Dim light melatonin patterns in unaffected offspring of parents with bipolar disorder: A case-control high-risk study

Circadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP). This case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated. 185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD. The main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size. These findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD.