Schizophrenia

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Questions and Answers

What is a potential effect of L-DOPA in susceptible individuals?

Decreased dopamine receptor sensitivity

Increased dopamine production without side effects

Enhanced mood stabilization

Triggered psychotic episodes (correct)

What is the primary action of chlorpromazine?

It decreases dopamine turnover

It acts as a dopamine receptor antagonist (correct)

It increases dopamine release in the brain

It enhances dopamine transporter activity

What evidence contradicts the dopamine hypothesis in schizophrenia?

Corroborated findings from consistent PET scans

No consistent evidence for increased dopaminergic transmission (correct)

Elevated levels of D1 receptors in the mesolimbic region

Increased levels of dopamine release observed in drug-naive patients

What is a noted discrepancy with the dopamine hypothesis related to treatment effects?

Delayed onset of treatment benefits (A) Signup and view all the answers

Which conclusion can be drawn regarding dopamine receptors in schizophrenia?

Drug treatment effects may influence receptor measurements post-mortem (D) Signup and view all the answers

What role does the DISC 1 gene play in the context of schizophrenia?

Regulates dopamine homeostasis (B) Signup and view all the answers

Which psychosocial factor can precipitate the onset of schizophrenia?

Stress (B) Signup and view all the answers

What brain structural abnormality has been associated with schizophrenia?

Ventricular enlargement (D) Signup and view all the answers

What is a significant structural finding in the brains of individuals with schizophrenia?

Decreased numbers of small neurons in superficial layers (B) Signup and view all the answers

Which environmental factor is associated with a higher incidence of schizophrenia in offspring?

Viral infection during pregnancy (D) Signup and view all the answers

What hormonal response is noted in schizophrenia patients within an emotionally charged home environment?

Blunted cortisol response (C) Signup and view all the answers

How does the COMT gene relate to schizophrenia?

It breaks down dopamine (B) Signup and view all the answers

What are cytoarchitectural abnormalities associated with in the context of schizophrenia?

Differences in neuronal size distribution (B) Signup and view all the answers

What role does DISC1 play in relation to neuronal migration?

It interacts with proteins mutated in lissencephaly. (C) Signup and view all the answers

What is a primary function of antipsychotics in the treatment of schizophrenia?

They block dopamine receptors. (B) Signup and view all the answers

Which of the following is a goal for improving therapy for schizophrenia?

To aim for early and accurate diagnosis. (A) Signup and view all the answers

What is the significance of Clozapine as an antipsychotic?

It is an atypical antipsychotic with a unique action. (B) Signup and view all the answers

Which factor complicates the expression of schizophrenia?

An interaction between genetic and environmental factors. (A) Signup and view all the answers

What is the primary cause of premature death in people with schizophrenia?

Suicide (C) Signup and view all the answers

Which of the following best describes the symptoms associated with schizophrenia?

A mix of positive and negative symptoms including hallucinations and cognitive impairment (B) Signup and view all the answers

Which statement is true regarding the genetic basis of schizophrenia?

Monozygotic twins show a concordance rate of approximately 48%. (B) Signup and view all the answers

What is a critical difficulty in treating schizophrenia?

The episodic nature of the disorder complicates consistent treatment. (A) Signup and view all the answers

Which of the following is highlighted as a limitation of current schizophrenia treatments?

They may not address the full spectrum of symptoms. (D) Signup and view all the answers

What role does stress play in the context of schizophrenia?

It is a major precipitating factor for the illness. (C) Signup and view all the answers

How might the prospects for understanding and treating schizophrenia improve in the future?

Through advancements in neurobiological research and targeted therapies. (C) Signup and view all the answers

Which type of hallucination is most commonly experienced by individuals with schizophrenia?

Auditory hallucinations (B) Signup and view all the answers

Which brain structure is associated with positive symptoms of schizophrenia?

Temporal lobe (D) Signup and view all the answers

What is indicated about the left hemisphere in individuals with schizophrenia during verbal tasks?

Lateralization appears disrupted in schizophrenia. (A) Signup and view all the answers

Which of the following best describes the relationship between genetics and environment in schizophrenia?

Genetics and environment synergistically affect the condition. (B) Signup and view all the answers

What is hypofunctionality of the dorsal-lateral prefrontal cortex cited as in schizophrenia?

The orchestra without a conductor metaphor. (D) Signup and view all the answers

What neurochemical changes are generally observed in the frontal cortex of individuals with schizophrenia?

Lower levels of dopamine, glutamate, and GABA. (A) Signup and view all the answers

Which brain dysfunction is primarily involved in negative symptoms of schizophrenia?

Prefrontal cortex dysfunction. (D) Signup and view all the answers

Which of the following statements about dopamine in schizophrenia is accurate?

Dopamine is implicated due to indirect evidence. (D) Signup and view all the answers

What is a notable structural change found in the brains of individuals with schizophrenia?

Enlarged ventricles and decreased size of the temporal lobe. (A) Signup and view all the answers

Which COMT allele is associated with a linkage to schizophrenia?

Valine 108 (D) Signup and view all the answers

What role does Neuregulin play in relation to schizophrenia?

It regulates neuronal differentiation and migration. (D) Signup and view all the answers

What is the effect of increased neuregulin signaling on the NMDA receptor according to current hypotheses?

Reduces its function (D) Signup and view all the answers

Which protein does the DISC1 interact with in the context of schizophrenia?

LIS1 (A) Signup and view all the answers

What is the observed condition regarding the prefrontal cortex (PFC) in brain imaging related to schizophrenia?

