Back to Basics: Psychotic
Spectrum Disorders
Sharman Robertson Bsc MD
FRCPC
Format: Summary of Kaplan and
Sadock’s “ Synopsis of
Psychiatry”
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Schizophrenia
Other Psychotic Disorders
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Schizophreniform disorder
Brief psychotic disorder
Schizoaffective disorder
Delusional disorder
Psychosis NOS
Schizophrenia:
Epidemiology
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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
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Epidemiology (Cont.)
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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.)
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Incidence and prevalence roughly
similar world-wide
Substance use
30-50% alcohol dependence
• Cannabis dependence 15-25%
• Cocaine dependence 5-10%
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Etiology
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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:
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Diathesis or vulnerability is acted on by
stressful event resulting in production of
the illness
Neurobiology
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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
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Neurobiology (Cont.)
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? Abnormal cell migration along radial
glial cells during embryo-genesis
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? Early pre-programmed cell death
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Hippocampal pyramidal cell disarray
Loss of associative neuron axons and
dendrites ->decreased brain volume
Environment plays part as evidenced by
only 50% concordance rate in MZ twins
Neuroanatomy
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Limbic system:
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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
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Neuroanatomy
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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
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Neurochemistry;
Dopamine
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Dopamine (DA) hypothesis:
Over-activity of DA in certain brain areas ie
mesolimbic and mesocortical areas
• Evidence:
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Efficacy of DA blocking medications
Psychotomimetic effect of stimulants
? Too much DA release, too many DA
receptors
• DA levels actually low in prefrontal cortex
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Serotonin
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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
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Norepinephrine (NE)
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Long term anti-psychotic use 
decreased activity in alpha-1 and alpha2 receptors in locus ceruleus
NA system modulates DA system
? NA system abnormalities may affect
relapse rate
GABA,Glutamate, CCK,
Neurotensin
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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
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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
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? Viral
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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
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Other Theories
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Immunological abnormalities:
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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
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Other Theories
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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
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Emil Kraeplin: Dementia
Praecox
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One of first to characterize a psychotic
illness separate from BAD;
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Early onset
Chronic deteriorating course
Primary sx delusions and hallucinations
Cognitive impairment
Not clearly episodic as was BAD
Eugen Bleuler:
Schizophrenia
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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
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First rank symptoms:
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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
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Sudden delusional thoughts
Perceptual disturbances
Perplexity
Depressive and euphoric feelings
Emotional impoverishment
DSMIV Diagnosis of
Schizophrenia
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A Criteria: two or more during a significant
portion of one month (less if successfully
treated)
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1) delusions
2) hallucinations
3) disorganized speech
4) grossly disorganized or catatonic behavior
5) negative symptoms (affective flattening, alogia,
avolition)
DSMIV Diagnosis of
Schizophrenia
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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
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Subtypes of Schizophrenia
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Paranoid
Disorganized
Catatonic
Undifferentiated
Residual
Based on clinical presentation
• NOT closely correlated with different
prognoses
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Paranoid
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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)
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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
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Undifferentiated
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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
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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:
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IQ and developmental level
• Culture
• Educational level
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Positive Symptoms
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Delusions: Firm, fixed, false beliefs
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Paranoid
Grandiose
Religious
Somatic
Referential
Pseudo-philosophical
Control
Positive Symptoms
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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
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Negative Symptoms
(Deficit Symptoms)
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Affective flattening, blunting
Alogia: poverty of rate or content of
speech
Thought blocking
Autism
Ambivalence
Negative Symptoms
(Deficit Symptoms)
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Anhedonia-asociality
Avolition-apathy
Poor self-care
Inattention
Associated with CT abnormalities, less
treatment responsiveness
Disturbances of
Affect/Mood
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Reduced emotional responsiveness
Unregulated, inappropriate emotional
discharge:
Terror, rage
• Anxiety, depression
• Perplexity
• Happiness, euphoria, ecstasy
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Thought Disorders
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Core symptoms of schizophrenia
Thought content
• Thought form
• Thought process
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Visible in speech and written language
Thought Content
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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
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Loosening of
associations
Derailment
Circumstantiality
Tangientiality
Neologisms
Word salad
Echolalia
Mutism
• Clanging
• Verbigeration
• Incoherence
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Though Process
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Flight of ideas
Though blocking
Prolonged response
latency
Inattention
Perseveration
Impaired abstraction
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Over-inclusion
Violence
Rates of violence in schizophrenia are higher
than rates in the general public
• Risk factors act synergistically;
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Untreated
• Active substance use
• Active alcohol use
• Past history of violence
• Persecutory or erotomanic delusions
• Neurological deficits
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Suicide
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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
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Differential Diagnosis
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Substance intoxication or
withdrawal
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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
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Neurological:
Epilepsy, esp. TLE
• Neoplasm
• Trauma to frontal or limbic areas
• Wernike-Korsakoff’s
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Infectious:
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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
