Schizophrenia Spectrum and Other Psychotic

Disorders — Bullet-Point Summary

General Overview
 Schizophrenia is not a single disease; it likely comprises multiple disorders with
heterogeneous etiologies.
 Presents with variable changes in perception, emotion, cognition, thinking, and
behavior.
 Symptoms vary across patients and over time, but overall the illness is severe and
long-lasting.
 Onset: usually before age 25; persists lifelong.
 Affects all social classes.
 Patients and families often face inadequate care and social ostracism due to stigma and
ignorance.
 One of the most common severe mental disorders, yet its essential nature remains
unclear.
 Sometimes referred to as:
o A syndrome
o A group of disorders
o A spectrum (DSM-5 term: schizophrenia spectrum disorders)
 Diagnosis is based solely on psychiatric history and mental status examination.
o No laboratory test exists for schizophrenia.

Public Health & Societal Impact

 Significant early onset + chronic course → heavy needs for hospital care,
rehabilitation, and long-term support.
 Financial burden in the U.S. is thought to exceed that of all cancers combined.
 Patients comprise 15–45% of the homeless population; approx. 5% become homeless
yearly.
 Globally, schizophrenia is among the top 25 leading causes of disability, despite
relatively low prevalence.
 Indirect costs (impact on families, caregivers, society) are enormous and often
underestimated.

Clinical Presentation
Diagnosis Considerations

 No sign or symptom is pathognomonic for schizophrenia; all can occur in other

conditions.
 Diagnosis requires:
o Detailed history (course, fluctuations)
o Consideration of education, intellectual ability, and cultural/subcultural
background.
 Abnormal abstract thinking may simply reflect low education or low IQ, not
schizophrenia.
 Cultural practices (e.g., religious, ritualistic) must be interpreted in context.

Appearance & Behavior

 Appearance ranges from:
o Disheveled, agitated, screaming
o To obsessively groomed, silent, immobile
 Behavioral features:
o Bizarre postures
o Agitation or violence, often in response to hallucinations
o Poor grooming, poor hygiene, dressing inappropriately warm
o Tics, stereotypies, mannerisms
o Echopraxia (imitating examiner’s movements)

Catatonia
 Catatonic stupor: lifeless appearance with muteness, negativism, automatic obedience.
 Waxy flexibility: formerly common, now rare.
 Less extreme catatonia:
o Marked social withdrawal
o Lack of spontaneous speech/movement
o Absence of goal-directed behavior
o Immobilization; brief, minimal responses; movement only when instructed
o Odd clumsiness or stiffness

Neurologic Signs
 Neurologic hard and soft signs more common than in other psychiatric disorders.
  Soft signs include:
o Dysdiadochokinesia (impaired rapid alternating movements)
o Astereognosis (inability to recognize objects by touch)
o Primitive reflexes
o Reduced dexterity
 Associated with:
o Increased illness severity
o Affective blunting
o Poor prognosis
 Other neurologic abnormalities:
o Tics, stereotypies, grimacing
o Impaired fine motor skills
o Abnormal motor tone and movements
o Many patients unaware of their abnormal movements
 Smooth pursuit eye movement deficits (saccadic intrusions)
 Elevated blink rate → may reflect increased dopaminergic activity

Parietal Lobe–Like Symptoms

 Inability to perceive prosody or inflect speech
 Apraxia (difficulty performing tasks)
 Right–left disorientation
 Lack of concern about the disorder

Mood Symptoms
 Two primary affective abnormalities:
o Reduced emotional responsiveness (flat/blunted affect, anhedonia)
o Inappropriate or excessive emotions (rage, ecstasy, terror, extreme anxiety)
 Flat affect may be due to:
o The illness itself
o Antipsychotic side effects (parkinsonism)
o Depression
→ Challenging to differentiate
 Emotional experiences may include:
o Feelings of omnipotence, religious ecstasy
o Fear of soul disintegration
o Anxiety about cosmic destruction
o Perplexity, isolation, ambivalence, depression
Thought Disorders (Formal Thought Disorder)
 Core feature of psychotic disorders.
 Affects process of thinking, not just content.
 Thought may be:
o Vague, stilted (mild)
o Loosening of associations (more severe)
 Types include:
o Circumstantiality- Speech includes excessive, unnecessary details but
eventually reaches the point.
o Tangentiality- Speech goes off-topic and never returns to the original point
o Perseveration- Persistent repetition of a word, idea, or response despite a
change in question or context.
o Neologisms- Made-up words that have idiosyncratic meaning only to the
speaker
o Echolalia- Repetition of another person’s words like an echo, often immediate
o Verbigeration (meaningless repetition)- Meaningless, stereotyped, and
continuous repetition of phrases or sentences.
o Word salad- Completely disorganized, incoherent mixture of words and
phrases without logical connection.
o Mutism- Absence of speech, despite the physical ability to speak.

Delusions (Thought Content)

 Common types:
o Persecutory
o Grandiose
o Religious
o Somatic
 Examples:
o Belief that external entities control thoughts/behavior
o Belief in extraordinary ability to control external events
o Preoccupation with esoteric, symbolic, or abstract concepts
o Implausible somatic delusions (e.g., aliens in testicles interfering with fertility)

Loss of Ego Boundaries

 Blurring between self and external world.
 Includes:
o Ideas of reference (TV/newspaper messages meant personally)
 o Thought control (external forces controlling mind)
o Thought broadcasting (others hearing one’s thoughts)
o Thought insertion/withdrawal
o Sense of fusion with objects or people
o Cosmic identity (fusion with the universe)
 May lead to uncertainty regarding gender or sexual orientation
(Important: NOT the same as gender identity problems).

Hallucinations
 Any of the five senses can be affected, but auditory hallucinations are most common.
 Typical auditory hallucinations:
o Threatening, obscene, accusatory, or insulting voices.
o Two or more voices may talk to each other.
o Voices may comment on the patient’s actions.
 Visual hallucinations occur but are less common.
 Tactile, olfactory, and gustatory hallucinations are unusual → should prompt
consideration of underlying medical or neurologic disorder.
 Cenesthetic hallucinations:
o Unfounded sensations involving bodily organs.
o Examples:
 Burning in the brain.
 Pushing sensation in blood vessels.
 Cutting sensation in bone marrow.
o May also include bodily distortions.

Cognition
 Patients are typically oriented to person, place, and time.
 Disorientation → consider medical or neurologic brain disorder.
 Incorrect/bizarre answers may stem from delusions, not true disorientation.
 Memory usually intact on mental status exam.
o Testing may be difficult due to poor attention.
 Subtle cognitive impairments:
o Attention
o Executive functioning
o Working memory
o Episodic memory
 Cognitive impairment is a better predictor of functional outcome than severity of
psychotic symptoms.
 Present from first episode and remains relatively stable early in the illness.
 Small subgroup may develop late-life dementia (not due to Alzheimer’s).
 Cognitive deficits also present in nonpsychotic relatives.
  These impairments are targets for pharmacological and psychosocial treatment trials.

Insight, Judgment, and Reliability

 Patients typically have poor insight into the nature/severity of their illness.
 Poor insight → poor treatment compliance.
 Insight should be evaluated across domains:
o Awareness of symptoms.
o Awareness of interpersonal difficulties.
o Understanding reasons for these difficulties.
 Useful clinically for treatment planning and theoretically for understanding affected
brain areas (e.g., parietal lobes).
 Reliability is not worse than other psychiatric patients.
o But illness requires collateral verification of information.

Safety Concerns
 During acute illness, patients may be agitated, have poor impulse control, or reduced
social sensitivity.
 Impulsive behaviors may appear socially inappropriate (e.g., grabbing another patient’s
cigarettes, abruptly changing TV channels, throwing food).
 Some impulsive acts may be due to command hallucinations (suicide or violence).

Violence

 Untreated schizophrenia → higher rates of violent behavior (excluding homicide).

 Increased odds of violence: 49–68% compared with general population.
 Risk factors:
o Persecutory delusions.
o Previous violence.
o Neurologic deficits.
 Clinician feeling fearful during interview → an internal cue that patient may become
violent.
o Interview should be terminated or conducted with an attendant.

Suicide

 Leading cause of premature death in schizophrenia.

 Lifetime prevalence of suicidality: ~34.5%.
 Suicide attempts: 20–50% of patients.
 Long-term suicide rate: 10–13%.
  DSM-5 estimate: 5–6% die by suicide (likely underestimated).
 Often occurs without warning.
 Major depressive episode is the strongest risk factor.
o Up to 80% of patients experience major depression at some point.
 Paradox: Those with better prognosis (fewer negative symptoms, better emotion and
abstract thinking) may have higher suicide risk.
 High-risk profile:
o Young man.
o Previously high functioning.
o Decline from earlier level.
o Realizes dreams may not come true.
o Has lost faith in treatment.
 Other contributors: command hallucinations, substance abuse.
 2/3 of patients who commit suicide saw a clinician within 72 hours prior to death.
 Clozapine may reduce suicidal ideation in high-risk patients.
 Adjunctive antidepressants may help treat comorbid depression.

Homicide

 Patients with schizophrenia are not more likely to commit homicide than general
population.
 When homicide occurs, it may be for unpredictable or bizarre reasons tied to
hallucinations or delusions.
 Predictors:
o History of past violence.
o Dangerous behavior during hospitalization.
o Hallucinations or delusions involving violent content.

