Schizophrenia is a complex mental disorder with a range of symptoms that can severely impact daily life. It's characterized by positive symptoms like hallucinations, negative symptoms like lack of motivation, and cognitive issues affecting memory and thinking.

The causes of schizophrenia are still not fully understood, but research points to a mix of genetic and environmental factors. Treatment typically involves antipsychotic medications and therapy, aiming to manage symptoms and improve quality of life for those affected.

Schizophrenia Symptoms

Positive, Negative, and Cognitive Symptoms

• Positive symptoms are additional behaviors not seen in healthy individuals
  • Hallucinations (auditory, visual, tactile, or olfactory experiences without external stimuli)
  • Delusions (fixed, false beliefs not based on reality)
  • Disorganized speech (incoherent or tangential speech)
  • Grossly disorganized or catatonic behavior (bizarre, agitated, or immobile behavior)
• Negative symptoms reflect a decrease in or lack of normal behaviors
  • Diminished emotional expression (flat affect or reduced facial expressions and gestures)
  • Avolition (decreased motivation to initiate or complete goal-directed activities)
  • Alogia (diminished speech output or poverty of speech content)
  • Anhedonia (decreased ability to experience pleasure from normally enjoyable activities)
  • Asociality (lack of interest in social interactions or relationships)
• Cognitive symptoms involve impairments in executive functions
  • Problems with working memory (difficulty holding and manipulating information in mind)
  • Attention deficits (difficulty focusing on relevant stimuli and filtering out distractions)
  • Slowed processing speed (reduced ability to quickly process and respond to information)
  • Impaired abstract thinking (difficulty understanding and using abstract concepts)
• Diagnostic criteria require the presence of at least two symptoms (with at least one being a positive symptom) for a significant portion of time during a one-month period

Symptom Impact on Functioning

• Positive, negative, and cognitive symptoms can significantly impair an individual's daily functioning
  • Difficulty maintaining employment or academic performance
  • Strained interpersonal relationships and social withdrawal
  • Impaired self-care and independent living skills
• The severity and combination of symptoms can vary widely among individuals with schizophrenia
• Symptoms typically emerge in late adolescence or early adulthood, with a slightly earlier onset in males compared to females

Schizophrenia Etiology

Neurodevelopmental Hypothesis

• Proposes that schizophrenia results from disruptions in early brain development leading to abnormalities in brain structure and function that manifest as symptoms later in life
• Factors contributing to neurodevelopmental disruptions
  • Genetic vulnerabilities (inherited risk factors that interact with environmental factors)
  • Prenatal infections (maternal influenza, toxoplasmosis, or rubella during pregnancy)
  • Obstetric complications (hypoxia, low birth weight, or prenatal malnutrition)
• Evidence supporting the neurodevelopmental hypothesis
  • Structural brain abnormalities (enlarged ventricles, reduced cortical volume) in individuals with schizophrenia
  • Cognitive and social impairments often precede the onset of psychotic symptoms
  • Increased risk of schizophrenia associated with prenatal and perinatal complications

Dopamine Hypothesis

• Suggests that schizophrenia is associated with an imbalance in dopamine neurotransmission, particularly in the mesolimbic and mesocortical pathways
• Excess dopamine activity in the mesolimbic pathway is thought to contribute to positive symptoms
  • Mesolimbic pathway projects from the ventral tegmental area to the nucleus accumbens and limbic regions
  • Increased dopamine release in this pathway may lead to aberrant salience attribution and psychotic experiences
• Reduced dopamine activity in the mesocortical pathway may be associated with negative and cognitive symptoms
  • Mesocortical pathway projects from the ventral tegmental area to the prefrontal cortex
  • Decreased dopamine transmission in this pathway may result in impaired executive functioning and motivation
• Evidence supporting the dopamine hypothesis
  • Effectiveness of antipsychotic medications that block dopamine D2 receptors in reducing positive symptoms
  • Psychostimulants (amphetamine, cocaine) that increase dopamine release can induce psychotic symptoms in healthy individuals
  • Neuroimaging studies showing increased dopamine synthesis and release in the striatum of individuals with schizophrenia

