Schizophrenia and Other Psychotic Disorders Anita S. Kablinger MD Associate Professor Departments of Psychiatry of Pharmacology LSUHSC-Shreveport 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 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 Mood disorders “Functional” disorders Schizophrenia “spectrum” disorders P S Y C H O S I S Substance induced Delirium Dementia Amnestic d/o “organic” mental disorders 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 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 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. Talking Points 1% prevalence Early onset, M>F Early, aggressive treatment decreases long-term problems Multiple subtypes- catatonic, disorganized, paranoid, undifferentiated, residual Schizophrenia Diagnostic features 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 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 Clinical features: Formal Thought Disorders Neologisms Tangentiality Derailment Loosening of associations (word salad) Private word usage Perseveration Nonsequitors Clinical features: Delusions Paranoid/persecutory Ideas of reference External locus of control Thought broadcasting Thought insertion, withdrawal Jealousy Guilt Grandiosity Religious delusions Somatic delusions Clinical features: Hallucinations Auditory Visual Olfactory Somatic/tactile Gustatory Clinical features: Behavior Bizarre dress, appearance Catatonia Poor impulse control Anger, agitation Stereotypies Clinical features: Mood and Affect Inappropriate affect Blunting of affect/mood Flat affect Isolation or dissociation of affect Incongruent affect 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 Psychotic Disorders Onset Schizophrenia Usually insidious Delusional disorder Brief psychotic disorder Symptoms Many Course Duration Chronic >6 months Varies Delusions (usually only insidious) Chronic >1 mo. Sudden Limited <1 mo. Varies Psychosocial Factors Expressed emotion Stressful life events Low socioeconomic class Limited social network Some factors rejected as causal “Schizophrenogenic Mother” “Skewed” family structure 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 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 Anatomical abnormalities Enlargement of lateral ventricles Smaller than normal total brain volume Cortical atrophy Widening of third ventricle Smaller hippocampus Physiologic studies: PET and SPECT Generally normal global cerebral flow Hypofrontality Failure to activate dorsolateral prefrontal cortex (problem-solving, adaptation, coping with changes) Biochemical factors: The dopamine hypothesis All typical antipsychotics block D2 with varying affinities Dopamine agonists can precipitate a psychosis Amphetamines Cocaine L-dopa Dopamine systems Cell bodies Projections Functions Clinical implications Nigrostriatal Mesolimbic Substantia Nigra Caudate and putamen Movement Extrapyramidal symptoms, dystonias, Tardive dyskinesia Ventral tegmental area, subst. nigra Accumbens amygdala Olfactory tubercle Emotions, affect, memory Positive symptoms Mesocortical Ventral tegmental area Prefrontal Cortex Thought, volition, memory Blockade here can worsen negative symptoms. Typical Neuroleptics Low potency: Chlorpromazine Thioridazine Mesoridazine High potency: Haloperidol Fluphenazine Thiothixene Loxapine (mid) Neuroleptic (typicals): side effects Acute dystonia Parkinsonian side effects (EPS) Akathisia Tardive dyskinesia Sedation, orthostasis, QTC prolongation, anticholinergic, lower seizure threshold, increased prolactin Atypical Antipsychotics: Risperidone Olanzapine Quetiapine Clozapine Ziprasidone Aripiprazole (new-partial DA agonist) 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 Atypical Antipsychotics: Side Effects Sedation Hyperglycemia, new-onset diabetes Anticholinergic effects Less prolactin elevation QTC prolongation Some EPS Increased lipids 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