Psychiatric and Cognitive Impacts of 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome is a recurrent copy number variant characterised by a hemizygous microdeletion on chromosome 22. It confers a markedly elevated risk for neuropsychiatric conditions, most notably schizophrenia spectrum disorders, anxiety, mood disturbances and attention-deficit/hyperactivity. Cognitive impairments are pervasive and often precede psychiatric onset. Core deficits span executive functions—particularly working memory and cognitive flexibility—episodic memory, complex cognition and social cognition. Neuroanatomical studies reveal altered cortical thickness and surface area, reduced volumes in hippocampal, thalamic and amygdala subregions, and disrupted white matter microstructure in cortico-cortical and cortico-thalamic pathways. Neurochemical assays indicate an excitatory/inhibitory imbalance in temporal lobe structures, with increased glutamatergic markers and reduced GABAergic tone correlating with hippocampal atrophy in individuals exhibiting psychotic symptoms. Longitudinal data suggest that neurocognitive decline—especially in executive domains—drives functional deterioration and the emergence of prodromal psychosis. These findings underscore the importance of early cognitive profiling, neuroimaging biomarkers and targeted interventions to mitigate psychiatric progression and improve long-term outcomes.

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Psychiatric and Cognitive Impacts of 22q11.2 Deletion Syndrome publication trend

The graph below shows the total number of articles in psychiatric and cognitive impacts of 22q11.2 deletion syndrome across all publications each year (not limited to Nature Index journals).

Technical terms

Copy number variant (CNV): A structural genomic alteration in which sections of the genome are deleted or duplicated, affecting gene dosage.

Executive functions: High-order cognitive processes including working memory, inhibitory control and cognitive flexibility essential for goal-directed behaviour.

Psychosis spectrum symptoms: A range of subthreshold and full-blown manifestations such as attenuated hallucinations, delusional ideas and negative symptoms.

Excitatory/inhibitory imbalance: A disruption in the balance between glutamatergic excitation and GABAergic inhibition within neural circuits.

Hippocampal atrophy: A reduction in hippocampal volume often associated with excitotoxic damage and linked to memory impairment.

Fractional anisotropy (FA): A diffusion MRI metric reflecting the directional coherence of water diffusion, used to assess white matter integrity.

References

1. Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications. Molecular Psychiatry (2024).
2. Excitatory/Inhibitory Imbalance Underlies Hippocampal Atrophy in Individuals With 22q11.2 Deletion Syndrome With Psychotic Symptoms. Biological Psychiatry (2023).
3. Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations. Neuropsychopharmacology (2024).