1. Delusions
2. Hallucinations
3. Disorganized speech (thought process derailments)
4. Grossly disorganized or catatonic behavior
5. Negative symptoms: affective flattening, alogia, avolition

• Major impairment in social or occupational functioning
• Duration of at least 6 months

Paranoid Schizophrenia - Special Features

• Persistent persecutory delusions (delusions of being followed, poisoned, or harmed)
• Auditory hallucinations - voices commenting or commanding
• Relatively preserved personality compared to other subtypes - the patient can function in routine activities (a "preserved island" of the personality)
• The chronic form with auditory hallucinations is sometimes called paraphrenia (an older term for chronic paranoid schizophrenia)
• Othello syndrome (morbid jealousy) is considered a form of paranoid schizophrenia - the person has fixed delusions of infidelity about a spouse/partner and may assault or murder them

Medicolegal Aspects of Schizophrenia

• Violent crimes: Schizophrenics may commit crimes without apparent motive or with impulsive violence
  • In hebephrenic type: the impulse may not be present in consciousness at the time of the act
  • In catatonic type: the stage of excitement may lead to wild, unprovoked homicidal attacks on strangers
  • In paranoid type: acting under delusional persecution - "killing in self-defense" in response to imagined threat
• A schizophrenic is generally not criminally responsible (insanity defense), as they lack the capacity for rational volition

3. MANIC-DEPRESSIVE PSYCHOSIS (BIPOLAR DISORDER)

• Mania (extreme elation/excitement)
• Depression (extreme sadness/withdrawal)

Mania

• Patient is excited, restless, and talkative
• Euphoria disproportionate to the circumstances
• Delirious mania (most severe form): clouding of consciousness, disorientation, impulsiveness
• Auditory and visual hallucinations may be present
• Delusions of grandeur followed by delusions of persecution
• Patient may commit violent acts under persecutory delusions

Depression

• More common than mania
• Depressed mood and loss of interest not warranted by circumstances
• Refusal to take food, lack of personal attention, suicidal tendencies
• Hallucinations and delusions are common (imaginary evil or danger)
• Every patient with depression is potentially suicidal
• Homicidal behavior is not uncommon:
  • May be committed in a confusional state or as an irresistible impulse (e.g., a mother throwing a child out of a window)
  • Homicidal behavior particularly toward emotionally significant persons (family members)
  • Shop-lifting is characteristic of the depressive state - typically a middle-aged woman of means in a state of confusion, as a "cry for help"

Medicolegal Aspects of Manic-Depressive Psychosis

4. INVOLUTIONAL PSYCHOSIS

• Depressive disorder with psychotic features (when depression predominates)
• Delusional disorder (when non-bizarre delusions are the main feature without full schizophrenic syndrome)

• Onset in middle to late life (involutional period)
• Prominent agitation and anxiety
• Depressive delusions: guilt, nihilism (Cotard's syndrome), hypochondriasis
• Persecutory delusions without the personality disintegration seen in schizophrenia
• No prior psychiatric history
• Better response to treatment than schizophrenia

• Hormonal changes (menopause)
• Cerebrovascular disease (post-stroke psychosis - right inferior frontal gyrus involvement is a risk factor)
• Neurodegenerative disease (Parkinson's disease psychosis - treated with pimavanserin, a 5-HT2A inverse agonist)
• Neurological and systemic conditions (SLE with neuropsychiatric involvement, CNS vasculitis)

5. ANTIPSYCHOTIC PHARMACOTHERAPY

First-Generation (Typical) Antipsychotics

• Mechanism: D2 receptor antagonism
• Prototype: Chlorpromazine (first antipsychotic); Haloperidol (more D2-selective)
• Effective for: Positive symptoms (hallucinations, delusions)
• Limitations: Extrapyramidal side effects (EPS) including tardive dyskinesia; not effective for negative symptoms

Second-Generation (Atypical) Antipsychotics

• Mechanism: Lower D2 affinity + faster dissociation from D2 + additional 5-HT2A blockade; lower receptor occupancy time
• Advantages: Fewer EPS, less prolactin elevation
• Examples: Clozapine, risperidone, olanzapine, quetiapine, aripiprazole

• All atypical antipsychotics carry risk of metabolic syndrome (obesity, dyslipidemia, glucose dysregulation)
• A systematic review found no clear differences among agents for maintenance treatment and relapse prevention

6. PROGNOSIS

• Goldman-Cecil Medicine International Edition, pp. 3764-3765
• Goodman & Gilman's Pharmacological Basis of Therapeutics, pp. 313-321
• Parikh's Textbook of Medical Jurisprudence, Forensic Medicine and Toxicology, pp. 490-493
• Bradley and Daroff's Neurology in Clinical Practice