Back to Basics: Psychotic Spectrum Disorders

Sharman Robertson Bsc MD FRCPC

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

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

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

Epidemiology (Cont.)

• Incidence and prevalence roughly similar world-wide

• Substance use• 30-50% alcohol dependence• Cannabis dependence 15-25%• Cocaine dependence 5-10%

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

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

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

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

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

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

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

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

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

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

? 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

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

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

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

Eugen Bleuler: Schizophrenia

• Schizophrenia = split-mind• Split between thought, emotion and

behavior• Not necessarily deteriorating• Most important symptoms

4 A’s: autism, affective flattening, ambivalence, associations loose

• Accessory symptoms: hallucinations and delusions

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

Second Rank Symptoms

• Sudden delusional thoughts• Perceptual disturbances• Perplexity• Depressive and euphoric feelings• Emotional impoverishment

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)

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

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

Subtypes of Schizophrenia

• Paranoid• Disorganized• Catatonic• Undifferentiated• Residual

• Based on clinical presentation• NOT closely correlated with different

prognoses

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

Disorganized (Hebephrenic)

• Primitive, disorganized, disinhibited, vague, aimless behavior

• Onset <25 years• Pronounced thought disorder• Poor reality contact• Poor self-care• Inappropriate affect, grimacing

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

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

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

Positive Symptoms

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

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

Negative Symptoms (Deficit Symptoms)

• Affective flattening, blunting • Alogia: poverty of rate or content

of speech • Thought blocking• Autism• Ambivalence

Negative Symptoms (Deficit Symptoms)

• Anhedonia-asociality• Avolition-apathy• Poor self-care• Inattention• Associated with CT abnormalities,

less treatment responsiveness

Disturbances of Affect/Mood

• Reduced emotional responsiveness• Unregulated, inappropriate

emotional discharge:• Terror, rage• Anxiety, depression• Perplexity• Happiness, euphoria, ecstasy

Thought Disorders

• Core symptoms of schizophrenia• Thought content• Thought form• Thought process

• Visible in speech and written language

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

Thought Form

• Loosening of associations

• Derailment• Circumstantiality• Tangientiality• Neologisms• Word salad• Echolalia

• Mutism• Clanging• Verbigeration• Incoherence

Though Process

• Flight of ideas• Though blocking• Prolonged

response latency• Inattention• Perseveration• Impaired

abstraction

• Over-inclusion

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

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

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

General Medical Conditions

• Neurological:• Epilepsy, esp. TLE• Neoplasm• Trauma to frontal or limbic areas• Wernike-Korsakoff’s

• Infectious:• HIV, neurosyphilis, CJD, herpes

encephalitis

General Medical Conditions

• Metabolic:• Hyper/hypothyroidism,

hyper/hypoparathyroidism• Acute intermittent porphyria• Homocystinuria • Wilson’s disease

• Auto-immune:• SLE• Cerebral lipoidosis

General Medical Conditions

• Poisoning:• Heavy metals• CO• Solvents

• Nutritional:• B12, folate deficiency

Psychiatric Illness

• Mood:• BAD• Major Depression with psychotic

features• Schizoaffective disorder

• Psychotic Spectrum Disorders:• Delusional disorder• Brief psychotic disorder• Schizophreniform disorder

Psychiatric Disorders

• Personality Disorders:• Paranoid PD• Schizotypal PD• Schizoid PD

• Anxiety Disorders:• OCD• Panic disorder

Psychiatric Disorders

• Pervasive developmental disorders:• Asperger’s disorder• Infantile autism

• Factitious disorder• Malingering ($ or legal gain)

Course

• Prodrome• Active Phase: active positive and

negative symptoms• Residual Phase: attenuated

positive symptoms and negative symptoms

Prodrome

• Lead in to schizophrenia• Marked by variable symptoms:

• Depression, anxiety, conduct disorder symptoms, confusion, substance and alcohol misuse, attenuated positive symptoms, negative symptoms, cognitive impairment

• May last a year or more• Onset adolescence usually• Often difficult to determine due to poor

specificity

Course

• First episode:• Duration of untreated psychosis

associated with worse outcome• Associated with greatest potential for

full recovery to baseline• Treat early and aggressively with

multi-modal approach• Pattern of illness during the first 5

years indicates course

Course

• Relapses:• Harder to treat• Longer duration• Less responsive to medication• Less likely to return to baseline

