Schizophrenia

Key topics to cover:

  • Symptoms of schizophrenia (positive, negative, and cognitive).

  • Phases of schizophrenia (prodrome, acute, remission, relapse).

  • Causes of schizophrenia (genetic and environmental).

  • Pathophysiological mechanisms behind schizophrenia.

Major Psychoses Overview

Examples: - Schizophrenia, schizoaffective disorder, delusional disorder.

  • Schizophrenia is the most significant due to its prevalence, early onset, and chronic, disabling nature

Schizophrenia Prevalence

  • Affects up to 1% of the population.

  • Cultural, ethnic, and socioeconomic factors influence diagnosis and understanding.

  • More prevalent in urban areas.

  • Gender differences: earlier onset and more severe symptoms in men.

Symptoms of Schizophrenia

  • Positive symptoms: Hallucinations (auditory), delusions (unshakable belief e.g. being spied on), disorganized thought/speech, motor symptoms.

  • Negative symptoms: Social withdrawal, anhedonia, lack of motivation, emotional flatness.

  • Cognitive symptoms: Impaired working memory, impaired selective attention, impaired comprehension.

  • Affective symptoms: Mood disturbances, such as depression and anxiety, which can significantly impact daily functioning.

  • DSM5: Two or more of these symptoms must persist for at least SIX months to be classed as schizophrenia.

  • Diagnosis is done through history taking/interviews and standardized assessments, which help to rule out other mental health disorders and ensure accurate identification of the condition e.g. PANSS(Positive and Negative Syndrome Scale).

Insight

  • Lack of insight is a hallmark of schizophrenia. Patients often do not realize they are ill or in need of treatment.

Phases of Schizophrenia

  1. Prodrome phase: Often mistaken for anxiety or depression in late teens/early adulthood. can be triggered by stress.

  2. Acute/Active phase: Onset of Positive symptoms, difficulty distinguishing reality.

  3. Remission: Symptoms improve with treatment.

  4. Relapse: Recurrence of symptoms after improvement.

    • Schizophreniform - positive symptoms for at least a month but less than six months.

Causes of Schizophrenia (Aetiology)

  • Genetics: Schizophrenia isn’t directly inherited but tends to run in families.

  • Twin studies show a 50% chance of schizophrenia if one twin has it.

  • Specific genes are linked, like COMT, DISC1, and GRM3.

  • Environmental factors: Early-life stress, drug use (especially cannabis), maternal infections, and birth complications.

Stress and Drug Use

  • Stressors like moving countries, loss of a loved one, and substance abuse increase the risk of schizophrenia.

  • Drug use, particularly cannabis and stimulants, is linked to early-onset schizophrenia.

Main Dopamine pathways

  1. The mesolimbic pathway: a critical dopaminergic pathway that originates in the ventral tegmental area (VTA) and projects to limbic structures, particularly the hippocampus and the amygdala. Its primary function is to mediate reward, motivation, and emotional processing, relying on dopamine as its main neurotransmitter. The hyperactivity is believed to play a significant role in the positive symptoms of schizophrenia, such as hallucinations and delusions.

  2. The mesocortical pathway: originates in the ventral Tegmental Area (VTA) and projects to the frontal cortex. Associated with cognitive functions and negative symptoms, including emotional flattening, lack of motivation and anhedonia. The hypoactivity of it is associated with the negative symptoms of Schizophrenia.

  3. The nigrostriatal pathway: a critical dopaminergic pathway that originates in the substantia nigra and projects to the striatum. Its primary function is to regulate motor control and coordination, and it relies on dopamine as its main neurotransmitter. dysfunction of it is associated with Parkinson’s disease.

  4. The tuberoinfundibular pathway: Regulates the release of prolactin from the pituitary gland, and its disruption can lead to hormonal imbalances and side effects related to antipsychotic medications.

Pathophysiology – Dopamine Hypothesis:

  • Dopamine system: Schizophrenia is thought to involve an overactivity of dopamine in the mesolimbic system (positive symptoms) and underactivity in the mesocortical system (negative symptoms).

  • Dopamine antagonists help control positive symptoms but do not fully explain the disorder.

    • if the receptor is blocked and prevented the activity of DA, the symptoms reduce.

Brain Structure Abnormalities:

  • Enlarged lateral ventricles-smaller hippocampus and reduced grey matter.

  • overall brain size is slightly smaller

  • Differences in brain structure are not found in all patients, but they are common.

Hypofrontality

  • Decreased blood flow and activity in the prefrontal cortex. This may contribute to cognitive symptoms and poor decision-making.

NMDA Receptor Hypofunction

  • NMDA (glutamate) receptor hypoactivity may explain some of the cognitive and negative symptoms.

  • ketamine blocks NMDA-receptors which is associated with positive symptoms of schizophrenia.

  • Animal models show decreased social interaction and responsiveness to antipsychotics in NMDA-reduced states.

Serotonin Involvement

  • LSD, a 5-HT agonist, causes hallucinations, suggesting a serotonin involvement.

  • if you block serotonin receptors, symptoms reduce.

  • Many antipsychotics block serotonin receptors.

  • Key focus areas:

Name and classify schizophrenia symptoms.

Understand the potential causes and pathophysiological mechanisms.

Review questions encourage self-assessment of knowledge.