Back to Basics: Psychotic Spectrum Disorders

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Back to Basics Psychotic Spectrum Disorders

• Sharman Robertson Bsc MD FRCPC

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Format Summary of Kaplan and Sadocks Synopsis
of Psychiatry

• Schizophrenia
• Other Psychotic Disorders
• Schizophreniform disorder
• Brief psychotic disorder
• Schizoaffective disorder
• Delusional disorder
• Psychosis NOS

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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, mean21 years
• females 25-35 years, mean27 years

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Epidemiology (Cont.)

• Fertility rates close to that of general
  population
• 80 have significant concurrent medical illness
  and only 50 of this is diagnosed
• gt75 smoke
• Suicide is leading cause of mortality 15 success
  rate

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Epidemiology (Cont.)

• 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

• 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

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Neurobiology

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

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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
  -gtdecreased brain volume
• Environment plays part as evidenced by only 50
  concordance rate in MZ twins

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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
• Huntingtons associated with basal ganglia
  pathology, psychosis and AIM

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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

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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

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Serotonin

• 5HT-2 blockade reduces psychotic symptoms and
  prevents movement D/Os caused by D2 blockade
• Second generation anti-psychotics (SGAs) have
  potent 5HT-2 blockade ie
• Risperidone, olanzapine, seroquel
• Older clozapine

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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

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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

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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

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? 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

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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

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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

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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

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Eugen Bleuler Schizophrenia

• Schizophrenia split-mind
• Split between thought, emotion and behavior
• Not necessarily deteriorating
• Most important symptoms 4 As autism, affective
  flattening, ambivalence, associations loose
• Accessory symptoms hallucinations and delusions

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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

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Second Rank Symptoms

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

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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)

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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

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DSMIV Diagnosis of Schizophrenia

• C continuous signs of the disturbance for gt 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

• Paranoid
• Disorganized
• Catatonic
• Undifferentiated
• Residual
• Based on clinical presentation
• NOT closely correlated with different prognoses

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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

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Disorganized (Hebephrenic)

• Primitive, disorganized, disinhibited, vague,
  aimless behavior
• Onset lt25 years
• Pronounced thought disorder
• Poor reality contact
• Poor self-care
• Inappropriate affect, grimacing

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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

• 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 patients
  context
• IQ and developmental level
• Culture
• Educational level

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Positive Symptoms

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

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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

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Negative Symptoms (Deficit Symptoms)

• Affective flattening, blunting
• Alogia poverty of rate or content of speech
• Thought blocking
• Autism
• Ambivalence

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Negative Symptoms (Deficit Symptoms)

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

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Disturbances of Affect/Mood

• Reduced emotional responsiveness
• Unregulated, inappropriate emotional discharge
• Terror, rage
• Anxiety, depression
• Perplexity
• Happiness, euphoria, ecstasy

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Thought Disorders

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

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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

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Thought Form

• Loosening of associations
• Derailment
• Circumstantiality
• Tangientiality
• Neologisms
• Word salad
• Echolalia

• Mutism
• Clanging
• Verbigeration
• Incoherence

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Though Process

• Flight of ideas
• Though blocking
• Prolonged response latency
• Inattention
• Perseveration
• Impaired abstraction

• Over-inclusion

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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

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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

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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

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General Medical Conditions

• Neurological
• Epilepsy, esp. TLE
• Neoplasm
• Trauma to frontal or limbic areas
• Wernike-Korsakoffs
• Infectious
• HIV, neurosyphilis, CJD, herpes encephalitis

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General Medical Conditions

• Metabolic
• Hyper/hypothyroidism, hyper/hypoparathyroidism
• Acute intermittent porphyria
• Homocystinuria
• Wilsons disease
• Auto-immune
• SLE
• Cerebral lipoidosis

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General Medical Conditions

• Poisoning
• Heavy metals
• CO
• Solvents
• Nutritional
• B12, folate deficiency

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Psychiatric Illness

• Mood
• BAD
• Major Depression with psychotic features
• Schizoaffective disorder
• Psychotic Spectrum Disorders
• Delusional disorder
• Brief psychotic disorder
• Schizophreniform disorder

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Psychiatric Disorders

• Personality Disorders
• Paranoid PD
• Schizotypal PD
• Schizoid PD
• Anxiety Disorders
• OCD
• Panic disorder

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Psychiatric Disorders

• Pervasive developmental disorders
• Aspergers disorder
• Infantile autism
• Factitious disorder
• Malingering ( or legal gain)

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Course

• Prodrome
• Active Phase active positive and negative
  symptoms
• Residual Phase attenuated positive symptoms and
  negative symptoms

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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

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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

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Course

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

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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

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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

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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

• 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 SSx
• Perinatal trauma
• No remission in 3 years
• Many relapses

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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

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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

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Treatment

• Patient and family psychoeducation
• Definition of schizophrenia
• Provision of information and available supports
• Schizophrenia society
• Reading materials

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Treatment

• Group and individual therapy
• Social skills training
• Vocational rehabilitation
• Supportive therapy
• Managing anxiety groups
• CBT
• Family therapy
• Supervised living, Case management, ACTT

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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

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Dopamine Receptor Antagonists

• 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

• 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

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Atypical Antipsychotics

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

• Some evidence points to neuroprotective effects
  and cognitive enhancement

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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

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Treatment

• Acute, non-emergent
• Choose medication based on
• Past response
• Side effect profile
• Patient preference
• Route
• Cost
• Availablity

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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

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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 SEs present switch
  to another SGA
• Use lowest possible dose
• Higher doses needed in acute phase and may be
  lowered in maintenance

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Brief Psychotic Disorder

• Acute, transient psychotic disorder
• 1 day- lt 1 month
• Symptoms may resemble schizophrenia with
  delusions and hallucinations
• May develop in response to a traumatic stressor
• Symptoms often reflect stressful event

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Brief Psychotic Disorder

• Temporal relationship to the trauma
• Usually benign course, eventual return to
  baseline function
• Uncommon
• Pts in 20s and 30s
• ? More in women and lower SES
• Often seen in patients with histrionic,
  narcissistic, borderline, paranoid, schizotypal
  PD

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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

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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

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Schizophreniform Disorder

• Duration gt 1 month lt 6 months
• Similar to schizophrenia
• Less than half as common as schizophrenia
• 0.2 lifetime prevalence

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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

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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

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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

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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
• FgtM

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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

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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

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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

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Schizoaffective Disorder Treatment

• Mood stabilizers
• Antidepressants use SSRIs due to possibility of
  switch to mania with TCAs
• Antipsychotics
• Benzodiazepines

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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

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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

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Delusional Disorder

• More suspiciousness, jealousy in relatives of
  affected patients
• Diagnosis changes to schizophrenia or mood
  disorder in lt 10
• Family studies do not support link to either mood
  disorders or schizophrenia

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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

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Delusional Disorder Risk Factors

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

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Delusional Disorder

• Types
• Erotomanic de Clerambaults syndrome
• Jealous Othello syndrome
• Persecutory
• Somatic
• Grandiose
• Mixed
• Capgras familiar people replaced by doubles
• Fregolis phenomena family can transform
  themselves to look like strangers
• Cotards syndrome pt believes they have lost
  loved ones, status, job, internal organs

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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

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Delusional Disorder Treatment

• Difficult to treat
• Antipsychotics
• ? Pimozide more effective in somatic delusions
• Separation for Shared Psychotic Disorder
• Psychotherapy