Back to Basics: Psychotic Spectrum Disorders

1. Back to Basics: Psychotic Spectrum Disorders Sharman Robertson Bsc MD FRCPC

2. Format: Summary of Kaplan and Sadock’s “ Synopsis of Psychiatry” • Schizophrenia • Other Psychotic Disorders • Schizophreniform disorder • Brief psychotic disorder • Schizoaffective disorder • Delusional disorder • Psychosis NOS

3. Schizophrenia: Epidemiology • Lifetime prevalence 1% • Annual incidence 0.5-5/10,000 • Male = female • Disproportionate number in low SES in industrialized nations • Onset • males 10- 25 years, mean=21 years • females 25-35 years, mean=27 years

4. Epidemiology (Cont.) • Fertility rates close to that of general population • 80% have significant concurrent medical illness and only 50% of this is diagnosed • >75% smoke • Suicide is leading cause of mortality 15% success rate

5. Epidemiology (Cont.) • Incidence and prevalence roughly similar world-wide • Substance use • 30-50% alcohol dependence • Cannabis dependence 15-25% • Cocaine dependence 5-10%

6. Etiology • Likely not single illness, but group of disorders with heterogeneous causes • Patients show a range of presentations, response to treatment and outcomes • Stress-diathesis model: • Diathesis or vulnerability is acted on by stressful event resulting in production of the illness

7. Neurobiology • Dysfunction in one area can lead to dysfunction in interconnected area • Limbic system-may be primary site of pathology • Frontal cortex:impaired abstraction • Basal ganglia : abnormal involuntary mvts • Cerebellum : cognitive dysmetria

9. Neurobiology (Cont.) • ? Abnormal cell migration along radial glial cells during embryo-genesis • Hippocampal pyramidal cell disarray • ? Early pre-programmed cell death • Loss of associative neuron axons and dendrites ->decreased brain volume • Environment plays part as evidenced by only 50% concordance rate in MZ twins

10. Neuroanatomy • Limbic system: • Decreased size of amygdala, hippocampus, parahippocampal gyrus on MRI • Basal ganglia and cerebellum: • 25% of drug naïve patients have abnormal involuntary movements • Huntington’s associated with basal ganglia pathology, psychosis and AIM

11. Neuroanatomy • CT scan evidence of • Increased size of lateral and third ventricles • Decreased cortical, cerebellar volume • More negative symptoms, soft neurological signs, increased EPS with meds, poor premorbid adjustment if CT scan shows abnormalities

12. Neurochemistry; Dopamine • Dopamine (DA) hypothesis: • Over-activity of DA in certain brain areas ie mesolimbic and mesocortical areas • Evidence: • Efficacy of DA blocking medications • Psychotomimetic effect of stimulants • ? Too much DA release, too many DA receptors • DA levels actually low in prefrontal cortex

13. Serotonin • 5HT-2 blockade reduces psychotic symptoms and prevents movement D/O’s caused by D2 blockade • Second generation anti-psychotics (SGA’s) have potent 5HT-2 blockade ie: • Risperidone, olanzapine, seroquel • Older: clozapine

14. Norepinephrine (NE) • Long term anti-psychotic use  decreased activity in alpha-1 and alpha-2 receptors in locus ceruleus • NA system modulates DA system • ? NA system abnormalities may affect relapse rate

15. GABA,Glutamate, CCK, Neurotensin • Loss of inhibitory GABA-ergic cells in hippocampus  hyperactivity of DA and NA neurons • Several hypotheses; hyperactivity, hypoactivity, glutamate-induced neurotoxicity linked with schizophrenia • CCK and neurotensin levels altered in psychosis

16. Eye Movement Disorders • Frontal eye fields implicated • Patients and unaffected relatives have disorders of smooth visual pursuit and disinhibition of saccades • ? Trait marker for schizophrenia independent of treatment and clinical state

17. ? Viral • Most controlled neuro-immunological studies do not support this • No genetic evidence of viral infection • Circumstantial evidence: • More physical anomalies at birth • More winter/late-spring births • geographical clusters of adult cases • 2nd trimester influenza exposure

18. Other Theories • Immunological abnormalities: • Some data support auto-immune brain anti-bodies in a subset of schizophrenia • Neuro-endocrine abnormalities: • Blunted release of GH and PRL following GnRH or TRH stimulation • Decreased LH/FSH concentrations

19. Other Theories • Genetic factors: • 50% concordance in MZ twins • 40% if both parents have schizophrenia • 10% if DZ twin or other first degree relative • Multiple chromosomal sites support polygenic origin of schizophrenia

20. Emil Kraeplin: Dementia Praecox • One of first to characterize a psychotic illness separate from BAD; • Early onset • Chronic deteriorating course • Primary sx delusions and hallucinations • Cognitive impairment • Not clearly episodic as was BAD

21. Eugen Bleuler: Schizophrenia • Schizophrenia = split-mind • Split between thought, emotion and behavior • Not necessarily deteriorating • Most important symptoms4 A’s: autism, affective flattening, ambivalence, associations loose • Accessory symptoms: hallucinations and delusions

22. Kurt Schneider • First rank symptoms: • Audible thoughts • Voices commenting • Voices arguing, discussing • Somatic passivity • Thought broadcasting, insertion and withdrawal • Delusional perceptions • Volitional problems: made affect and impulses

23. Second Rank Symptoms • Sudden delusional thoughts • Perceptual disturbances • Perplexity • Depressive and euphoric feelings • Emotional impoverishment

