Schizophrenia as Neurologic Disorder

Genetics of Schizophrenia
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1% in general population

* There is a genetic predisposition to developing schizophrenia, but schizophrenia is NOT a "genetic" disorder. (Genetics is only a partial contributor. What is inherited is a vulnerability to factors playing a role in developing the illness. One's genetic make-up controls how sensitive we are to certain aspects of our environment. Genes can be turned on or off in response to environmental conditions.)

* Multiple genes are involved. These multiple pathways and the gene overlap may account for the different forms of schizophrenia and the various schizophrenia spectrum disorders.

* Note that only 1/3 of individuals with schizophrenia have a (known) family history of the disorder (in their first or second degree relatives).

* Genetic mutations can play a role also: 3-4 times more (nonspecific) genetic glitches were found in schizophrenic patients. (Genetic glitches are DNA duplications or omissions in the genetic code; they influence how neuronal circuits get sculptured; this can lead to signals not getting filtered out and could create hallucinations, thought problems, and general "overload.")
synaptic pruninga process whereby the synaptic connections in the brain that are used are preserved, and those that are not used are lostHypofrontality in Schizophrenia- PET scans reveal reduced neural activity within frontal lobes of schizophrenicsReduced functional connectivity Frontal-striatalVentral frontal-caudate connectivity reduced in 19 first episode schizophrenia and unaffected relativesglutamate hypothesis of schizophreniaproposal that schizophrenia relates in part to deficient activity at glutamate synapses, especially in the prefrontal cortexEvidence for glutamate hypothesisDrugs like PCP block glutamate and produce psychotic like experiences Genes associated with Schiz affectglutamate receptor proteins Egan et al 2004 Imaging with SPECT shows lower NMDA binding Pilowsky et al 2005Connectomicsexamination of connectivity pathways in the braintraditional antipsychoticsblock dopamine receptors Haldol, Thorazine, ProlixinTreat Positive Symptoms onlyMany movement side effectssecond generation antipsychoticsblock serotonin and dopamine Zyprexa, Seroquel, Clozaril, Risperdal, Geodon, Side Effects: less movement, weight gain, diabetes Treat positive and negative symptoms