Medical School · Year 2 · Psychiatry · includes a quiz and discussion video

Lecture 5: Psychotic Disorders

Unit 2.6: Psychiatry

Learning Objectives

By the end of this lecture, students will be able to:

1. Define psychosis and describe its core features
2. Explain the diagnostic criteria for schizophrenia
3. Describe the neurobiology of schizophrenia
4. Explain the pharmacological treatment with antipsychotics
5. Describe other psychotic disorders
6. Explain the approach to first-episode psychosis

Lecture Outline

I. Psychosis: Definition and Core Features

Psychosis refers to a loss of contact with reality characterized by a constellation of symptoms that impair the ability to accurately perceive and interpret the external world. The core features of psychosis include delusions and hallucinations, which together are often termed positive symptoms because they represent an addition of abnormal experiences to the normal mental state. Additional features include disorganized thought and behavior and negative symptoms representing a reduction or absence of normal functions.

Positive symptoms of psychosis include delusions, which are fixed false beliefs that are not amenable to change in light of conflicting evidence; hallucinations, which are sensory perceptions occurring in the absence of an external stimulus; disorganized speech, reflecting formal thought disorder with phenomena such as tangential thinking and loose associations; and grossly disorganized or catatonic behavior. These symptoms are most prominent during acute psychotic episodes and are generally responsive to antipsychotic medication.

Negative symptoms represent deficits in normal emotional and behavioral functions and are particularly challenging to treat. Affective flattening refers to reduced expression of emotions through facial expression, voice tone, and gestures. Alogia, or poverty of speech, involves reduced speech output or content. Avolition refers to decreased motivation and initiation of goal-directed activities. Anhedonia is the inability to experience pleasure from previously enjoyable activities. Asociality represents reduced interest in and engagement with social relationships.

The causes of psychosis span multiple categories. Primary psychiatric disorders include schizophrenia, schizoaffective disorder, brief psychotic disorder, and other schizophrenia spectrum conditions. Mood disorders including major depressive disorder and bipolar disorder can present with psychotic features. Substance-induced psychosis can result from intoxication with stimulants, hallucinogens, or cannabis, or from withdrawal states. Medical conditions causing psychosis include delirium from any cause, dementia, encephalitis, brain tumors, and autoimmune encephalitis. Medications including corticosteroids, anticholinergics, and dopamine agonists can also precipitate psychosis.

<image>Panel A displays the definition of psychosis as loss of reality contact with the two core features (delusions and hallucinations) in a central diagram, surrounded by additional features (disorganized thought/behavior, negative symptoms). Panel B illustrates positive symptoms with icons: delusions (fixed belief bubble), hallucinations (sensory perception without stimulus), disorganized speech (fragmented word patterns), disorganized behavior (erratic figure). Panel C shows negative symptoms as deficits from normal: affective flattening (expressionless face), alogia (empty speech bubble), avolition (unmotivated figure), anhedonia (inability to enjoy previously pleasurable activities), asociality (isolated figure). Panel D presents the differential diagnosis of psychosis categorized as primary psychiatric, mood with psychosis, substance-induced, medical conditions, and medication-induced.</image>

II. Schizophrenia: Epidemiology and Course

Schizophrenia affects approximately one percent of the population worldwide, representing one of the most significant psychiatric disorders in terms of disability and societal impact. The disorder affects men and women equally, though the age of onset differs, with men typically developing symptoms in the late teens to early twenties while women present in the late twenties to early thirties. Life expectancy is reduced by fifteen to twenty years compared to the general population, reflecting increased rates of suicide, cardiovascular disease, and other medical comorbidities.

Multiple risk factors contribute to schizophrenia development. Genetic factors are substantial, with heritability estimated at approximately eighty percent and a polygenic architecture involving hundreds of risk alleles. Having a first-degree relative with schizophrenia increases risk to approximately ten percent. Prenatal and obstetric complications including maternal infections, malnutrition, and birth complications are associated with increased risk. Urban birth and upbringing, migration and minority status, and adolescent cannabis use all contribute to risk. These factors likely interact with genetic vulnerability in complex gene-environment interactions.

