Schizophrenia - extra

Glutamate Hypothesis

Schizophrenia is linked to underactive NMDA glutamate receptors, affecting brain signaling and development.

NMDA Receptor

A glutamate receptor involved in learning and memory; blocked in schizophrenia, leading to neural dysfunction.

PCP and Ketamine

NMDA antagonists that can cause schizophrenia-like symptoms, supporting the glutamate hypothesis.

Disinhibited Glutamate

Reduced NMDA activity weakens GABA inhibition, causing overactive dopamine in the limbic system.

Positive, Negative, and Cognitive Symptoms

All three can be explained by NMDA hypofunction: too much dopamine in some areas, too little in others.

Heritability of Schizophrenia

Schizophrenia is highly heritable but not caused by a single gene; many genes increase susceptibility.

DISC1 Gene

A gene involved in brain development and synapse function, once thought to raise schizophrenia risk.

Paternal Age Effect

Children of older fathers have a higher risk of schizophrenia due to sperm cell mutations.

Monozygotic Twin Concordance

~48% chance of both twins having schizophrenia, showing strong genetic influence.

Polygenic Risk

Schizophrenia results from small effects of many genes rather than one dominant mutation.

Early Neurodevelopmental Model

Prenatal disruptions in brain development lie dormant until adolescence triggers symptoms.

Late Neurodevelopmental Model

Schizophrenia arises from abnormal adolescent brain changes, especially during synaptic pruning.

Two-Hit Hypothesis

Schizophrenia develops after both early developmental disruption and adolescent stress or pruning.

Synaptic Pruning

The brain eliminates excess synapses during adolescence; excessive pruning may cause schizophrenia.

Premorbid Signs

Subtle behavioral or motor deficits in childhood that appear before schizophrenia symptoms.

Microglia

Immune cells in the brain that help with pruning, inflammation, and brain maintenance.

Microglial Activation

Overactivation of microglia may damage brain circuits, contributing to schizophrenia.

Primed Microglia

Microglia activated by prenatal infection may overreact during adolescence, triggering symptoms.

PET Imaging Evidence

Shows increased microglial activity in patients and high-risk individuals.

Antibiotic and Antipsychotic Effects

Some treatments reduce microglial activation, improving schizophrenia symptoms.

Oestrogen Hypothesis

Estrogen protects against schizophrenia by modulating neurotransmitters and promoting brain health.

17β-estradiol

The most potent form of estrogen; has neuroprotective effects.

Later Onset in Women

Women often develop schizophrenia later than men, likely due to estrogen protection.

Menopause and Risk

Schizophrenia symptoms in women may worsen around menopause when estrogen levels drop.

Better Prognosis in Women

Women generally respond better to treatment and experience less severe symptoms.