Schizophrenia and Psychosis

What is the lifetime prevalence of schizophrenia?

1-.1.5% (meaning 1-100 people)

Give examples of negative symptoms// What cognitive symptoms occur in schizophrenia?

Blunted affect, social withdrawal, avolition, alogia, anhedonia, poor motivation, difficulty with abstract thinking // Impaired working memory, poor executive function, attention deficits.

How does age of onset differ by sex?

Men show an earlier onset; estrogen may delay onset in women.

What makes schizophrenia one of the most dangerous mental illnesses?

Exceptionally high suicide risk—up to 50% attempt, risk is 170× general population.

Why is schizophrenia economically costly?

High hospitalization rates (25% of beds), social security use, long-term care, and lost productivity.

What major structural brain change is commonly seen in schizophrenia? What areas are seen to be affected and what does each possibly contribute to?

Cerebral atrophy with reduced volume in the basal ganglia (motor and +sxs), temporal cortex (hallucinations), frontal cortex (-sxs and cog sis), and hippocampus (affects disorganization).

Are neurons lost in schizophrenia?

No, the number of neurons is generally normal, but they have smaller somas and reduced dendritic branching, impairing connectivity

What is white matter? And how is damage associated with in schizophrenia?

It is the myelinated axons that connect brain regions // It disrupts communication between brain regions and impairs functional connectivity

Positive symptom clusters are linked to abnormal connectivity between the ___ and ___

caudate nucleus and dorsolateral prefrontal cortex

What does hypofrontality refer to?

Reduced functioning of the prefrontal cortex.

Which symptoms are most strongly linked to prefrontal cortex dysfunction?

Negative and cognitive symptoms.

What major question remains about the brain changes seen in schizophrenia?

Whether they are the cause of the disorder or a consequence of illness progression or treatment.

What immune abnormalities are seen during the first episode of schizophrenia? // How do antipsychotic medications affect cytokine levels?

Elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines // They generally return cytokine levels toward normal.

What prenatal factor significantly increases the risk of schizophrenia in offspring?

Maternal viral infection, especially during the second trimester

Which brain cells mediate neuroinflammation in schizophrenia?

Microglia

What do microglia typically do? What happens when microglial homeostasis is disrupted?

Detect infections or injury, Produce cytokines, synaptic pruning, Phagocytosis, Maintain homeostasis to avoid damaging healthy tissue // Prolonged inflammation, excessive synaptic pruning, and potential neuronal damage.

What evidence suggests neuroinflammation contributes to the development of schizophrenia?

Increased microglial activation occurs before symptom onset

What is the likely genetic contribution to schizophrenia?

A polygenic architecture where many genes each confer small risk.

How much does schizophrenia risk increase if a close relative is affected?

About 12× higher.

How can cytokines disrupt early brain development?

By affecting neurogenesis, neuronal migration, and cell survival.

What do developmental errors in schizophrenia primarily involve?

Abnormal brain development, including irregular cortical connections and structural abnormalities.

What infant behaviors may predict future schizophrenia risk?

Passivity, apathy, and reduced responsiveness to verbal commands.

What childhood characteristics are more common in individuals who later develop schizophrenia?

Attention deficits, difficulty with information processing, impaired fine motor control, negative facial expressions, social withdrawal, and unusual motor movements.

How do developmental signs support the neurodevelopmental model of schizophrenia?

They show abnormalities occurring long before symptoms, indicating early brain development problems contribute to the disorder.

What does the biopsychosocial model suggest about schizophrenia?

The disorder arises from an interaction between biological vulnerability, environmental stressors, and psychological coping capacity.

What environmental and social stressors can contribute to triggering schizophrenia in someone with biological vulnerability?

Chronic stress, trauma, social adversity, poverty or urban living, family conflict, and substance use (especially adolescent cannabis use).

What does it mean that someone is “pushed beyond their ability to cope” in the context of schizophrenia?

Environmental or social stress exceeds a person’s coping resources, triggering symptoms in someone with biological vulnerability.

What is the DA Hypothesis

postulates that schizophrenia is caused by overactivity of dopamine signaling, especially at D2 receptors, leading to positive symptoms.

What major evidence supports the dopamine hypothesis of schizophrenia?

Stimulants increase dopamine and can induce psychosis, while dopamine antagonists reduce symptom

Patients with SCPT have elevated DA even in the ___ stage // What structural receptor change involving dopamine receptors is seen in schizophrenia, and where does it occur?

prodromal // There is increased D2 receptor density in the basal ganglia, nucleus accumbens, and substantia nigra, regions involved in reward, motivation, and movement.

