Aberrant amygdala subregion volumes in youth at high risk for bipolar disorder predict antidepressant-induced adverse events.

In 30 seconds

This randomized controlled trial examined whether baseline amygdala subregion volumes were associated with antidepressant-related adverse events in 105 youth with a first-degree relative with bipolar I disorder and current depression or anxiety; 51 healthy controls provided a comparison for brain volumes. High-risk youth had smaller volumes in several amygdala subregions and larger basal and accessory basal nuclei than controls. Among escitalopram-treated youth, smaller cortical and left medial nuclei volumes were associated with fewer arousal-related adverse events, while larger basal nuclei volumes were associated with more. These associations were not observed in the placebo group.

Key findings

• Compared with healthy controls, high-risk youth had reduced volumes in several subregions and increased bilateral basal and accessory basal nuclei volumes.
• In escitalopram-treated youth, smaller bilateral cortical and left medial nucleus volumes were associated with fewer arousal-related adverse events.
• Larger bilateral basal nuclei volumes were associated with more arousal-related adverse events in escitalopram-treated youth; these associations were not reported in placebo recipients.

Why it matters

The findings link specific amygdala subregion volumes with arousal-related adverse events during escitalopram treatment in youth at familial risk for bipolar disorder. They suggest a possible neurostructural correlate of treatment tolerability and offer a basis for further study of biological factors associated with antidepressant-related activation in this population.

What to keep in mind

The reported associations do not establish that amygdala volumes cause adverse events or can reliably predict them in clinical practice.