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CORNELL HD 3700 - Schizophrenia Diagnosis and Treatment
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HD 3700 1st Edition Lecture 16Outline of Last Lecture I. Bipolar DisordersII. Hamlet “associates” to the playersIII. Diagnostic criteria for SchizophreniaIV. The Schizophrenic SpectrumV. Case Study: JimOutline of Current LectureI. To Be or Not To BeII. Schizophrenia, schizotypes, and endophenotypesIII. First Generation (typical) AntipsychoticsIV. Second Generation AntipsychoticsCurrent LectureI. To Be or Not To Be- Hamlet is going to put on a play – if Claudius reacts with guilt / fear then Hamlet will be able to tell and kill him- Puritan movement was gathering steam at this time- Hamlet is being a Puritan preacher – “get thee to a nunnery” to Ophelia- The speech “To Be or Not To Be” is a disquisition on suicide –meant to be a directcontrast to the previous soliloquy o Meant to appear stiff and erudite, it’s priming Hamlet to act like a Puritan minister towards Opheilao Shakespeare is trying to show us how Hamlet’s mood changeso If I could just die, I wouldn’t have to suffer anymoreo What if after death our consciousness continues? “To die perchance to dream”o To be lost in love, to be abused—what if you could just end that with a blade?o Hamlet is saying it is human that some of us choose death given how hardlife iso We don’t know what happens after deatho Talking about what will happen after he murders the king—he will be killed too—imagining life after deatho He is losing his resolve to seek his revengeo Then he sees Ophelia—“go thee to a nunnery” - Claudius—Hamlet is not crazy, there’s something in his soul over which his melancholy sits and I do fear the hatch (like a chicken hatching an egg) and will be some danger o Claudius is thinking of himself—it is he who had melancholy brooding in his heart—to kill his brother and steal his wifeo Perception through identificationo We will send Hamlet to England—orders that when Hamlet gets to England he will be executedII. Schizophrenia, schizotypes, and endophenotypes- SCZ: The Neurodevelopmental Disodero Start with a genetic liabilityo Add intrauterine trauma, infection, stress Women who get the flu during the second trimester disrupts the process of the neurons setting themselves up to develop the brainand increases the vulnerability to SCZ Sometimes this will not show until a break, or it may show up as the person having a certain “weirdness” throughout their life before resulting in a breako Add environmental, psychological stresso And you have a “schizotype” someone expressing some symptoms of neurological deficits, or …o Prodromal or acute onset schizophrenia after puberty …o For the most part, bipolar and SCZ start after puberty (childhood SCZ / bipolar is very rare)- Schizotypy and SCZ: a developmental modeloo You can test and pick up on the schizotypy –vulnerability to SCZ o SZ gene leads to soft neurological differences (i.e. poor eye tracking), social influences interact with genotype so if you get the second hit (major stressors, bad acid trip), you might come down with SCZ or Schizotypal Personality Disorder, or show some deviance on lab indicatorso These are all “schizotypes” - If only a fraction of people with schizophrenia liability develop schizophrenia…o Then we don’t have to study only people with schizophrenia. We can study people with schizophrenic liability … we call them schizotypes, and the ways that they differ from healthy comparison subjects are called endophenotypes.- What is an “endophenotype”?o A measurable component unseen by the unaided naked eye along the pathway between disease and distal genotype.o It may be neurophysiological, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature.o Represents a simpler clue to genetic underpinnings than the disease syndrome itselfo Followed endophenotypes throughout life and some of them developed SCZ and some did noto Candidate endophenotypes Working memory deficits Oculomotor function Glial cell abnormalities Sensory motor gating- Confirmed deficits in schizotypes: bridging schizotypy and SCZo Sustained attention / vigilanceo Abstraction abilityo Working memoryo Attentional inhibitiono Smooth pursuit eye movement o Antisaccade performanceo Thought disordero Personality/Psychopathology- How does SCZ develop?o There needs to be a second hit other than genetic vulnerabilityo Mother having flu during second trimestero A bad acid trip- How is this happening neuroanatomically?o Something happens during the second trimester of pregnancy – a time when neurons are migrating to what will develop into the ventricles of the brain.o Seems as though the neurons don’t “set up properly” leading to a “cascade” of deficits which, during the anatomical and hormonal changes in adolescence, leads to the first schizophrenic episode.o Our consciousness does not filter properly (same thing happens in autism) No balance for how to associate your experienceIII. First Generation Antipsychotics- Back to the dopamine pathwayso The dilemma: We can’t target specific areas of the brains with medication… so if you lower DA in the mesolimbic area, you’re lowering it EVERYWHERE ELSE, such as in the mesocortical, nigrostriatal, and tuberinfundibular pathways.- If you reduce levels of dopamine in the brain…o Too much DA in mesolimbic – pos. sx Presence of mental features that should not be thereo Too little DA in mesocortical – neg.sx The loss or absence of mental functioning (paucity of thought etc)o Too little DA in nigrostriatal – parkinsons sx.o Too little DA in tuberoinfundibular, breast milk secretionIV. Second Generation Antipsychotics- The Miracle (well, alright, the important advance) of Atypical, 2nd Generation medications which, by targeting specific DA receptors & other innovations, greatly reduce the terrible side effects of the first generation of neuroleptics. - Serotonin–dopamine antagonist- Serotonin receptors (5HT2A)o Inhibit DA release in adjacent DA neuronso So if you block those receptors, dopamine is released- Why is this important?o Essentially, the D2 antagonists inhibit the release of dopamine in dopaminergic neurons in these key pathways, while the 5HT2A inhibitors in adjoining seratonergic neurons causes the release of dopamine in those neurons … which allows psychiatrists to lower dopamine overall, but not too much. This a bit like mixing hot and cold faucets to


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CORNELL HD 3700 - Schizophrenia Diagnosis and Treatment

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