Serial multiple mediating roles of anxiety and thyroid-stimulating hormone in the relationship between depression and psychotic symptoms in young adults with anxious depression

Psychotic symptoms (PS) frequently occur in young adults with anxious depression (AD), yet the mediators of the associations between depression and PS remain unclear. This study aimed to investigate the prevalence and risk factors of PS in first-episode and drug-naïve (FEDN) young adults with AD and attempted to elucidate the relationship between thyroid-stimulating hormone (TSH) levels, anxiety, depression, and PS, as well as to identify potential mediating roles. 369 FEDN young adults with AD were recruited. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale's positive subscale, the Hamilton Depression Rating Scale (HAMD), and the Hamilton Anxiety Rating Scale (HAMA). Fasting glucose, lipids, and thyroid function were also collected. The prevalence of PS in young adults with AD (21.68 %) was 12.24 times higher than in non-AD patients. The HAMD scores (P = 0.005, OR = 1.23), HAMA scores (P < 0.001, OR = 1.62), and TSH levels (P = 0.025, OR = 1.20) were significant predictors of PS. The combined area under the curve value for distinguishing young adults with AD with and without PS was 0.86. We also identified serial multiple mediating effects of TSH levels and anxiety on the association of depression with PS. These findings emphasize the role of anxiety and TSH levels as serial mediators of the association between depression and PS. Therefore, when treating PS in young adults with AD, it is important to focus not only on depression, but also on TSH levels and anxiety to maximize benefit.