Deviations From Normative Amygdala Connectivity Associated With Psychosis in Youth

A lack of normative development of amygdala connectivity in youths with psychosis spectrum disorders may lead to better understanding of the neural basis of affective impairments in psychosis.

Researchers have identified an association between psychosis spectrum disorders in youth and a lack of normative development in the amygdala. Their findings were published in the American Journal of Psychiatry.

Resting-state functional neuroimaging data were obtained from 1062 individuals between the ages of 10 and 25 years from 4 existing study samples in the United States. The final neuroimaging data set comprised typically developing control participants (n=622), individuals with psychosis spectrum disorders (n=194), and individuals with other psychopathology (n=246). Positive and negative symptoms were assessed by summing the relevant Structured Interview for Prodromal Syndromes and PRIME Screen-Revised responses. Investigators compared developmental changes in amygdala-to-whole-brain connectivity in the typically developing control group with that of the psychosis group. The normative range derived from control participants was used to assess deviations in connectivity observed in youths with psychosis spectrum disorder and other psychopathology.

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Age-related decreases in connectivity strength between the centromedial amygdala and 19 clusters were observed. Children exhibited positive centromedial amygdala connectivity, and adults exhibited near-zero levels of connectivity. In comparison with typically developing youths, youths with psychosis spectrum disorders experienced significant deviations from typical centromedial amygdala connectivity development in the following regions: left ventrolateral prefrontal cortex, right thalamus, left dorsolateral prefrontal cortex, left caudate, left putamen, and right middle occipital gyrus. However, control patients and patients with psychosis spectrum disorder did exhibit similar patterns of developmental decreases in connectivity between the centromedial amygdala and parahippocampal cortex, frontal eye fields, and posterior cingulate, precentral, and postcentral cortices. No significant inverse age-by-group interactions were observed between the typically developing group and the other psychopathology group.

Per brain maturation deviation scores, greater age-related deviation in centromedial amygdala-thalamus connectivity was associated with greater severity of positive symptoms in the psychosis spectrum group (P =.01). During late childhood and adolescence, lower amygdala-thalamus connectivity was also associated with greater positive symptom severity (P =.01). This association was not observed for the other psychopathology group.

These data may help elucidate the neural basis for psychosis and inform predictive models for symptomatology in youths with the disorder. Further research is necessary to better characterize psychosis spectrum disorder and develop appropriate interventions.


Jalbrzikowski M, Murty VP, Tervo-Clemmens B, Foran W, Luna B. Age-associated deviations of amygdala functional connectivity in youths with psychosis spectrum disorders: relevance to psychotic symptoms [published online January 18, 2019]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.18040443