Schizophrenia: • What are the different types of symptoms in S ? Know examples of each kind. What kind of brain dysfunction seems to be implicated in each?• Symptoms include some combination of:• Positive: (appears last)• Hallucinations• Perceptions of stimuli that aren’t actually present• Usually auditory but can involve other sensory systems (olfactory common)• Increased activity in the thalamus, hippocampus, and cortex• Delusions• Beliefs that are contrary to fact• Grandeur, persecution, or control• Thought disorder• Disorganized irrational thinking• Difficulty arranging thought logically or sorting out plausible conclusions from absurd ones• Jumping conversation, meaningless words• Abnormal interaction between thalamus, cortex, and cerebellum• This may lead to hallucinations, delusions, and other symptoms• Disorganized behavior:• Movement disorder• Inappropriate emotion expressions• Negative symptoms: (appear first)• Behaviors that are absent that should be present, such as:• Flattened emotional response• Poverty of speech• Lack of initiative and persistence• Anhedonia (inability to feel pleasure)• Social withdrawal• Cognitive symptoms: (appear second)• Difficulty sustaining attention• Low psychomotor speech• Poor learning and memory• Poor abstract thinking• Poor problem solving• Closely related to negative symptoms; may involve some brain regions• *All symptoms may be caused by developmental or degenerative process affecting certain brain regions*• What brain abnormalities are sometimes found in the brains of schizophrenic patients?• Inactivation in several regions of the left frontal lobe• Cortical thinning• Lower than normal activity in L hemisphere• Less activity in left temporal lobe• Smaller cell bodies, especially in hippocampus and prefrontal cortex• Smaller anterior hippocampus• R planum temporale is equal or bigger than left• Increased ventricle size• Most likely due to loss of brain tissue• Everyone loses some cerebral gray matter with age, loss is greater in S• What is the role of heredity in schizophrenia? What is evidence of a complex interaction b/t the environment and genetics (remember that we are talking in part about the prenatal environment)?• Adoption studies:• More resemblance to biological parents than adoptive parents• One study showed that home (adoptive) environment must be somehow dysfunctional for effect from biological parents to manifest• Especially increased if bio mom is schizophrenic, could represent poor prenatal environment • Twin studies:• MZ > DZ > siblings• MZ still have just 48% concordance• Studies of children of dizygotic and monozygotic twins discordant for S suggest heritability that confers susceptibility• See slide 9 from schizophrenia• In utero:• Placenta delivers nutrients to fetus, waste to mom, barrier for toxins and infectious agents• Greater concordance of S in monochorionic (share placenta) twins (60%) vs. dichorionic (each has own placenta) monozygotic twins (10.7%)• Strong evidence for interaction between heredity and environment during prenatal development• Many genes:• Mutation in gene for DISC1 (disrupted in S 1)• Involved in regulation of neurogenesis (embryonic and adult), neuronal migration, function of PSD at excitatory synapses, function of mitochondria• Found in families with high incidence of S• Increase chance of developing S by 50x• Increased paternal age:• Caused by mutations in spermatocytes, which divide every 16 days after puberty (so ~540 times by age 35)• Epigenetics• What are some complications of pregnancy and childbirth that increase the risk of schizophrenia? Understand the evidence for viral exposure prenatally as a risk factor for S.• Epidemiology:• Exposure to viral illness during 2nd trimester• Seasonality effect: More S births during later winter-early spring• Could reflect maternal contraction of viral illness during particular time of development • In this case, winter flu season peaks during 2nd trimester• Other data suggest that if mom was exposed to certain viruses during 2nd trimester (regardless of season)  increased risk of S in offspring• Vitamin D deficiency• Maternal thiamine (Vitamin B1) deficiency during pregnancy• Maternal substance abuse, especially tobacco use• Also paternal tobacco use, 2nd hand smoke• Birth and pregnancy complications:• Pregnancy:• Mom with diabetes• Rh-incompatibility• Bleeding• Preeclampsia• Abnormal fetal development• Low birth weight• Congenital malformations• Reduced head circumference• Complications during delivery:• Emergency C-section• Oxygen deprivation• Atonic uterus• Interruption of bloodflow• * If no relatives with S , it is more likely that at least one of these complications occurred, and these individuals are more likely to develop S at earlier age*• Evidence for abnormal brain development:• More abnormal movements and flat expressions in children who eventually became S (old family movies)• Less sociability, deficient psychomotor functioning, poor school performance• Minor physical abnormalities (head, eyes, ears, hands, feet, mouth); increase risk in those with family member from 11.9% to 30.8%• Loss of cortical tissue• Brain abnormalities that occur prenatally may account for poor social behavior and academic performance• Positive symptoms may occur due to rapid degeneration near time of “onset”• In adolescence, pruning normally occurs• The degeneration doesn’t continue • Degeneration began in parietal lobes and moved rostrally• Symptoms, especially hallucinations, were correlated with brain regions losing tissue• What is the dopamine hypothesis of schizophrenia? Is dopamine elevated everywhere? Understand the evidence for a direct connection b/t dopamine and psychotic symptoms. What is hypofrontality, how is it related to increased dopamine in some brain regions and decreased dopamine in others? How do these changes in dopamine in various brain regions play a role in the positive and negative symptoms of schizophrenia?• Positive symptoms caused by over activity of synapses between dopaminergic neurons of VTA and neurons in nucleus accumbens and amygdala• Antipsychotic drugs block dopamine receptors (chlorpromazine)• Effectiveness in blocking D2 receptors = effectiveness in preventing positive symptoms of S•