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Back to Basics: Psychotic Spectrum Disorders
Sharman Robertson Bsc MD FRCPC
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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
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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, mean=21 years• females 25-35 years, mean=27 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
• >75% 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 cortex:impaired 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 ->decreased 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• Huntington’s 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/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)
• 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 A’s: 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 >= 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 <25 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 patient’s 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-Korsakoff’s
• Infectious:• HIV, neurosyphilis, CJD, herpes
encephalitis
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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
• 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:• Asperger’s 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 S+Sx• 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• Methotrimeprazin
e• 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 SE’s 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- < 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 20’s and 30’s• ? 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 >= 1 month < 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
• F>M
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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 SSRI’s due to
possibility of switch to mania with TCA’s
• 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 < 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 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
• “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