Schizophrenia

  • Most severe neuropsychiatric illness

  • .28% prevalence in population = 20+ million people

    • 2.2 million people in the US right now have schizophrenia

    • 200,000 are homeless

  • No sex difference

  • 1/3 of all hospital beds

  • Symptoms begin 18-25 years old

Symptoms

  • Positive

    • Hallucinations

    • Delusions

    • Paranoia

  • Negative

    • Loss of motivation

    • Apathy

    • Asocial behavior

    • Loss of affect (mood)

    • Poverty of speech

  • Cognitive

    • Impaired working memory

    • Reduced attention span

    • Dissociated thoughts

    • Impaired executive function


Symptoms in teenagers (early symptoms)

  • Withdrawing from friends and family

  • Not doing well in school

  • Trouble sleeping

  • Feeling irritable or depressed

  • Lacking motivation

Not hallucinations, delusions, disorganization

Risk Factors for Schizophrenia

  • Genetics - heritability of .79

  • More moderate risk factors

    • Winter birth

      • Maternal viral infection

    • Maternal malnutrition

    • Perinatal injury

    • Solar flares at birth

    • Growing up in urban area

    • Minority group

Mechanisms of Schizophrenia - dopamine

  • 1949- Chlorpromazine

    • D2 receptor antagonist

  • Increased release of dopamine is linked to psychotic behavior

    • Drugs (amphetamine, cocaine) —- psychotic behaviors

  • Dopamine release is higher during psychotic episode than between

  • But, only explain positive behaviors

Mechanisms of Schizophrenia- glutamte

  • Hypofunction of NMDA receptors

  • PCP and ketamine are NMDA receptor blockers

  • PCP and ketamine cause both positive and negative symptoms of schizophrenia

  • Glutamate activity controls dopamine activity

  • But glutamate signaling is complicated and glutamate is everywhere

Mechanisms of Schizophrenia- GABA

  • GAB67 is an enzyme involved in synthesis of GABA

  • GAD67 is decreased (up to 30%) in DLPFC in schizophrenia

Disconnection hypothesis of schizophrenia

  • Schizophrenia arises from disrupted



    Putting it all together

  • Schizophrenia invovled

    • Increased dopamine activity

    • Decreased glutamate activity

    • Decreased GABA activity

    • Hypoconnectivity

    • Over-pruning dendrites

    • Genetics