Schizophrenia -major, serious psychotic disorder characterized by wide range of features affecting thought process (main), perception, speech, affect and cognition

– 1% of population Begins before age 25 Persists throughout life Clinical presentations – may vary Treatment response – may vary Courses of illness – may vary No laboratory test - diagnosis History - diagnosis MSE - diagnosis Cause unknown, developmental, cure not

known`

Neuroimaging and neuropathologic techniques (advances and refinement – frontal lobe, amygdale, hippocampus, parahippocampal gyrus, cerebellum

Introduction of atypical antipsychotic like clozapine (drugs effective in reducing negative symptoms)

Increased interest in the psychosocial factors affecting schizophrenia

Morel - “demence precoce” (deteriorated patients, illness began in adolescence)

Kraeplin – “dementia precox” (longterm deteriorating course/hallucination/delusions) vs manic-depressive psychosis

Bleuler – “schizophrenia” (presence of schisms between thought, emotion and behavior) (split mind)

Not split personality (called dissociative indentity disorder) 4 A’s (associational disturbance, affective disturbance, autism,

ambivalence) (association, affect, autism, ambivalence) Langfeldt – 2 groups: true schizophrenia (insidious,

derealization, depersonalization, autism, emotional, blunting) vs. schizophrenia like psychosis

Other names: nuclear/ process / non-remitting schizophrenia Schneider – first rank symptoms for schizophrenia

Prevalence rate – 1% / 1/100 (will develop schizophrenia during their lifetime

Annual incidence range – 0.5 – 5.0 / 10,000 Equal prevalence in men and women, earlier onset in men Peak ages of onset late teens – mid twenties (10-25 for men) (25-35

for women) Men- more likely with negative symptoms Women – better social functioning vs men, prior to disease onset Outcome for female schizophrenia is better vs. male Reproductive factors, medical illness, suicide risk, substance use,

population density Socioeconomic factors: downward drift hypothesis : social causation hypothesis Stress of immigration – abrupt culture change as a stress Schizophregenic cultures and families Impact on economics Hospitalization and homelessness

Stress – Diathesis Model: integration of biological, psychosocial, environmental factors – specific volurability (diathesis)

When acted on by STRESS – schizophrenia symptoms develop

Either biological on environmental or both

Neurobiology – cause of schizophrenia is unknown

- limbic system, frontal cortex, cerebellum and basal ganglia – involved, interconnected (limbic system: potential site for primary pathologic process)

- basis for brain abnormality: abnormal development vs. degeneration of neuron after development

- nature-nurture theory always in mind - studies on factors regulating gene expression

Dopamine hypothesis: Too much dopamine activity, hyperdopaminergia

positive symptoms 2 observations – antipsychotic drugs (dopamine

receptor antagonist) Drugs that increase dopamine activity

amphetamine / psychomimetic (either much release of dopamine, too many dop receptors, hypersensitivity of dop receptor or combination)

Mesocortical / mesolimbic tracts are implied Positive correlation between high pretreatment

concentration of homovanillic acid (dop metabolic); decline of HA in symptoms improvement in some patient

Serotonin – maybe involved in negative symptoms

Noradrenalin / Norepinephrine – modulates dopamine (predisposes a patient to relapse frequently)

GABA – loss of inhibitory GABAergic neurons lead to hyperactivity of dopamine receptors

Glutamine – related to hyperactivity glutamate induced neurotoxicity (phencyclidine – PCP, a glutamate antagonist symptoms of schizophrenia)

Neuropeptides – cholecystokinin and neurotensin involvement

Limbic system and basal ganglia Cerebral cortex, thalamus and brainstem Reduced density of the axons, dendrites and synapses

– loss of brain volume (in schizophrenia) Theory: excessive pruning of synapses during

adolescence Limbic system – emotion control, decreased size of

amygdale, hippocampus and para hippocampal gyrus Basal ganglia – movement control, cell loss, reduced

volume of globus pallidus and substancia nigra Limbic system and basal ganglia problem account for

negative symptoms Frontal lobe – cognition – hypofrontality in PET scans

Computed tomography scans – enlarged lateral third ventricles (related to negative symptoms) abnormal cerebral asymmetry, reduction cortical volume, brain density changes

Magnetic resonance imaging – enlarged cerebral ventricles (in twin studies 40-50% of other twin even without symptoms)

Functional MRI – difference in sensorimotor cortex activation and decreased blood flow to occipital lobes vs. normal control subjects

Magnetic resonance spectroscopy - measures specific molecules (high levels of ATP – low activity of the brain)

Position emission tomography – decreased blood flow to the dorsolateral prefrontal cortex during tasks.

