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Neurobiological Factors in Schizophrenia

Neurobiological Factors in Schizophrenia. Overview. Definition of Schizophrenia: Clinical Features Component Symptoms Endophenotype testing Mechanisms Etiology of Schizophrenia: Current Evidence GABA control of network function Dopamine Hypothesis NMDA/Network Hypothesis

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Neurobiological Factors in Schizophrenia

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  1. Neurobiological Factors in Schizophrenia

  2. Overview • Definition of Schizophrenia: Clinical Features • Component Symptoms • Endophenotype testing • Mechanisms • Etiology of Schizophrenia: Current Evidence • GABA control of network function • Dopamine Hypothesis • NMDA/Network Hypothesis • Genetic and Environmental Factors

  3. According to data from the NIMH Epidemiological Catchment Area study, the lifetime prevalence of schizophrenia is: • A. 0.01%. • B. 0.1%. • C. 1%. • D. 5%.E. 10%

  4. According to data from the NIMH Epidemiological Catchment Area study, the lifetime prevalence of schizophrenia is: • A. 0.01%. • B. 0.1%. • C. 1%. • D. 5%.E. 10%

  5. Which of the following specific populations has the highest prevalence of schizophrenia? • a. Child with one schizophrenic parent • b. Non-twin sibling of a schizophrenic patient • c. Monozygotic twin of a schizophrenic patient • d. Child of two schizophrenic parents • e. Dizygotic twin of a schizophrenic patient

  6. Which of the following specific populations has the highest prevalence of schizophrenia? • a. Child with one schizophrenic parent • b. Non-twin sibling of a schizophrenic patient • c. Monozygotic twin of a schizophrenic patient • d. Child of two schizophrenic parents • e. Dizygotic twin of a schizophrenic patient

  7. NIMH Schizophrenia afflicts 1% of the general population 10% of people with an immediate family member with the disorder will also develop the disorder Someone with an identical twin with the disorder has a 40-65% chance of developing the disorder

  8. The most common eye-tracking movement abnormality in patients withschizophrenia is • inaccurate saccades (hypermetric or hypometric). • impaired initiation of saccades (ocular apraxia). • inappropriate saccades (saccadic intrusions). • impersistence of gaze (large amplitude saccadic intrusions). • abnormal saccadic velocity (slow saccades).

  9. The most common eye-tracking movement abnormality in patients withschizophrenia is • inaccurate saccades (hypermetric or hypometric). • impaired initiation of saccades (ocular apraxia). • inappropriate saccades (saccadic intrusions). • impersistence of gaze (large amplitude saccadic intrusions). • abnormal saccadic velocity (slow saccades).

  10. Which of the following features is associated with a poor prognosis in patients with schizophrenia? • a. Positive symptoms • b. Married • c. Early age onset • d. Precipitating factors • e. Family history of bipolar disorder

  11. Which of the following features is associated with a poor prognosis in patients with schizophrenia? • a. Positive symptoms • b. Married • c. Early age onset • d. Precipitating factors • e. Family history of bipolar disorder

  12. Which of the following is NOT a likely characteristic of childhood-onset schizophrenia? • a. Chronic course • b. Unfavorable prognosis • c. Acute onset • d. Hallucinations • e. Delusions

  13. Which of the following is NOT a likely characteristic of childhood-onset schizophrenia? • a. Chronic course • b. Unfavorable prognosis • c. Acute onset • d. Hallucinations • e. Delusions

  14. Clinical Components of Schizophrenia:Symptom Types • Positive • Negative • Cognitive • Delusions • Halucinations • Thought Disorder • Flat Affect • Poverty of Thought • Loss of Motivation • Social Withdrawal • Distractability • Impaired Working Memory • Disruption of Executive Function

  15. Early-Onset Schizophrenia: Positive Symptoms: • Hallucinations • Delusions • Disorganized Speech • Disorganized or catatonic behavior Negative Symptoms: • Flattened affect • Anergia (lack of energy) • Alogia (complete lack of speech) • Avolition (lack of motivation) • Social withdrawal Cognitive Symptoms: • Borderline mental retardation

  16. Which of the following features characterizes patients with schizophrenia who smoke cigarettes? • Lower incidence of positive symptoms • Less vulnerable to tardive dyskinesia • Require more antidepressant medication • Require more neuroleptic medication • Require more depot neuroleptic medication