Symptoms of Schizophrenia: Three

Groupings
1. Positive Symptoms (presence of abnormal behaviors)
 Present and observable; associated with acute psychotic episodes.
 Primarily disorders of thought and presentation.
 Include hallucinations, delusions, bizarre behavior, and positive formal thought disorder.

Examples of Positive Symptoms (Table 5-1)

Hallucinations

 Auditory hallucinations
o Voices commenting.
 o Voices conversing.
 Somatic or tactile hallucinations
 Olfactory hallucinations
 Visual hallucinations

Delusions

 Persecutory delusions.
 Delusions of jealousy.
 Delusions of guilt or sin.
 Grandiose delusions.
 Religious delusions.
 Somatic delusions.
 Delusions of reference.
 Delusions of being controlled.
 Delusions of mind reading.
 Thought broadcasting.
 Thought insertion.
 Thought withdrawal.

Bizarre behavior

 Clothing and behavior abnormalities.

 Social and sexual behavior disturbances.
 Aggressive behavior.
 Repetitive or stereotyped behavior.

Positive formal thought disorder

 Derailment.
 Tangentiality.
 Incoherence.
 Illogicality.
 Circumstantiality.
 Pressure of speech.
 Distractible speech.
 Clanging.

2. Negative Symptoms (absence of normal behaviors)

 Also called deficit symptoms.
 Associated with illness progression.
 Include absence of affect, thought, motivation, pleasure, and attention.
Examples of Negative Symptoms (Table 5-2)

Affective flattening or blunting

 Unchanging facial expressions.

 Decreased spontaneous movement.
 Paucity of expressive gestures.
 Poor eye contact.
 Affective nonresponsivity.
 Inappropriate affect.
 Lack of vocal inflections.

Alogia

 Poverty of speech.
 Poverty of content of speech.
 Blocking.
 Increased latency of response.

Avolition–apathy

 Poor grooming and hygiene. Lack of motivation and inability to start or complete goal
directed activities
 Impersistence at work or school.
 Physical anergia.

Anhedonia–asociality

 Reduced recreational interests and activities.

 Decreased sexual interest and activity.
 Lack of intimacy and closeness.
 Poor relationships with friends.

Attention

 Social inattentiveness.
 Inattentiveness during testing.

3. Cognitive Symptoms (impairments in normal cognitive

functions)
 Often subtle but highly impairing.
 Major contributors to disability.
  Include:
o Impairments in attention.
o Working memory deficits
o Executive functioning impairments. (Plan, organize, goal-directed thoughts,
cognitive flexibility, inhibitory control)

Presentation in Special Populations

1. Schizophrenia in Children and Adolescents
 Rare but possible.
 Diagnostic challenge—must differentiate from intellectual disability and autism.
 Diagnosis based on same symptoms as adults.
 Insidious onset, chronic course, unfavorable prognosis.

2. Schizophrenia in Older Adults (Late-Onset

Schizophrenia)
 Onset after age 45.
 More common in women.
 Predominantly paranoid symptoms.
 Favorable prognosis.
 Good response to antipsychotic medication.

Diagnosis of Schizophrenia
General Points
 Patient must show evidence of a psychotic disorder.
 Hallucinations or delusions are not mandatory.
 Diagnosis requires any two psychotic symptoms (DSM-5).
 Symptoms must persist:
o DSM-5: at least 6 months.
o ICD-10: at least 1 month.
 DSM-5 includes course specifiers describing real clinical situations.
Catatonic Type Schizophrenia
 Now rare in Europe and North America.
 Characterized by marked disturbance in motor function, including:
o Stupor.
o Negativism.
o Rigidity.
o Excitement.
o Posturing.
 Rapid alternation between excitement and stupor may occur.

Associated Features

 Stereotypies- repetition of activity

 Mannerisms- odd and peculiar way of perf an activity
 Waxy flexibility.
 Mutism (very common).
 Need for supervision during catatonic excitement to prevent harm.
 May require medical care due to:
o Malnutrition.
o Exhaustion.
o Hyperpyrexia.
o Self-inflicted injury.

DSM-5 vs ICD-10 Diagnosis of Schizophrenia

(Table 5-3)
DSM-5
 Diagnostic name: Schizophrenia.
 Duration: ≥6 months.
 Symptoms:
o Delusions.
o Hallucinations.
o Disorganized speech.
o Disorganized behavior or catatonia.
o Negative symptoms.
 Required number: ≥2 symptoms, with at least one of:
o Delusions.
o Hallucinations.
 o Disorganized speech.
 Exclusions:
o Substance-induced.
o Other medical conditions.
o Other psychiatric conditions.
 Functional impairment required.
 Specifier: "With catatonia" (requires ≥3 catatonic symptoms).
 Course specifiers:
o First episode (acute/partial remission/full remission).
o Multiple episodes (acute/partial remission/full remission).
o Continuous.
o Unspecified.

ICD-10
 Diagnostic name: Schizophrenia.
 Duration: ≥1 month.
 Symptoms include:
o Thought distortions.
o Perceptual disorders.
o Negative affect (often blunted).
o Possible cognitive dysfunction.
o Other symptoms:
 Thought echo.
 Thought insertion/withdrawal.
 Thought broadcasting.
 Delusional perception.
 Delusions of control/influence/passivity.
 Hallucinatory voices.
 Disorganized thinking.
 Negative symptoms.
 Subtypes (ICD-10 classifies subtypes explicitly):
o Paranoid schizophrenia.
o Hebephrenic schizophrenia.
o Catatonic schizophrenia.
o Undifferentiated schizophrenia.
o Residual schizophrenia.
o Simple schizophrenia.
o Other/unspecified schizophrenia.

Catatonia Symptoms (ICD-10 specifier)

 Decreased psychomotor activity or stupor.

 Catalepsy.
 Waxy flexibility.
  Mutism.
 Negativism.
 Posturing.
 Odd mannerisms.
 Stereotypic behaviors.
 Agitation.
 Grimacing.
 Echolalia.
 Echopraxia.

Subtypes of Schizophrenia – Previous DSM

Versions
 Previous DSM editions included schizophrenia subtypes based on clinical features:
o Paranoid subtype
o Disorganized subtype
o Catatonic subtype
o Undifferentiated subtype
o Residual subtype
 DSM-5 does NOT include these subtypes because:
o Their validity was frequently questioned.
o They had weak relationships to biological variables.
o They showed poor long-term stability.
o They had poor predictive value.
 ICD-10 continues to include these subtypes.

Schizoaffective Disorder
General Description

 Disorder with features of both schizophrenia and mood disorders.

 Patients may fall into one of six categories:
1. Schizophrenia + mood symptoms.
2. Mood disorder + symptoms of schizophrenia.
3. Both full mood disorder and full schizophrenia.
4. A third psychosis unrelated to schizophrenia or mood disorder.
5. Disorder on a continuum between schizophrenia and mood disorder.
6. Combination of the above possibilities.
 Often used as a preliminary diagnosis when clinicians are uncertain.
 Unclear if it is a:
 o Subtype of schizophrenia,
o Subtype of mood disorder,
o Simultaneous expression of both,
o Entirely distinct third type of psychosis.

 Most likely: a heterogeneous group including all possibilities.

 Genetic overlap exists between schizophrenia and mood disorders, supporting overlap
theories.

DSM-5 Diagnostic Considerations

 Clinician must:
o Accurately diagnose the mood episode (manic or depressive).
o Determine exact length of mood episodes (often difficult).
 Duration matters because:

1. Psychotic symptoms must occur independently of mood symptoms → requires

knowing when mood episode ends.
2. The relative duration of mood vs psychosis should be roughly equal →
requires tracking the entire course.

Table 5-4 – Diagnostic Comparison (Summary)

DSM-5

 Diagnostic name: Schizoaffective disorder.

 Duration:
o Mood symptoms present majority of time during illness.
o ≥2 weeks of psychotic symptoms without mood symptoms.
 Symptoms:
o Meets criteria for major depressive or manic episode.
o Meets criteria for schizophrenia.
 Psychosocial impact: Functional impairment.
 Exclusions:
o Substance use
o Other mental illness
o Medical conditions
 Specifiers:
o Bipolar Type (manic episode)
o Depressive Type (depressive episode)
o With catatonia
 Course specifiers:
o First episode—acute/partial remission/full remission
o Multiple episodes—acute/partial/full remission
o Continuous
 o Unspecified

ICD-10

 Diagnostic name: Schizoaffective disorders (several types).

 Symptoms:
o Symptoms of affective episode AND schizophrenia.
 Subtypes:
o Manic type
o Depressive type
o Mixed type
o Other/unspecified
 Course specifiers: Same as DSM-5.

Schizophreniform Disorder
General Description

 Symptoms similar to schizophrenia but duration differs:

o Lasts ≥1 month but <6 months.
o Patient returns to baseline level of functioning.
 A heterogeneous disorder:
o Some resemble schizophrenia.
o Others resemble mood disorders.
 Acute psychotic disorder with:
o Rapid onset
o Lack of long prodromal phase
 Functional impairment may occur during episode, but no progressive decline.
 Requires ≥2 psychotic symptoms like schizophrenia.
 If symptoms last >6 months, consider schizophrenia.