What is the DA Imbalance Hypothesis

states that schizophrenia results from excess dopamine activity in the mesolimbic pathway causing positive symptoms and reduced dopamine activity in the mesocortical pathway causing negative and cognitive symptoms.

According to the neurodevelopmental model, what causes positive symptoms? What causes negative symptoms?

Hyperactive subcortical dopamine cells due to loss of cortical inhibition // decreased PFC (mesocortical) function

What neurotransmitter is central to the glutamate hypofunction hypothesis?

Glutamate acting at NMDA receptors.

How can low glutamate explain both types of dopamine abnormalities in schizophrenia?

Low glutamate reduces cortical dopamine (AKA Hypofrontality) (negative symptoms) and fails to activate inhibitory pathways, leading to excess mesolimbic dopamine (positive symptoms).

What early-life factors may contribute to mesocortical dysfunction in schizophrenia?

Genetic vulnerability and prenatal viral infection or inflammation.

What are neuroleptics?

An older term for antipsychotics, named for their ability to reduce emotionality and psychomotor activity.

What structural feature do phenothiazines share?

A characteristic three-ring structure with variable functional groups.

How quickly do classic neuroleptics reduce mania and hyperactivity? What effect do they have on Pos and neg symptoms

within few doses // Positive symptoms improve slowly; negative symptoms generally do not improve.

What proportion of schizophrenia patients are treatment-resistant?

one third

What is the primary mechanism of action for classic neuroleptics?

High-affinity drugs bind strongly at low doses, affecting potency and side-effect profile.

D2 receptor antagonism.

What happens to dopamine firing initially after D2 blockade

It increases due to blocked autoreceptors.

Why does dopamine firing later decrease during chronic treatment?

Upregulation of autoreceptors increases sensitivity, reducing DA synthesis and release.

Upregulation of autoreceptors increases sensitivity, reducing DA synthesis and release.

Reduced dopamine increases prolactin, causing galactorrhea (milk production)and gynecomastia (breast enlargement)

What causes Parkinsonism in patients taking classic neuroleptics?

Dopamine blockade in the nigrostriatal pathway.

what is tardive dyskinesia and how is it treated ? Does it persist

A long-term motor side effect involving involuntary facial and tongue movements.// VMAT2 inhibitorsrsis // yes it persists even after stopping medication

What is the most serious side effect of neuroleptics? and what are hallmark symptoms?

neuroleptic malignant syndrome (NMS) // Fever, rigidity, altered consciousness, and autonomic instability.

What type of factors increase NMS risk?

Certain genetic predispositions.

What is the main advantage of atypical antipsychotics over classic neuroleptics?

They reduce positive symptoms with fewer extrapyramidal motor side effects and lower risk of prolactin elevation.

What are the three main mechanisms of atypical antipsychotics?

Selective D2 antagonism, partial dopamine agonism, and broad-spectrum receptor blockade.

Which atypical antipsychotics act as selective D2 antagonists?

Sulpiride and amisulpride.

What receptors do selective D2 antagonists primarily target?

What receptors do selective D2 antagonists primarily target?

What major risks are associated with selective D2 antagonists?

Hormonal side effects and potential fatal blood disorders.

What is another name for partial dopamine receptor agonists?

Dopamine system stabilizers.

How do partial D2 agonists reduce both positive and negative symptoms?

They decrease dopamine where it is too high and increase it where it is too low.

What is the prototypical broad-spectrum antipsychotic?

Clozapine

Why is clozapine especially important clinically?

It is the most effective treatment for treatment-resistant schizophrenia and improves negative and cognitive symptoms.

Which dangerous side effect of clozapine requires routine blood monitoring? // What are common side effects of broad-spectrum antipsychotics like clozapine?

Agranulocytosis.// Weight gain, hypersalivation, lowered seizure threshold, cardiovascular issues.

Do broad-spectrum antipsychotics cause EPS?

Usually minimal, unless doses are very high.

Why do schizophrenia patients smoke at such high rates?

Nicotine may improve attention and sensory processing through acetylcholine pathways.

How might enhancing D1 receptor activity help cognitive symptoms?

It may improve prefrontal cortex function and reduce hypofrontality.

What is a potential problem with drugs that enhance NMDA receptor activity?

They may cause hyperexcitability and seizures.

How might anti-inflammatory drugs help schizophrenia symptoms?

By reducing excessive dopamine activity in some pathways and increasing dopamine where it is low, improving both positive and negative symptoms.