Schizophrenia Spectrum and Psychotic Disorders

Overview of Psychiatric Disorders and Learning Objectives

  • Distribution of Topic Points:

    • Schizophrenia spectrum & other psychotic disorders: 1414
    • Obsessive Compulsive and Related Disorders: 66
    • Trauma- & stressor-related disorders: 66
    • Somatic symptom & related disorders: 44

  • Learning Outcomes:

    • Distinguish the specific signs and symptoms associated with psychosis.
    • Compare and contrast various psychotic disorders based on signs, symptoms, clinical course, and prognosis.
    • Discuss comprehensive management strategies for psychotic disorders.

  • Literature Sources:

    • Boland, R, & ML Verduin: Kaplan & Sadock’s Synopsis of Psychiatry, 12th edition (2022).
    • Stahl, Stephen M.: Stahl’s Essential Psychopharmacology, 5th edition (2021).
    • Diagnostic & Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR), February 2022.

Fundamental Concepts of Psychosis

  • Psychosis Definition:

    • Grossly Impaired Reality Testing: This occurs when a person incorrectly evaluates the accuracy of their perceptions and thoughts. They make incorrect inferences regarding external reality, maintaining these beliefs even when presented with contrary evidence.
    • Loss of Ego Boundaries: A lack of a clear sense of where the patient’s own body, mind, and influence end, and where those of other animate and inanimate objects begin.

  • Core Psychotic Symptom Domains:     Each diagnosis in the Schizophrenia Spectrum involves one or more of the following five domains:

    1. Delusions (Core Domain Item)
    2. Hallucinations (Core Domain Item)
    3. Disorganized Speech (Core Domain Item)
    4. Disorganized Behavior
    5. Negative Symptoms

Key Clinical Features and Definitions

  • Delusions:

    • Definition: Fixed false beliefs.
    • Bizarreness: Delusions are considered bizarre if they are clearly implausible and not understandable to same-culture peers. They do not derive from ordinary life experiences.
    • Loss of Control Delusions: Express a loss of control over mind or body (e.g., thought withdrawal, thought insertion, delusions of control).
    • Conviction: Clinicians must note the degree of conviction held despite clear or reasonable contradictory evidence.
    • Specific Syndromes:
      • Capgras Syndrome: The belief that a familiar person has been replaced by an impostor.
      • Fregoli’s Phenomenon: The belief that familiar persons assume the guise of strangers.
      • Cotard’s Syndrome: A nihilistic delusion involving the loss of possessions, status, strength, and bodily organs.

  • Hallucinations:

    • Definition: Perceptual experiences that occur without an external stimulus.
    • Types: May occur in any sensory modality; however, auditory hallucinations are the most common in psychotic disorders.
    • Sensorium Context: Must occur in the context of a clear sensorium.
    • Normal Variations: Hallucinations that occur while falling asleep (hypnagogic) or waking up (hypnopompic) are considered within the range of normal experiences and are not psychotic symptoms.
    • Cenesthetic Hallucination: Specifically describes a burning sensation in the brain or other visceral sensations.

  • Disorganized Thinking (Speech):

    • Refers to formal thought disorders.
    • The symptom must be severe enough to substantially impair effective communication.

  • Grossly Disorganized or Abnormal Motor Behavior:

    • Includes Catatonia: Can manifest as rigidity or stupor lasting hours or days.
    • Other signs: Performing strange movements, staying in uncomfortable positions without shifting, or erratic/extreme movement.
    • Echolalia: The repetition of words or behaviors.

  • Negative Symptoms:

    • Associated with Schizophrenia but less prominent in other psychotic disorders.
    • Blunted Affect: Diminished facial and vocal expressions, poor eye contact, and minimal use of gestures.
    • Avolition: Apathy and lack of motivation for relationships or activities, leading to poor grooming and hygiene and decreased involvement in work or school.
    • Asociality: Reduced social interaction, emotional withdrawal, and few friends.
    • Anhedonia: Difficulty or inability to anticipate future pleasure, few leisure activities, and lack of interest in sexual activity.
    • Alogia: Short or monosyllabic answers; decreased communication using few words.

  • Cognitive Symptoms:

    • Refers to the lack of ability to understand and process information adequately.
    • Features: Poor memory, poor concentration/attention, poor judgment and insight, and difficulty in decision-making.

