Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression.

Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD.

We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05).

Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD.

We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD.

We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances.

An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.