Schizophrenia Overview and Pathophysiology

Schizophrenia

• A devastating, chronically debilitating disorder
• One of the most leading causes of disability among adults
• Onset typically occurs in late adolescence or early adulthood (15-40 years)
• Rarely occurs before adolescence or after 40 years old
• Prevalence is equal in men and women, but symptoms appear earlier in males (15-24 years) compared to females (25-34 years)
• Etiology remains unknown
• Genetic relatives of patients with schizophrenia have a 10% risk of developing the disorder

Pathophysiology

• Dopamine hypothesis: psychosis is caused by excessive dopamine in the brain
• Chlorpromazine, the first antipsychotic medication, was a postsynaptic dopamine antagonist
• Drugs that increase dopamine (e.g., cocaine, amphetamines) worsen or cause psychotic symptoms
• Data reveal a more complex picture with both hyperdopaminergic and hypodopaminergic brain regions in schizophrenia
• Positive symptoms possibly associated with DA-receptor hyperactivity in the mesolimbic pathway
• Negative symptoms and cognitive impairment linked to DA-receptor hypofunction in the mesocortical pathway
• Malfunctioning N-methyl-d-aspartate (NMDA) receptors impact dopaminergic activity in the mesolimbic and mesocortical pathways
• NMDA antagonists (e.g., phencyclidine, ketamine) can cause schizophrenia-like symptoms, including positive and negative symptoms and cognitive impairments
• Speculation regarding a role for serotonin receptor antagonism in antipsychotic efficacy, with many second-generation antipsychotics (SGAs) active at serotonin receptors
• Serotonin receptor binding may modulate dopamine activity in mesocortical pathways

Clinical Presentation

• Positive Symptoms (Psychotic): Presence of abnormal behaviors that should not be present

  • Hallucinations (distortions or exaggerations of perception): commonly auditory, but also visual, olfactory, gustatory, tactile
    • Voices may be threatening or commanding
  • Delusions (fixed false beliefs):
    • Beliefs despite invalidating evidence
    • May be bizarre or paranoid in nature, causing suspiciousness
    • Delusions of reference
    • Religious delusions
    • Grandiosity
    • Paranoid delusions (belief that one is being targeted or harmed)
    • Thought broadcasting and thought insertion
  • Thought disorder (illogical thought and speech):
    • Loosening of associations
    • Tangentiality
    • Word salad
    • Disorders of the stream or speed of thoughts (e.g., pressure of thought), leading to pressured speech

• Negative Symptoms: Absence of normally expected behaviors

  • Lack of social drive (avolition): No motivation for anything, including eating or sleeping
  • Apathy: no emotional response to things
  • Anhedonia: Inability to experience pleasure or interest in activities once enjoyed
  • Asociality: Lack of desire to interact socially; may be withdrawn

• Cognitive Impairment:

  • Impaired attention
  • Impaired processing speed
  • Impaired verbal, visual memory and working memory (does not learn from mistakes)
  • Impairment of problem-solving and executive functioning
  • Decreased IQ

• Other:

  • People with schizophrenia may appear uncooperative, suspicious, hostile, anxious, or aggressive
  • Mood changes may be present (normal, depressed or euphoric)
  • Psychotic and depressive symptoms often impair hygiene and self-care
  • Sleep and appetite disturbances are common
  • Comorbid medical disorders (e.g., obesity, Type 2 diabetes, chronic obstructive pulmonary disease) are prevalent due to sedentary lifestyles, poor diet, and cigarette smoking
  • Drug abuse (cannabis and cocaine) and alcohol use is prevalent

Course and Prognosis

• Most patients fluctuate between acute episodes and remission; complete remissions are uncommon
• Periods between episodes may include some residual symptoms
• Onset of symptoms is usually insidious, often preceded by a prodromal phase
• Prodromal phase: gradual development of symptoms that may go unnoticed until a major symptom occurs; includes social withdrawal, loss of interest, and deterioration in hygiene and grooming
• Acute/Active phase: full-blown episode of psychotic behavior; includes hallucinations, delusions and disordered thinking
• Stabilization phase: acute symptoms begin to decrease, lasting several months
• Stable phase: symptoms have markedly declined and may not be present; non-psychotic symptoms (such as anxiety and depression) may be present; shortened life expectancy, which is primarily due to suicide, cardiovascular diseases, accidents, or compromised self-care; lifetime risk of suicide is 5-10%

Diagnosis

• Diagnosis is clinical; no specific lab tests exist
• Rule out other causes of psychosis
• Meets DSM-5 diagnostic criteria (at least two of listed positive symptoms, including hallucinations or delusions, or disorganized speech or behavior, observed over a month; significant social or occupational dysfunction; some symptoms must be present for at least 6 months; exclude schizoaffective disorder, mood disorder with psychotic features, substance use, and general medical conditions.)
• Symptom monitoring: uses various scales (e.g., Positive and Negative Symptom Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) Scale)

Mortality

• Schizophrenia affects years of life, with potential life lost estimated at 14.5 years

Comorbidities

• Suicidality: significantly higher risk
• Hypertension, diabetes mellitus, dyslipidemia (often not treated in individuals with schizophrenia)

Other

• Many individuals diagnosed with schizophrenia experience long-term illness, family history of suicide or depression, past history of suicide, drug abuse, paranoia, and a higher number of medications

Explore the complexities of schizophrenia, a debilitating disorder that affects many adults. This quiz covers its onset, prevalence, etiology, and the dopamine hypothesis related to its symptoms and treatment. Understand the interplay between genetics and neurobiology in this critical mental health condition.