Course

 60–80% later develop schizophrenia.

 Others:
o Experience recurrent time-limited episodes.
o A few have only a single lifetime episode.

Table 5-5 – Diagnostic Comparison

DSM-5
  Name: Schizophreniform disorder.
 Duration: ≥1 month but <6 months.
 Symptoms: Same as schizophrenia:
o Delusions, hallucinations, disorganized speech, disorganized/catatonic behavior,
negative symptoms.
 Specifiers:
o With catatonia
o With good prognostic features (need ≥2):
 Psychotic symptoms within 4 weeks of initial change
 Confusion
 Good premorbid functioning
 No negative symptoms
o Without good prognostic features

ICD-10

 Name: Acute and transient psychotic disorder.

 Duration: <1 month on average.
 Symptoms:
o Similar to schizophrenia
o Includes thought echo, insertion, withdrawal, delusional perception, etc.
o May include polymorphic, unstable symptoms.
 If symptoms persist, diagnosis → schizophrenia.

Brief Psychotic Disorder

General Description

 Sudden onset of psychosis lasting:

o ≥1 day but <1 month
o Followed by full remission and return to baseline.
 Acute and transient psychotic syndrome.
 Uncommon disorder.
 Occurs more frequently in:
o Younger adults (20s, 30s)
o Women > men
 Patterns differ distinctly from schizophrenia.

Epidemiological Notes

 More frequent in:

o Low socioeconomic groups
o Those exposed to disasters or major cultural transitions (e.g., immigrants).
  Age of onset:
o Higher in industrialized settings.
o Lower in developing countries.

Etiology

 Unknown.
 Common in persons with personality disorders.
 Major psychosocial stressors increase risk.

Symptoms

 Must include ≥1 major psychotic symptom:

o Hallucinations
o Delusions
o Disorganized thoughts
o Abrupt onset
 May also include:
o Labile mood
o Confusion
o Impaired attention
o Emotional volatility
o Strange/bizarre behavior
o Screaming or muteness
o Impaired memory
 Some symptoms resemble delirium → medical assessment required.

Table 5-6 – Diagnostic Comparison

DSM-5

 Name: Brief psychotic disorder.

 Duration: ≥1 day but <1 month; return to baseline.
 Symptoms:
o Same as schizophrenia except negative symptoms not included.
 Required symptoms:
o At least 1 of first 3:
 Delusions
 Hallucinations
 Disorganized speech
o ± disorganized/catatonic behavior.
 Exclusions:
o Culturally sanctioned behaviors
o Substance use
o Other medical/mental conditions
  Specifiers:
o With marked stressors
o Without marked stressors
o With catatonia
o With peripartum onset (during pregnancy or ≤4 weeks postpartum)

ICD-10

 Does not distinguish between brief psychotic disorder and acute transient psychotic
disorder (defined in Table 5-5).

Delusional Disorder – Exam Notes (Bullet

Points)
Definition & Core Features
 Diagnosis is made when a person exhibits one or more delusions for ≥1 month.
 Delusions cannot be attributed to another psychiatric disorder.
 Delusions are often nonbizarre:
o Situations that can occur in real life (e.g., being followed, infected, secretly
loved).
o Phenomena are possible but not true.
 Several delusion types may be present.

DSM-5 vs ICD-10 Comparison (Key Points)

Diagnostic Name

 DSM-5: Delusional Disorder

 ICD-10: Delusional Disorder

Duration

 Minimum ≥1 month in both DSM-5 and ICD-10.

Symptoms

 DSM-5: Delusions (specifiers for types).

 ICD-10: Delusions; may have persistent hallucinations (usually mild).

Required Number of Symptoms

  DSM-5: ≥1 delusion.
 ICD-10: ≥1 delusion.

Psychosocial Consequences

 DSM-5: No marked functional impairment.

 ICD-10: Similar emphasis on relatively preserved functioning.

Exclusions

 Must not be better explained by:

o Schizophrenia
o Another medical condition
o Substance use
o Another mental illness
o Personality disorder (DSM-5)
o Psychosis, psychogenic reaction (ICD-10)

DSM-5 Specifiers
Types of Delusions

 Erotomanic: someone (often high-status) is in love with the patient.

 Grandiose: beliefs involving exceptional talent, power, or identity.
 Jealous: belief that partner is unfaithful.
 Persecutory: belief of being harmed, conspired against, spied on.
 Somatic: belief of bodily defects or illness.
 Mixed: more than one type without a single dominant theme.
 Unspecified: symptoms don’t fit other categories.

Content Specifier

 With bizarre content:

o Not related to reality/life experience.
o Not possible (e.g., thoughts being removed by aliens).

Course Specifiers

 First episode – acute

 First episode – partial remission
 First episode – full remission
 Multiple episodes – acute
 Multiple episodes – partial remission
  Multiple episodes – full remission
 Continuous
 Unspecified

Clinical Presentation
 Patients are:
o Usually well groomed, well dressed.
o No gross disintegration of personality or daily functioning.
o May appear eccentric, odd, suspicious, or hostile.
o Frequently litigious; may show this during interview.
 Mental Status Examination:
o Appears normal except for the delusional system.
 Patients may try to engage clinicians as allies in their delusions.
o Clinician should not collude → worsens confusion and future distrust.

Mood

 Mood is consistent with delusion content:

o Grandiose delusions → euphoric mood.
o Persecutory delusions → suspicious mood.
 Mild depressive symptoms often present.

Hallucinations

 By definition: no prominent or sustained hallucinations.

 If present: usually auditory, mild.

Cognition

 Generally normal, apart from delusional belief system.

Types of Delusional Disorders

 Persecutory (most common)
 Jealous (common)
 Erotomanic
 Somatic
 Grandiose
 Mixed
 Unspecified
Epidemiology & Etiology
 Rare disorder; epidemiology not well known.
 Likely a heterogeneous group of conditions.
 Etiology unknown; multiple theories.
 Many individuals function well and never seek psychiatric help.
 Often discovered when:
o Evaluated for another psychiatric disorder (e.g., MDD).
o Medical doctors notice odd responses during evaluation for medical issues.
 Disorder tends to be stable over time.

Prognosis
 Limited reliable prognosis data.
 Better prognosis:
o Persecutory
o Somatic
o Erotomanic
 Worse prognosis:
o Grandiose
o Jealous

Other Psychotic Disorders (Related Notes)

Miscellaneous Psychotic Presentations
 Some patients have psychotic symptoms not fitting classic categories, e.g.:
o Persistent auditory hallucinations only
o Delusions with marked mood symptoms
o Very transient psychotic symptoms
o Patient has full insight into their delusions or hallucinations

Shared Psychotic Disorder (Folie à Deux)

Definition

 Delusional symptoms in a person closely associated with someone who already has
delusional disorder.

Characteristics

 Transfer of delusion from primary case (dominant, chronically ill) to secondary case
(less intelligent, more passive, gullible, low self-esteem).
 Occurs after long-term, close relationship and social isolation.
 More common in:
o Sister–sister
o Husband–wife
o Mother–child
o Mostly occurs in families.
 If separated:
o Secondary case may abandon delusion but not always.

Risk Factors

 Old age
 Low intelligence
 Sensory impairment
 Cerebrovascular disease
 Alcohol abuse
 Possible genetic predisposition to idiopathic psychoses

Other Forms

 Folie simultanée:
o Two people become psychotic simultaneously and share delusion.
 Folie à trois/quatre/cinq/famille:
o More than two individuals involved (very rare)

OBJECTIVE TESTS FOR

SCHIZOPHRENIA & PSYCHOTIC
DISORDERS — BULLET POINT NOTES
General Points
 Schizophrenia and psychotic disorders are clinical diagnoses.
 No objective test is sufficiently sensitive or specific for diagnosis.
  Most tests are used to rule out other causes of psychosis (e.g., syphilis, anti-NMDA
receptor encephalitis).
 Some tests show average group-level abnormalities in schizophrenia (not diagnostic).

Objective Tests
Electrophysiological Tests

 Computerized EEG
o Shows differences in event-related potentials when comparing schizophrenia
patients vs. healthy controls.
o Not diagnostic → only useful in research.

Serologic Tests

 Used to rule out:

o Infections (e.g., syphilis)
o Autoimmune disorders (e.g., anti-NMDA receptor encephalitis)
o Metabolic or systemic causes of psychosis.

Diagnostic & Rating Scales for Schizophrenia

Purpose
 Mainly used in research and to measure symptoms/outcomes, not to diagnose.

Common Symptom Rating Scales

 PANSS (Positive and Negative Syndrome Scale)
o Tracks positive, negative, and general psychopathology symptoms.
 BPRS (Brief Psychiatric Rating Scale)
o Measures severity of psychotic symptoms.

Assessment of Extrapyramidal Symptoms

 SAS (Simpson Angus Scale): checks for drug-induced parkinsonism.
 AIMS (Abnormal Involuntary Movement Scale): evaluates tardive dyskinesia.
 BARS (Barnes Akathisia Rating Scale): assesses akathisia.
Psychological Testing
Neuropsychological Performance
 Patients with schizophrenia generally show:
o Poor vigilance
o Memory deficits
o Impaired concept formation
 Consistent with dysfunction of the frontotemporal cortex.

