NROSCI 1030 Exam 2 Study Guide Lectures 8 14 Lecture 8 2 4 Schizophrenia Diagnosing a Psychiatric Disorder Symptoms groups of characteristic features that can be physically assessed Syndrome groups of symptoms clustered or occurring together Disease a discrete illness with a discrete pathology and etiology Validation of Diagnosis Clinical course is the disease progressive or cyclic Mental history events that occur early in life in middle age or later in life Response to treatment Genetic profile history of affective disorders like bipolar or depression in the family Biochemical hormonal abnormality Diagnostic and Statistical Manual DSM Criteria for Schizophrenia Hallmark of the Disorder Hallucinations primarily auditory visual hallucinations are rare Delusions bizarre in nature incongruent with the way the person feels Thought disorder incoherent speech loosening of associations no sequencing of ideas Posturing holding odd positions for a very long time Waxy flexibility act like a wax figure Deterioration in Function Social cognitive functioning inability to hold their position in life Duration Prodromal phase before schizophrenia patients have bizarre ideas First psychotic break positive symptoms added on to a normal personality including delusions hallucinations and thought disorder Residual phase negative symptoms missing from a normal personality inability to converse with other people Negative symptoms are always there while the positive symptoms come and go Disorganization syndrome can t organize life and thoughts non linear thought processes Cognitive decline is also present one of the most debilitating Psychosis Mental disturbance characterized by misinterpretations of perception delusions hallucinations and disordered thinking Not limited to schizophrenia it can also be seen in depression and bipolar disorder Delusions patients misinterpret what s there in bizarre ways Hallucinations perceiving things that are not there usually auditory in nature Lecture 9 2 6 Schizophrenia Etiology Genetics risk of schizophrenia is 10 times higher in relatives As the number of shared genes increases the risk increases Schizophrenia can also arise sporadically without any genetic history of schizophrenia Cannabis use in people with certain genetic predisposition increased risk Parents who have schizotypy characteristics of schizophrenia but not full blown schizophrenia may have children with schizophrenia History and Drug Findings of Schizophrenia Transmethylation if you methylate serotonin you could get an LSD like compound Aadrenochrome drug very unstable compound made in the adrenal gland intensely hallucinogenic Robin Murray took urine from schizophrenics and placed it on TLC found one spot called a pink spot that stood out in all schizophrenics Amphetamine can lead to amphetamine psychosis it release DA and NE has a structure that resembles DA strengthens link of schizophrenia to DA excess Amphetamine 500 mg day for 1 week leads to psychosis leads to a 20 30 fold increase in DA turnover single dose of an antipsychotic drug will reverse this increase by blocking DA LSD hallucinations are primarily visual in nature heightened emotional response or affect in comparison to schizophrenia producing a flattened affect Dopamine Hypothesis of Schizophrenia Amphetamine and L DOPA can lead to schizophrenia and worsen it in schizophrenics DA antagonists are the antipsychotic drugs Imaging when schizophrenics are given amphetamine they release more DA PCP PCP phencyclidine dissociative anesthetic that produces psychosis very much like schizophrenia it mimics the positive negative and cognitive symptoms PCP given to schizophrenics could not be distinguished from relapse it functions for over a week in schizophrenics while PCP given to a normal individual lasts for 7 hours Works very potently on glutamate receptors specifically on NMDA receptors binds at the PCP binding site very selective to prevent the flow of ions through the channel it only functions when the channel is open distinguishing it as a use dependent blocker PCP interferes with a lot of cognitive symptoms especially with executive functions mainly working memory Cannabis Slightly higher risk of developing schizophrenia with cannabis intake It has to do with the COMT gene which is higher in cortical areas in schizophrenics COMT gene is in the 158th position which has to do with valine or methionine methionine methionine low COMT activity valine valine high COMT activity Schizophrenics get a big decrease in DA in the prefrontal cortex coupled with marijuana they have a much higher risk of getting schizophrenia Animals Models of Schizophrenia Weinberger looked at schizophrenia in twins schizophrenic twin always had a smaller hippocampus than the normal twin Weinberger conducted ventral hippocampal lesions in neonatal rats when these rats grew up they began to show signs of schizophrenia with increased response to PCP and amphetamines and deficits in working memory they did not show these signs until they reached adulthood Human equivalent of a ventral hippocampus is hyperactive in schizophrenic rats Ventral hippocampus projects to prefrontal cortex and the ventral striatum ventral striatum connects to ventral pallidum which connects to VTA DA neurons Ventral pallidum is a very powerful inhibitory structure it keeps a number of the DA neurons from firing glutamate input on these DA neurons causes burst firing instead of normal firing the more neurons firing the more burst firing there is this system controls DA response in schizophrenia As the ventral hippocampus is hyperactive in schizophrenics this causes an orienting response this filtering system is unresponsive constantly in a state of hypervigilance cannot distinguish relevant from irrelevant info aberrant salience Schizophrenia patients all display a loss of GABA neurons that have paralbumin which strongly binds calcium and lets the system polarize much faster from hyperpolarization Due to a paralbumin GABA loss of inhibition the hippocampus is overactive overactivating DA neurons and causing burst firing Lecture 10 2 11 Schizophrenia 1st Generation Antipsychotic Drugs Classical antipsychotic drugs called neuroleptics They treat psychosis but also cause motor side effects Ex Haloperidol causes antipsychotic effects as well as extrapyramidal side effects it causes depolarization block in the VTA as well as the SN 2nd Generation Antipsychotic Drugs Atypical antipsychotic drugs Ex