  17. Which of the following features characterizes patients with schizophrenia who smoke cigarettes? • Lower incidence of positive symptoms • Less vulnerable to tardive dyskinesia • Require more antidepressant medication • Require more neuroleptic medication • Require more depot neuroleptic medication

  18. A patient who is being treated for schizophrenia has improved and stabilized on haloperidol 10 mg per day. The patient develops acute extrapyramidal symptoms. Which of the following events is the most likely cause? • a. Use of a hallucinogen • b. Cessation of smoking • c. Addition of phenobarbital • d. Addition of phenytoin • e. Discontinuation of paroxetine

  19. A patient who is being treated for schizophrenia has improved and stabilized on haloperidol 10 mg per day. The patient develops acute extrapyramidal symptoms. Which of the following events is the most likely cause? • a. Use of a hallucinogen • b. Cessation of smoking • c. Addition of phenobarbital • d. Addition of phenytoin • e. Discontinuation of paroxetine

  20. A patient with schizophrenia has had a poor response to three adequate trials of antipsychotic medications. The next therapeutic strategy to use includes: • a. the addition of paroxetine. • b. the addition of diazepam. • c. a crossover to depot haloperidol. • d. the addition of carbamazepine. • e. a crossover to clozapine.

  21. A patient with schizophrenia has had a poor response to three adequate trials of antipsychotic medications. The next therapeutic strategy to use includes: • a. the addition of paroxetine. • b. the addition of diazepam. • c. a crossover to depot haloperidol. • d. the addition of carbamazepine. • e. a crossover to clozapine.

  22. A patient who is being treated for schizophrenia has improved and stabilized on haloperidol 10 mg per day. The patient develops a return of characteristic psychotic symptoms following the addition of a medication for another condition. Which of the following medications is the most likely cause? • a. Atenolol • b. Efavirenz • c. Doxycycline • d. Carbamazepine • e. Pravastatin

  23. A patient who is being treated for schizophrenia has improved and stabilized on haloperidol 10 mg per day. The patient develops a return of characteristic psychotic symptoms following the addition of a medication for another condition. Which of the following medications is the most likely cause? • a. Atenolol • b. Efavirenz • c. Doxycycline • d. Carbamazepine • e. Pravastatin

  24. Testing For Schizophrenia: Endophenotypes

  25. Network dysfunction in schizophrenia

  26. Fletcher and Frith. Nature Reviews Neuroscience, 2009

  27. Brain Activity Changes in Schizophrenia: Importance of the Prefrontal Cortex

  28. White Matter Tract Disruption in Schizophrenia Cortical Connectivity Regional Connectivity

  29. Abnormal Network Synchrony in Schizophrenic Patients Esslinger et al. Science 2009

  30. Fletcher and Frith. Nature Reviews Neuroscience, 2009

  31. How might there be altered connectivity in schizophrenia? Investigations of networks

  32. Networks Disrupted in Schizophrenia Cognitive Deficits, Delusional Thinking, Impaired Executive Function Sensory-Motor Gating, Hallucinations Salience Detection, Distractability Memory Deficit, False Memories

  33. Possible Mechanism of Network Disruption after Loss of Normal Function in Interneurons

  34. Changes in markers of GABAergic Interneurons in Schizophrenia

  35. Changes in marker of GABAergicInterneurons in Schizophrenia

  36. Local Cortical Network Disruption in Schizophrenia

  37. Dopamine Hypothesis of Schizophrenia: Methods of Treatment

  38. Actions of Dopamine on PFC Function

  39. Possible Mechanisms For the Involvement of Dopamine in Schizophrenia

  40. The NMDA Hypothesis of Schizophrenia: Psychotomimetic Drugs • PCP, a noncompetative NMDAR antagonist, produces symptoms similar to Schizophrenia

  41. Structure of the NMDA receptor

  42. Changes in Network Activity Associated with NMDA Receptor Antagonists

  43. Chronic Application of NMDAR Antagonists Recapitulates Interneuronal Changes Seen in Schizophrenia Cortical Parvalbumin Positive Structures

  44. Schizophrenia is a developmental disorder Early detection of mutations and modulation of dysfunctional circuits during critical period may be the optimal treatment

  45. Susceptibility Genes in Schizophrenia

  46. Schizophrenia: Many Targets, Few Treatments

  47. Abnormal Trafficking of NMDA Receptors In Schizophrenia

  48. Mutations in Dysbindin Gene Are Linked to Increase in Incidence of Schizophrenia

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