Background: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. Aims: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. Methods: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Results: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. Conclusion: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

Introduction: Bipolar Disorder (BD) is a disabling condition with suicidal behavior as one of the most common adverse outcomes. The purpose of the present research is to investigate the relationship between lifetime suicide attempts and the clinical factors/biochemical parameters in a large sample of bipolar patients. Methods: A total of 561 patients, consecutively hospitalized for BD in Milan and Monza (Italy), were recruited. Data about the demographic and clinical variables, as well as the values of blood analyses, were collected. The groups identified according to the presence/absence of lifetime suicide attempts were compared using univariate analyses. Then, three preliminary binary logistic regressions and a final logistic regression model were performed to identify the clinical and biochemical parameters associated with lifetime suicide attempts in BD. Results: Lifetime suicide attempts in BD were predicted by a longer duration of untreated illness (DUI) (p = 0.005), absence of lifetime psychotic symptoms (p = 0.025), presence of poly-substance use disorders (p = 0.033), comorbidity with obesity (p = 0.022), a last mood episode of manic polarity (p = 0.044), and lower bilirubin serum levels (p = 0.002); higher total cholesterol serum levels showed a trend toward statistical significance (p = 0.058). Conclusions: BD patients with lifetime suicide attempts present unfavorable clinical features. Some specific biochemical characteristics of bipolar patients may represent potential markers of suicidal behavior and need to be better investigated to identify new targets of treatment in the framework of personalized medicine. These preliminary findings have to be confirmed by further studies in different clinical settings.

Introduction: Psychotic symptoms occur in more than half of patients affected by Bipolar Disorder (BD) and are associated with an unfavorable course of the disorder. The objective of this study is to identify the differences in the clinical and biochemical parameters between bipolar patients with or without psychotic symptoms. Methods: A total of 665 inpatients were recruited. Demographic, clinical, and biochemical data related to the first day of hospitalization were obtained via a screening of the clinical charts and intranet hospital applications. The two groups identified via the lifetime presence of psychotic symptoms were compared using t tests for quantitative variables and χ² tests for qualitative ones; binary logistic regression models were subsequently performed. Results: Patients with psychotic BD (compared to non-psychotic ones) showed a longer duration of hospitalization (p < 0.001), higher Young Mania Rating Scale scores (p < 0.001), lower Global Assessment of Functioning scores (p = 0.002), a less frequent history of lifetime suicide attempts (p = 0.019), less achievement of remission during the current hospitalization (p = 0.028), and a higher Neutrophile to Lymphocyte Ratio (NLR) (p = 0.006), but lower total cholesterol (p = 0.018) and triglycerides (p = 0.013). Conclusions: Patients with psychotic BD have a different clinical and biochemical profile compared to their counterparts, characterized by more clinical severity, fewer metabolic alterations, and a higher grade of inflammation. Further multi-center studies have to confirm the results of this present study.

Introduction: Bipolar disorder (BD) affects over 1% of the global population and significantly impacts psychosocial functioning and life expectancy. This manuscript has the objective of investigating gender differences in the clinical and biochemical parameters of patients affected by BD. Methods: This retrospective cross-sectional study examined 672 patients diagnosed with BD in psychiatric wards in Milan and Monza. Clinical data and biochemical parameters were collected on the first day of hospitalization. Independent sample t-tests, chi-square tests and binary logistic regressions were performed to identify gender differences in BD. Results: With regard to univariate analyses, women were found to be more susceptible to psychiatric comorbidities (χ² = 12.75, p < 0.01), medical comorbidities (χ² = 45.38, p < 0.01), obesity (χ² = 6.75, p = 0.01) and hypercholesterolemia (χ² = 23.54, p < 0.01), as well as to having more mood episodes in the year prior to hospitalization (t = 5.69, p < 0.01). Men were found to be more likely to develop psychotic symptoms (χ² = 4.40, p = 0.04), to be tobacco smokers (χ² = 15.13, p < 0.01) and to have substance abuse disorders (χ² = 14.66, p = <0.01). Logistic regression analyses showed that women compared to men showed more psychiatric comorbidity (p < 0.01), higher Global Assessment of Functioning (GAF) scores (p = 0.05) and higher total cholesterol plasma levels (p < 0.01); however, they also had fewer red blood cells (p < 0.01) and lower creatinine plasma levels (p < 0.01). Conclusions: Female patients (compared to males) exhibited higher levels of global functioning despite the higher frequency of psychiatric comorbidity and susceptibility to metabolic complications; consistent with earlier studies, female patients also showed higher cholesterol levels. Further studies will have to confirm the present findings and identify gender-related clinical pathways for the management of BD.