The prodromal phase precedes frank psychosis and can last from months to years. During this phase, individuals may show social withdrawal, decline in academic or occupational functioning, unusual beliefs not yet meeting criteria for delusions, and perceptual disturbances not yet meeting criteria for hallucinations. Identifying individuals in the prodrome has become a focus of early intervention efforts aimed at preventing or delaying transition to psychosis.

The course of schizophrenia typically follows a pattern with distinct phases. The prodromal phase involves subtle nonspecific symptoms. First-episode psychosis represents the emergence of frank positive symptoms. The pattern after the first episode varies considerably, with some individuals experiencing recovery or remission, others experiencing episodic courses with relapses and remissions, and others developing chronic symptoms. Long-term outcome studies suggest roughly one-third of patients have good outcomes, one-third have moderate outcomes, and one-third have poor outcomes with significant disability.

<image>Panel A presents epidemiological data: 1% worldwide prevalence, equal sex ratio with earlier male onset (late teens-early twenties) versus female onset (late twenties-early thirties), 15-20 year reduction in life expectancy. Panel B displays risk factors in concentric circles: genetic (80% heritability, polygenic) at center, prenatal/obstetric complications, environmental factors (urban, migration, cannabis), gene-environment interactions in outer rings. Panel C illustrates the prodromal phase as a transition period showing declining function, subtle symptoms (social withdrawal, unusual beliefs, perceptual disturbances), and progression toward first psychotic episode. Panel D shows the disease course as a trajectory graph with prodrome, first episode, and variable subsequent courses (recovery, episodic, chronic) with outcome statistics (1/3 each for good, moderate, poor outcomes).</image>

III. Schizophrenia Diagnostic Criteria

DSM-5 Criterion A requires two or more of five symptom types present for a significant portion of time during a one-month period, with the stipulation that at least one of the symptoms must be delusions, hallucinations, or disorganized speech. The five Criterion A symptoms are delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms. This requirement ensures that diagnosis is not based solely on negative symptoms or disorganized behavior without the presence of reality distortion.

Additional criteria further define the diagnosis. Criterion B requires functional decline, with level of functioning in work, interpersonal relations, or self-care markedly below the level achieved prior to onset. Criterion C specifies a duration requirement of at least six months, which may include prodromal or residual periods as long as at least one month includes active-phase symptoms meeting Criterion A. Criterion D requires exclusion of schizoaffective disorder and depressive or bipolar disorder with psychotic features. Criterion E excludes substance-induced and medical causes. Criterion F addresses individuals with a history of autism spectrum disorder or communication disorder.

Specifiers describe the current status and course pattern. First episode specifiers indicate whether the patient is currently in acute episode, partial remission, or full remission. Multiple episodes specifiers similarly describe acute, partially remitted, or fully remitted status. Continuous indicates that symptoms meeting Criterion A have been present for the majority of the illness course. Severity is rated on a five-point scale for each Criterion A symptom.

The duration requirements are critically important for differential diagnosis. Active-phase symptoms (Criterion A) must be present for at least one month. The total illness duration, including prodromal and residual periods, must be at least six months. If symptoms resolve completely within one to six months, schizophreniform disorder is diagnosed. If symptoms resolve completely within less than one month, brief psychotic disorder is diagnosed. These duration thresholds reflect the prognostic significance of symptom persistence.

<image>Panel A displays Criterion A as a diagram with five symptoms (delusions, hallucinations, disorganized speech, disorganized/catatonic behavior, negative symptoms), with a bracket indicating at least one of the first three must be present. Panel B shows the additional criteria as a checklist: functional decline (Criterion B), 6-month duration with 1-month active phase (Criterion C), schizoaffective and mood disorders excluded (Criterion D), substance/medical excluded (Criterion E). Panel C illustrates specifiers as a flow diagram: first episode or multiple episodes, each with acute/partial remission/full remission options, plus continuous and severity rating options. Panel D displays the duration requirements on a timeline comparing schizophrenia (6+ months with 1+ month active), schizophreniform (1-6 months), and brief psychotic disorder (less than 1 month).</image>

