NROSCI 1030Exam # 2 Study Guide Lectures: 8 - 14Lecture 8 (2/4): SchizophreniaDiagnosing 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 etiologyValidation 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 abnormalityDiagnostic and Statistical Manual (DSM) Criteria for SchizophreniaHallmark 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 ofideas- Posturing: holding odd positions for a very long time- Waxy flexibility – act like a wax figureDeterioration in Function- Social/cognitive functioning: inability to hold their position in lifeDuration- 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 debilitatingPsychosis- 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 natureLecture 9 (2/6): SchizophreniaEtiology- 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 schizophreniaHistory 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 byblocking DA- LSD hallucinations are primarily visual in nature; heightened emotional response (or affect) in comparison to schizophrenia producing a flattened affectDopamine 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 DAPCP- 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 overa 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 schizophreniaAnimals 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 firingLecture 10 (2/11): Schizophrenia1 st Generation