Comprehensive Neuropsychological Batteries

 Halstead–Reitan Neuropsychological Battery

 Luria–Nebraska Neuropsychological Battery
 Common abnormalities:
o Bilateral frontal & temporal lobe dysfunction
o Impairments in:
 Attention
 Retention time
 Problem-solving
o Motor impairments, possibly due to brain asymmetry.

Intelligence Tests
 Schizophrenia patients:
o Tend to have lower IQ scores than psychiatric and general population controls.
o Low intelligence often present at illness onset.
o Intelligence may decline further as the disorder progresses.

Projective & Personality Tests

 Rorschach Test and TAT
o May reveal bizarre ideation.
 MMPI (Minnesota Multiphasic Personality Inventory)
o Often abnormal in schizophrenia.
o Limited contribution to diagnosis or treatment planning.
DIFFERENTIAL DIAGNOSIS OF
PSYCHOTIC DISORDERS

1. Secondary Psychotic Disorders (Medical

Causes)
General Principles
 Evaluate aggressively for medical causes when:
o Symptoms are unusual, rare, or
o There is any change in consciousness.
 Obtain:
o Complete family history (medical, neurologic, psychiatric).
 Always consider medical causes even in:
o Patients already diagnosed with schizophrenia (e.g., could still have a brain
tumor).

Table 5-8 — Medical Etiologies of Delusional Syndromes

(Bullet Format)
A. Neurodegenerative Disorders

 Alzheimer’s disease
 Pick disease
 Huntington disease
 Basal ganglia calcification
 Multiple sclerosis
 Metachromatic leukodystrophy

B. Other CNS Disorders

 Brain tumors (temporal lobe or deep hemispheric)

 Epilepsy (especially complex partial seizures)
 Head trauma (e.g., subdural hematoma)
 Anoxic brain injury
 Fat embolism
C. Vascular Disease

 Atherosclerotic vascular disease (diffuse temporoparietal or subcortical lesions)

 Hypertensive encephalopathy
 Subarachnoid hemorrhage
 Temporal arteritis

D. Infectious Diseases

 HIV/AIDS
 Encephalitis lethargica
 Creutzfeldt–Jakob disease
 Syphilis
 Malaria
 Acute viral encephalitis

E. Metabolic Disorders

 Hypercalcemia
 Hyponatremia
 Hypoglycemia
 Uremia
 Hepatic encephalopathy
 Porphyria

F. Endocrinopathies

 Addison disease
 Cushing syndrome
 Hyperthyroidism / Hypothyroidism
 Panhypopituitarism

G. Vitamin Deficiencies

 Vitamin B12 deficiency

 Folate deficiency
 Thiamine deficiency
 Niacin deficiency

H. Medications

 Adrenocorticotropic hormones
 Anabolic steroids
 Corticosteroids
 Cimetidine
 Antibiotics (cephalosporins, penicillin)
  Disulfiram
 Anticholinergic agents

I. Substances

 Amphetamines
 Cocaine
 Alcohol
 Cannabis
 Hallucinogens

J. Toxins

 Mercury
 Arsenic
 Manganese
 Thallium

2. Mood Disorders with Psychotic Features

Major Depressive Episode with Psychosis
 Delusions/hallucinations usually mood-congruent:
o Guilt
o Self-depreciation
o Deserved punishment
o Incurable illness
 Psychotic symptoms resolve completely with depression remission.
 Severe depression may cause:
o Loss of functioning
o Poor self-care
o Social withdrawal
→ Must not be confused with negative symptoms.

Bipolar Disorder (Mania)

 Often has:
o Mood-congruent grandiose delusions
o Sometimes hallucinations
 Flight of ideas may mimic thought disorder.
 Key distinction:
o In mania, associative links are preserved → just rapid.
3. Personality Disorders
 Disorders with schizophrenia-like features:
o Schizotypal Personality Disorder
o Schizoid Personality Disorder
o Borderline Personality Disorder
 Features:
o Symptoms are milder.
o Lifelong pattern → no clear date of onset.
 Severe OCPD may mimic an underlying psychotic process.

4. Malingering & Factitious Disorders

Mimicking schizophrenia
 Malingering:
o Intentional, for external gain (financial, legal).
 Factitious disorder:
o Symptoms produced without clear gain; less aware of their behavior.

Challenges
 Hard to convincingly imitate schizophrenia before an experienced clinician.
 Some genuine schizophrenia patients may:
o Exaggerate symptoms for hospital admission or increased assistance.

COMORBIDITY (Bullet-Point Format)

Substance Use Disorders
 Extremely common in schizophrenia; lifetime prevalence ~74%.
 Most common comorbid substances: tobacco, alcohol, cannabis, cocaine.
 Almost 50% will have a severe drug/alcohol problem at some point.
 Explanatory models:
o Diathesis–stress model: biological vulnerability + stress (e.g., substance use) →
schizophrenia.
 o Self-medication hypothesis: substances used to reduce symptoms or medication
side effects.
o Shared vulnerability model: shared genetic/environmental risks affecting key
neural circuits (e.g., reward pathways), increasing both substance use during
adolescence and schizophrenia risk.

Complex Partial Epilepsy

 Schizophrenia-like psychosis more frequent in complex partial seizures, especially
temporal lobe epilepsy.
 Risk factors:
o Left-sided seizure focus
o Medial temporal lesion
o Early seizure onset
 Some symptoms overlap; may indicate temporal lobe dysfunction in schizophrenia as
well.

Obesity
 Patients have higher BMI than general population.
 Causes:
o Antipsychotic-induced weight gain
o Poor diet, reduced physical activity
 Consequences: higher risk of:
o Cardiovascular disease
o Diabetes
o Hyperlipidemia
o Obstructive sleep apnea

Diabetes Mellitus
 Increased risk of Type II diabetes.
 Linked to:
o Obesity
o Direct diabetogenic effects of some antipsychotics.
Cardiovascular Disease
 Many antipsychotics affect cardiac electrophysiology.
 Additional independent risk factors common in schizophrenia:
o Smoking
o Obesity
o Diabetes
o Hyperlipidemia
o Sedentary lifestyle
 Together → increased cardiac morbidity and mortality.

HIV
 Risk of HIV is 1.5–2× higher than general population.
 Likely due to risk behaviors:
o Unprotected sex
o Multiple partners
o Increased drug use

Chronic Obstructive Pulmonary Disease (COPD)

 Higher rates in schizophrenia patients.
 Smoking is a major contributor; unclear if other factors also contribute.

Rheumatoid Arthritis
 Schizophrenia associated with lower risk of rheumatoid arthritis.
 Inverse relationship observed in multiple studies.
 GWAS: negative genetic correlations → possible shared pathways but opposite risks.
 Mechanism still unclear; ongoing research.

COURSE OF SCHIZOPHRENIA
Onset of Schizophrenia
Premorbid Signs and Symptoms

 Appear before prodromal symptoms.

 Common premorbid personality traits:
o Schizoid or schizotypal traits
o Quiet, passive, introverted
o Few friends in childhood
 Adolescents may:
o Have no close friends, no dating
o Avoid team sports
o Prefer solitary activities (TV, music, gaming)
 Sudden onset of OCD-like behaviors may be part of prodrome.
 Early symptoms often misdiagnosed as:
o Malingering
o Chronic fatigue syndrome
o Somatic symptom disorder
 Families often think the illness starts at first hospitalization, but earlier signs typically
present for months to years.
 Signs may include:
o Somatic complaints (headaches, pain, digestive issues)
o Declining occupational/social/personal functioning
o Increased interest in abstract ideas, philosophy, religion, occult
 Additional prodromal symptoms:
o Peculiar behavior
o Abnormal affect
o Unusual speech
o Bizarre ideas
o Strange perceptual experiences

Emergence of Symptoms

 Typically begins in adolescence.

 Prodrome lasts days to months, sometimes ≥1 year.
 Triggered by stressors such as:
o Starting college
o Substance use
o Death of a family member
 Eventually progresses to overt psychotic symptoms.

Duration / Pattern of Illness

  Classic course = exacerbations and remissions.
 After first psychotic episode → partial recovery → relatively normal functioning → later
relapse.
 First 5 years after diagnosis predict long-term course.
 Each relapse → further decline in baseline functioning.
 Historically, incomplete return to baseline differentiated schizophrenia from mood
disorders.
 Postpsychotic depression may occur.
 Lifelong vulnerability to stress.
 Positive symptoms decrease over time, while negative symptoms may worsen.
 Approximately one-third maintain some functional social existence; the remainder
struggle with:
o Aimlessness
o Inactivity
o Multiple hospitalizations
o Homelessness, poverty (especially in urban areas)

OTHER DISORDERS (Course

Comparisons)
Schizoaffective Disorder
 Course is between schizophrenia and mood disorders.
 Prognosis: better than schizophrenia but worse than bipolar or major depressive
disorder.

Schizophreniform Disorder
 Patients who do not progress to schizophrenia have a better outcome than schizophrenia
patients.