IV. Schizophrenia Symptom Domains

Delusions in schizophrenia can take multiple forms, each with characteristic content. Persecutory delusions involve the belief that one is being targeted, followed, harassed, or conspired against. Referential delusions involve the belief that ordinary events have special personal significance, such as believing television programs contain messages directed at oneself. Grandiose delusions involve beliefs about having special powers, importance, or identity. Erotomanic delusions involve the belief that another person, often of higher status, is in love with the individual. Somatic delusions involve false beliefs about body functioning. Control delusions encompass thought insertion, withdrawal, and broadcasting. Bizarre delusions are clearly implausible and not derived from ordinary life experience and are particularly characteristic of schizophrenia.

Hallucinations in schizophrenia are most commonly auditory, occurring in approximately seventy percent of patients. Auditory hallucinations typically take the form of voices that may comment on the individual's actions, converse with each other about the individual, or issue commands. Visual hallucinations are less common than in delirium and should prompt consideration of substance intoxication or medical causes. Tactile, olfactory, and gustatory hallucinations are relatively rare and may suggest organic etiologies.

Disorganized symptoms reflect impairment in the organization of thought and behavior. Formal thought disorder manifests in speech as loose associations where ideas shift between unrelated topics, tangentiality where responses drift away from the topic, derailment where speech becomes increasingly incoherent, and in severe cases word salad with completely incomprehensible speech. Disorganized behavior may include unpredictable agitation, inappropriate emotional responses, or behaviors that appear bizarre and purposeless to observers. Catatonia represents a spectrum of motor abnormalities.

Negative symptoms are increasingly recognized as central to schizophrenia's morbidity and treatment resistance. Blunted affect appears as reduced emotional expression. Alogia manifests as poverty of speech content or output. Avolition presents as decreased motivation and goal-directed activity. Anhedonia involves inability to experience pleasure. Asociality involves reduced desire for and engagement in social relationships. These symptoms are measured using scales such as the Scale for the Assessment of Negative Symptoms and contribute significantly to functional impairment.

<image>Panel A illustrates delusion types with icons: persecutory (being followed), referential (TV sending messages), grandiose (crown representing special powers), control (thought bubbles being inserted/removed), bizarre (clearly implausible content). Panel B shows hallucination types with auditory as most common (70%, voice bubbles commenting or conversing), visual (less common, suggest organic cause), and tactile/olfactory/gustatory (rare, suggest organic cause). Panel C displays disorganized symptoms: thought disorder (fragmented speech patterns showing loose associations, tangentiality, word salad), disorganized behavior (unpredictable, bizarre actions), catatonia (motor abnormalities). Panel D presents negative symptoms on a reduction scale showing diminished affect, speech, motivation, pleasure, and social engagement compared to normal levels.</image>

V. Schizophrenia Neurobiology

The dopamine hypothesis remains the foundational model for understanding schizophrenia neurobiology. The mesolimbic pathway, projecting from the ventral tegmental area to the nucleus accumbens and limbic structures, is hypothesized to be hyperactive in schizophrenia, producing positive symptoms including delusions and hallucinations. The mesocortical pathway, projecting to the prefrontal cortex, is hypothesized to be hypoactive, contributing to negative symptoms and cognitive impairment. All effective antipsychotic medications block D2 dopamine receptors, with clinical potency correlating with D2 binding affinity.

Other neurotransmitter systems are implicated in schizophrenia pathophysiology. The glutamate hypothesis proposes that NMDA receptor hypofunction contributes to symptoms, supported by the observation that NMDA antagonists like phencyclidine and ketamine can produce schizophrenia-like symptoms in healthy individuals. Serotonin is relevant given that atypical antipsychotics have significant 5-HT2A antagonism, which may contribute to their efficacy for negative symptoms. GABA interneuron dysfunction is implicated in gamma oscillation abnormalities and cortical information processing deficits.

Structural brain changes in schizophrenia are well documented through neuroimaging studies. Ventricular enlargement, particularly of the lateral and third ventricles, is one of the most replicated findings. Reduced gray matter volume is observed in the frontal and temporal cortices. The hippocampus shows reduced volume bilaterally. These changes appear progressive, continuing after symptom onset, suggesting ongoing neurodegenerative or neurodevelopmental processes.