Schizophrenia Subtypes

Paranoid Schizophrenia

• Characterized by prominent delusions and hallucinations with relatively intact cognitive functioning and affect
• Delusions are often persecutory (belief that one is being harassed, followed, or plotted against) or grandiose (belief in having exceptional abilities, wealth, or fame)
• Hallucinations are typically auditory (hearing voices that comment on one's behavior or give commands)
• Paranoid schizophrenia has a later onset and better prognosis compared to other subtypes

Disorganized Schizophrenia

• Involves disorganized speech, behavior, and flat or inappropriate affect with less prominent delusions and hallucinations
• Disorganized speech may include loose associations, tangentiality, or incoherence ("word salad")
• Disorganized behavior may involve childlike silliness, unpredictable agitation, or inappropriate sexual behavior
• Flat affect is characterized by a lack of emotional expressiveness, while inappropriate affect involves emotional responses inconsistent with the situation

Catatonic Schizophrenia

• Marked by unusual motor behaviors, such as excessive and purposeless movement or rigid, fixed postures
• Catatonic excitement involves agitated, repetitive movements or purposeless overactivity
• Catatonic stupor is characterized by immobility, mutism, and posturing (maintaining rigid, awkward positions for extended periods)
• Other catatonic features may include echolalia (repeating others' words) or echopraxia (mimicking others' movements)

Other Schizophrenia Subtypes and Related Disorders

• Undifferentiated schizophrenia is diagnosed when symptoms do not clearly fit into other subtypes or when multiple subtypes are present
• Residual schizophrenia is characterized by a history of at least one episode of schizophrenia but currently with only negative symptoms or attenuated positive symptoms
• Brief psychotic disorder involves the sudden onset of psychotic symptoms lasting less than one month, often in response to a stressful event
• Schizophreniform disorder is characterized by schizophrenia-like symptoms lasting between one and six months
• Schizoaffective disorder involves a combination of schizophrenia symptoms and mood disorder symptoms (depression or mania)

Schizophrenia Treatment

Antipsychotic Medications

• First-line treatment for schizophrenia, primarily targeting dopamine receptors
• Effective in reducing positive symptoms but have limited efficacy for negative and cognitive symptoms
• First-generation (typical) antipsychotics (haloperidol, chlorpromazine)
  • Associated with a higher risk of extrapyramidal side effects (tardive dyskinesia, parkinsonism, akathisia)
  • Extrapyramidal side effects result from dopamine blockade in the nigrostriatal pathway
• Second-generation (atypical) antipsychotics (risperidone, olanzapine, quetiapine)
  • Have a lower risk of extrapyramidal side effects due to their action on both dopamine and serotonin receptors
  • May cause metabolic side effects (weight gain, diabetes, dyslipidemia)
• Clozapine, an atypical antipsychotic, is often used for treatment-resistant schizophrenia but requires regular blood monitoring due to the risk of agranulocytosis

Psychosocial Interventions

• Used in conjunction with antipsychotic medications to improve functioning, reduce relapse, and enhance medication adherence
• Cognitive-behavioral therapy (CBT) helps patients identify and challenge distorted thoughts and beliefs, develop coping strategies, and improve problem-solving skills
• Family psychoeducation involves educating family members about schizophrenia, improving communication, and reducing expressed emotion (critical or overprotective attitudes)
• Social skills training focuses on improving patients' ability to interact with others, manage social situations, and develop independent living skills
• Supported employment and education programs help patients achieve vocational and academic goals by providing job coaching, accommodations, and ongoing support

Treatment Challenges and Approaches

• Medication non-adherence is common and can lead to relapse and rehospitalization
  • Strategies to improve adherence include long-acting injectable antipsychotics, patient education, and collaborative decision-making
• Negative and cognitive symptoms often persist despite antipsychotic treatment
  • Novel pharmacological targets (glutamate, nicotinic receptors) and cognitive remediation therapy are being explored to address these symptoms
• Relapse prevention requires ongoing medication management, psychosocial support, and monitoring for early warning signs of relapse
• Early intervention during the prodromal phase (before the full onset of psychotic symptoms) may delay or prevent the development of schizophrenia
• A comprehensive, individualized approach that combines medication, psychosocial interventions, and support services is essential for optimizing outcomes and quality of life for individuals with schizophrenia