Anxiety severity, childhood trauma and clinical outcomes in euthymic patients with mood disorders

Background: Anxiety symptoms are common in mood disorders and may persist during euthymic periods. Childhood trauma is associated with anxiety, depressive symptoms and a more severe illness course. However, the relationships between anxiety severity, childhood trauma, quality of life (QoL) and prospective mood episode recurrence during euthymia remain insufficiently understood. This study investigated whether moderate-to-severe anxiety is associated with childhood trauma, poorer QoL and mood episode recurrence in euthymic patients with mood disorders.

Methods: Participants were selected from the Mood Disorder Cohort Research Consortium. Euthymia was defined as the absence of a current depressive, hypomanic or manic episode at assessment and within the preceding two months, as confirmed by trained psychiatrists. Data from the earliest visit fulfilling this criterion were used. Participants with baseline data were included in cross-sectional analyses, and those with time-to-recurrence data were included in the Kaplan-Meier analysis. Anxiety severity was assessed using the Beck Anxiety Inventory (BAI), and participants were classified into minimal-to-mild anxiety (BAI <16) and moderate-to-severe anxiety (BAI ≥16) groups. Group differences were examined using t-tests and Fisher’s exact tests. Logistic regression examined associations between Childhood Trauma Questionnaire (CTQ) scores and anxiety severity, adjusting for sex, age, diagnosis, socioeconomic status, age at onset, Montgomery-Åsberg Depression Rating Scale (MADRS) score and Young Mania Rating Scale (YMRS) score. QoL was assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and analysed using adjusted linear regression. Time to mood episode recurrence was examined using Kaplan-Meier survival analysis and compared using the log-rank test.

Results: Among 495 enrolled participants, 19 with a mood episode at assessment or within the preceding two months and 66 with missing data were excluded. The final cross-sectional analytic sample comprised 410 participants, including 262 with minimal-to-mild anxiety and 148 with moderate-to-severe anxiety. Compared with the minimal-to-mild anxiety group, the moderate-to-severe anxiety group showed earlier age at onset (16.78±4.19 versus 18.18±4.77 years, p=0.002), higher MADRS scores (20.70±9.32 versus 8.42±8.05, p<0.001), higher YMRS scores (2.86±4.40 versus 1.97±3.36, p=0.035), and higher CTQ total scores (59.01±16.87 versus 45.59±14.28, p<0.001). In adjusted logistic regression, CTQ total score was associated with moderate-to-severe anxiety (odds ratio [OR]=1.06, 95% confidence interval [CI]=1.04-1.08, p<0.001), along with MADRS score (OR=1.15, 95% CI=1.11-1.18, p<0.001). All CTQ subscales were significantly associated with moderate-to-severe anxiety (adjusted ORs=1.11–1.18, all false discovery rate [FDR]-corrected p≤0.047). Moderate-to-severe anxiety was associated with lower physical health, psychological and environmental QoL scores (β=-1.36, FDR-corrected p<0.001; β=-1.16, FDR-corrected p=0.002; and β=-0.91, FDR-corrected p=0.008). In the Kaplan-Meier analysis of 127 participants with time-to-recurrence data, including 83 with minimal-to-mild anxiety and 44 with moderate-to-severe anxiety, the moderate-to-severe anxiety group showed lower recurrence-free survival probability (log-rank p=0.008).

Conclusions: In euthymic patients with mood disorders, moderate-to-severe anxiety was associated with greater childhood trauma burden, poorer physical, psychological and environmental QoL, and lower recurrence-free survival probability in Kaplan-Meier analysis. These findings suggest that clinically significant anxiety during euthymia may identify a vulnerable subgroup characterised by early adversity and persistent functional impairment. The results highlight the potential importance of trauma-informed assessment and monitoring of residual anxiety during euthymic periods.

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