Schizophrenia Spectrum and Dissociative Disorders

Schizophrenia Spectrum Disorders: Core Definitions

• Disorganization in Schizophrenia:

  • Disorganized Thinking: This is typically inferred from the patient's speech.

    • Tangentiality: Moving from one topic to another where the logical connection is visible but the orator never returns to the original point.

    • Derailment/Loose Associations: Shifting between ideas that are completely unrelated or only obliquely connected.

    • Word Salad: Speech that is so severely disorganized that it is nearly incomprehensible; it resembles receptive aphasia in its lack of semantic coherence.

  • Grossly Disorganized Motor Behavior: This can manifest in several ways, ranging from "childlike silliness" to "excessive agitation."

  • Catatonia: Defined as a marked decrease in reactivity to the environment. Detailed examples include:

    • Echolalia: The pathological, senseless repetition of a word or phrase just spoken by another person.

    • Echopraxia: The repetitive imitation of the movements of another person.

    • Perseveration: The repetition of a particular response (such as a word, phrase, or gesture) regardless of the absence or cessation of a stimulus.

Diagnostic Criteria for Schizophrenia (DSM-5)

• Criterion A (Core Symptoms): The presence of $2$ or more of the following, each for a significant portion of time during a $1$-month period. At least one must be from the first three categories:

  1. Delusions.

  2. Hallucinations.

  3. Disorganized speech.

  4. Grossly disorganized or catatonic behavior.

  5. Negative symptoms (e.g., flat affect, anhedonia, alogia, cognitive deficits).

• Functioning (Criterion B): Functioning in one or more major areas (social, occupational, self-care) must be impaired for a significant period of time.

• Duration (Criterion C): Continuous signs of the disturbance must persist for at least $6$ months. This total period must include at least $1$ month of active-phase symptoms (Criterion A).

• Exclusions (Criterion D & E):

  • Schizoaffective disorder and depressive or bipolar disorders with psychotic features must be ruled out. This means either no mood episodes occurred during active symptoms, or they were present for only a minority of the total illness duration.

  • The disturbance is not due to the physiological effects of a substance (e.g., drug of abuse, medication) or another medical condition.

• Developmental Consideration (Criterion F): If there is a history of Autism Spectrum Disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are present for at least $1$ month.

Etiology and Neurobiological Pathways

• Dopamine Hypothesis: It is hypothesized that an excess of dopamine in the mesolimbic tract is responsible for the positive psychotic symptoms (hallucinations/delusions).

• Glutamate Hypothesis: Underactive NMDA glutamate receptors may contribute to schizophrenia symptoms.

• GABA Hypothesis: Gamma-amino-butyric acid (GABA) interneurons help regulate prefrontal cortical function; abnormalities in these interneurons may contribute to symptoms, particularly relevant in catatonia.

• Acetylcholine (ACh) and Nicotine: A vast majority of individuals with schizophrenia are smokers. It is suggested that nicotine stimulates a subset of ACh receptors, providing symptomatic relief.

  • Clinical Caveat: Tars in cigarette smoke stimulate liver enzymes, specifically CYP1A2. This results in the increased metabolism and decreased blood levels of many antipsychotics.

• Key Brain Pathways:

  • Mesolimbic pathway: Associated with reward and positive symptoms.

  • Mesocortical pathway: Associated with cognitive and negative symptoms.

  • Nigrostriatal pathway: Associated with motor control (EPS issues).

  • Tuberoinfundibular pathway: Associated with prolactin regulation.

Epidemiology and Prognostic Factors

• Prevalence: Approximately up to $1\%$ worldwide.

• Age of Onset: Generally between adolescence and mid-$30s$.

  • Men: Peak incidence of the first psychotic break is early- to mid-$20s$.

  • Women: Peak incidence is late-$20s$.

  • Childhood: Symptoms are considered rare in children.

• Course of Illness: Onset is usually slow and gradual, though abrupt onsets occur.

• Prognosis: Negative symptoms are more closely correlated with a poor long-term prognosis than positive symptoms.

• Deficit Schizophrenia: Consists of approximately $20\%$ of cases. Characteristics include:

  • Predominantly male patients.

  • Positive family history of schizophrenia.

  • Generally poor prognosis.

Mental Status Examination Findings

• Appearance: Frequently unkempt, disheveled, and malodorous during the acute phase of the illness.

• Behavior: Disorganized, abnormal motor movements (such as Extrapyramidal Symptoms/EPS), agitation, or suspiciousness.

• Thought Process: Can include tangentiality, flight of ideas, loose associations, clang associations, thought blocking, thought insertion, and thought withdrawal/broadcasting.

• Thought Content: Perceptual disturbances including various hallucinations and/or delusions.

Pharmacological Interventions and Clinical Considerations

• First-Generation (FGA) vs. Second-Generation Antipsychotics (SGA):

  • While metas-analyses (except for clozapine) show no improved efficacy of one over another for positive symptoms, SGAs generally have a lower incidence of Extrapyramidal Symptoms (EPS).

• Specific Medications:

  • Clozapine (Clozaril): Highly effective but not used first-line due to the risk of agranulocytosis.

  • Vraylar (cariprazine): Has shown specific benefit for treating negative symptoms compared to risperidone.

  • Paliperidone (Invega): Only FDA-approved medication specifically for Schizoaffective Disorder (Tablet: Invega; LAI: Invega Sustenna).

