Schizophrenia and Psychosis

Vocabulary-style flashcards covering the clinical features, demographics, genetics, neurobiology, and treatment of schizophrenia based on the Oxford University lecture.

Psychoses

A category of psychiatric disorders that includes schizophrenia, bipolar disorder (manic depression), and delusional disorders.

• features delusions, hallucinations, and lack of insight

• mood and anxiety disorders =neurosis

Delusions

False beliefs held with complete conviction despite contrary evidence, which are not culturally appropriate and usually have personal significance (often persecutory or bizarre).

Hallucinations

Sensations perceived as genuine without an external stimulus that can occur in any modality, though they are usually auditory.

Positive Symptoms

Clinical features of schizophrenia including delusions, hallucinations, and thought disorder; they are often the focus of acute phases.

Negative Symptoms

Clinical features of schizophrenia characterized by a lack of drive, social interaction, and speech, often associated with chronic impairment.

Diagnostic Systems

The two primary systems used to diagnose schizophrenia: $ICD-11$ (World Health Organisation) and $DSM-5$ (American Psychiatric Association).

Schizophrenia Epidemiology

Affects approximately $0.8\%$ of the population worldwide, has an equal sex ratio, and a typical age of onset between $7$ and $70$ years (usually in the $20s$).

Schizophrenia Mortality

Increased mortality by a factor of $3$ due to suicide (approx. $10\%$) and natural causes, with life expectancy reduced by more than $15$ years.

Antipsychotics (Neuroleptics)

• The mainstay medication for schizophrenia, such as Chlorpromazine or Olanzapine, which works by blocking $D2$ dopamine receptors.

• nothing effectively treats negative or cognition symptoms

Clozapine

An antipsychotic medication that is more effective than others but has limited use due to toxicity.

Heritability of Schizophrenia

The estimated genetic contribution to the disorder, calculated at approximately $80\%$ (range $73\text{-}95\%$).

Probandwise Concordance Rates

The likelihood of an individual having schizophrenia if their twin has it: $48\%$ for Identical ($MZ$) twins and $17\%$ for Fraternal ($DZ$) twins.

SNPs (Single Nucleotide Polymorphisms)

Genetic risk factors that cumulatively explain the majority of heritability, though individual effects are tiny; much of this risk is shared with bipolar disorder and autism.

CNVs (Copy Number Variants)

• Rare lengths of DNA deleted or duplicated that have a big effect size on schizophrenia risk when present.

• rare but large effect

Macroscopic Brain Changes

Structural alterations including ventricular enlargement, a $-3\%$ decrease in brain volume and weight, and relatively smaller hippocampus and thalamus.

Hypofrontality

• A finding in functional brain imaging ($fMRI$) where patients show a failure to activate the prefrontal cortex during working memory tasks.

• Symptom-specific activation: temporal lobe during auditory hallucinations; increased hippocampal activation/blood flow during delusions

Aberrant Salience Theory

A cognitive neuroscience model proposed by Kapur that links neuropsychology to the dopamine hypothesis.

Dopamine Hypothesis

• The theory that excess presynaptic dopamine function (increased synthesis and release) in the striatum underlies positive symptoms.

• Presynaptic (increased synthesis/release)

• State, not trait — correlates with symptom severity

• Begins during the prodrome

• Affects some dopamine circuits more than others

• Greater excess → better response to antipsychotics

Glutamate — "NMDA receptor hypofunction"

• NMDA antagonists induce psychosis; agonists can improve it

• Hypofunction especially affects parvalbumin-subtype GABA interneurons

• Schizophrenia genes affect NMDA receptor pathways

• Anti-NMDAR antibodies may cause some "schizophrenia" cases (autoimmune)

• Glutamate abnormalities may precede dopamine ones; possibly distinct glutamate-primary vs dopamine-primary subtypes

• Glutamate = major target of novel drug therapies

Neurodevelopmental Hypothesis

The theory that schizophrenia is a disorder of brain development grounded in prenatal or perinatal origins, supported by an absence of gliosis or neurodegeneration.

Environmental Risk Factors

External factors including obstetric complications, urbanicity, migration, maternal infections, and early cannabis use.

Bottom-up

(perceptual/attentional)

Top-down

cognitive impairment/prefrontal dysfunction

Genes × Environment interaction

• Example study: placenta biology converges with genetic risk for schizophrenia (Ursini et al. 2018, Nature Medicine)

• Integrated model: Genetic predisposition + environmental factors (obstetric complications, urbanicity) → aberrant early brain development → altered maturational processes (synaptic circuitry, myelination, apoptosis) → impaired functioning (intellectual, social), triggered/worsened by precipitants (stress, psychoactive drugs) → schizophrenia