2 Neuroscience2.11 Integrated neurobiology of syndromes and states
2.11.10 Neurocognitive deficits in psychotic disorders
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Written by Resident Doctor Committee · Published
Affected domains
Cognition in schizophrenia averages 1 to 1.5 standard deviations below controls, with wide variation between people.
Domain | Impairment |
|---|---|
Processing speed | Large deficit on timed tasks |
Attention | Poor sustained attention, variable responses |
Working memory | Verbal and visuospatial |
Learning and episodic memory | Poor encoding and retrieval |
Executive function | Planning, flexibility, abstraction, inhibition |
Social cognition | Emotion recognition, mentalising; independently affects outcome |
Recognition exceeds free recall, which points to a retrieval problem, unlike the poor recognition and marked forgetting of hippocampal amnesia.
Trait and endophenotype evidence
Cognitive differences precede psychosis, persist between episodes and appear in milder form in unaffected relatives.
This makes cognition a candidate endophenotype, though the findings overlap with bipolar disorder.
Course and function
Childhood differences are mild, ultra high-risk people show intermediate impairment, and cognition often falls further around the first episode.
Cognition is then usually stable: progressive, dementia-like decline is not the usual course.
Cognition predicts work, independence and social function better than positive symptoms do, which supports cognitive remediation and vocational support.
Circuits
System | Finding | Correlate |
|---|---|---|
Dorsolateral prefrontal cortex | Inefficient activation under load | Working memory, executive control |
Hippocampus | Weak prefrontal coupling | Episodic memory |
Cortico-cerebellar-thalamo-cortical circuit | Cognitive dysmetria (Andreasen) | Timing of mental activity |
White matter | Reduced fractional anisotropy | Processing speed |
Prefrontal inefficiency describes the finding better than universal hypofrontality.
Neurochemical models
Model | Evidence | Limitation |
|---|---|---|
Dopamine D1 hypofunction | Working memory follows an inverted U with prefrontal dopamine | No proven D1 treatment |
N-methyl-D-aspartate (NMDA) receptor hypofunction | Ketamine; NMDA receptor encephalitis | Glutamatergic drugs lack reliable benefit |
Gamma-aminobutyric acid (GABA) interneurone dysfunction | Reduced glutamic acid decarboxylase (GAD67), altered parvalbumin interneurones | May be secondary to NMDA hypofunction |
Synaptic pruning | Fewer cortical spines, complement gene findings | Confounded by illness and treatment |
Electrophysiology
Measure | Finding in psychosis |
|---|---|
Mismatch negativity | Reduced amplitude |
P300 | Lower amplitude, delayed latency |
Gamma synchrony | Reduced, including 40 Hz auditory response |
P50 sensory gating | Reduced suppression to paired clicks |
Relatives also show smooth pursuit and antisaccade abnormalities, but overlap with healthy values means no measure diagnoses an individual.
Reversible contributors
Symptoms, mood, poor sleep, substances and physical illness (obesity, diabetes, hypertension, sleep apnoea, smoking, thyroid disease) all lower scores.
Sedation, extrapyramidal effects and anticholinergic burden worsen cognition, so review procyclidine, high doses and polypharmacy.
Test after acute symptoms settle, and interpret scores against education, language and premorbid ability.
Psychosis, delirium and dementia
Feature | Psychosis | Delirium | Dementia |
|---|---|---|---|
Onset | May predate psychosis | Hours to days | Months to years |
Course | Relatively stable | Fluctuating | Progressive |
Consciousness | Clear | Altered | Clear early |
Memory | Retrieval difficulty | Poor registration | Poor encoding in Alzheimer disease |
Orientation | Preserved | Often impaired | Declines |
Hallucinations | Often auditory | Often visual | Visual in Lewy body disease |
Investigate new decline for delirium, medication, substances, physical illness and dementia rather than putting it down to schizophrenia.