Imaging suggest neuropathologic theory of schizophrenia

Implications: electrophysiology, eye movement dysfunction, psychoneuroimmunology psycho

 

Literature: potentially heterogenous genetic basis

- Table of prevalence of schizophrenia in specific population (show this)

- Adoption studies – genetic implications

Controversial: Nature-nurture : brain disease expressed with psychosocial

factors influence

Freud (fixations, regression in response to frustration and conflict, ego defect, ego disintegration)

Mahler – separation individuation problem Never achieves object constancy Sullivan – disturbance in interpersonal

relatedness

Learning theories – poor models for learning Children who later have schizophrenia learn

irrational reaction and thinking by imitating parents who have their own problem

Double bind theories conflicting messages Schisms and skeud families Pseudomutual and pseudo hostile families –

suppress emotional expression Expressed emotion – high EE  Social theories – industrialization and

urbanization impact on cause of schizophrenia

DSM IV TR ICD 10 The presence of hallucinations or delusions

not necessary for a diagnosis of schizophrenia

IMPAIRED functioning, although not DETERIORATION, may be present during the active phase of the illness

Symptoms persist for at least 6 months Absent diagnosis for Schizoaffective and

mood disorders

-Paranoid - Disorganized - Catatonic - Undifferentiated - Residual

Psychological Testing Findings – poor performance

- vigilance , memory and concept for motion are affected

  Intelligence Tests – tend to score lower - intelligence MAY continue to

deteriorate with progression of the illness

 

Projective and Personality tests Rorschach and thematic apperception

test (TAT) – bizarre ideations Personality tests – may show

associated personality traits (schizoid, schizotyped, paranoid)

Stages of Schizophrenia A. Prodromal - insidious onset, subtle changes in social, school,

job activities / (negative symptoms) - schizoid at first, withdrawn/ not sociable/

unproductive, suspicions/ strange ideas/ bothered by what people think

 B. Active - psychotic features set in (positive symptoms) - mumbling, hallucinations, delusions, telling to self C. Residual - symptoms subside, return to premorbid / normal

functioning is difficult (negative symptoms persist)

Remission and exacerbations Observe first 5 years since diagnosis –

determine course School, occupation and social relationships-

difficulty getting back Many don’t marry, 10-15% suicide, 50%

attempt suicide

Type I, Type II patients - High Positive Symptom: Hallucination – usually auditory Delusions – persistency, bizarre Looseness of association Disorganized thinking and

behavior Irrelevant speech Neologisms

Alogia – decreased or limited speech Affective blunting – flat, blank,

constricted/restricted Avolition – lack of initiative Anhedonia – lack of pleasure depression related anhedonia vs.

schizophrenia

Symptoms Mild orModerate

Severe or Extreme

Symptoms Mild or Moderate

Severe or Extreme

Negative symptomsAffective flattening Unchanging facial expression Decreased spontaneous movements Paucity of expressive gestures Poor eye contact Affective nonresponsivity Inappropriate affect Lack of vocal inflectionsAlogia Poverty of speech Poverty of content of speech Blocking Increased response latencyAvolition-apathy Grooming and hygiene Impersistence at work or school Physical anergia

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Positive symptomsHallucinations Auditory Voices commenting Voices conversing Somatic-tactile Olfactory VisualDelusions Persecutory Jealousy Guilt, sin Grandiose Religious Somatic Delusions of

reference Delusions of being

controlled

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Symptoms Mild or Moderate

Severe or Extreme

Symptoms Mild or Moderate

Severe or Extreme

Anhedonia-asociality Recreational interests, activities Sexual interest, activity Intimacy, closeness Relationship with friends, peersAttention Social inattentiveness Inattentiveness during testing