Prognosis

• Lifelong vulnerability to illness• Episodes of active psychosis• Residual symptoms• Cognitive impairment and negative

symptoms:• Longest lasting, most difficult to treat

• Failure to return to baseline demarcates schizophrenia from mood disorders

Prognosis

• Twelve month relapse rates;• No medication: 75%• Medication: 15-25%

• 1/3 able to lead relatively normal lives• 1/3 moderate symptoms• 1/3 deteriorating course• 25% of this population are drug resistant• 50% of drug resistant respond well to

clozapine

Good Prognositic Signs

-Late onset-Obvious

precipitating factors

-Acute onset-Good pre-morbid

social, academic, work function

-Mood sx-Married

• Family hx mood disorder

• Good supports• Positive

symptoms

Poor Prognostic Signs

• Early onset• No precipitant• Insidious onset• Poor premorbid

function• Withdrawn, autistic

behavior• Single, divorced,

widowed• assaultiveness

• Family hx schizophrenia

• Poor support systems

• Negative symptoms• Neurological S+Sx• Perinatal trauma• No remission in 3

years• Many relapses

Assessment

• Assessment of predisposing, precipitating, perpetuating and protective factors:• Genetic: family medical and psychiatric hx• General medical conditions eg head injury, seizure

disorder• Substance misuse• Learning disorders• Perinatal illness, trauma• Psychological trauma, abuse• Legal problems• Past psychiatric history • Supports, strengths

Assessment

• Physical with full neurological exam• CBC, lytes, BUN, Cr, AST, ALT, Ca,

PO4, TSH, B12, folate, fasting glucose and lipid profile

• Urinalysis and drug screen• EKG• EEG +/- CT, MRI

Treatment

• Patient and family psychoeducation:• Definition of schizophrenia• Provision of information and available

supports• Schizophrenia society• Reading materials

Treatment

• Group and individual therapy:• Social skills training• Vocational rehabilitation• Supportive therapy• Managing anxiety groups• CBT• Family therapy

• Supervised living, Case management, ACTT

Pharmacology

• Dopamine receptor antagonists:• Older classes of medications• Extra pyramidal symptoms

• Tremor, parkinsonism, rigidity, akathesia

• TD, NMS• Work well on positive symptoms• May cause negative symptoms in

higher dose

Dopamine Receptor Antagonists

• Haloperidol• Zuclopenthixol• Fluanxol• Perphenazine• Loxapine• Methotrimeprazin

e• Chlorpromazine

• Low potency meds have more sedative, anticholinergic and alpha blocking properties

• Higher potency drugs have higher rates of EPS and TD

5HT/DA Blocking Drugs, Second Generation Antipsychotics, Atypicals

• As effective on positive symptoms as first generation antipsychotics

• Perhaps superior on negative symptoms

• Less potential for EPS, TD, NMS (although it can occur)

• More potential for endocrinological illness:• Obesity, DM, Dyslipidemia, CVS disease

Atypical Antipsychotics

• Clozapine• Risperidone• Olanzapine• Quetiapine • Ziprasidone (USA)• Aripiprazole (USA)

• Some evidence points to neuroprotective effects and cognitive enhancement

Treatment

• Acute phase, emergency:• Safety-suicide, aggression• Use intra-muscular antipsychotics

(haldol, olanzapine) and benzodiazepines

• Watch for EPS and have cogentin available

• May need restraints• Have staff available

Treatment

• Acute, non-emergent:• Choose medication based on:

• Past response• Side effect profile• Patient preference• Route• Cost• Availablity

Antipsychotic selection

• Usually choose second generation ie risperidone, seroquel, olanzapine based on side effects and patient characteristics:• ? Obese, family hx DM, Obesity CVS

disease olanzapine not first choice• ? sexual dysfunction, menstrual

irregularity risperidone not first choice

Antipsychotic Trials

• Define target symptoms• Try mono therapy first• Trial length = 4-6 weeks at adequate

dosage• Usually start with SGA• If medication ineffective or SE’s present

switch to another SGA• Use lowest possible dose• Higher doses needed in acute phase and

may be lowered in maintenance

Brief Psychotic Disorder

• Acute, transient psychotic disorder• 1 day- < 1 month• Symptoms may resemble schizophrenia

with delusions and hallucinations• May develop in response to a traumatic

stressor• Symptoms often reflect stressful event

Brief Psychotic Disorder

• Temporal relationship to the trauma • Usually benign course, eventual return

to baseline function• Uncommon • Pts in 20’s and 30’s• ? More in women and lower SES• Often seen in patients with histrionic,

