Schizophrenia Spectrum and Other Psychotic Disorders – Comprehensive Bullet-Point Notes

Introduction

• Schizophrenia spectrum = heterogeneous group; “syndrome,” not single disease

• Affects perception, emotion, cognition, thinking, behavior; course usually chronic, onset <25 y

• Financial burden in U.S. > all cancers combined; 15–45\% of homeless population; global top-25 cause of disability

Epidemiology & Impact

• Lifetime prevalence \approx 0.7\% (range 0.4–1.0\%)

• Incidence shows 5\times variation across studies due to methods

• Sex: equal prevalence; men earlier onset (peak 10–25 y), women bimodal (second peak >40 y)

• Seasonality: excess winter/early-spring births (N. Hemisphere Jan–Apr; S. Hemisphere Jul–Sep)

• Risk factors: obstetric complications, maternal malnutrition/infection, urban upbringing, cannabis (heavy use ↑ risk \sim40\%), childhood trauma, cognitive deficits

• Reduced risk: rheumatoid arthritis (negative genetic correlation)

Clinical Presentation

General

• No single pathognomonic sign; rely on longitudinal history + MSE

• Presentations range from disheveled, screaming to obsessively groomed, mute

• Symptom fluctuation; consider education, intelligence, culture

Appearance & Behavior

• Poor grooming, warm clothing, tics, stereotypies, mannerisms, echopraxia

• Case AB illustrates disorganized, child-like behavior, regression

Catatonia

• Stupor, mutism, negativism, waxy flexibility; can alternate with excitement

• Less-extreme: social withdrawal, minimal speech/movement

• Risks: malnutrition, hyperpyrexia, self-injury; require monitoring

Neurological Signs

• Soft signs: dysdiadochokinesia, astereognosis, primitive reflexes, ↓ dexterity

• Hard signs: tics, tone changes, abnormal ocular pursuit, ↑ blink rate (hyper-DA)

• Nondominant parietal signs: prosody deficits, apraxia, right–left disorientation

Mood & Affect

• Negative: flat/blunted affect, anhedonia

• Positive: inappropriate rage, ecstasy, terror, ambivalence

• Differentiate from drug-induced parkinsonism or depression

Thought Process (Formal Thought Disorder)

• Loose associations, circumstantiality, tangentiality, neologisms, echolalia, word salad, mutism

Thought Content (Delusions)

• Persecutory, grandiose, religious, somatic; ideas of reference, thought control/broadcasting, thought insertion/withdrawal, loss of ego boundaries, cosmic identity

Hallucinations

• Auditory most common (voices commenting/conversing)

• Visual common; olfactory, gustatory, tactile rare ⇒ rule out medical causes

• Cenesthetic sensations: burning brain, pushing vessels, cutting marrow

• Case of 48-y-o man valuing hallucinated 17th-century courtiers

Cognition

• Oriented; subtle deficits in attention, working & episodic memory, executive function

• Cognitive impairment predicts functional outcome > psychosis severity

Insight, Judgment, Reliability

• Classic poor insight → non-adherence; assess domains specifically

Safety Concerns

• Violence ↑ 49–68\% vs general pop; risk: persecutory delusions, past violence, neuro deficits

• Suicide: lifetime attempt 20–50\%; death 5–13\% (young men with insight/decline highest risk). Clozapine ↓ suicidality

• Homicide not ↑ except in specific cases

Symptom Clusters

Positive (Table 5-1)

• Hallucinations, delusions, bizarre behavior, positive FTD

Negative (Table 5-2)

• Affective flattening, alogia, avolition, anhedonia-asociality, attentional deficits

Cognitive

• Impaired attention, working memory, executive function

Special Populations

• Childhood-onset: insidious, chronic, poor prognosis; distinguish from ASD/ID

• Late-onset (>45 y): more women, predominantly paranoid, better prognosis

Diagnostic Criteria (DSM-5 vs ICD-10)

• 2+ core symptoms (delusions, hallucinations, disorganized speech, disorganized/catatonic behavior, negative) for \ge6 mo (DSM-5) / \ge1 mo (ICD-10)

• Specify course: first-episode (acute/partial/full), multiple episodes, continuous, unspecified

• Catatonia specifier: \ge3 of stupor, catalepsy, waxy flexibility, mutism, etc.