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Delusions of mind reading

Thought broadcasting

Thought insertion Thought

withdrawalBizarre behavior Clothing,

appearance Social, sexual

behavior Aggressive/agitated behavior Repetitive/Stereotyped behaviorPositive formal

thought disorder

Derailment Tangentiality Incoherence Illogicality Circumstantiality Pressure of speech Distractible speech Clanging

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Kurt Schneider Criteria

1. First-rank symptoms a. Audible thoughts b. Voices arguing or discussing or both c. Voices commenting d. Somatic passivity experiences e. Thought withdrawal and other experiences of influenced thought f. Thought broadcasting g. Delusional perceptions h. All other experiences involving volition, made affects, and made impulses

2. Second-rank symptoms a. Other disorders of perception b. Sudden delusional ideas c. Perplexity d. Depressive and euphoric mood changes e. Feelings of emotional impoverishment f. “…and several others as well”

New Haven Schizophrenia Index

1. a. Delusions: not specified or other-than-depressive 2 points

b. Auditory hallucinations

c. Visual hallucinations

d. Other hallucinations

2. a. Bizarre thoughts

b. Autism or grossly unrealistic private thoughts

c. Looseness of associations, illogical thinking, overinclusion

d. Blocking

e. Concreteness

f. Derealization

g. Depersonalization

3. Inappropriate affect 1 point

4. Confusion 1 point

5. Paranoid ideation (self-referential thinking, suspiciousness) 1 point

6. Catatonic behavior

a. Excitement

b. Stupor

c. Waxy flexibility

d. Negativism

e. Mutism

f. Echolalia

g. Stereotyped motor activity

Scoring: To be considered part of the schizophrenic group, the patient must score on Item 1 or Item 2a, 2b, or 2c and must receive a total score of at least 4 points

any one: 2 points

any one: 2 points

either: 2 points

each: 1 point

any one: 1 point

Auditory Hallucination – multiple voices, running commentary (usually derogatory in

third person) - Thought insertion - Thought blocking - Thought withdrawal - Thought echoing - Thought broadcasting - Delusion of control (passivity of

feelings) - Primary delusional perception

auditory hallucinations – most important (high frequency, reliability and specificity)

- delusion of control – most reliable - neologisms – most specific (98% from

schizophrenia, 2% from organic problem

Good Outcome: Acute onset Short duration Mood symptoms Stable pre-morbid Married (before illness) No family history Upper social class

Good Prognosis Poor Prognosis

Late onsetObvious precipitating factors

Acute onsetGood premorbid social, sexual,

and work historiesMood disorder symptoms

(especially depressive disorders)

MarriedFamily history of mood

disordersGood support systemsPositive symptoms

Young onsetNo precipitating factorsInsidious onsetPoor premorbid social, sexual, and work historiesWithdrawn, autistic behaviorSingle, divorced, or widowedFamily history of schizophreniaPoor support systemsNegative symptomsNeurological signs and

symptomsHistory of perinatal traumaNo remissions in 3 yearsMany relapsesHistory of assaultiveness

Features weighing towards Good to Poor Prognosis in Schizophrenia

General Description (precox feelings) - Mood, Feelings and Affect - Perceptual disturbances – hallucinations,

cenesthetic hallucinations, illusions - Thought Thnking – thought content, form of

thought, thought process - Impulsiveness, violence, suicide, homicide - Orientation – usually intact - Memory – intact, some minor cognitive

deficiencies - Judgement or Insight – lack of or poor insight - Reliability – no less reliable than any other

psychiatric patient

Neurologic Examination – soft neurologic signs

  Eye Examination – disorders of smooth

pursuit (saccadic movement) elevated blink rate hyperdopaminergia

Delusional Disorder Schizophreniform Disorders Schizoaffective Disorders Shared Psychotic Disorders Brief Psychotic Disorders Psychotic Disorders due to general medical condition Substance Induced Psychotic Disorders Mood Disorders Personality Disorders Drug Induced Psychosis Temporal Lobe Epilepsy

