1	Schizophrenia
2	Overview Probably consists of more than one disorder Is the most devastating disorder Occurs in about 1% of the population Another 2-3% have Schizotypal Personality Disorder No major sex differences in prevalence rates Costs of care >30 Billion Dollars annually Many homeless are untreated or stop meds. Generally, Is a disorder of thought and emotion Is not a “split-personality” disorder.
3	Characterized by Disorganized Thoughts Hallucinations Delusions Bizarre behaviors
4	Two Different Types of Schizophrenic Symptoms Positive Negative Often are preceded by Prodromal signs Social Isolation Odd Behavior and Ideas Poor Hygiene Blunted Affect
5	Positive Symptoms Usually occur during psychotic episodes Usually involve distinct abnormal behaviors Includes Delusions Hallucinations Disorders of thought
6	Delusions Are beliefs that are contrary to reality Can involve Control Grandeur Persecution
7	Hallucinations Are perceptions that occur in the absence of stimuli Can be Visual Auditory (Most Common) Olfactory Tactile
8	Disorders of Thought Can be Disorganized Irrational
9	Negative Symptoms Usually occurs during non-psychotic periods. Generally involves a loss of normal behaviors Reduced speech Low initiative Social withdrawal Diminished affect
10	Diagnosis Must be continuously ill for at least 6 months. Need to have one psychotic phase where you have Delusions Hallucinations Disordered thoughts, incoherence, or other symptoms. See DSM IV for more detail
11	Many Subtypes of Schizophrenia Based on the symptoms that are presented. Paranoid Catatonic Disorganized Others
12	Causes of Schizophrenia
13	Many Different Hypotheses Genetics Brain Abnormality Hypothesis Dopamine Hypothesis
14	Genetic Contributions Highly probable schizophrenia is genetic Is probably not caused by one gene Would show in all monozygotic twin studies. Is probably caused by the combination of several genes. Not totally sure which ones Has been identified with genes on Chromosome 22 and Chromosome 6.
15	Brain Abnormality Hypothesis Identified by CT and Cerebral Blood Flow Studies Some Patients have one or more of the following. Reduction of blood flow to the left Globus Pallidus Problems in the frontal lobes Medial temporal lobe is thinner Anterior Hypothalamus is smaller (especially left side) Lateral and third ventricles are enlarged Sulci are also enlarged (especially in the temporal and frontal lobes Indicated reduced numbers of neurons.
16	Causes of Brain Damage Birth trauma (obstetrical issues) Viral infections that impair neural development during the second and third trimester. Nutritional issues Others
17	Conclusion Not purely a genetic problem Not purely a abnormality problem Is probably a combination problem triggered by an environmental event E.g., Infants exposed to influenza during second and third trimesters. Not really sure what causes the disorder
18	Dopamine Hypothesis Contends: Positive symptoms occur due to increased levels of Dopamine. Get increased stimulation of Dopaminergic synapses
19	History Larobit Was looking for a drug to calm patients before neurosurgery. Found Chlorpromazine worked very well. Hypothesized it might be used on other patients Delay and Deniker found that high dosages of Chlorpromazine calmed patients with schizophrenia or manic-depressive symptoms
20	Chloropromazine and other Phenothiazines Part of the drug group – Typical Antipsychotics Other Typical Antipsychotics Butyrophenones (Haloperidol) Thioxanthenes (chlorprothixene) Have clear effects on schizophrenia Block Delusions Hallucinations Disordered thinking
21	Atypical Antipsychotics Are another group of drugs Are better for negative symptoms and cognitive problems Also have fewer side effects Includes Clozapine Risperidone Olanzapine
22	Atypical Antipsychotics Bind to D3 and D4 receptors Are in the limbic system and cortex Few in the BG Reason for few extrapyramidal side effects
23	Support for Hypothesis Drugs that increase dopamine levels (Amphetamine, Cocaine) can produce positive symptoms of schizophrenia Drugs that block DA receptors also reverse schizophrenia
24	Which Receptors? At least five types of Dopamine receptors D1 – D5 D1 and D5 (D1a) Increase CAMP Are in the cortex, hippocampus, caudate nucleus D2 Group (D2, D3, D4) decrease CAMP Are in the caudate, putamen, nucleus accumbens, amygdala, hippocampus, parts of the cortex. Are also in the caudate and putamen.
25	Four Major Systems for Dopamine Tuberoinfundibular Nigrostriatal Mesolimbic Mesocortical
26	Nigrostriatal Contributes to Parkinson’s Disorder May be involved with short-term and long- term antipsychotic side effects. Short-Term Hand tremor Muscle rigidity Long Term Tardive Dyskinesia
27	Mesolimbic Several structures Is involved with emotion and memory. Symptoms of thought and perception disturbances are characteristic of schizophrenia and psychomotor epilepsy Carlsson Hypothesizes the positive symptoms result from overactivity of this system
28	Mesocortical Originates in ventral tegmental area Projects to the cortex (especially prefrontal cortex) Prefrontal cortex is involved in Motivation Planning Attention Social Behavior Hypothesized to be involved with negative symptoms of schizophrenia
29	Weinberger Contents two dopamine systems are impacted by schizophrenia Increased activity of mesolimbic pathway through D2 group (especially D4) are associated with Positive symptoms. Decreased activity of mesocortical connections in prefrontal cortex is associated with negative symptoms.
30	How? Mesocortical pathway to prefrontal cortex inhibits the mesolimbic pathway Primary effect of schizophrenia is a reduction of inhibition Leads to disinhibition in mesolimbic pathway Get symptoms
31	Drugs Many types Given on the basis of symptoms and potency needed Can be Typical or Atypical depending on the symptoms.
32	Some Drug Names Highest to lowest potency Chlorpromazine Clozapine Molindone Moperone Haloperidol Pimozide Spiperone Many others can be imserted in the list.
33	Drug Side Effects Include Autonomic problems (dry mouth) Skin-eye pigmentation Breast development Tardive dyskinesia: facial tics and gestures Others Side effects cause people to stop their medications.
34	Conclusion Severe disorder Most people can be treated effectively Many people stop taking their medications Revolving door syndrome Future, work on decreasing drug side effects Examine the genetics associated underlying the disorder.