• Subtypes (paranoid, hebephrenic, catatonic, undifferentiated, residual) retained in ICD-10 only

Related Psychotic Disorders

Schizoaffective

• Mood episode present majority; \ge2 wk psychosis w/o mood; bipolar vs depressive type

Schizophreniform

• Same symptoms as schizophrenia; duration 1–6 mo; 60–80\% convert

Brief Psychotic Disorder

• Sudden onset; duration 1 d–<1 mo; return to baseline; with/without stressors/peripartum

Delusional Disorder

• Nonbizarre delusions \ge1 mo; minimal impairment; erotomanic, grandiose, jealous, persecutory, somatic, mixed

Shared Psychosis (folie à deux)

• Induced delusion in closely associated, socially isolated pair/group; management ⇒ separation

Objective Tests & Rating Scales

• No diagnostic lab test; workup to exclude medical causes (e.g., syphilis, anti-NMDA encephalitis)

• Neuro tests: abnormal EEG ERPs (↓ P300), eye-tracking deficits, prepulse inhibition ↓

• Rating: PANSS, BPRS (symptoms); AIMS, SAS, BARS (EPS)

• Neuropsych: Halstead–Reitan, Luria–Nebraska (frontal/temporal deficits)

Differential Diagnosis

• Secondary psychoses: metabolic, endocrine, infectious, neurologic, toxins (Table 5-8)

• Mood disorders with psychotic features (mood-congruent)

• Personality disorders (schizotypal, schizoid, borderline)

• Malingering / factitious

Comorbidities

• Substance use disorders (lifetime \approx74\%); shared vulnerability

• Obesity, DM-II, CVD, COPD (↑ smoking), HIV (risk behaviors)

• Complex partial epilepsy (left temporal focus) ↑ psychosis

Course & Prognosis

• Premorbid: schizoid traits, social isolation

• Prodrome: somatic complaints, odd interests; lasts months–years

• Pattern: exacerbations & remissions; each relapse ↓ baseline functioning

• Positive ↓ over time; negative may ↑

• Outcomes: 20–30\% good; 40–60\% severe persistent; life expectancy −\sim20 y

• Positive prognostic factors: acute onset, female, developed country; negative: insidious onset, early age, poor premorbid, cognitive deficits (Table 5-9)

Treatment Overview

Hospitalization

• Indications: Dx clarification, safety (SI/HI), gross dysfunction; short stays 4–6 wk effective

Pharmacotherapy

First-episode / Acute (4–8 wk)

• Start 2nd-generation antipsychotic unless contraindicated

• IM options for agitation: haloperidol, fluphenazine, olanzapine, ziprasidone; adjunct lorazepam

Maintenance

• Continue \ge12 mo after first episode; multiple episodes ⇒ indefinite

• Relapse rates: treated 16–23\%/yr vs untreated 53–72\%/yr

Choice & Dosing

• Efficacy similar; select by side-effect profile (Table 5-10)

• Clozapine for treatment-resistant or suicidality; monitor ANC weekly ×6 mo, biweekly ×6 mo, monthly

LAI Formulations

• Fluphenazine decanoate, haloperidol decanoate, risperidone, paliperidone, olanzapine pamoate, aripiprazole; improve adherence, need oral overlap initially

Side-Effect Management

• EPS (parkinsonism, dystonia, akathisia): ↓ dose, switch, add anticholinergic or \beta-blocker (e.g., propranolol 30–90 mg)

• Tardive dyskinesia: annual risk 3–5\% (young) higher in elderly; prevent with lowest dose; switch to clozapine if severe