SCHIZOPHRENIA — PROGNOSIS &

TREATMENT (BULLET-POINTS)

PROGNOSIS
Life Expectancy & Mortality
  Schizophrenia is associated with up to 20% reduction in life expectancy.
 Higher mortality rates from:
o Accidents
o Natural causes
 Increased mortality cannot be explained by institution- or treatment-related factors.
 Possible contributors:
o Clinical difficulty in diagnosing/treating medical and surgical conditions in these
patients
o Clinical neglect in some cases

Remission & Long-Term Outcome

 Reported remission rates: 10–60%.

 Reasonable estimate: 20–30% of patients can lead somewhat normal lives.
 20–30% continue to have moderate symptoms.
 40–60% remain significantly impaired for life.
 Overall prognosis:
o Schizophrenia patients fare much worse than mood disorder patients.
o But 20–25% of mood disorder patients are also severely impaired in long-term
follow-up.

Prognostic Indicators

 In the first 5–10 years after first hospitalization:

o Only 10–20% show a good outcome.
o >50% have a poor outcome, characterized by:
 Repeated hospitalizations
 Symptom exacerbations
 Episodes of major mood disorders
 Suicide attempts
 Schizophrenia does not always deteriorate progressively.
 Several factors predict good prognosis (Table 5-9).

Negative Symptoms

 Rare in schizophreniform disorder.

 When present → poor prognostic sign.
 Many with negative symptoms later develop schizophrenia.

TREATMENT APPROACH
General Principles
  Antipsychotics = mainstay of schizophrenia treatment.
 Psychosocial treatments (including psychotherapy) augment improvement.
 Because schizophrenia is complex, no single approach is sufficient.
 Psychosocial modalities must be integrated with pharmacotherapy.
 Combined treatment = better outcomes than either alone.

PROGNOSTIC FACTORS (TABLE 5-9)

Positive Prognostic Factors

 Acute onset
 Female sex
 Living in a developed country

Poor Prognostic Factors

 Insidious onset
 Childhood or adolescent onset
 Poor premorbid functioning
 Cognitive impairment
 Hospitalization

HOSPITALIZATION
Trends and Stats

 Major reductions in long-term institutionalization since 1950s due to:

o Effective antipsychotics
o Political and social changes
 Readmissions common: 40–60% within 2 years of first hospitalization.
 Schizophrenia patients occupy:
o ~50% of all psychiatric hospital beds
o ~16% of all psychiatric treatment recipients

Indications for Hospitalization

 Diagnostic clarification
 Medication stabilization
 Risk of suicide or homicide
 Grossly disorganized/inappropriate behavior
 Inability to meet basic needs:
 o Food
o Clothing
o Shelter
 Establishing links with community support systems

Hospitalization Duration & Environment

 Short stays (4–6 weeks) are as effective as long-term stays.

 Active behavioral programs are more effective than custodial care.
 Treatment plan goals:
o Self-care
o Quality of life
o Employment
o Social relationships
 Coordination with aftercare during hospitalization:
o Family homes
o Foster families
o Board-and-care homes
o Halfway houses
 Daycare centers + home visits help reduce rehospitalization.

PHARMACOTHERAPY
Acute Phase Treatment

 Patients often present with severe psychotic symptoms needing immediate care.
 Acute phase lasts 4–8 weeks.
 Antipsychotics = first-line in both acute and maintenance phases.
 Table 5-10 lists second-generation and key first-generation antipsychotics.

Choosing an Antipsychotic

 Most guidelines: start with second-generation antipsychotics (SGAs).

 Effective across a broad symptom range.
 Differences in efficacy are minimal; side-effect profiles are the key factor.

Managing Agitation in Acute Psychosis

 Medications used:
o Antipsychotics
o Benzodiazepines
 Intramuscular antipsychotics → faster calming.
 Advantages:
 o Single IM injection (first- or second-generation) can calm without excessive
sedation.
 Low-potency first-generation drugs → more sedation + postural hypotension.
 IM ziprasidone & olanzapine:
o Similar EPS profile to oral forms
o Do not cause substantial EPS
o Advantage over haloperidol/fluphenazine (which may cause dystonia/akathisia)
 Rapid-dissolving oral olanzapine = useful alternative to IM injections.
 Benzodiazepines (e.g., lorazepam):
o Reliable oral or IM absorption
o Reduce required antipsychotic dose

SIDE EFFECT MANAGEMENT

General Issue

 Side effects begin before clinical improvement.

 Patients may experience significant side effects even before benefit.

Extrapyramidal Side Effects (EPS)

 Common with:
o Most first-generation antipsychotics
o Some second-generation antipsychotics (less frequent)
 EPS types:
o Parkinsonism- resting tremors, muscular rigidity, bradykinesia (slowness of
movement), stooped posture
o Dystonias- upward deviation of eyes, twisting of the neck, jaw/tongue spasms
o Akathisia- inability to sit still, inner discomfort/anxiety, constant pacing or
shifting from foot to foot

Treating EPS

 Options:
o Reduce antipsychotic dose
o Add antiparkinson medication
o Switch to a drug with lower EPS risk
 Anticholinergic antiparkinson drugs → most effective but cause:
o Dry mouth
o Constipation
o Blurred vision
 o Memory loss
o Only partially effective
 β-blockers (e.g., propranolol 30–90 mg/day) helpful for akathisia
 Prophylactic antiparkinson meds considered for:
o Those with history of EPS
o High-dose high-potency antipsychotic use
o Young men (higher dystonia risk)

High Sensitivity to EPS

 Some patients experience severe EPS even at necessary therapeutic doses.

 For these individuals:
o Switch to medications with lower EPS risk.
 Risperidone:
o Can cause EPS even at 0.5 mg
o Higher risk >6 mg/day
 Olanzapine and ziprasidone:
o Dose-related parkinsonism & akathisia

Tardive Dyskinesia (TD)

 20–30% of long-term first-generation antipsychotic users develop TD.

 Annual incidence:
o 3–5% for young patients
o Much higher in elderly
 Can be severely disabling (affecting walking, breathing, eating, talking).
 High risk:
o Patients sensitive to acute EPS
o Patients with cognitive/mood disorders

Onset Timeline

 Movements begin:
o During antipsychotic treatment
o Within 4 weeks of stopping oral antipsychotic
o Within 8 weeks of stopping depot antipsychotic

Risk With SGAs

 SGAs have lower risk, but risk still exists.

Prevention & Management

1. Use lowest effective dose

 2. Prescribe cautiously in:
o Children
o Elderly
o Mood disorder patients
3. Regular exams for TD symptoms
4. Consider dose reduction or switching on appearance of TD
5. If worsening:
o Stop antipsychotic
o Switch
o Clozapine → effective for severe TD or tardive dystonia

Other Side Effects

 Sedation & postural hypotension

o More common with low-potency FGAs (e.g., perphenazine)
o Most severe during initial dosing
o May delay reaching therapeutic dose
o Sedation may persist → interferes with daily functioning
 Prolactin elevation
o All antipsychotics increase prolactin
o Leads to:
 Galactorrhea
 Irregular menses
 Decreased libido & sexual dysfunction
 Possible decreased bone density/osteoporosis
o Based on higher prolactin states (tumors); unclear if applies at lower elevations

Health Monitoring for SGAs

 Because SGAs affect insulin metabolism, monitor:

o BMI
o Fasting glucose
o Lipid profile
 Weigh patients & calculate BMI every visit for at least 6 months after med change.

CLOZAPINE
 Most effective antipsychotic, especially for treatment-resistant schizophrenia.
 Major side effects:
 o Agranulocytosis (~0.3%)
o Seizures (up to 5% at >600 mg)
o Myocarditis (rare)
o Hypersalivation
o Sedation
o Tachycardia
o Weight gain
o Postural hypotension

Monitoring Requirements

 Mandatory blood monitoring system:

o First 6 months: weekly
o Next 6 months: biweekly
o Thereafter: monthly

Treatment Position

 Used after failure of at least two antipsychotic trials.

Duration and Prophylaxis (Maintenance Phase)

 Maintenance/stable phase = relative remission stage.
 Goals:
o Prevent psychotic relapse.
o Improve patient functioning.
 Newer antipsychotics ↓ risk of tardive dyskinesia → reduced concerns about long-term
use.
 Patients in this phase usually show minimal psychotic symptoms.
 Relapse rates:
o With antipsychotic treatment: 16–23% relapse within 1 year.
o Without medications: 53–72% relapse within 1 year.
 First-episode psychosis:
o Maintain treatment for at least 1 year.
o High relapse risk persists for 5 years.
o Some experts believe 1 year is inadequate, especially for those working or
studying (higher functional loss if relapse occurs).
 Two or more psychotic episodes:
o Most experts recommend indefinite treatment.

Acute Treatment Failures

1. Addressing Noncompliance

 Noncompliance with long-term antipsychotics is very high: 40–50% become

noncompliant within 1–2 years.
 Long-acting injectable (LAI) antipsychotics help improve adherence, especially in high-
risk patients.
 Evidence (especially real-world) supports that LAIs ↓ relapse and ↑ adherence.
 Oral supplementation required initially until LAI plasma levels stabilize.
 Available LAI formulations include:
o Fluphenazine
o Haloperidol
o Risperidone
o Paliperidone
o Aripiprazole
o Olanzapine
 Advantages of LAIs:
o Clinicians can quickly detect noncompliance and intervene before the drug effect
ends.
o More stable blood levels → easier to find minimum effective dose.
o Many patients prefer injections to daily pills.