Functional brain changes complement the structural findings. Hypofrontality refers to reduced activation of the prefrontal cortex during cognitive tasks requiring executive function. The default mode network shows abnormal activity patterns, with failure to appropriately deactivate during task performance. Connectivity analyses reveal altered functional connections between brain regions, particularly between frontal and temporal areas. These findings inform understanding of the cognitive deficits that are core features of schizophrenia.

<image>Panel A illustrates the dopamine hypothesis with a brain diagram showing the mesolimbic pathway (hyperactive, producing positive symptoms) and mesocortical pathway (hypoactive, producing negative/cognitive symptoms), with D2 receptor blockade as treatment target. Panel B displays other neurotransmitter hypotheses: glutamate (NMDA hypofunction, supported by PCP/ketamine effects), serotonin (5-HT2A role in atypical antipsychotics), GABA (interneuron dysfunction). Panel C shows structural changes on brain imaging: enlarged ventricles (lateral and third), reduced gray matter (frontal, temporal), reduced hippocampal volume. Panel D presents functional findings: hypofrontality (reduced prefrontal activation during cognitive tasks), default mode network abnormalities (failure to deactivate), altered connectivity patterns (disrupted frontal-temporal connections).</image>

VI. Antipsychotic Medications

First-generation antipsychotics, also termed typical or conventional antipsychotics, exert their effects primarily through dopamine D2 receptor blockade. High-potency agents such as haloperidol and fluphenazine are more likely to cause extrapyramidal symptoms but less likely to cause sedation and anticholinergic effects. Low-potency agents such as chlorpromazine cause more sedation and anticholinergic effects but less EPS. Medium-potency agents such as perphenazine offer intermediate profiles. Long-acting injectable formulations are available for haloperidol and fluphenazine, improving adherence.

Second-generation antipsychotics, also termed atypical antipsychotics, generally combine D2 antagonism with significant 5-HT2A antagonism and often have faster dissociation from D2 receptors. Clozapine is the most effective antipsychotic but is reserved for treatment-resistant cases due to the risk of agranulocytosis requiring regular blood monitoring. Olanzapine is highly effective but associated with significant weight gain and metabolic effects. Risperidone can cause EPS at higher doses and elevates prolactin. Quetiapine is sedating and used for insomnia but has metabolic effects. Aripiprazole is a partial D2 agonist with lower metabolic risk but can cause akathisia. Ziprasidone has lower metabolic effects but requires food for absorption and has QT prolongation concerns.

The mechanism of action for all effective antipsychotics involves D2 receptor blockade. Typical antipsychotics achieve their effect primarily through tight, sustained D2 blockade. Atypical antipsychotics are proposed to differ through additional 5-HT2A blockade, faster dissociation from D2 receptors allowing more physiologic dopamine signaling, or partial agonism at D2 receptors. These differences may explain the lower EPS liability and potential advantages for negative symptoms seen with atypicals.

Antipsychotic side effects are substantial and influence treatment selection. Metabolic effects including weight gain, diabetes, and dyslipidemia are particularly prominent with olanzapine and clozapine. Extrapyramidal symptoms including acute dystonia, parkinsonism, akathisia, and tardive dyskinesia are more common with typical antipsychotics. Anticholinergic effects include dry mouth, constipation, and urinary retention. Cardiac effects include QT prolongation with ziprasidone and thioridazine. Hyperprolactinemia is common with risperidone. Neuroleptic malignant syndrome is a rare but life-threatening reaction to dopamine blockade.