24. DSMIV Diagnosis of Schizophrenia • A Criteria: two or more during a significant portion of one month (less if successfully treated) • 1) delusions • 2) hallucinations • 3) disorganized speech • 4) grossly disorganized or catatonic behavior • 5) negative symptoms (affective flattening, alogia, avolition)

25. DSMIV Diagnosis of Schizophrenia • Only one A criterion needed if delusions are bizarre or hallucinations are of a running commentary or voices conversing with each other • B: Social/ Occupational Dysfunction

26. DSMIV Diagnosis of Schizophrenia • C: continuous signs of the disturbance for >= 6 months, prodromal, active, residual symptoms • D: not due to mood disorder or schizoaffective disorder (mood symptoms are brief relative to duration of active and residual symptoms) • E: not due to substance or general medical condition • F: if PDD is present must have clear cut delusions and hallucinations for one month

27. Subtypes of Schizophrenia • Paranoid • Disorganized • Catatonic • Undifferentiated • Residual • Based on clinical presentation • NOT closely correlated with different prognoses

28. Paranoid • Preoccupation with one encapsulated delusional system or auditory hallucinations • Delusional content = persecution or grandeur • Later onset than catatonic or disorganized • Less impairment of emotional responses, and behavior • Later onset usually means established social life and supports, better coping skills

29. Disorganized (Hebephrenic) • Primitive, disorganized, disinhibited, vague, aimless behavior • Onset <25 years • Pronounced thought disorder • Poor reality contact • Poor self-care • Inappropriate affect, grimacing

30. Catatonic • Relatively rare • Marked disturbance of motor functioning • Require supervision to prevent physical harm to self or others, exhaustion, hyperpyrexia • Stupor, mutism • Rigidity • Waxy flexibility, stereotypies, mannerisms • Posturing • Stupor alternating with agitation

31. Undifferentiated • Not clearly fitting any other single type of schizophrenia • Residual Type: • Schizophrenia is still evident, but patient does not meet full A criteria or specific subtype • Cognitive impairments common • Attenuated and negative symptoms

32. Clinical Picture • No one symptom is pathognomonic of schizophrenia, symptoms can change with time • Must take signs and symptoms as part of patient’s context: • IQ and developmental level • Culture • Educational level

33. Positive Symptoms • Delusions: Firm, fixed, false beliefs • Paranoid • Grandiose • Religious • Somatic • Referential • Pseudo-philosophical • Control

34. Positive Symptoms • Hallucinations: sensory perceptions in absence of external stimuli • Auditory (most frequent) • Visual • Cenesthetic • Olfactory* • Gustatory* • * ? metabolic or neurological causes • Less association with CT abnormalities, better response to treatment

35. Negative Symptoms (Deficit Symptoms) • Affective flattening, blunting • Alogia: poverty of rate or content of speech • Thought blocking • Autism • Ambivalence

36. Negative Symptoms (Deficit Symptoms) • Anhedonia-asociality • Avolition-apathy • Poor self-care • Inattention • Associated with CT abnormalities, less treatment responsiveness

37. Disturbances of Affect/Mood • Reduced emotional responsiveness • Unregulated, inappropriate emotional discharge: • Terror, rage • Anxiety, depression • Perplexity • Happiness, euphoria, ecstasy

38. Thought Disorders • Core symptoms of schizophrenia • Thought content • Thought form • Thought process • Visible in speech and written language

39. Thought Content • Overvalued ideas • Delusions • Loss of ego boundaries ie where patients own body, mind and influence begin and where those of other animate and inanimate objects begin

40. Loosening of associations Derailment Circumstantiality Tangientiality Neologisms Word salad Echolalia Mutism Clanging Verbigeration Incoherence Thought Form

41. Flight of ideas Though blocking Prolonged response latency Inattention Perseveration Impaired abstraction Over-inclusion Though Process

42. Violence • Rates of violence in schizophrenia are higher than rates in the general public • Risk factors act synergistically; • Untreated • Active substance use • Active alcohol use • Past history of violence • Persecutory or erotomanic delusions • Neurological deficits

43. Suicide • 50% attempt • 10-15% succeed • Risk factors: • Undiagnosed depression • Command auditory hallucinations • Need to escape symptoms • Young, male, well educated, awareness of losses, living alone

44. Differential Diagnosis • Substance intoxication or withdrawal • Cocaine, amphetamines, ecstasy, LSD, PCP, anabolic steroids • Alcohol, benzodiazepine, barbiturate, GHB withdrawal • Prescription medications: L-dopa, steroids, anti-retrovirals, anti-tubercular agents

45. General Medical Conditions • Neurological: • Epilepsy, esp. TLE • Neoplasm • Trauma to frontal or limbic areas • Wernike-Korsakoff’s • Infectious: • HIV, neurosyphilis, CJD, herpes encephalitis

46. General Medical Conditions • Metabolic: • Hyper/hypothyroidism, hyper/hypoparathyroidism • Acute intermittent porphyria • Homocystinuria • Wilson’s disease • Auto-immune: • SLE • Cerebral lipoidosis

47. General Medical Conditions • Poisoning: • Heavy metals • CO • Solvents • Nutritional: • B12, folate deficiency

48. Psychiatric Illness • Mood: • BAD • Major Depression with psychotic features • Schizoaffective disorder • Psychotic Spectrum Disorders: • Delusional disorder • Brief psychotic disorder • Schizophreniform disorder

49. Psychiatric Disorders • Personality Disorders: • Paranoid PD • Schizotypal PD • Schizoid PD • Anxiety Disorders: • OCD • Panic disorder

50. Psychiatric Disorders • Pervasive developmental disorders: • Asperger’s disorder • Infantile autism • Factitious disorder • Malingering ($ or legal gain)