2. Selecting Second Treatment Options

 In acute schizophrenia:
o ~60% achieve complete remission or only mild symptoms.
o ~40% show improvement but continue to have persistent positive symptoms.
 Meta-analysis:
o Lack of improvement by Week 2 = low likelihood of later benefit → consider
switching medication.
 Better to consider response along a spectrum (degree of improvement) rather than
responder vs nonresponder.
 Some severely resistant patients may require chronic institutional care.
 Others show partial improvement but continue to have hallucinations or delusions.

Adequate Drug Trial

 Adequate trial = 4–6 weeks at a therapeutic dose.

 Mild improvement during this period may continue for 3–6 months.
 Plasma concentration monitoring can confirm adequate dosing:
o Levels most established for first-generation antipsychotics.
o Less rationale for checking levels in second-generation antipsychotics.
 Low plasma level may indicate:
 o Noncompliance or partial compliance.
o Rapid metabolism.
o Poor absorption.
o → Increasing the dose may help.
 If plasma level is high → consider whether side effects are limiting therapeutic response.

If Poor Response to Treatment

 Increasing dose above usual therapeutic levels rarely improves outcome.

 Switching to another antipsychotic is preferred.

Role of Clozapine

 Clozapine is effective for poor responders to other antipsychotics.

 Double-blind studies show strongest benefits:
o In patients with the most severe psychotic symptoms.
o In those who previously responded poorly to other antipsychotics.

Adjunctive Medications (Mixed Success)

 Lamotrigine
 Mirtazapine
 Donepezil
 D-alanine
 D-serine
 Estradiol
 Memantine
 Allopurinol

Other Somatic Treatments

Electroconvulsive Therapy (ECT)

 Studied in both acute and chronic schizophrenia.

 In recent-onset schizophrenia:
o ECT ≈ antipsychotics in effectiveness.
o More effective than psychotherapy alone.
  Combining ECT + antipsychotics > antipsychotics alone.
 Antipsychotics should be continued during and after ECT.

Neuromodulation

 Preliminary studies show potential benefit for:

o Hallucinations
o Negative symptoms
 Techniques studied:
o Transcranial magnetic stimulation (TMS)
o Transcranial direct current stimulation (tDCS)

Psychosurgery

 No longer considered appropriate treatment.

 Still performed in rare, experimental cases for severe and intractable schizophrenia.

Psychosocial Therapy – Bullet Points

General Principles
 Psychotherapy is an essential component of schizophrenia treatment.
 Combined therapy (psychotherapy + medication) → better adherence, fewer negative
symptoms, improved functioning.
 No single psychotherapeutic approach proven superior; structured approaches preferred
over open-ended/exploratory ones.
 Psychosocial therapies aim to improve:
o Social abilities
o Self-sufficiency
o Practical/vocational skills
o Interpersonal communication
 Goal: help severely ill persons achieve independent living.
 Delivered in hospitals, outpatient centers, community mental health centers, day
hospitals, home-based care, and social clubs.

Cognitive Behavioral Therapy (CBT)

 Used to:
 o Improve cognitive distortions
o Reduce distractibility
o Correct judgment errors
o Reduce delusions and hallucinations in some patients
 Best suited for patients with some insight; usually offered after acute episode resolves.
 Components:
o Cognitive restructuring
o Self-monitoring
o Graded coping skills
 Evidence:
o One RCT shows benefit as sole treatment.
o Most experts recommend CBT as an adjunct to antipsychotics.

Social Skills Training (Behavioral Skills Therapy)

 Targets non-psychotic social/behavioral deficits:
o Poor eye contact
o Delayed responses
o Odd facial expressions
o Lack of spontaneity
o Poor emotion perception in others
 Techniques:
o Video modeling (patient + others)
o Role-play
o Homework assignments for practicing skills
 Benefits:
o Reduces relapse rates
o Reduces hospitalization needs

Group Therapy
 Improves social functioning; reduces negative symptoms.
 Focus:
o Real-life plans
o Daily problems
o Relationships
 Types: behavioral, psychodynamic/insight-oriented, supportive.
 Dynamic insight therapy not very useful for many schizophrenia patients.
 Benefits:
o Reduces social isolation
o Improves cohesiveness
 o Enhances reality testing
 Supportive groups most helpful.

Family-Oriented Therapies
 Effective in reducing relapse and rehospitalization.
 Includes:
o Psychoeducation
o Problem-solving training
o Practical guidance
 Particularly useful because patients often return home in partially remitted states.
 Intensive short-term family therapy (even daily) can be helpful.
 Focus:
o Immediate issues
o Anticipating/avoiding trouble
o Quick resolution when problems arise
 Family members may unintentionally push patient too quickly into normal routines.
 Therapy must also address:
o Understanding of schizophrenia
o Discussion of the psychotic episode
o Reducing shame via open discussion
o Managing fear of symptoms
 Therapist must manage emotional intensity in sessions.
 High emotional expression during sessions can worsen recovery.

Case Management
 Ensures coordination of multidisciplinary services (psychiatrists, social workers, OTs,
etc.).
 Responsibilities:
o Appointment tracking
o Treatment adherence
o Home visits
o Accompanying patient to work if needed
 Effectiveness depends on the case manager’s competence.
 Small caseload (<20 patients) improves outcomes; often difficult due to system
constraints.
Assertive Community Treatment (ACT)
 Developed in Madison, Wisconsin (1970s).
 Features:
o Multidisciplinary team (case manager, psychiatrist, nurse, primary care
physician).
o Fixed caseload.
o Services delivered wherever needed.
o 24/7 availability.
o Mobile, intensive support.
 Services include:
o Home-delivered medications
o Mental + physical health monitoring
o In-vivo social skills training
o Frequent family contact
 High staff-to-patient ratio (1:12).
 Very effective in reducing rehospitalization.
 Limitations: labor-intensive, expensive.
 Evidence:
o Low-quality but suggests intensive case management ↓ hospitalization time, ↑
treatment adherence.
o Case management most effective when integrated with ACT.

Individual Psychotherapy
 Provides additive benefits alongside medication.
 Requires:
o Safe therapeutic environment
o Therapist reliability
o Appropriate emotional distance
o Genuineness
 Psychotherapy for schizophrenia requires:
o Long-term engagement (think in decades, not months).
 Strong therapeutic alliance predicts:
o Lower dropout rates
o Better medication adherence
o Good outcomes at 2-year follow-up
 Challenges:
o Patients may fear closeness
o May become suspicious, anxious, hostile, or regressive
 Therapist approach:
o Respect distance and privacy
o Be direct, patient, sincere, sensitive
 o Avoid premature informality
o Avoid exaggerated warmth (may be misinterpreted)

Vocational Therapy & Supported Employment

 Helps patients regain or develop work skills.
 Settings:
o Sheltered workshops
o Job clubs
o Part-time/transitional employment
 Employment is both a marker of and path toward recovery.
 Some patients can perform excellent or specialized work despite illness.
 Supported employment:
o Focuses on competitive jobs
o Strong evidence for helping patients obtain/maintain employment
o Improves self-esteem
o Reduces treatment need
o Less consistent impact on overall illness course

Art Therapy
 Benefits:
o Provides an outlet for intense internal imagery
o Facilitates communication
o Helps externalize frightening internal experiences

Cognitive Remediation (Cognitive Training)

 Behavioral therapy aimed at improving cognitive processes.
 Uses computer-based exercises to:
o Strengthen neural networks
o Improve working memory
o Enhance cognitive functioning
 Leads to improved social functioning.
 Meta-analysis: medium effect size.
NAMI (National Alliance on Mental Illness)
 Provides:
o Support groups for patients + families
o Practical guidance on navigating healthcare systems
o Emotional support
 Advocates for:
o Destigmatization of mental illness
o Government awareness of patient/family needs
o Rights of persons with mental illness

EPIDEMIOLOGY OF SCHIZOPHRENIA &

OTHER PSYCHOTIC DISORDERS
Incidence & Prevalence

 Worldwide lifetime prevalence ≈ 0.7%.

 Meta-analysis (101 studies, 1990–2015):
o Mean global lifetime prevalence of psychotic disorders = 7.49/1000 (~0.75%).
o Five-fold variation across studies due to:
 Different populations/settings
 Different diagnostic criteria
 Different included diagnoses
 Study quality differences
 In the U.S.:
o 0.05% of the total population treated for schizophrenia annually.
o Only ~50% of schizophrenia patients receive treatment.

Sex Differences

 Equal prevalence in men and women.

 Men:
o Earlier onset.
o 50% hospitalized before age 25.
o More negative symptoms.
 Women:
o ~33% hospitalized before age 25.
o Better premorbid social functioning.
o Better overall outcome.
Age of Onset

 Men: peak onset 10–25 years.

 Women: peak onset 25–35 years, with bimodal distribution:
o Second peak in middle age.
o 3–10% have onset after age 40.
 90% of treated patients are between 15–55 years.
 Rare onset <10 or >60 years.
 Late-onset schizophrenia = onset after 45 years.

Other Factors Affecting Epidemiology

Seasonality of Birth

 Higher risk if born in winter/early spring.

