Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness.

Publication date: Feb 12, 2020

22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group.

Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female).

Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen’s d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen’s d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder.

In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

Ching, C.R.K., Gutman, B.A., Sun, D., Villalon Reina, J., Ragothaman, A., Isaev, D., Zavaliangos-Petropulu, A., Lin, A., Jonas, R.K., Kushan, L., Pacheco-Hansen, L., Vajdi, A., Forsyth, J.K., Jalbrzikowski, M., Bakker, G., van Amelsvoort, T., Antshel, K.M., Fremont, W., Kates, W.R., Campbell, L.E., McCabe, K.L., Craig, M.C., Daly, E., Gudbrandsen, M., Murphy, C.M., Murphy, D.G., Murphy, K.C., Fiksinski, A., Koops, S., Vorstman, J., Crowley, T.B., Emanuel, B.S., Gur, R.E., McDonald-McGinn, D.M., Roalf, Ruparel, K., Schmitt, J.E., Zackai, E.H., Durdle, C.A., Goodrich-Hunsaker, N.J., Simon, T.J., Bassett, A.S., Butcher, N.J., Chow, E.W.C., Vila-Rodriguez, F., Cunningham, A., Doherty, J., Linden, D.E., Moss, H., Owen, M.J., van den Bree, M., Crossley, N.A., Repetto, G.M., Thompson, P.M., and Bearden, C.E. Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness. 15230. 2020 Am J Psychiatry.

Concepts Keywords
Amygdala Control
Bipolar Disorder Deletion Syndrome
Brain Major depressive disorder
Caudate Illness
Cohort Psychosis idiopathic schizophrenia
Control Group Psychiatry
Convergence Medical specialties
Genetic Organ systems
Genetic Heterogeneity RTT
Hippocampus Psychopathology
Idiopathic Limbic system
Lateral Ventricle Neurology
Major Depressive Disorder Neuropsychiatry
Morphometry Hippocampus
Neuroimaging DiGeorge syndrome
Neuropsychiatric Schizophrenia
Obsessive Compulsive Disorder
Psychotic Illness


Type Source Name
disease MESH 22q11.2 Deletion Syndrome
disease MESH risk factors
disease MESH schizophrenia
drug DRUGBANK Tropicamide
disease MESH psychosis
disease MESH bipolar disorder
disease MESH major depressive disorder
disease MESH obsessive-compulsive disorder

Original Article

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