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What is the neurodevelopmental hypothesis of schizophrenia?

It proposes that schizophrenia originates from disruptions in early brain development, such as prenatal stress, infection, or malnutrition, which may not manifest until adolescence or early adulthood.

How does abnormal synaptic pruning contribute to schizophrenia?

During adolescence, the brain normally eliminates excess synapses. In schizophrenia, this pruning may be excessive or dysregulated, leading to loss of important neural connections and contributing to cognitive deficits.

What changes occur in dendritic spines and synaptic proteins in schizophrenia?

Postmortem studies show reduced dendritic spine density and lower levels of synaptic proteins, indicating impaired synaptic connectivity and plasticity in individuals with schizophrenia.

What is the role of gamma oscillations in schizophrenia?

Gamma oscillations (~40 Hz) are brain rhythms important for cognitive functions like attention and memory. In schizophrenia, these oscillations are disrupted due to impaired GABAergic interneurons, leading to cognitive deficits.

How is the dopamine system altered in schizophrenia?

There is hyperactivity of dopamine transmission in the striatum, which is associated with positive symptoms like hallucinations and delusions. Antipsychotic drugs target D2 dopamine receptors to reduce these symptoms.

What is the significance of GABAergic and glutamatergic dysfunction in schizophrenia?

Schizophrenia involves reduced markers of GABAergic and glutamatergic neurons, disrupting the balance between excitation and inhibition in the brain and impairing neural communication.

What genetic factors are associated with schizophrenia?

Schizophrenia is polygenic, involving over 100 genetic loci. Genes related to synaptic transmission, ion channels, and neurodevelopment contribute to risk. No single gene causes the disorder.

What is a CNV and how does the 22q11.2 deletion relate to schizophrenia?

A Copy Number Variant (CNV) is a deletion or duplication of a DNA segment. Deletion at chromosome 22q11.2 is one of the strongest genetic risk factors for schizophrenia, increasing risk by 30–40%.

How do microglia contribute to schizophrenia?

Microglia are brain immune cells involved in synaptic pruning. In schizophrenia, altered microglial activity may lead to excessive pruning and neuroinflammation, contributing to synaptic loss.

How do environmental factors interact with biology in schizophrenia?

Environmental risks like prenatal infection, childhood trauma, and cannabis use interact with genetic vulnerability to disrupt brain development and increase the likelihood of developing schizophrenia.