 Northern Hemisphere: Jan–Apr.
 Southern Hemisphere: Jul–Sep.

Maternal / Perinatal Factors

 Delivery complications.
 Maternal malnutrition.
 Maternal infections/illnesses.

Early Life Experiences

 Childhood trauma.
 Social isolation.
 Deprivation.

Urban Upbringing

 Being raised (more than being born) in cities ↑ risk.

 Dose-related effect: larger city → higher risk.

Cannabis Use

 Cannabis associated with psychosis.

 Heavy use ↑ schizophrenia risk by up to 40%.

Cognitive Deficit Risk

  Poor verbal learning, memory, slower processing speed may predict impending
psychosis.

Other Psychotic Disorders

Schizoaffective Disorder

 Less common than schizophrenia: 0.5–0.8%.

 Sex differences resemble mood disorders:
o Depressed subtype → more women.
o Bipolar subtype → equal sexes; more common in younger individuals.
 Women tend to have later onset than men.

Schizophreniform Disorder

 Incidence/prevalence not well known.

 ~Half as common as schizophrenia.
 More common in men.
 Most common in adolescents and young adults.
 Relatives more likely to have mood disorders (often with psychotic features).

NEUROBIOLOGY OF SCHIZOPHRENIA

Anatomic Findings
Cerebral Ventricles

 CT: lateral & third ventricle enlargement.

 Reduction in cortical volume, especially early in disease.
 Mixed evidence on progression:
o Some studies → abnormalities present at onset & non-progressive.
o Others → progressive pathology.

Reduced Symmetry

 Reduced symmetry in temporal, frontal, occipital lobes.

 Suggests disrupted brain lateralization during fetal neurodevelopment.
Limbic System

 Decreased size of:

o Amygdala
o Hippocampus
o Parahippocampal gyrus
 Hippocampus also shows:
o Glutamate transmission abnormalities
o Neuronal disorganization (seen in tissue sections).

Prefrontal Cortex

 Postmortem evidence of anatomical abnormalities.

 Functional imaging shows hypofunction.
 Symptoms resemble those with prefrontal lobotomy/frontal lobe syndromes.

Thalamus

 Volume shrinkage in some studies.

 Medial dorsal nucleus → fewer neurons.
 30–45% reduction in neurons, oligodendrocytes, astrocytes.
 Not due to antipsychotics: similar findings in neuroleptic-naive patients.

Basal Ganglia & Cerebellum

 Abnormal movements in schizophrenia even without medication → implicates these

regions.
 Movement disorders in basal ganglia diseases (e.g., Huntington’s, Parkinson’s) often
include psychosis → theoretical relevance.
 Inconclusive findings on cell loss/volume reduction.
 ↑ D2 receptors in caudate, putamen, nucleus accumbens (possibly medication-related).
 Serotonergic involvement suggested due to efficacy of serotonin-antagonist
antipsychotics.

Physiologic Findings
Functional Imaging

 PET:
o ↑ Dopamine in ventral striatum.
o ↓ Dopamine in frontal cortex.
 MR spectroscopy:
o ↑ Glutamate (prefrontal, medial temporal).
 o ↓ N-acetyl aspartate (marker of neurons) in hippocampus & frontal lobes.

Electrophysiology

 EEG abnormalities:
o Increased sensitivity to activation (e.g., spikes after sleep deprivation).
o ↓ Alpha, ↑ theta & delta activity.
o Possible ↑ epileptiform activity.
o Possible ↑ left-sided abnormalities.
 Sensory filtering deficits:
o Difficulty ignoring irrelevant sounds → contributes to auditory hallucinations.
o Believed to have genetic basis.

Evoked Potentials

 P300:
o Smaller amplitude in schizophrenia.
o Originates in medial temporal limbic structures.
o Abnormal in high-risk children as well.
 Other abnormalities:
o N100
o Contingent Negative Variation (CNV)
 Pattern:
o Larger early evoked potentials (↑ sensitivity).
o Smaller late evoked potentials (↓ higher-order processing).

Eye Movement Dysfunction

 Defects in smooth pursuit & saccadic inhibition.

 Seen in 50–85% of patients.
 Present in 10% or fewer of normal controls.
 Also seen in first-degree relatives → possible trait marker.
 Independent of drug treatment.

Prepulse Inhibition Deficits

 Failure of normal startle suppression by a weak prepulse.

 Found in patients and their relatives.
 Controlled by dopamine → supports dopamine role.

Neurotransmitters & Receptors

Dopamine
  Excessive dopamine release correlates with positive symptoms.
 PET shows:
o ↑ subcortical dopamine synthesis & content (especially associative striatum).
 These changes:
o Precede illness onset.
o Are present in high-risk individuals.
o Predict treatment response.

Glutamate & GABA

 ↑ Glutamate, especially prefrontal & temporal regions.

 ↓ GABA; loss of GABAergic neurons in hippocampus.

Other receptor findings

 ↓ Muscarinic & nicotinic receptors in caudate-putamen, hippocampus, and prefrontal

cortex.
 Leads to cognitive impairments.
 NMDA receptor hypofunction due to glutamate/dopamine imbalance.

Psychoneuroimmunology
 Immune abnormalities in schizophrenia:
o ↓ T-cell IL-2 production.
o ↓ peripheral lymphocyte number & responsiveness.
o Abnormal cellular/humoral reactivity to neurons.
o Presence of antibrain antibodies.
 Supports hypotheses of:
o Neurotoxic viral involvement
o Autoimmune processes
 Related findings:
o Autoimmune diseases (e.g., SLE encephalitis) can produce psychosis.
o Anti-NMDA receptor encephalitis can mimic early schizophrenia.

Psychoneuroendocrinology
 Many studies report neuroendocrine differences between schizophrenia patients and
healthy controls.
 Dexamethasone suppression test (DST) abnormalities reported in subgroups of
schizophrenia patients.
o However, DST lacks practical or predictive value for diagnosis.
  Some findings show decreased luteinizing hormone (LH) and follicle-stimulating
hormone (FSH).
o May correlate with age of onset and duration of illness.
 Two endocrine abnormalities associated with negative symptoms:
o Blunted prolactin and growth hormone release after GnRH (gonadotropin-
releasing hormone) or TRH (thyrotropin-releasing hormone) stimulation.
o Blunted growth hormone release following apomorphine stimulation.

Infections
 Support for infections in schizophrenia is mostly indirect.
 Higher likelihood of schizophrenia in those born in winter months → suggests a
season-specific factor (possibly viral).
 Epidemiologic studies:
o Increased schizophrenia risk after prenatal influenza exposure during multiple
flu epidemics.
o Strongest association when exposure occurs during the second trimester.
 Influenza is more common in winter, consistent with seasonality findings.
 Other evidence supporting viral involvement:
o ↑ physical anomalies at birth.
o ↑ pregnancy and birth complications.
o Seasonality of birth patterns compatible with viral infections.
o Geographical clusters of adult schizophrenia cases.
o Seasonality of hospitalizations for psychosis.
 Viral theories are attractive because certain viruses can cause localized CNS pathology
that matches schizophrenia symptoms without causing overt febrile encephalitis.

Environmental Factors
 Other prenatal/perinatal risk factors contributing small but significant risk:
o Birth complications.
o Trauma after delivery.
o Nutritional deficiencies.
o Any factor impairing healthy neurodevelopment.

Genetics of Schizophrenia
Inheritance Patterns
 Twin & family studies since the 1930s show schizophrenia is highly heritable.
 Heritability = 60–80%.
 Risk increases with closeness of genetic relationship:
o Monozygotic twins: ~50% concordance.
o Dizygotic twins: 4–5× lower than monozygotic twins.
o Similar low rates in other first-degree relatives (siblings/parents/offspring).
 Declining rates in second- and third-degree relatives support genetic loading patterns.
 Adoption studies:
o Higher schizophrenia rates among biological relatives of adopted-away
individuals with schizophrenia.
o Lower rates among adoptive relatives → strong evidence for genetic
contribution.
 Monozygotic twin discordance shows genetics alone are insufficient → environmental
factors must interact with vulnerability.
o Supports the vulnerability–liability model (gene × environment interaction).

Paternal Age Effect

 Higher schizophrenia risk in individuals born to fathers > 60 years.

 Possibly due to epigenetic damage accumulating in sperm with age.

Genetic Studies
 Exact mode of inheritance is unknown.
 Multiple genes implicated; many findings are associative and may be chance.
 Modern techniques transforming research:
o Comparative genomic hybridization
o SNP chips
o Next-generation sequencing (NGS)
o GWAS
o CRISPR/Cas9
 Candidate genes commonly involve synaptic transmission, including:
o Monoamine receptor genes.
o Genes for glutamate release and signaling.

Dopamine-Related Genes

 Many studies focus on dopamine regulation genes due to dopamine’s central role in
schizophrenia.
 Example:
 o COMT polymorphisms → enzyme involved in dopamine metabolism (& other
catecholamines).

Copy Number Variations (CNVs)

 CNVs may account for 2–5% of schizophrenia cases.

 These variants are highly penetrant but rare.
 Often involve genes for synaptic function and neurodevelopment.
 Example:
o 22q11.2 microdeletion → causes velocardiofacial (DiGeorge) syndrome,
associated with psychosis.
o Incidence ~ 1 in 4,000 births.

