Abstract
BACKGROUND: There is limited research examining the natural trajectories of depression and anxiety, how these trajectories relate to baseline neural circuit function, and how symptom trajectory-circuit relationships are impacted by engagement in lifestyle activities including exercise, hobbies, and social interactions. To address these gaps, we assessed these relations over three months in untreated participants. METHODS: 262 adults (59.5% female, mean age 35) with symptoms of anxiety and depression, untreated with pharmacotherapy or behavioral therapy, completed the DASS-42, WHOQOL, and custom surveys at baseline and follow-up to assess symptoms, psychosocial function, and lifestyle activity engagement. At baseline, participants underwent fMRI under task-free and task-evoked conditions. We quantified six circuits implicated in these symptoms: default mode, salience, negative and positive affect, attention, and cognitive control. RESULTS: From baseline to 3 months, some participants demonstrated a natural improvement in anxiety (24%) and depression (26%) symptoms. Greater baseline salience circuit connectivity (pFDR=0.045), specifically between the left and right insula (pFDR=0.045), and greater negative affect circuit connectivity elicited by sad faces (pFDR=0.030) were associated with anxiety symptom improvement. While engagement in lifestyle activities were not associated with anxiety improvements, engagement in hobbies moderated the association between negative affect circuit connectivity and anxiety symptom improvement (p = 0.048). LIMITATIONS: The observational design limits causal inference. CONCLUSIONS: Our findings highlight the role of the salience and negative affect circuits as potential circuit markers of natural anxiety symptom improvements over time. Future studies that identify biomarkers associated with symptom improvements are critical for the development of personalized treatment targets.