Hypofunctionality (C) Signup and view all the answers

In the context of schizophrenia, what is responsible for chromosomal translocation linked to the DISC1 gene?

Familial inheritance (B) Signup and view all the answers

What is primarily noted about the expression of DISC1 during neuronal development?

It is increased. (D) Signup and view all the answers

Which of the following best summarizes the proposed symptoms related to PFC and subcortical systems in schizophrenia?

PFC shows hypofunctionality while subcortical systems exhibit excessive activity. (C) Signup and view all the answers

Study Notes

Schizophrenia Overview

Suicide is the leading cause of premature death in people with schizophrenia.
An estimated 10% to 13% of deaths among individuals with schizophrenia are due to suicide.

Topics of Study

Symptoms and Causes
Antipsychotics and the Dopamine Hypothesis
Genetics and Beyond the Dopamine Hypothesis
Workshop on an exam question

Learning Outcomes

Critically assess neurobiological hypotheses for schizophrenia.
Discuss the difficulties in treating schizophrenia.
Describe the main drugs used to treat schizophrenia, and their mechanisms of action.
Discuss limitations of the drugs used to treat schizophrenia.
Outline experimental approaches used to study the neurobiological basis of schizophrenia.
Comment on how prospects for understanding and treating schizophrenia could improve in the future.

Schizophrenia Part 1: Symptoms and Causes

Swiss psychiatrist Eugen Bleuler (1908) coined the term "fragmentation of cognitive processes and personality" to describe schizophrenia.
Schizophrenia often begins in adolescence.
Symptoms are complex and varied.
Stress can trigger episodes of illness.
Episodes of illness frequently occur.

Symptoms of Schizophrenia

Positive symptoms: Hallucinations (mainly auditory, "inner speech"), thought disorders, and stereotypical behaviors.
Negative symptoms: Poverty of affect, cognitive impairment, and temporal disorientation.

Time Course of Schizophrenia

Symptoms of schizophrenia often vary in their onset.
Mood symptoms, anxiety, and substance use can be present preceding the onset of the illness.
Positive symptoms increase in severity during the progressive phase.
Negative symptoms are also apparent and may persist.
Cognitive deficits are often evident, remaining stable over the course of the illness.
Residual symptoms can include prolonged cognitive issues, and mood disturbances.

Causes of Schizophrenia

1. Genetic: Supported by high concordance rates in monozygotic twins (48%). The genetic basis of schizophrenia is complex, involving thousands of risk loci and their interactions.
- DISC1 (Disrupted in Schizophrenia 1 gene)
- COMT (catechol-O-methyl transferase gene)
- Neuregulin
2. Psychosocial: Adolescent onset, stress can precipitate illness, higher relapse rate in emotionally charged home environments, and blunted cortisol response.
3. Structural Brain Damage: Some studies show ventricular enlargement and decreased volume in the temporal lobe, especially the hippocampus. However, no gliosis, meaning no neurodegenerative changes. (Questions remain about early brain injury, obstetric complications, and developmental abnormalities.)
4. Viral Infection: Higher incidence in patients born in late winter or spring. Hypothesis proposes that exposure to a virus during the second trimester of pregnancy may increase the risk of schizophrenia in the child. This remains a hypothesis and possible mechanisms for this link need further investigation.

Current Understanding

Genetic susceptibility plays a role, but the environment can influence the expression of genes.
Positive symptoms are linked to the temporal lobe.
Negative symptoms are linked to the prefrontal cortex.

Schizophrenia Part II: Neurochemical Imbalances

Regional changes: Dopamine and glutamate may be higher in the basal ganglia and dopamine, glutamate, and GABA lower in the frontal cortex.

Schizophrenia Part II: Antipsychotics and the Dopamine Hypothesis

Indirect evidence links dopamine to schizophrenia: Reserpine (an antipsychotic) and amphetamines (induce toxic psychosis in susceptible individuals), and L-DOPA (can trigger psychotic episodes).
Chlorpromazine, acts as a dopamine receptor antagonist.
- Chlorpromazine increases dopamine turnover.
The dopamine hypothesis proposes that excess dopamine neurotransmission in the mesolimbic and mesocortical regions of the brain contributes to schizophrenia symptoms.

Atypical Antipsychotics

More effective against negative symptoms, less sedation.
Reduced adverse effects on movement disorders. Atypical antipsychotics include clozapine, quetiapine, olanzapine, risperidone, aripiprazole, asenapine, and paliperidone.

Site of Brain Dysfunction

1. Limbic Structures: (e.g. temporal lobe) decreased in size & increased activity in some parts.
2. Dominant Cerebral Hemisphere: Dysfunction in the left hemisphere(e.g. Broca's area), influencing verbal function.
3. Prefrontal Cortex: Underfunction, "Orchestra without a conductor" impairment.
4. Basal Ganglia: Site of action for antipsychotics.

Summary of Recent Advances

Evidence for involvement of the prefrontal cortex and subcortical dopamine function in positive and negative symptoms of schizophrenia.

Conclusions on Schizophrenia Research

Increase understanding of the genetic basis of the disorder and mechanisms for the illness.
Inform development of new models and improved treatments for schizophrenia.
Understanding the complex interaction between environmental and genetic factors that may exacerbate the disorder.
Aim for early, accurate diagnosis.
Develop treatments that mitigate the disorder's impact on patients.

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Description

This quiz explores the potential effects of L-DOPA, particularly in individuals who may be susceptible to its side effects. Understanding these effects is crucial for managing treatments effectively and ensuring patient safety. Join us to test your knowledge about L-DOPA and its implications.