HD 3700 1st Edition Lecture 16 Outline of Last Lecture I Bipolar Disorders II Hamlet associates to the players III Diagnostic criteria for Schizophrenia IV The Schizophrenic Spectrum V Case Study Jim Outline of Current Lecture I To Be or Not To Be II Schizophrenia schizotypes and endophenotypes III First Generation typical Antipsychotics IV Second Generation Antipsychotics Current Lecture I 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 direct contrast to the previous soliloquy o Meant to appear stiff and erudite it s priming Hamlet to act like a Puritan minister towards Opheila o Shakespeare is trying to show us how Hamlet s mood changes o If I could just die I wouldn t have to suffer anymore o 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 hard life is o We don t know what happens after death o Talking about what will happen after he murders the king he will be killed too imagining life after death o He is losing his resolve to seek his revenge o 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 wife o Perception through identification o We will send Hamlet to England orders that when Hamlet gets to England he will be executed II Schizophrenia schizotypes and endophenotypes SCZ The Neurodevelopmental Disoder o Start with a genetic liability o 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 brain and 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 break o Add environmental psychological stress o 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 model o o 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 indicators o 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 itself o Followed endophenotypes throughout life and some of them developed SCZ and some did not o Candidate endophenotypes Working memory deficits Oculomotor function Glial cell abnormalities Sensory motor gating Confirmed deficits in schizotypes bridging schizotypy and SCZ o Sustained attention vigilance o Abstraction ability o Working memory o Attentional inhibition o Smooth pursuit eye movement o Antisaccade performance o Thought disorder o Personality Psychopathology How does SCZ develop o There needs to be a second hit other than genetic vulnerability o Mother having flu during second trimester o 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 experience III First Generation Antipsychotics Back to the dopamine pathways o 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 there o 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 secretion IV Second Generation Antipsychotics The Miracle well alright the important advance of Atypical 2 nd 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 neurons o 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 make warm water Even though DA is released in the Mesocortical Nigrostriatal Tuberinfundibular Pathways o Serotonin 2A antagonism fortunately fails to reverse D2 antagonism in the mesolimbic system If serotonin 2A antagonism reverses at least in part