• Long-Acting Injectables (LAI):

  • Used for patients with poor oral medication adherence.

  • FGA LAIs: Haldol-D, Prolixin decanoate.

  • SGA LAIs: Risperdal Consta, Uzedy, Perseris, Invega Sustenna, Invega Trinza, Invega Halfyera, Abilify Maintena.

  • Frequency: Dosing ranges from $q2\text{weeks}$ to $q6\text{months}$.

  • Requirement: A PO (oral) trial must be conducted first to establish tolerance. Some require continuing the PO dose alongside the injection until therapeutic levels are reached.

Side Effects of Antipsychotic Medications

• Extrapyramidal Side Effects (EPS):

  • Akinesia: A lack of movement.

  • Akathisia: Subjective internal restlessness, often seen as constant movement, pacing, or restless legs.

  • Dystonia: Slow, sustained muscle contractions/movements.

  • Oculogyric Crises: A specific dystonic reaction where the eyes roll back into the head.

  • Pseudo-Parkinsonism: Symptoms mimicking Parkinson's disease.

  • Tardive Dyskinesia (TD): A neurological syndrome resulting in slow, rhythmic, automatic stereotyped movements. "Tardive" implies a late onset.

Tardive Dyskinesia Management

• Prevention: Use antipsychotics only when necessary at the lowest effective dose.

• Intervention: Consider switching the patient to Clozapine (Clozaril).

• VMAT2-Inhibitors: FDA-approved treatments for TD.

  • Tetrabenazine: High cost noted ().\n * **Valbenazine (Ingrezza)**: High cost noted ().

  • Deutetrabenazine (Austedo): High cost noted ().\n * **Caution**: These agents must be used with caution in patients with a history of depression or suicidal ideation.\n\n# Brief Psychotic Disorder\n\n* **DSM-5 Criteria**: Presence of at least one symptom (Delusions, Hallucinations, Disorganized speech, or Grossly disorganized/catatonic behavior).\n* **Duration**: At least 1$day but less than$1 month.\n* **Outcome**: Eventual full return to the premorbid level of functioning.\n* **Differential**: Must rule out drug intoxication or withdrawal, which is the most frequent medical cause of sudden psychosis.\n\n# Delusional Disorder and Specialized Types\n\n* **DSM-5 Criteria**: Presence of one or more delusions for a duration of 1 month or longer.\n* **Distinction from Schizophrenia**: Criterion A for schizophrenia has **never** been met. If hallucinations are present, they are not prominent and are tied to the delusion (e.g., tactile hallucinations of insects in a delusion of infestation).\n* **Functioning**: Functioning is NOT markedly impaired, and behavior is not obviously bizarre outside the delusion's context.\n* **Types**:\n * **Erotomanic Type**: Convinced another person (often of higher status) is in love with them despite no evidence; often involves stalking behavior.\n * **Somatic Type**: Delusion involves bodily functions or sensations. \n * **Delusional Parasitosis**: Specific belief that the skin is infested with insects.\n\n# Schizoaffective Disorder: Criteria and Management\n\n* **Description**: A period of illness where a major mood episode (depressive or manic) is concurrent with Criterion A of schizophrenia.\n* **Key Timing Requirement**: Delusions or hallucinations must occur for 2 or more weeks in the **absence** of a major mood episode at some point during the lifetime of the illness.\n* **Clinical Course**: \n * Lifetime prevalence is 0.3\%.\n * More common in females than males.\n * Prognosis is better than schizophrenia but worse than pure mood disorders.\n* **Treatment**: Second-generation antipsychotics are often used off-label as monotherapy. If mood symptoms persist, lithium or valproate (for mania) or SSRIs (for depression) are added.\n\n# Differentiating Psychotic and Mood Disorders\n\n* **Schizophreniform Disorder**: Same criteria as schizophrenia, but the total disease length is >1$month and$<6 months. Often a precursor to a schizophrenia diagnosis.\n* **Mood Disorder with Psychotic Features**: Psychosis occurs **only** during the mood episode (depression or mania). Delusions/hallucinations are NOT present for 2 weeks without the mood disorder. \n * **Depression (SIGECAPS)**: Sleep, Interest, Guilt, Energy, Cognition, Appetite, Psychomotor, Suicide.\n * **Mania (DIGFAST)**: Distractible, Irresponsibility, Grandiose, Flight of ideas, Activity increase, Sleep decrease, Talkative.\n\n# Dissociative Disorders\n\n* **Definition**: Disorders characterized by a disconnection from reality. Often considered compensatory mechanisms to detach from trauma (abuse, war, surgery).\n* **Subtypes**:\n * **Dissociative Identity Disorder (DID)**: Formerly "multiple personalities." 70\%$$ of patients with DID have attempted suicide.

  • Dissociative Amnesia: Inability to recall autobiographical memory associated with trauma.

  • Dissociative Fugue: A subtype of amnesia involving sudden, unexpected travel or bewildered wandering away from home, combined with an inability to recall the past.

  • Depersonalization/Derealization Disorder: Feelings of detachment from one's self or surroundings.

• Malingering vs. Genuine DID:

  • Those feigning DID (for gain or exculpation) often over-sensationalize symptoms like amnesia and seem to "enjoy" the disorder.

  • Genuine patients are typically ashamed of and overwhelmed by their symptoms.