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General Medical
Conditions
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Poisoning:
Heavy metals
• CO
• Solvents
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Nutritional:
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B12, folate deficiency
Psychiatric Illness
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Mood:
BAD
• Major Depression with psychotic features
• Schizoaffective disorder
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Psychotic Spectrum Disorders:
Delusional disorder
• Brief psychotic disorder
• Schizophreniform disorder
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Psychiatric Disorders
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Personality Disorders:
Paranoid PD
• Schizotypal PD
• Schizoid PD
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Anxiety Disorders:
OCD
• Panic disorder
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Psychiatric Disorders
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Pervasive developmental disorders:
Asperger’s disorder
• Infantile autism
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Factitious disorder
Malingering ($ or legal gain)
Course
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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:
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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
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Course
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First episode:
Duration of untreated psychosis associated
with worse outcome
• Associated with greatest potential for full
recovery to baseline
• Treat early and aggressively with multimodal approach
• Pattern of illness during the first 5 years
indicates course
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Course
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Relapses:
Harder to treat
• Longer duration
• Less responsive to medication
• Less likely to return to baseline
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Prognosis
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Lifelong vulnerability to illness
Episodes of active psychosis
Residual symptoms
Cognitive impairment and negative
symptoms:
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Longest lasting, most difficult to treat
Failure to return to baseline demarcates
schizophrenia from mood disorders
Prognosis
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Twelve month relapse rates;
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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
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Poor Prognostic Signs
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Early onset
No precipitant
Insidious onset
Poor premorbid
function
Withdrawn, autistic
behavior
Single, divorced,
widowed
assaultiveness
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Family hx
schizophrenia
Poor support
systems
Negative symptoms
Neurological S+Sx
Perinatal trauma
No remission in 3
years
Many relapses
Assessment
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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
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Assessment
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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
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Patient and family psychoeducation:
Definition of schizophrenia
• Provision of information and available
supports
• Schizophrenia society
• Reading materials
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Treatment
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Group and individual therapy:
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Social skills training
Vocational rehabilitation
Supportive therapy
Managing anxiety groups
CBT
Family therapy
Supervised living, Case management, ACTT
Pharmacology
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Dopamine receptor antagonists:
Older classes of medications
• Extra pyramidal symptoms
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Tremor, parkinsonism, rigidity, akathesia
TD, NMS
• Work well on positive symptoms
• May cause negative symptoms in higher
dose
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Dopamine Receptor
Antagonists
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Haloperidol
Zuclopenthixol
Fluanxol
Perphenazine
Loxapine
Methotrimeprazine
Chlorpromazine
Low potency meds
have more sedative,
anticholinergic and
alpha blocking
properties
• Higher potency
drugs have higher
rates of EPS and TD
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5HT/DA Blocking Drugs, Second
Generation Antipsychotics, Atypicals
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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:
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Obesity, DM, Dyslipidemia, CVS disease
Atypical Antipsychotics
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Clozapine
Risperidone
Olanzapine
Quetiapine
Ziprasidone (USA)
Aripiprazole (USA)
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Some evidence
points to
neuroprotective
effects and cognitive
enhancement
Treatment
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Acute phase, emergency:
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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
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Acute, non-emergent:
Choose medication based on:
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Past response
Side effect profile
Patient preference
Route
Cost
Availablity
Antipsychotic selection
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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
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Antipsychotic Trials
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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
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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
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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
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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
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Not due to:
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Schizophrenia
Schizoaffective disorder
Mood disorder
A general medical condition
Substance abuse, intoxication or
withdrawal
Treat with antipsychotics and benzos
Schizophreniform Disorder
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Duration >= 1 month < 6 months
Similar to schizophrenia
Less than half as common as
schizophrenia
0.2% lifetime prevalence
Schizophreniform Disorder
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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
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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
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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
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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:
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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
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Schizoaffective Disorder:
Clinical Picture
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Contiguous period of illness with:
Criteria A for schizophrenia +
• Major depressive episode OR
• Mania OR
• Mixed episode OR
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During this same episode there were
delusions and hallucinations for 2 weeks
without prominent mood symptoms
Schizoaffective Disorder:
Clinical Picture
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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
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Mood stabilizers
Antidepressants: use SSRI’s due to
possibility of switch to mania with TCA’s
Antipsychotics
Benzodiazepines
Delusional Disorder
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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
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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
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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
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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
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Advanced age
Sensory impairment
Isolation
Recent immigration
Family history
Delusional Disorder
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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
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Shared Psychotic Disorder
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“Folie a Deux”:
Pt develops delusion of another after
associating closely with them
• Secondarily delusional pt
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Is gullible, passive, less intelligent
May abandon delusion once separated
Primary delusional pt is more dominant,
chronically delusional
Delusional Disorder:
Treatment
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Difficult to treat
Antipsychotics
? Pimozide more effective in somatic
delusions
Separation for Shared Psychotic
Disorder
Psychotherapy