What is delusion? (1) false belief (2) fixed or unshakable (3) unexplainable on the basis of individual

socio, religion, cultural background

Overvalued ideas – can be explained by socio, religious, cultural background

- Prevalence: 0.025-0.03%; much rarer than schizophrenia

- Main feature: presence of systematized, encapsulated, non bizarre delusions

- There is no severe/ bizarre deterioration - Personality remains to be generally the same - Types of Delusional Disorder: - Persecutory - Erotomania (de Clerembault’s

syndrome) - Jealous (Othello’s syndrome) - Somatic - Grandiose

COURSE AND PROGNOSIS Identifiable stressor(warrant concern or

suspicion accompanies the onset) Sudden onset more common vs insiduous Usually among below average intelligence Premorbid personality-extroverted,

dominant, hypersensitive Concernsuspicionselaborateconsume

much of the person’s attention and finally Delusional

50% of px-recover after long term ff up 20% of px- decrease in symptoms 30% of px-no change Good prognosis:high level of occupational,

social & functional adjustments, onset <30 y/o, sudden onset, short duration of illness & presence of precipitating factors

Persecutory, somatic, erotic delusions are thought to have better prognosis vs px with grandiose & jealous delusions

TREATMENT• Success depends on effective therapeutic

doctor-patient relationship-which is difficult to establish

• Patients don’t complain about psychiatric symptoms & often takes medicine against their will-even psychiatrists may be drawn to their delusional state

• Psychotherapy-TRUST• Mark of successful treatmentsatisfactory

social adjustment vs abatement of px’s delusions

• Hospitalization

COURSE AND PROGNOSIS Issue: what happens to person with illness

over time?◦ 60-80%-progress to Schizophrenia◦ 20-40%- not known◦ Some 2-3 episodesdeteriorate to Schizophrenia◦ Some single episode continue to Schizophrenia

TREATMENT 3-6 month anti psychotic medications Psychotherapy

Most Schizophreniform patients progress to full blown Schizophrenia despite treatment

COURSE AND PROGNOSIS Due to uncertainty and evolving diagnosis

of Schizo-affective disorders, it is difficult to determine the long term prognosis

Presumed: schizo features=worse prognosis

affective features= good prognosis

TREATMENT Antipsychotic

+Moodstabilizer/Antidepressant

Patients should be kept apart isolated- different units and no conntact

The healthier of the two will give up delusional belief(sometimes without any other therapeutic intervention)

The sicker of the two will maintain the false fixed belief

COURSE AND PROGNOSIS Less than 1 month 50% will later display chronic psychiatric

disordereither Schizophrenia or Mood D/O Good prognosis-50-80% have no further

major psychiatric problems.

A. Prominent hallucinations and delusions. B. There is evidence from histoory, physical examination, or

laboratory findings that the disturbance is the direct physiological consequence of a general medical condition.

C. The disturbance is not accounted for by another mental disorder.

D. The disturbance does not occur exclusively during the course of delirium.

A. Prominent hallucinations and delusions. Note: Do not include hallucinations if the person has insight that they are substance induced.

B. There is evidence from history, physical examination, or laboratory findings of either (1) or (2).

(1) the symptoms in criterion A developed during, within a month of Substance Intoxication or withdrawal

(2) medication used is etiologically related to the disturbance C. The disturbance is not accounted for by a psychotic disorder that is

not substance induced. Evidence that the symptoms are better accounted for by a Psychotic Disorder that is not substance use (or medication use); the symptoms persist for a substantial period of time (about a month) after the cessation of acute withdrawal or severe intoxication, or a substantially in excess of what would be expected given the type or amount of the substance use or the duration of use; or there is evidence suggests the existence of an independent non-substance induced psychotic disorder (e.g., history of recurrent non-substance related episodes).

D. The disturbance does not occur exclusively during the course of delirium.

TREATMENT Hospitalization Rx-anti psychotic/Mood stabilizers Psychotherapy