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Mind and brain are two sides of one coin; Disorders of the mind* are disorders of the brain. * schizophrenia, depression, anxiety, psychopathy, etc. Schizophrenia • Clinical features • Etiology (cause) – Genetic – Environmental • Neurobiology & Pharmacotherapy Clinical features • Positive symptoms: Characteristics displayed by schizophrenics that are not typical present in healthy individuals. • Negative symptoms: Absence of characteristics that are typical present in healthy individuals. – Clinical features • Positive symptoms: Characteristics displayed by schizophrenics that are not typical present in healthy individuals. – Hallucinations – Delusions – Disorganized speech - Socially awkward behavior • Negative symptoms: Absence of characteristics that are typical present in healthy individuals. – Hallucinations: Sample item from Scale for the assessment of positive symptoms • Have you ever heard voices commenting on what you are thinking or doing? – What do they say? Delusions: items from Peters Delusion Inventory Clinical features • Positive symptoms – Hallucinations – Delusion – Disorganized Speech High Dopamine – Socially awkward behavior (disorganized) • Negative symptoms* – Poverty of speech – flat affect, apathy, anhedonia – Decreased motor activity • Cognitive symptoms* – Working memory, attention * non-specific A very debilitating disease Hypofrontality male All ethnic groups/geography Lifetime prevalence = 1% First diagnosis at 20 yrs of age Prodrome at 17 yrs of age female 10 20 30 40 50 years Jennen-Steinmetz et al 1997 Early detection is key, as delayed treatment: - increases brain damage, - shows less recovery Some signs present at childhood: - neuromotor functions - sociability - emotions prodrome 1st acute episode relapse relapse residual phase Time course: - positive symptoms are evident in the acute episodes - negative symptoms increase gradually (although they can precede the positive ones, as in the prodrome) Schizophrenia • Clinical features • Etiology (cause) – Genetic: – Environmental • Neurobiology & Pharmacotherapy Given that somebody is schizophrenic, what is the likelihood that you will suffer from schizophrenia? (in %) identical twin 48 fraternal twin 17 1 9 sibling 1 0 20 40 60 general population Increased risk with closer genetic distance If biological parent is schizophrenic: 17% - Age of father (not of mother) - Spermatocytes divide more frequently than oocytes, so increase chance of mutation (it’s not a Y chromosome mutation) - Environmental impact on a genetic factor Schizophrenia • Clinical features • Etiology (cause) – Genetic: – Environmental • Neurobiology & Pharmacotherapy Viral hypothesis (flu) • Seasonal (previous slide) • Urban • Flu epidemic Maternal influenza during fetal development (2nd trimester) Stress hypothesis • Flu is just a stressor • Other stressors during 2nd trimester also increase risk: – Underweight mother – Underweight newborn – Famine (due to thiamine deficiency post-famine?) – Your husband is killed – Increased cortisol • stress video • may also explain disease onset in adolescence Pre-morbid development • Schizotypal personality disorder at adolescence – – – – – Social anxiety Affective abnormalities Eccentric behavior Unusual ideas (e.g., persistent belief in ESP) Unusual sensory experiences • (not strong enough to be delusions or hallucinations) • Relation between SPD and schizo (20-40% of SPD -> schizo), familial link Of those showing warning signs (prodromal phase) • 1/3 gets better as they enter adulthood • 1/3 continues to experience mild symptoms • 1/3 develops schizophrenia or other psychosis This latter group has the higher cortisol levels at prodrome Cortisol levels increase with puberty (even in normal kids) a disruptive family environment (stressor) is a risk factor. Further evidence for cortisol hypothesis: in animal models, cortisol increase during pregnancy leads to abnormal hippocampus in the offspring Schizophrenia • Clinical features • Etiology (cause) – Genetic: – Environmental • Neurobiology & Pharmacotherapy Positive symptoms: due to dopamine • Antipsychotic drugs (D2 blockers) • DA agonists (e.g., cocaine) Negative Symptoms: Frontal lobe lesion 20 … some lessons for life • • • • Flu Vaccine Reduce maternal stress (physical & psychological) Reduce teenager’s stress Raise concern about friend/relative when you deem doing so is warranted. • Support early treatment (when onset is evident) http://www.sfnsw.org.au/schizophrenia/symptoms.htm http://www.emory.edu/EMORY_MAGAZINE/spring2000/inquiry.html Summary