2. Schizophrenia and Other Psychotic Disorders Anita S. Kablinger MD Associate Professor Departments of Psychiatry of Pharmacology LSUHSC-Shreveport

3. What is Psychosis? Generic term “Break with Reality” Symptom, not an illness Caused by a variety of conditions that affect the functioning of the brain. Includes hallucinations, delusions and thought disorder

4. Differential Diagnosis Medical/surgical/ substance-induced Psychotic d/o due to GMC Dementias Delirium Medications Substance induced Amphetamines Cocaine Withdrawal states Hallucinogens Alcohol Mood disorders Bipolar disorder Major depression with psychotic features

5. PSYCHOSISPSYCHOSIS Mood disorders Schizophrenia “spectrum” disorders “organic” mental disorders Substance induced Delirium Dementia Amnestic d/o “Functional” disorders

6. Differential Diagnoses: (Cont) Personality disorders Schizoid Schizotypal Paranoid Borderline Antisocial Miscellaneous PTSD Dissociative disorders Malingering Culturally specific phenomena: Religious experiences Meditative states Belief in UFO’s, etc

7. Workup of New-Onset Psychosis: “Round up the usual suspects” Good clinical history Physical exam, ROS Labs/Diagnostic tests: Metabolic panel CBC with diff B12, Folate RPR, VDRL Serum Alcohol Urinalysis Thyroid profile URINE DRUG SCREEN!!! CSF/LP HIV serology CT or MRI EEG

8. Talking Points Schizophrenia is not an excess of dopamine. The differentiation between “functional” and “organic” is artificial. Schizophrenia and other psychiatric illnesses are syndromes. Schizophrenia is a diagnosis of exclusion.

9. Talking Points 1% prevalence Early onset, M>F Early, aggressive treatment decreases long-term problems Multiple subtypes- catatonic, disorganized, paranoid, undifferentiated, residual

10. Schizophrenia Diagnostic features

11. DSM-IV Diagnosis of Schizophrenia Psychotic symptoms (2 or more) for at least one month Hallucinations Delusions Disorganized speech Disorganized or catatonic behavior Negative symptoms

12. Diagnosis (cont.) Impairment in social or occupational functioning Duration of illness at least 6 mo. Symptoms not due to mood disorder or schizoaffective disorder Symptoms not due to medical, neurological, or substance-induced disorder

13. Clinical features: Formal Thought Disorders Neologisms Tangentiality Derailment Loosening of associations (word salad) Private word usage Perseveration Nonsequitors

14. Clinical features: Delusions Paranoid/persecutory Ideas of reference External locus of control Thought broadcasting Thought insertion, withdrawal Jealousy Guilt Grandiosity Religious delusions Somatic delusions

15. Clinical features: Hallucinations Auditory Visual Olfactory Somatic/tactile Gustatory

16. Clinical features: Behavior Bizarre dress, appearance Catatonia Poor impulse control Anger, agitation Stereotypies

17. Clinical features: Mood and Affect Inappropriate affect Blunting of affect/mood Flat affect Isolation or dissociation of affect Incongruent affect

18. Positive vs. negative symptoms Positive symptoms Delusions Hallucinations Behavioral dyscontrol Thought disorder Negative symptoms (Remember Andreasen’s “A”s) Affective flattening Alogia Avolition Anhedonia Attentional impairment

19. Psychotic Disorders Schizo- phrenia Usually insidious ManyChronic>6 months Delusional disorder Varies (usually insidious) Delusions only Chronic>1 mo. Brief psychotic disorder SuddenVariesLimited<1 mo. Onset SymptomsCourseDuration

20. Psychosocial Factors Expressed emotion Stressful life events Low socioeconomic class Limited social network

21. Some factors rejected as causal “Schizophrenogenic Mother” “Skewed” family structure

22. Genetic factors: (The evidence mounts…) Monozygotic twins (31%-78%) vs dizygotic twins 4-9% risk in first degree relatives of schizophrenics Adoption studies Linkage, molecular studies

23. Genetics of Schizophrenia: The take-home message Vulnerability to schizophrenia is likely inherited “Heritability” is probably 60-90% Schizophrenia probably involves dysfunction of many genes

24. Anatomical abnormalities Enlargement of lateral ventricles Smaller than normal total brain volume Cortical atrophy Widening of third ventricle Smaller hippocampus

25. Physiologic studies: PET and SPECT Generally normal global cerebral flow Hypofrontality Failure to activate dorsolateral prefrontal cortex (problem-solving, adaptation, coping with changes)

26. Biochemical factors: The dopamine hypothesis All typical antipsychotics block D 2 with varying affinities Dopamine agonists can precipitate a psychosis Amphetamines Cocaine L-dopa

27. Dopamine systems Nigro- striatal Substantia Nigra Caudate and putamen Move- ment Extrapyramidal symptoms, dystonias, Tardive dyskinesia Meso- limbic Ventral tegmental area, subst. nigra Accumbens amygdala Olfactory tubercle Emotions, affect, memory Positive symptoms Meso- cortical Ventral tegmental area Prefrontal Cortex Thought, volition, memory Blockade here can worsen negative symptoms. Cell bodiesProjections Functions Clinical implications

28. Typical Neuroleptics Low potency: Chlorpromazine Thioridazine Mesoridazine High potency: Haloperidol Fluphenazine Thiothixene Loxapine (mid)

29. Neuroleptic (typicals): side effects Acute dystonia Parkinsonian side effects (EPS) Akathisia Tardive dyskinesia Sedation, orthostasis, QTC prolongation, anticholinergic, lower seizure threshold, increased prolactin

30. Atypical Antipsychotics: Risperidone Olanzapine Quetiapine Clozapine Ziprasidone Aripiprazole (new-partial DA agonist)

31. Atypical antipsychotics: Broader spectrum of receptor activity (Serotonin, dopamine, GABA) May be better at alleviating negative symptoms and cognitive dysfunction Clozaril (clozapine) associated with agranulocytosis, seizures

32. Atypical Antipsychotics: Side Effects Sedation Hyperglycemia, new-onset diabetes Anticholinergic effects Less prolactin elevation QTC prolongation Some EPS Increased lipids

33. Psychosocial Treatment Education, compliance #1 Hospitalize for acute loss of functioning Outpatient treatment is rehabilitative Psychoanalysis, exploratory therapies have limited value Families should be involved