Brain Structure and Psychosis Overview

Study Notes

Brain Structure and Function

The brain is divided into three main parts: forebrain, midbrain, and hindbrain.
The forebrain is responsible for complex functions.
The cerebellum is involved in motor control and learning.
The brainstem handles basic functions like the release of serotonin, adrenaline, and dopamine.

Psychosis

Symptoms: Positive symptoms (new, e.g., hallucinations, delusions) and negative symptoms (lost, e.g., social withdrawal).
Risk Factors:
- Genetic predisposition (50% genetic, 50% environmental; strong heritability, polygenetic risk; 50% chance in identical twins).
- Environmental factors (obstetric complications, childhood trauma, immigration status, cannabis use).
Early Intervention: Crucial to reduce duration of untreated psychosis (DUP). Longer DUP correlates with worse outcomes.
Neurotransmitter Imbalance: Glutamate ("go") and GABA ("stop") are implicated. Dopamine plays a significant role.

Dopaminergic Pathways

There are four main dopaminergic pathways: mesolimbic, mesocortical, nigrostriatal, and tuberinfundibular.
These pathways are distinguished by their origin and termination points.
Five types of dopamine receptors (D1, D2, etc.) exist.

Mesolimbic Pathway

This pathway regulates the limbic system, associated with emotions (fear response) and reward processing (pleasure).
Salient (threat) evaluation is also regulated.
Psychosis can involve hyperactivity in the salience component.
Drug abuse targets the reward system, causing feelings of pleasure; chronic use disrupts salience and can lead to drug-induced psychosis.

Mesocortical Pathway

This pathway regulates the prefrontal cortex (PFC), involved in cognition, motivation, and social behaviors.
Dysfunction (hypoactivity) results in negative symptoms of psychosis like cognitive impairment and social withdrawal.

Nigrostriatal Pathway

This pathway is involved in movement control via the basal ganglia.
Antipsychotics can disrupt this pathway leading to movement difficulties.

Tuberinfundibular Pathway

This pathway regulates the hypothalamic-pituitary-adrenal (HPA) axis, which controls hormone regulation.
Antipsychotics can disrupt this, potentially causing hormonal imbalances.

Antipsychotics

Mechanism of Action: They modulate the dopaminergic system, specifically targeting D2 receptors as postsynaptic dopamine antagonists.
Dosage: Ideally bind to 60-70% of dopamine receptors.
Effects on Mesolimbic Pathway: Suppressing pleasure/threat evaluation can cause dysphoria (lack of pleasure).
Effects on Mesocortical Pathway: Further suppression can worsen negative symptoms (the positive symptom benefits might be counter-balanced).
Generations: First-generation antipsychotics worsened negative/cognitive symptoms. Second-generation antipsychotics showed improvements in these areas without causing movement problems.

Clozapine

Clozapine is a very effective second-generation antipsychotic.
It carries intense side effects (sedation, drooling), requiring regular blood monitoring.
Used as a last resort after failing two other antipsychotics.
Predictive psychopharmacology is impossible; what works for one patient does not guarantee success for another.

Long-Term Antipsychotic Effects

Positive symptom control is established, but long-term effects are not extensively proven in the research.
Some individuals may never fully recover without medication, suggesting lasting impact of the disorder.
Efficacy of long-term maintenance is well-documented.
Antipsychotic use does not appear to directly change the brain structure.
Dopamine cell "sensitization" is possible, by increased response over time.

Polypharmacy

Multiple medications are often used, potentially increasing the risk for treatment-resistant psychosis.
Polypharmacy is controversial in practice; one medication at a time is preferred.

Side Effects

Dopamine Blocking: While blocking dopamine in mesolimbic pathway is desirable, it can cause side effects in other brain areas.
Extrapyramidal Side Effects:
- Acute dystonia – muscle spasms.
- Akathisia – inner restlessness.
- Parkinsonism – movement stiffness.
- Tardive dyskinesia – abnormal mouth/lip movements.
Cardiometabolic Side Effects (with second-gen):
- Increased risk of obesity/diabetes/cardiovascular disease as a result of effects on hypothalamus, lipids, and glucose/insulin regulation.

Mortality

Psychosis can reduce lifespan by 15-20 years.

Future Research

Refining population-based strategies.
Developing drugs with reduced side effects.
Encouraging adherence to treatment.
Creating new medications.
Investigating acetylcholine (as in dementia) and glutamatergic drugs.

Description

Explore the intricate workings of brain structure and its connection to psychosis. This quiz covers the main parts of the brain, key symptoms of psychosis, and factors influencing its development. Understanding these components is essential for early intervention and better outcomes.

Brain Structure and Psychosis Overview

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Questions and Answers

What type of symptoms are characterized by the loss of social engagement in psychosis?

Which dopaminergic pathway is responsible for regulating pleasure and emotion?

What is a significant risk factor contributing to the development of psychosis?

In treating psychosis, what effect does the inhibition of the mesocortical system typically result in?

What type of antipsychotic is most effective but also carries significant side effects such as sedation?

Which of the following is NOT a pathway categorized within the dopaminergic system?

What kind of side effect results in muscle spasms when using certain antipsychotics?

What effect do first-generation antipsychotics typically have on cognitive and negative symptoms?

What is the recommended practice concerning polypharmacy in psychosis treatment?

What long-term effect is generally accepted regarding antipsychotics?