<image>Panel A presents first-generation antipsychotics categorized by potency: high potency (haloperidol, fluphenazine—more EPS, less sedation), medium potency (perphenazine), low potency (chlorpromazine—more sedation and anticholinergic, less EPS). Panel B displays second-generation antipsychotics with key features: clozapine (most effective, agranulocytosis risk), olanzapine (effective, metabolic effects), risperidone (EPS at high doses, prolactin), aripiprazole (partial agonist, akathisia), others. Panel C illustrates mechanisms comparing typical (tight D2 blockade) with atypical (D2 + 5-HT2A blockade, faster D2 dissociation, or partial D2 agonism). Panel D shows side effect profiles as a comparison matrix with metabolic, EPS, anticholinergic, cardiac, and prolactin effects rated for different antipsychotic classes.</image>

VII. Schizophrenia Treatment Approach

Acute psychosis requires immediate attention to safety, thorough assessment, and initiation of treatment. Safety considerations include de-escalation techniques, a safe environment, and if necessary, seclusion or restraint as a last resort. Medical assessment should exclude organic causes of psychosis through physical examination, laboratory testing, and neuroimaging when indicated. Antipsychotic medication should be initiated, with oral formulations preferred when the patient will accept them and intramuscular formulations available for acute agitation. Hospitalization is often necessary during acute episodes.

First-episode psychosis warrants special treatment considerations to optimize outcomes. Lower antipsychotic doses are typically effective and better tolerated, as antipsychotic-naive individuals are more sensitive to medication effects. Longer trial durations of six to eight weeks should be allowed before concluding that a medication is ineffective. Monotherapy with a single antipsychotic is preferred, avoiding polypharmacy. Comprehensive early intervention programs combining medication with psychosocial support have demonstrated improved outcomes. Treatment should continue for at least one to two years after remission of the first episode.

Maintenance treatment is essential given the high relapse rate when medication is discontinued. Approximately eighty percent of patients who discontinue antipsychotics after their first episode will relapse within two years. Long-term treatment, often indefinite, is recommended for most patients. Long-acting injectable antipsychotics can significantly improve adherence and reduce relapse risk. Regular monitoring for metabolic effects, movement disorders, and other side effects is necessary throughout treatment.

Treatment-resistant schizophrenia is defined as failure to respond adequately to trials of at least two different antipsychotic medications at adequate doses and duration. Clozapine is the only medication with demonstrated efficacy for treatment-resistant schizophrenia and should be offered to these patients despite its side effect profile. Clozapine requires regular monitoring of white blood cell count and absolute neutrophil count due to agranulocytosis risk, initially weekly and gradually decreasing to monthly. Close monitoring of metabolic parameters and symptoms is also essential.

<image>Panel A illustrates acute psychosis management as a flowchart: safety assessment → medical workup → antipsychotic initiation → hospitalization if needed, with decision points for de-escalation and medication route (oral vs IM). Panel B shows first-episode considerations: lower doses (showing dose comparison), longer trials (6-8 week timeline), monotherapy preference, early intervention program components, 1-2 year minimum treatment duration. Panel C displays maintenance treatment rationale: 80% relapse rate without medication (declining curve), long-acting injectable option improving adherence, ongoing monitoring requirements. Panel D presents treatment resistance pathway: failed 2 adequate trials → clozapine initiation → monitoring schedule (weekly → biweekly → monthly WBC/ANC) with metabolic monitoring throughout.</image>

VIII. Psychosocial Interventions for Schizophrenia

Cognitive-behavioral therapy for psychosis has an evidence base for reducing positive symptom severity and distress. For delusions, CBT-p involves examining the evidence for and against delusional beliefs, generating alternative explanations, and developing coping strategies. For hallucinations, interventions focus on developing strategies to manage voices, reducing distress associated with voice-hearing, and testing beliefs about voices. For negative symptoms, behavioral activation and scheduling can improve engagement and activity. CBT-p does not replace antipsychotic medication but provides additional benefit.

Family interventions are among the most well-supported psychosocial treatments for schizophrenia. Psychoeducation helps family members understand the illness, recognize symptoms and warning signs, and understand treatment. Communication training focuses on reducing high expressed emotion, characterized by criticism, hostility, and emotional overinvolvement, which is associated with relapse. Problem-solving skills help families manage stressors and conflicts. Meta-analyses demonstrate that family intervention reduces relapse rates.