Common Alleles

 Most genetic risk due to hundreds of common alleles, each with small effect size.
 GWAS findings:
o Multiple implicated loci including DRD genes (dopamine receptors).
o Other genes related to:
 Glutamate function
 Calcium signaling
 Dendritic spine formation
 Neurodevelopmental processes
 Increasing focus on genes regulating the immune system and synaptic pruning.

Regulatory (Non-Coding) Genes

 Many schizophrenia-associated genes do not code for proteins.

 Instead, they influence:
o Transcription
o Gene expression regulation
o Epigenetic mechanisms

Endophenotypes
 Heterogeneity in schizophrenia → genetic signals may be obscured.
 Researchers aim to identify endophenotypes that map better to genetics.
 Prepulse inhibition is a strong candidate (also abnormal in relatives).
 Other measurable endophenotype traits exist and allow for quantitative analysis.
THE PSYCHOLOGY OF
SCHIZOPHRENIA – BULLET POINTS

Family Dynamics
 Early study of 4-year-old British children:
o Children rated as having a poor mother–child relationship had a six-fold
increase in schizophrenia risk.
o Causality unclear:
 Poor relationship may precede disorder.
 OR child’s early disease-related deficits may impair closeness.
 Adoption findings:
o Children adopted away from biological mothers had higher schizophrenia risk if
raised in adverse environments.
 Kibbutz study:
o Children of schizophrenic mothers raised in kibbutzim had higher
schizophrenia rates than those raised in family homes.
 No well-controlled evidence that any specific family pattern causes schizophrenia.
 Some individuals with schizophrenia come from dysfunctional families, but so do many
without psychiatric illness.
 Important clinical caution:
o Pathologic family behavior should not be overlooked.
o Dysfunction can significantly increase emotional stress on a vulnerable patient.

ETIOLOGY

Biologic Theories
Dopamine Hypothesis

 Simplest formulation: schizophrenia results from too much dopaminergic activity.

 Theory evolved from two main observations:
o Efficacy and potency of antipsychotic drugs correlate with D2 receptor
antagonism.
o Drugs that increase dopamine (cocaine, amphetamine) are psychotomimetic.
 Supportive evidence:
 o Dopamine-regulated functions (e.g., prepulse inhibition) are abnormal in
schizophrenia.
 The basic theory does not specify:
o Whether excess activity comes from too much dopamine, too many receptors,
receptor hypersensitivity, or combinations.
o Which dopamine pathways are specifically involved.
 Historical model:
o Dysfunction of mesolimbic pathway linked to positive symptoms.
o Supported by:
 Seizures/tumors in mesolimbic regions → schizophrenia-like symptoms.
 Amphetamines affect nucleus accumbens; antipsychotics in this area
reverse effects.
 Later findings:
o Striatum plays a major role (traditionally associated with motor function).
o Functional neuroimaging:
 Most significant dopamine abnormalities found in dorsal striatum.
 Seen in both patients and high-risk individuals.
o Striatum's integrative role:
 Helps explain associative deficits.
o Role in habit formation:
 Supports view of psychosis as rigid, habitual thinking with difficulty
considering alternative explanations.

Serotonin

 Current hypotheses: serotonin excess may cause both positive and negative symptoms.
 Clozapine:
o Strong serotonin antagonist.
o Effectiveness in reducing positive symptoms supports serotonin-based models.

GABA

 Some patients show loss of GABAergic neurons in the hippocampus.

 GABA regulates dopamine activity.
 Loss of inhibitory GABA neurons → dopaminergic hyperactivity.

Neuropeptides

 Neuropeptides such as substance P and neurotensin:

o Located alongside catecholamines and indoleamines.
 o Influence neurotransmitter activity.
 Altered neuropeptide function may facilitate or inhibit neuronal firing patterns.

Glutamate

 Phencyclidine (PCP), a glutamate antagonist, produces schizophrenia-like syndrome.

 Multiple hypotheses:
o Hyperactivity
o Hypoactivity
o Glutamate-induced neurotoxicity

Acetylcholine and Nicotine

 Some studies suggest:

o Deficits in muscarinic and nicotinic receptors.
 These receptors help regulate systems involved in cognition, which is impaired in
schizophrenia.

Neural Circuits (Disconnect Hypothesis)

 Shift from localized lesion models to neural circuit dysfunction models.

 Basal ganglia and cerebellum:
o Reciprocally connected with frontal lobes.
o Abnormal frontal activity may originate from dysfunction in these areas, not just
frontal lobe pathology.
 Possible developmental lesion in dopaminergic tracts to PFC:
o Leads to disturbances in prefrontal and limbic functions.
o Produces positive symptoms, negative symptoms, and cognitive deficits.
 Significant findings:
o Relationships between:
 Hippocampal abnormalities
 Prefrontal cortex metabolism/function
 Neural circuits and symptom types:
o Anterior cingulate–basal ganglia–thalamocortical circuit → positive
symptoms.
o Dorsolateral prefrontal circuit → primary negative/deficit symptoms.
 Cognitive impairments:
o Disrupted working memory circuits (PFC, cingulate, inferior parietal cortex,
hippocampus).
 Hallucinations:
 o Supported by imaging studies contrasting hallucinating vs non-hallucinating
patients.

Viruses, Neurotoxicity, Neuroinflammation

 Viral investigations:
o Most carefully conducted studies show no direct evidence of viral neurotoxicity.
o Epidemiological correlations exist but lack genetic confirmation.
 Autoimmune hypotheses:
o Some support for brain antibodies.
o Likely applies only to a subset.
 Neurotoxicity model:
o Psychosis increases stress/cortisol, → potential brain changes.
o Exogenous toxins (cannabis, alcohol) may contribute.
o Some evidence implicates antipsychotics.
o However, lack of neurodegeneration evidence weakens this model.
 Neuroinflammation:
o Many patients show immune activation markers.
o Some overlap between schizophrenia and autoimmune disorders.
 Genetic findings:
o GWAS show involvement of genes regulating immune response:
 Especially MHC region.
 Specific genes involved in synaptic pruning.

Schizophrenia as a Neurodevelopmental Disorder

 Evidence supporting neurodevelopmental model:

o Patients often had motor and cognitive impairments in childhood.
o Obstetric complications are risk factors.
o Cognitive deficits typically do not worsen significantly after onset.
 Neuropathological support:
o Lack of gliosis suggests abnormalities due to improper development rather than
degeneration.
 Genetic evidence:
o Many implicated genes are expressed prenatally.
o Some genes affect placental sensitivity to stress.
 Synaptic pruning:
o Strongest genetic links involve MHC C4 alleles.
o These genes regulate synaptic pruning during adolescence → symptoms emerge
during this period.
Multiple Dysfunction Model

 Schizophrenia likely involves:

o Multiple network dysfunctions rather than a single lesion.
 Hallucination circuitry:
o Visual hallucinations → occipital regions, striatum, thalamus.
o Auditory hallucinations → auditory cortex, hippocampus, amygdala, thalamus.
 Insight loss:
o Often linked to corticostriatal lesions and dopamine dysfunction.
 Affective reactions:
o Involve additional circuits beyond perceptual ones.
 Antipsychotics:
o Effective mainly for dopamine-related circuits.
o Limited effect on negative and cognitive symptoms.

Psychosocial Theories
General Concept

 Even if schizophrenia is a brain disorder, its course is influenced by:

o Psychosocial stress, similar to other medical illnesses.
 Each patient has:
o A unique psychological makeup.
 Psychodynamic theories may seem outdated but still inform understanding of:
o How patients experience their symptoms.
o How schizophrenia affects the psyche.

Psychoanalytic Theories
Freud

 Schizophrenia due to:

o Developmental fixations early in life → defects in ego development.

Mahler & Federn

 Focused on:
o Distortions in mother–infant relationship.
Harry Stack Sullivan

 Schizophrenia as:
o A disturbance in interpersonal relatedness.
o An adaptive method to avoid panic, terror, and self-fragmentation.
o Pathologic anxiety arises from cumulative early traumas.

Object Relations Deficit Model

 Normal process:
o People “introject” early relationships and use them to navigate new relationships.
 In schizophrenia:
o Neurodevelopmental defects distort filters interpreting environmental input.
o Introjected models become:
 Distorted, incomplete, and perceived as dangerous.
 Consequences:
o Relationship avoidance → fewer corrective experiences.
o Reality becomes terrifying → leads to alternate reality formation (psychosis).
 Strengths of the model:
o Explains both positive and negative symptoms.
o Provides treatment direction:
 Therapist supplies positive relational experiences for healthier introjection.

Common Themes Across Psychodynamic Approaches

 Psychotic symptoms have meaning.
 Grandiosity may follow injured self-esteem.
 Human relatedness may be experienced as terrifying.
 Insight-oriented psychotherapy:
o Mixed evidence for efficacy.
o More helpful when patients can integrate psychotic experiences.
o Renewed interest in combining long-term therapy with medication.

Learning Theories
 Children who later develop schizophrenia may:
o Learn irrational reactions and distorted thinking patterns from:
 Parents with significant emotional problems.
 Poor interpersonal relationships may arise from:
o Poor childhood models for learning social behavior.