Anxiety and depression are among the most prevalent and comorbid psychiatric conditions. However, anxiety-induced depression (AoD) remains understudied in terms of its longitudinal neurobiological progression and clinical consequences. This paper proposes a neuroprogressive model suggesting that AoD poses a higher risk of bipolar conversion, particularly toward Bipolar II or Rapid Cycling subtypes, due to its cumulative neurotoxic burden and structural vulnerabilities. We review literature on chronic stress–induced neurocircuit disruptions, including GABAergic overactivation, glucocorticoid accumulation, and synaptic scaffolding loss. Additionally, we explore how pharmacological overload (e.g., SSRIs, benzodiazepines) may exacerbate underlying fragility, particularly in adolescents. AoD is associated with reduced prefrontal-hippocampal coherence, abnormal pruning, and white matter dysintegrity, collectively accelerating affective instability and subtype-specific bipolar transitions. Recognizing AoD as a neurotoxic prodrome—not merely a depressive subtype—has implications for early diagnosis, neuroprotective intervention, and subtype prevention. Targeted treatment could reshape both the onset and trajectory of bipolar illness.
Jiayi Sun (Mon,) studied this question.