Supported employment using the Individual Placement and Support model has strong evidence for helping individuals with schizophrenia obtain competitive employment. The IPS model emphasizes rapid job search rather than prevocational training, competitive employment in integrated settings, attention to client preferences, ongoing support, and integration with mental health treatment. IPS consistently outperforms traditional vocational rehabilitation in randomized trials.

Other psychosocial interventions address specific functional domains. Social skills training targets interpersonal functioning through role-playing and behavioral rehearsal. Cognitive remediation addresses the cognitive deficits that are core features of schizophrenia through computerized or paper-and-pencil exercises. Assertive community treatment provides intensive, mobile, community-based services for individuals with severe illness who are difficult to engage in traditional outpatient care. Supported housing assists with obtaining and maintaining stable living situations.

<image>Panel A illustrates CBT for psychosis targeting different symptoms: delusions (examining evidence, alternative explanations), hallucinations (coping strategies, testing beliefs about voices), negative symptoms (behavioral activation). Panel B displays family intervention components: psychoeducation (illness understanding), communication training (reducing expressed emotion—criticism, hostility, overinvolvement shown declining), problem-solving skills, with relapse reduction outcome. Panel C presents the IPS model for supported employment with key elements: rapid job search, competitive employment, client preferences, ongoing support, integration with treatment. Panel D shows other interventions: social skills training (role-playing figures), cognitive remediation (brain exercises), ACT (mobile team providing services), supported housing (stable living assistance).</image>

IX. Other Psychotic Disorders

Schizoaffective disorder requires the presence of an uninterrupted period of illness during which there is a major mood episode concurrent with Criterion A symptoms of schizophrenia. Additionally, delusions or hallucinations must be present for at least two 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 illness duration. The diagnosis is subtyped as bipolar type if manic episodes have occurred or depressive type if only major depressive episodes have occurred. Treatment typically combines antipsychotics with mood stabilizers or antidepressants.

Brief psychotic disorder involves the sudden onset of at least one psychotic symptom including delusions, hallucinations, disorganized speech, or grossly disorganized or catatonic behavior. The duration is at least one day but less than one month, with eventual full return to premorbid level of functioning. Specifiers indicate whether the episode occurred with or without marked stressor or with postpartum onset. The prognosis is generally favorable, though some individuals later develop schizophrenia or other psychotic disorders.

Schizophreniform disorder has the same Criterion A symptoms as schizophrenia but differs in duration, lasting at least one month but less than six months. Approximately one-third of individuals recover completely, while the remaining two-thirds progress to schizophrenia or schizoaffective disorder. Good prognostic features include acute onset, confusion at peak of episode, good premorbid functioning, and absence of blunted affect.

Delusional disorder involves one or more delusions lasting at least one month without other schizophrenia Criterion A symptoms. The delusions are characteristically non-bizarre, meaning they involve situations that could occur in real life such as being followed, poisoned, infected, deceived by a spouse, or having a disease. Functioning is relatively preserved apart from the impact of the delusion itself. Subtypes are based on delusion content: erotomanic, grandiose, jealous, persecutory, somatic, mixed, and unspecified.

<image>Panel A illustrates schizoaffective disorder as a Venn diagram showing overlap of mood episode and psychotic symptoms, with the requirement that psychosis occurs both with and without mood symptoms, subtyped as bipolar or depressive. Panel B displays a duration comparison timeline: brief psychotic disorder (1 day to less than 1 month), schizophreniform (1-6 months), schizophrenia (6+ months). Panel C shows schizophreniform prognostic features: good features (acute onset, confusion, good premorbid function, preserved affect) associated with recovery (~1/3) versus poor features associated with progression to schizophrenia (~2/3). Panel D presents delusional disorder types with examples: erotomanic (someone of higher status in love), grandiose (special powers), jealous (partner unfaithful), persecutory (being targeted), somatic (body dysfunction), all characterized as non-bizarre (could actually occur).</image>

X. First-Episode Psychosis Evaluation and Special Considerations

The medical workup for first-episode psychosis aims to identify treatable underlying conditions that can present with psychotic symptoms. Basic laboratory testing should include complete blood count, comprehensive metabolic panel, and thyroid function tests. Urine drug screen is essential given the high frequency of substance-induced psychosis. Infectious disease testing including HIV and syphilis should be performed. Brain imaging, typically MRI, helps exclude structural lesions. When clinical presentation suggests, additional testing such as EEG for seizure evaluation, lumbar puncture for encephalitis, or autoimmune panels for anti-NMDA receptor encephalitis should be considered.

