Table of Contents

1. Etiology

1.1. Genetics

  • genes
    • alpha-7 nicotinic receptor, DISC1 GRM3 COMT NRG1 RGS4 G72 dystrobrevin and neureglin 1
  • family hx: likelihood increases with closeness of relationship
    • High proportion of variance
    • additive genetic effects
    • linked with schizotypal PD
    • 50% concordance with monozygotic twins (5x more than dizygotic)
    • +environmental contribution
    • mode of transmission unknown
  • age of father >60yo

1.2. Biochemical

  • Dopamine hypothesis
    • too much dopamine
    • from potency of antipsychotics at D2
    • cocaine and amphetamine increase dopamine and are psychotomimetic
    • mesocortical and mesolimbic tracts, also amygdala and caudate nucleus
    • severity of positive symptoms
  • Serotonin
    • too much
    • both + and - symptoms
    • clozapine and other second-gen anti-serotonin activity
  • Norepinephrine
    • anhedonia
    • neuronal degeneration within the norepinephrine reward neural system
    • inconclusive
  • GABA
    • loss of GABAergic neurons in hippocampus
    • has regulatory effect on dopamine
      • loss of inhibitory GABAergic
        • hyperactivity of dopaminergic neurorns
  • Neuropeptides
    • substance P and neurotensin
      • localized with catecholamine and indolamines and affect them
  • Glutamate
    • ingestion of phencyclidine (glutamate antagonist) produces an acute syndrome similar to schizophrenia
    • hyperactivity, hypoactivity, and glutamate-induced neurotoxicity

1.3. Neuropathalogy

  • Found pathology in end of 20th century
  • lateral and 3rd ventricle enlargement
    • static vs progressive is uncertain
  • reduced symmetry in temporal, frontal, and occipital lobes
    • indicative of disruption in brain lateralization during neurodevelopment
  • decrease in size of limbic system
    • amygdala, hippocampus, parahippocampal gyrus
    • hippocampus is also functionally abnormal
  • anatomical and functional abnormalities in prefrontal cortex
    • mimic those of frontal lobe syndromes
  • neuronal loss in thalamus
    • has reciprocal connections with prefrontal cortex
    • total neurons is reduced by 30-45%
  • Neural circuits
    • prefrontal cortex to hippocampus and cerebellum
    • anterior cingulate basal ganglia thalamo-cortical circuit
      • positive symptoms
    • dorsolateral prefrontal circuit
      • negative symptoms

2. Clinical syndrome

2.1. DSM-V criteria

  • 2+ of
    • delusions
    • hallucinations
    • disorganized speech
    • disorganized behaviour
    • negative symptoms: avolition, anhedonia, social withdrawal, affective blunting, alogia
  • level of functioning has deteriorated or not expected level in 1+ areas
  • 6+ months of disturbances (1 month of symptoms from criterion A)
  • r/o schizoaffective, mood+psychosis
  • not physiological
  • r/o Autism or communication d/o
  • specify
    • first/multiple/continuous/unspecified, currently in acute/partial/full
    • with catatonia

2.2. Natural Hx

  • Nothing is pathognomonic
  • premorbid
    • before the disease process evidences itself
    • schizoid or schizotypal PD as quiet, passive, introverted
    • as children: few friends
    • adolescent: no close friends, no dates, avoid team sports, enjoy watching tv shows and movies, games, exclusion of social activities
  • prodromal
    • somatic complaints dx as malingering, chronic fatigue syndrome, or somatization disorder
    • then family and friends notice decrease in functioning
    • may begin to show interest in abstract ideas, philosophy, occult or religious questions
    • peculiar behaviour, abnormal affect, unusual speech, bizarre ideas, strange perceptual disturbances

2.3. Types

  • weak relationship to biological variables, poor long-term stability, poor predictive value
  • Paranoid
    • preoccupation with one or more delusions or frequent auditory hallucinations
    • often delusions of persecution or grandeur
    • usually older first episode vs catatonic or disorganized
    • less regression of mental faculties, emotional responses, and behaivour
    • intelligence in areas not invaded by their psychosis tends to remain intact
  • Disorganized
    • marked regression to primitive, disinhibited, unorganized behaviour and absence of catatonia
    • usually early onset <25
    • active but aimless manner
    • thought disorder is pronounced, contact with reality is poor
    • usually inappropriate emotional and social responses
  • Catatonic
    • marked disturbance in motor function
    • stupor, negativism, rigidity, excitement, posturing
    • associated: stereotypies, mannerisms, waxy flexibility, mutism
  • Undifferentiated
    • don't fit anywhere
  • Residual
    • continuing evidence of schizophrenia disturbance, absence of complete set of active symptoms
    • emotional blunting, social withdrawal, eccentric behaviour, illogical thinking, mild loosening of associations
    • delusions or hallucinations, if present, are not prominent

2.4. Differential

  • Medical
    • Epilepsy
    • substance-induced
    • neoplasm
    • AIDS
    • vit B12 deficiency
    • encephalitis
    • brain deposits: CJD, wilson's, etc
  • Psychiatric
    • Schizoaffective
      • prominent mood symptoms for a significant duration, and 2 weeks of schizophrenia
    • Other specified and NOS psychosis
    • Delusional disorder
    • Brief psychotic disorder
    • Schizophreniform

Author: Armin

Created: 2023-02-16 Thu 00:05