• Metabolic: monitor BMI each visit ×6 mo, fasting glucose & lipids periodically

• Prolactin elevation: galactorrhea, ↓ libido, osteoporosis risk

Somatic Adjuncts

• ECT: effective for acute psychosis, augmentation; continue antipsychotics

• Neuromodulation (TMS, tDCS): emerging for hallucinations, negative symptoms

Psychosocial Interventions

• CBT: cognitive restructuring, coping; useful post-acute

• Social skills training: role-play, video feedback ⇒ ↓ relapse

• Group therapy: supportive, reality testing, ↓ isolation

• Family therapy: psychoeducation, problem solving; lowers relapse/hospitalization

• Case management / ACT: multidisciplinary 24/7 support, caseload ≤1:12

• Individual psychotherapy: long-term alliance, insight when possible

• Supported employment: competitive job placement; ↑ self-esteem

• Cognitive remediation: computer exercises ↑ working memory, medium effect size

• Art therapy: expression, communication

• NAMI: education, advocacy, destigmatization

Etiology & Pathophysiology

Genetics

• Heritability 60–80\%; monozygotic twin concordance \approx50\%

• GWAS: >100 loci incl. DRD2, glutamate, calcium, immune (MHC, C4 for synaptic pruning)

• CNVs: 22q11.2 deletion, rare but high-penetrance (~2–5\% cases)

• Age-of-father >60 y ↑ risk (epigenetic sperm damage)

Neuroanatomy

• CT/MRI: enlarged lateral & 3rd ventricles, ↓ cortical gray, hippocampal/amygdala shrinkage, thalamic neuron loss, prefrontal abnormalities, reduced hemispheric symmetry

• Basal ganglia D2↑ (drug vs illness?); cerebellar & cingulate circuit dysfunctions correlate with symptoms

Neurophysiology

• PET: ↑ synaptic dopamine in associative striatum; ↓ frontal DA

• MRS: ↑ glutamate (prefrontal/medial temporal), ↓ N-acetyl aspartate

• EEG: ↓ P300, abnormal N100, impaired sensory gating; eye-tracking & prepulse inhibition deficits (trait markers)

Neurochemistry

• Dopamine hypothesis: hyper-DA (mesolimbic/striatal) ⇒ positive symptoms; hypo-DA (mesocortical) ⇒ negative/cognitive

• Serotonin excess contributes; 5-HT antagonism (clozapine) benefits

• Glutamate NMDA hypofunction (PCP model) implicated; ↑ glutamate levels

• GABA interneuron loss in hippocampus; acetylcholine receptor deficits (muscarinic/nicotinic)

Immune & Infection

• Prenatal influenza (2nd trimester), winter births; maternal infection/malnutrition

• Autoimmune links: lupus, anti-NMDA encephalitis mimic psychosis

• Microglial over-pruning (C4 alleles) during adolescence ⇒ synaptic loss

Neurodevelopmental Model

• Early brain insults + genetic vulnerability ⇒ aberrant pruning, connectivity (disconnect hypothesis)

• Explains early motor/cognitive deficits, lack of gliosis, adolescent onset

Psychodynamic & Learning Theories (historical)

• Freud: early ego defects

• Sullivan: maladaptive interpersonal defense

• Object relations deficit: distorted introjects, fear of relatedness

• Learning: modeling from disturbed parents

Risk & Protective Factor Summary

• Positive prognostic: acute onset, female, later age, good premorbid, good support, mood symptoms, married, obvious precipitant, high SES

• Negative prognostic: early/insidious onset, male, social withdrawal, many negative symptoms, cognitive impairment, poor adherence, substance abuse

Key Numbers & Equations

• Lifetime prevalence \sim0.7\%, suicide mortality 5–13\%

• Relapse with meds \approx20\%/yr vs without >50\%/yr

• Clozapine agranulocytosis risk \approx0.3\%; seizure risk 5\% if >600 mg/day

• BMI monitoring: \text{BMI}=\dfrac{\text{kg}}{\text{m}^2} each visit ×6 mo after med change

Practical Implications

• Always rule out medical/neurologic causes when atypical features (late onset, olfactory/tactile hallucinations, fluctuating consciousness)

• Engage family & community resources early; psychoeducation critical

• Monitor metabolic & EPS side effects proactively; choose meds accordingly

• Combine pharmacologic + psychosocial approaches for best outcomes.