Substance-induced psychosis represents an important differential diagnosis. Stimulant intoxication with cocaine or methamphetamine commonly causes paranoia and may produce visual or tactile hallucinations. Cannabis use can trigger psychotic episodes in vulnerable individuals and is associated with earlier onset and worse outcomes in schizophrenia. Hallucinogens produce perceptual disturbances. Alcohol withdrawal can produce hallucinosis or delirium tremens. Phencyclidine produces a particularly severe presentation with agitation and violence. Distinguishing substance-induced psychosis from primary psychotic disorders requires observation over time, as symptoms of substance-induced psychosis should resolve with sustained abstinence.

Catatonia is a syndrome of motor abnormalities that can occur in schizophrenia, mood disorders, medical conditions, and as a separate entity. Signs include stupor, catalepsy with maintained posturing, waxy flexibility allowing limbs to be positioned by examiner, mutism, negativism with resistance to instructions, posturing, mannerisms, stereotypies, and echolalia or echopraxia. Importantly, treatment differs from typical psychosis: benzodiazepines are first-line treatment, and antipsychotics may actually worsen catatonia. Electroconvulsive therapy is highly effective for refractory cases.

Prognostic factors help predict outcome in schizophrenia. Better prognosis is associated with acute rather than insidious onset, later age of onset, female sex, prominent mood symptoms, good premorbid functioning, and shorter duration of untreated psychosis. Worse prognosis is associated with early and insidious onset, male sex, prominent negative symptoms, poor premorbid social and cognitive functioning, and prolonged untreated psychosis. These factors inform treatment planning and family counseling.

<image>Panel A displays the first-episode workup as a checklist: basic labs (CBC, CMP, TSH), urine drug screen, infectious disease testing (HIV, syphilis), brain imaging (MRI), and conditional tests (EEG, LP, autoimmune panel) with clinical triggers noted. Panel B shows substance-induced psychosis features by substance: stimulants (paranoia, visual/tactile hallucinations), cannabis (triggering in vulnerable, worse outcomes), hallucinogens (perceptual disturbances), alcohol withdrawal (hallucinosis, DTs), PCP (severe agitation, violence). Panel C illustrates catatonia signs (stupor, catalepsy, waxy flexibility, mutism, posturing) with treatment algorithm: benzodiazepines first-line, avoid antipsychotics (may worsen), ECT for refractory. Panel D presents prognostic factors in a balance diagram: better prognosis factors (acute onset, later age, female, mood symptoms, good premorbid function, short DUP) versus worse prognosis factors (insidious onset, early age, male, negative symptoms, poor premorbid function, long DUP).</image>

Summary

• Psychosis involves loss of contact with reality characterized by delusions, hallucinations, disorganized thought and behavior, and negative symptoms
• Schizophrenia requires at least two Criterion A symptoms for one month (at least one must be delusions, hallucinations, or disorganized speech), with total illness duration of at least six months
• Positive symptoms (delusions, hallucinations) result from mesolimbic dopamine hyperactivity; negative and cognitive symptoms from mesocortical hypoactivity
• First-generation antipsychotics primarily block D2 receptors; second-generation agents add 5-HT2A antagonism and have different side effect profiles
• Clozapine is uniquely effective for treatment-resistant schizophrenia but requires monitoring for agranulocytosis
• Schizoaffective disorder combines psychotic and mood symptoms, with psychosis occurring both with and without mood episodes
• Brief psychotic disorder lasts less than one month; schizophreniform lasts one to six months
• First-episode psychosis requires medical workup to exclude organic causes and substance-induced psychosis
• Catatonia is treated with benzodiazepines first-line; antipsychotics may worsen it
• Better prognosis is associated with acute onset, later age, female sex, good premorbid function, and shorter duration of untreated psychosis

Key Terms

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