Unit 16: Mental Illness II

LO: Differentiate between positive and negative symptoms and discuss cognitive deficits associated with schizophrenia

Schizophrenia symptoms are typically grouped into three categories:

Symptom Category	Characteristics	Examples
Positive Symptoms (Psychotic)	Symptoms that are abnormal and gained during the illness.	Delusions (fixed, false beliefs), Hallucinations (false sensory experiences, often auditory), and Disorganized Speech.
Negative Symptoms (Deficits)	Symptoms that represent a loss or absence of normal function.	Reduced expression of emotion (flat affect), Poverty of speech (alogia), and Lack of drive or motivation (avolition).
Cognitive Deficits	Problems with core mental functions.	Impairment in working memory, attention, and executive function (e.g., planning and problem-solving). These deficits are often present before the onset of positive symptoms.

LO: Discuss racial disparities in the diagnosis of schizophrenia 

In the United States, there is a significant racial disparity in the diagnosis of schizophrenia:

• Misdiagnosis: Black individuals are two to three times more likely to be diagnosed with schizophrenia than non-Hispanic white individuals.

• Overdiagnosis of Psychosis: The problem is specifically related to the overdiagnosis of psychosis (positive symptoms) among Black individuals presenting for care.

• Underdiagnosis of Affective Disorders: Conversely, Black individuals are often underdiagnosed with major depressive disorder and bipolar disorder, which may be misidentified as schizophrenia.

LO: Describe the brain differences observed in schizophrenia

Several structural and functional abnormalities are observed in the brains of individuals with schizophrenia:

• Enlarged Ventricles: The most consistently observed abnormality is the enlargement of the ventricles (fluid-filled spaces in the brain).

• Reduced Gray Matter: There is a reduced total volume of gray matter throughout the brain.

• Abnormal Cortical Structure:

  • The frontal lobes are reduced in size and show less metabolic activity (hypofrontality).

  • There are differences in the organization of the hippocampus.

  • Abnormal development and organization of the cortex are often seen in the frontal and temporal lobes.

These differences are thought to result from abnormal fetal development or abnormal synaptic pruning during adolescence.

LO: Discuss evidence that genes and environmental factors contribute to the development of schizophrenia

Schizophrenia is caused by an interaction between genetic vulnerability and environmental factors:

• Genetic Evidence:

  • Twin Studies: Concordance is significantly higher for monozygotic (identical) twins (up to 50%) than for dizygotic (fraternal) twins (17%), showing a strong heritable component.

  • Family Risk: The risk of developing schizophrenia is greatly increased for individuals with a close relative who has the disorder (e.g., 13% risk for children of one affected parent).

  • Polygenic: The disorder is polygenic, meaning many genes contribute to the overall risk.

• Environmental Evidence: Since identical twins are not 100% concordant, environment plays a crucial role. Environmental stressors can act as a "second hit" that interacts with the genetic predisposition to trigger the disorder.

LO: Describe the diathesis-stress model for schizophrenia

The Diathesis-Stress Model explains schizophrenia as the result of two interacting factors:

• Diathesis (Vulnerability): An individual inherits a genetic or developmental vulnerability (diathesis) that predisposes them to the disorder, such as an abnormality in brain development or connectivity.

• Stress (Trigger): An environmental or physiological stressor ("second hit") must interact with the diathesis to trigger the onset of symptoms. These stressors can include stressful life events, drug use, infections, or brain trauma.

LO: Explain the glutamate and dopamine hypotheses, and evidence for each

Two main neurochemical theories explain schizophrenia symptoms:

1. Dopamine Hypothesis:

   • Theory: The psychotic (positive) symptoms are due to excessive activation of D2 dopamine receptors in the brain.

   • Evidence:

     • Antipsychotic Drugs: All effective antipsychotic drugs block D2 receptors.

     • Dopamine Enhancers: Drugs that increase dopamine levels (e.g., amphetamines) can produce psychotic symptoms (positive symptoms).

2. Glutamate Hypothesis:

   • Theory: Schizophrenia symptoms are due to a reduction in glutamatergic signaling, specifically at the NMDA receptor. This is a broader model that may explain cognitive and negative symptoms.

   • Evidence:

     • NMDA Antagonists: Drugs that block NMDA receptors, such as PCP and ketamine, produce psychotic symptoms that closely mimic the full spectrum of schizophrenia, including positive (hallucinations) and negative (cognitive deficits) symptoms.

LO: Describe the primary treatments for schizophrenia

The primary treatments for schizophrenia are antipsychotic medications, divided into two generations:

1. First-Generation Antipsychotics (Typical):

   • Mechanism: Act as strong D2 dopamine receptor antagonists (blockers).

   • Effectiveness: Highly effective at controlling positive symptoms (e.g., hallucinations).

   • Side Effects: Associated with serious motor side effects, such as tardive dyskinesia (involuntary, repetitive movements).

2. Second-Generation Antipsychotics (Atypical):

   • Mechanism: Are also D2 receptor blockers but have a lower affinity for the D2 receptor and act on other receptors (e.g., serotonin receptors).

   • Effectiveness: Equally effective at treating positive symptoms, and are also effective at treating some negative and cognitive symptoms.

   • Side Effects: Cause fewer motor side effects, but are associated with metabolic side effects like weight gain and increased risk of diabetes.

Non-pharmaceutical methods, such as Transcranial Alternating Current Stimulation (tACS), are also being studied for specific symptoms like auditory hallucinations.