narcissistic, borderline, paranoid, schizotypal PD

Brief Psychotic Disorder

• Similar to “Bouffee Delirante”• Emotional lability, confusion,

inattention more common• Rule out delirium• 50% go on to have a mood disorder

or schizophrenia• 50-80% will not have further

problems

Brief Psychotic Disorder

• Not due to:• Schizophrenia• Schizoaffective disorder• Mood disorder• A general medical condition• Substance abuse, intoxication or

withdrawal• Treat with antipsychotics and

benzos

Schizophreniform Disorder

• Duration >= 1 month < 6 months• Similar to schizophrenia• Less than half as common as

schizophrenia • 0.2% lifetime prevalence

Schizophreniform Disorder

• Usually young adults• Family members more likely to

have mood disorders• Better outcome than schizophrenia• More affective symptoms• Episodic presentation like mood

disorders

Clinical Presentation

• Rapid onset, no prodrome• Delusions, hallucinations, negative

symptoms-similar to schizophrenia• Prodrome, active and residual

phases last at least one month but less than 6 months

• Patient is back to baseline by 6 months

• 60-80% progress to schizophrenia

Treatment

• May respond to treatment more rapidly

• May need to use mood stabilizer if mood component and recurrence are an issue

• Treat as for schizophrenia

Schizoaffective Disorder

• Has features of both schizophrenia and affective disorders

• 0.5-0.8% lifetime prevalence• ? Bipolar type more common in

younger patients and depressive type more common in older

• F>M

Schizoaffective Disorder

• Etiology unknown• Heterogeneous group:

• ? Related to mood disorders• ? Related to schizophrenia• ? An entity unto itself• ? All of these

• Difficult diagnosis to make as require temporal course

• Bipolar type, depressive types possible • Prognosis intermediate to schizophrenia and

mood disorders

Schizoaffective Disorder: Clinical

Picture• Contiguous period of illness with:

• Criteria A for schizophrenia +• Major depressive episode OR• Mania OR• Mixed episode OR

• During this same episode there were delusions and hallucinations for 2 weeks without prominent mood symptoms

Schizoaffective Disorder: Clinical

Picture• Mood symptoms are there for a

“substantial” part of the active and residual period ( 15-20 % of total episode)

• Not due to substance or general medical condition

Schizoaffective Disorder: Treatment

• Mood stabilizers• Antidepressants: use SSRI’s due to

possibility of switch to mania with TCA’s

• Antipsychotics• Benzodiazepines

Delusional Disorder

• Patient experiences nonbizarre (situations that could occur in real life) delusions for at least 1 month

• Criteria A for schizophrenia never met• Can have tactile and olfactory

hallucinations if congruent with delusion

• Function is not markedly impaired, behavior not obviously bizarre

Delusional Disorder

• Etiology unknown• Less common than schizophrenia

and mood disorders• Prevalence 0.03 %• Later onset than schizophrenia,

mean age 40y• Associated with recent immigration• Many married and employed

Delusional Disorder

• More suspiciousness, jealousy in relatives of affected patients

• Diagnosis changes to schizophrenia or mood disorder in < 10 %

• Family studies do not support link to either mood disorders or schizophrenia

Delusional Disorder

• Hallucinations transient, not prominent• Moods congruent to delusional content

and brief in duration• No marked though form

disorganization• Cognition intact• Sensorium intact• MSE remarkably normal given the

intensity of delusional system

Delusional Disorder: Risk Factors

• Advanced age• Sensory impairment• Isolation• Recent immigration• Family history

Delusional Disorder

• Types:• Erotomanic “de Clerambault’s syndrome”• Jealous “ Othello syndrome”• Persecutory • Somatic • Grandiose• Mixed • Capgras: familiar people replaced by doubles• Fregoli’s phenomena: family can transform

themselves to look like strangers• Cotard’s syndrome: pt believes they have lost

loved ones, status, job, internal organs

Shared Psychotic Disorder

• “Folie a Deux”:• Pt develops delusion of another after

associating closely with them• Secondarily delusional pt

• Is gullible, passive, less intelligent• May abandon delusion once separated

• Primary delusional pt is more dominant, chronically delusional

Delusional Disorder: Treatment

• Difficult to treat• Antipsychotics• ? Pimozide more effective in

somatic delusions• Separation for Shared Psychotic

Disorder • Psychotherapy