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Schizophrenia etiopathogenesis

SCHIZOPHRENIA ETIOPATHOGENESIS AND DIAGNOSIS

Psychotic syndrome whose name means “mental dissociation”

  • Prevalence males (15-25 y.o.) females (25-45 y.o.).
  • Higher incidence in monozygous twin
  • Risk of suicide 10%

CLINICAL COURSE

PRE-MORBID phase // PRO-DROMAL phase // ACUTE PHASE // STABILIZATION phase // CHRONIC STABILIZED phase // RESIDUAL SCHIZOPHRENIA

DIAGNOSTIC CRITERIA

POSITIVE symptoms (DAergic HYPERACTIVITY in the MESOLIMBIC SYSTEM)

DELIRIUM  

Neuroleptics block D2 receptors in the mesolimbic, so they are effective on positive symptoms, and not on negative and cognitive symptoms.

HALLUCINATIONS
DISORGANIZED THINKING
AGITATION

NEGATIVE symptoms (DAergic HYPERACTIVITY in the MESOCORTICAL SYSTEM)

  • BLUNTED AFFECTS (severe reduction in the expression of feelings) “blunted=insensibile”
  • ECHOLALIA (repeating the same words)
  • ALOGIA (opposite of eloquence)
  • APATHY (lack of will and passion)
  • ANHEDONIA (lack of pleasure)

COGNITIVE deficit (GLUTAMATergic HYPOACTIVITY (NMDA receptors) in the prefrontal cortex.

  • WORKING MEMORY DEFICIT (prefrontal cortex)
  • CONTROL OF DRIVING (orbitofrontal cortex)
  • MOOD DISORDERS ( anterior cingulate gyrus)

PATHOGENETIC HYPOTESIS

NEUROPATHOLOGICAL ALTERATIONS (detected by AUTOPSY, RMN, TAC)

  • Thalamo-cortical areas (thalamus nuclei, cingulate gyrus and anterior temporal gyrus) with enlargement of 3rd ventricle and the lateral ventricles.
  • Prerontal cortex with shrinkage layers (disorganization of cortical stratification and reduction of dendritic spines of pyramidal cells).
  • Alterations of cortical GABAergic chandelier cells, with DECREASE IN in parvalbumin, GAD67 (Glutamate decarboxylase an enzyme that catalyzes the carboxylation of glutamate to GABA), and GAT1 (GABA transporter).

GENETIC ALTERATIONS

[GENETIC ALTERATIONS + environmental factors (viral infections in the II trimester of pregnancy, perinatal hypoxia, use of cannabis)]. Susceptibility of PLEIOTROPIC GENES (genes which influence more than one developmental pathway) for schizophrenia are:

  • COMT gene (158-108, val7val) which lead to a decrease in DA TRANSMISSION. 22ND CHROMOSOME
  • DISC 1 gene (DISRUPTED IN SCHIZOPHRENIA 1) 1ST CHROMOSOME. Participate in regulation of cell proliferation, differentiation and migration of neuronal axons and dendrites formation (ARBORIZATION).
  • GSK-3β gene (glycogen synthase kinase 3) in the adult brain mediates SYNAPTIC PLASTICITY, DA-ERGIC TRANSMISSION.
  • Receptors for NEUREGULIN which are proteins very important in neurogenesis and embryogenesis CONNECTIVITY AMONG PYRAMIDAL NEURONS.
  • Lack of REELIN production IN CORTICAL GABAergic CELLS DURING EMBRIOGENESIS. Reelin is a glycoprotein that manage the movements of stem cells during embryogenesis, especially those in the cortex.

NEUROCHEMICAL (hypothesis)

  • NMDA receptor is a glutamic acid post synaptic ionotropic receptor (for Na+/Ca++intake and K+ outflow)
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