Diagnostic Categories and Duration Criteria

  • Schizophrenia Spectrum Disorders Breakdown:

    • Schizotypal (Personality) Disorder: Acute discomfort with close relationships plus cognitive or perceptual distortions and eccentricities. Beliefs and perceptions are below the threshold for a full psychotic diagnosis.
    • Brief Psychotic Disorder: Symptoms last from 1 day1\text{ day} to less than 1 month1\text{ month}. Requires one or more symptoms; negative symptoms are not included in Criterion A. Requires a full return to pre-morbid functioning.
    • Schizophreniform Disorder: Symptoms last from 1 month1\text{ month} to less than 6 months6\text{ months}. Requires two or more symptoms from Criterion A.
    • Schizophrenia: Duration of symptoms is at least 6 months6\text{ months}, including at least 1 month1\text{ month} of active-phase symptoms (Criterion A).
      • Active symptoms may be preceded by prodromal phases or followed by residual phases.
      • Residual/prodromal periods may manifest as negative symptoms or attenuated Criterion A symptoms.
    • Schizoaffective Disorder:
      • An uninterrupted period of illness with a major mood episode (depressive or manic) concurrent with Criterion A of schizophrenia.
      • Depressive episodes must include Criterion A1: Depressed mood.
      • Requires Delusions or Hallucinations for ≥2 weeks\ge 2\text{ weeks} in the absence of a major mood episode during the lifetime duration of the illness.
      • Mood symptoms must be present for the majority of the total duration of the active and residual portions of the illness.
    • Delusional Disorder: Duration of at least 1 month1\text{ month}. Hallucinations are not prominent and are related to the delusional theme. Functioning is not markedly impaired.

  • Specifiers (Used after 1 year1\text{ year} of duration):

    • First episode (Acute, partial remission, or full remission).
    • Multiple episodes (Acute, partial remission, or full remission).
    • Continuous; Unspecified; With catatonia.

Epidemiology and Etiology

  • Prevalence:

    • International incidence of all psychotic disorders: 26.6 per 100,000 person years26.6\text{ per } 100,000\text{ person years}.
    • Lifetime prevalence of all psychotic disorders: 3.06%−3.48%3.06\% - 3.48\%.
    • Specific Disorder Prevalence:
      • Schizophrenia: 0.87%0.87\%
      • Substance-induced psychosis: 0.42%0.42\%
      • MDD with Psychotic Features: 0.35%0.35\%
      • Schizoaffective disorder: 0.32%0.32\%
      • Bipolar I disorder: 0.24%0.24\%
      • Psychotic d/o due to Another Medical Condition (AMC): 0.21%0.21\%
      • Delusional disorder: 0.18%0.18\%
      • Schizophreniform disorder: 0.07%0.07\%

  • Demographics and Risks:

    • Gender: Equal prevalence in both genders.
    • Age of Onset: Earlier in men (10−25 years10 - 25\text{ years}). Females peak at 25−35 years25 - 35\text{ years}, with a second peak in middle age. Late onset is defined as >45 years> 45\text{ years} old.
    • Comorbidities: Lifetime prevalence of drug abuse is >40%> 40\%. Cannabis use (high levels) increases schizophrenia risk by 6X6X. 90%90\% of those with schizophrenia are nicotine dependent.

  • Genetic Prevalence in Specific Populations:

    • General Population: 1%1\%
    • Non-twin sibling of patient: 8%8\%
    • Child with one affected parent: 12%12\%
    • Dizygotic twin: 12%12\%
    • Child with two affected parents: 40%40\%
    • Monozygotic twin: 47%47\%

Neurobiology of Schizophrenia

  • Dopaminergic Pathways:

    1. Mesolimbic: Projects from Tegmentum to Limbic system. Hyperactivity here leads to positive symptoms.
    2. Mesocortical: Projects to Frontal Cortex. Hypoactivity here leads to negative symptoms.
    3. Nigrostriatal: Involved in motor control; blockade leads to extrapyramidal symptoms (EPS).
    4. Tuberoinfundibular: Regulates prolactin release from the pituitary.
    5. Incerto-hypothalamic: Arises from periaqueductal gray and hypothalamic nuclei; function is unknown. Note: An elevated blink rate reflects hyperdopaminergic activity.

  • The Dopamine Hypothesis:

    • Positive symptoms result from limbic system hyperactivity.
    • Negative symptoms result from frontal cortex hypoactivity.

  • Serotonin Pathways:

    • Ascend from the raphe nucleus to the basal ganglia, limbic system, and prefrontal cortex.
    • 5HT1A Stimulation: Acts as a Dopamine (DA) accelerator (increases DA release).
    • 5HT2A Stimulation: Acts as a DA brake (inhibits DA release).

