-Genetic transmission

-Brain structural/functional abnormalities

-Neurodevelopmental factors

Neurotransmitter Theories

-Family twin and adoptin studies

-Different genes may be responsible for different symtpms

     -a general diathesis may be inherited

-Family studies

     -the greater genetic similarity, the greater the risk

     -however, 87% of children of schizophrenic parent will not develop

     - 63% do not have 1st or 2nd degree relatives with the disorder

-twin studies

     mz concordance 48%

      - dz 17%

     -heritability i Finnish twin study 83%

     -symptoms, onset, course and prognosis may vary

     - epigenetic

         disordant twins showed numerous differences in molecular DNA structure than concordant

Adoption

     -adopted children 10x more likely to develop if biollogical parent has it

     -Finnish adoption study

         -190 adoptees matched to 192 nonrisk

         -mother with schizo spectrum disorder

-are some people carriers

     -1.7%with nonschizo parents

- Fischer

      - 21 mz twin pairs 41 dz twin pairs + offspring

      - risk of schizo for child if either parent or identical twin has schizo is 17%

-Biomarker linking phenotypical behviors with genetics; inherited

     -Eye tracking

        tracking across vf deficient

     -Cognitive deficits in emothion identification

         multiple family generations

     -Prepulse inhibition deficits

         inability to filter out unnecessary information

-Enlarged Ventricles

     -implies atrophy of brain tissue or adjacent brain areas have not fully developed

     -more often in men

     -enlargedment of third ventricle in proband and sme sex nonaffected sibling

     -more severe symptoms/less responsive to meds

     -correlate with

            -poor performance on cognitive tests

            -poor premorbid adjustment

            -poor response to treatment

-Prefrontal Cortex

     - dysfunction seems to occur before the onset

     - impairments on neuropsychological tests of pfc

     - smaller, less activity even in those who have not developed the disorder

     - individuals show low metabolic rates in DLPFC

-Abnormal connection between PFC and the amygdala and hippocampus

-Deteriorated brain areas may contribute to the different manifestations

-Neuroimaging studies show structural changes across the cortes from 13-18

-Neonatal vntral hippocampal lesion

     -experimental model of schizo

     -projection to PFC

     -aberrant development of PFC

-Congenital factors

     -damage durring gestation or birth

     -viral damage to fetal brain

        -schizo rates higher when mother had flu in 2nd trimester

        -Maternal exposure to parasite/herpes simplex

-Developmental Factors

     -prefrontal cortex matures in adolescence or early adulthood

     -dopamine activity lso peaks in adolescence

     -stress activates HPA system which triggers cortisol secretion

          -cortisol increases dopamine activity

-Dopamine Theory

     -Disorder due to excess levels of dopamine

     -The evidence

            -drugs alleviate symptoms reduce dopamine activity

            -neuroleptics produce negative side effects similar to PD

            -amphetamines, which increas dopamine levels, increase the positive symptoms

            -L=Dopa produces schizo like symptoms- increase synthesis

            -neuroimaging studies show more DA receptors and higher levels of DA in people with schizo

-DA theory doesnt completely explain disorder

     -antipsychotics block dopamine rapidly but symptom relief takes several weeks

     -to ev effective antipsychotics must reduce dopamine activity to below normal levels

     - many do not respond to phenothiazines or other DA antagonists

     - olanzapone effective for those not helped by traditional antipsychotics

-Mesolimbic pathway

     -excess numbers of DA receptors or oversensitive DA receptors in the striatum

     -antisychotics bind toD2 receptor in this area blocking DAs action

      - related to positive symptoms

-Unusually low DA in PFV mesocortical

     Deficiency in stimulation of D1 receptors

     Cogintibe deficits

     Related to negative symptoms

     Antipsychotics such as phenothiazine ineffective

-Serotonin neurons regulate DA neurons in mesolibmic pathway

-Deficiencies in GABA and Glutamate

     -PCP and ketamine cause positive symptoms

-Reaction to stress

     individual with schizo and their first-degree relatives more reactive to stress

-Socioeconomic status

     -Highest rates of schizo among urban poor

-Schizophrenogenic mother

     - overprotective and rejecting simultaneously

-Expressed emothin high

-Communication deviance

     - hostility and poor communication

-1st generation

     -Phenothiazines, butyrophenones

-Extrapyramidal Side effects

     -tardive dyskinesia- neurological disorder

     -akinesia-slowed motor, monotone,expressionless

     -maintenance dose

-2nd generation

     -Clozapine

          -binds to D4 recetor

          -impacts 5-ht

-Side effects

        -can impaire imune symptom function

        -seizures, dizziness, fatigue, drooling, weight gain

-Newer meds may improve cogintive functions

      - olanzapine

      - rixperidone

-Insulin coma therapy

-psychosurgery (profrontal lobotamies)

-ECT

-TMS for hallucinations; magnetic fields interrupt normal brain communication

-Family therapy to reduce expressed emotion

-Social skills training and role playing

-CBT

     -recognize and challenge delusional beliefs and expectation associated with negative symptoms

-Cognition enhancement therapy

     - improve attention, memory, problem solving and other cognitive based symptoms

- 40-60% recieve little to no care in a given yr

-discharged from hospital with little or no follow up

-end up in nursing homes homeless or in prison