  • Glutamate-Dopamine Interaction:

    • Mesolimbic Brake: Descending cortico-brainstem glutamate normally brakes the mesolimbic DA pathway via GABA interneurons. If glutamate projections are hypoactive, the brake fails, leading to mesolimbic hyperactivity and positive symptoms.
    • Mesocortical Accelerator: Glutamate projections synapse directly onto DA neurons in the VTA to excite them. If glutamate is hypoactive, mesocortical DA remains low, causing negative and cognitive symptoms.
    • Opposing 5HT Effects on Glutamate:
      • Stimulation of 5HT2A increases glutamate release (acting as a glutamate accelerator).
      • Stimulation of 5HT1A inhibits glutamate release (acting as a glutamate brake).

Pharmacological Management

  • Classes of Antipsychotics:

    • Typical (Conventional) D2 Antagonists: Block postsynaptic D2 receptors in mesocortical/mesolimbic pathways. Effective at 60%60\% occupancy; EPS occurs at ≥80%\ge 80\% occupancy.
    • Atypical Serotonin/Dopamine (5HT2A/D2) Antagonists: Combined D2 and 5HT2A antagonism. Utilize "rapid dissociation" (hit and run) to avoid persistent blockade and minimize EPS.
    • Dopamine D2 Partial Agonists: Modulate DA output to maintain efficacy while preserving motor function in the nigrostriatal pathway.

  • Drug Specifics (Examples):

    • Chlorpromazine: 50−1,600 mg50 - 1,600\,mg dosage.
    • Haloperidol: 1−20 mg1 - 20\,mg dosage.
    • Risperidone: 2−6 mg2 - 6\,mg dosage.
    • Paliperidone (Invega): Includes long-acting injectables like Sustenna (monthlymonthly), Trinza (every3monthsevery 3 months), Hafyera (every6monthsevery 6 months).
    • Olanzapine: 10−20 mg10 - 20\,mg dosage; available in oral disintegrating tablets (ODT).
    • Quetiapine: 300−800 mg300 - 800\,mg dosage.
    • Aripiprazole: 10−30 mg10 - 30\,mg dosage.

  • Side Effects of Typical Antipsychotics:

    • M1 Blockade: Constipation, blurred vision, dry mouth, drowsiness.
    • H1 Blockade: Weight gain, sedation.
    • Alpha-1 Blockade: Dizziness, decreased BP, drowsiness.
    • Tardive Dyskinesia: Quick, jerky movements of the face, tongue, and limbs; occurs in 5%5\% of patients every year.

  • Metabolic Concerns of Atypicals: Weight gain, diabetes, insulin resistance, dyslipidemia, and cardiovascular disease (CVD).

Phases of Treatment and Prognosis

  • Phase I: Acute Phase:

    • Goal: Rapid resolution of positive symptoms, aggression, and behavioral dyscontrol.
    • Response: Agitation improves in hours/days; hallucinations/delusions take weeks. Full response: 4−8 weeks4 - 8\text{ weeks}.

  • Phase II: Stabilization Phase:

    • Goal: Restore premorbid function and improve negative symptoms (which takes 6−12 weeks6 - 12\text{ weeks}).
    • Focus: Compliance, drug optimization, and psychosocial interventions.

  • Phase III: Stable Phase:

    • Goal: Relapse prevention and recovery optimization.

  • Course and Prognosis:

    • The pattern of the first 5 years5\text{ years} indicates the lifelong course.
    • Recovery Stats: 10−20%10 - 20\% have a good outcome; 1 in 51\text{ in } 5 achieves sustained recovery; >50%> 50\% have a poor outcome.
    • Prognostic Predictor: Cognitive impairment is the primary predictor of the level of function.

Questions & Discussion

  • Scenario 1: 32-year-old man distressing over sister in South Korea.

    • The man believed his sister died but felt relief when she was proven alive. This is not a delusion because the belief changed in the light of new evidence.

  • Scenario 2: 64-year-old widower hearing deceased wife's voice.

    • These are not considered psychotic because they occur while trying to fall asleep (hypnagogic) or are invoked by looking at photos, which are variations of normal grief/sensory experience.

  • Scenario 3: 24-year-old male after a car accident friend's death.

    • Presents with delusional thinking (aliens) for 2 weeks. Diagnosis: Brief psychotic disorder with a marked stressor (symptoms < 1\text{ month} post-accident).

  • Prognostic Question: What are the chances a monozygotic twin sister has the same disorder? 47%.