Biological correlates of treatment resistant depression: a review of peripheral biomarkers.

Introduction: Many patients fail to respond to multiple antidepressant interventions, being defined as "treatment-resistant depression" (TRD) patients. TRD is usually associated with increased severity and chronicity of symptoms, increased risk of comorbidity, and higher suicide rates, which make the clinical management challenging. Efforts to distinguish between TRD patients and those who will respond to treatment have been unfruitful so far. Several studies have tried to identify the biological, psychopathological, and psychosocial correlates of depression, with particular attention to the inflammatory system. In this paper we aim to review available studies assessing the full range of biomarkers in TRD patients in order to reshape TRD definition and improve its diagnosis, treatment, and prognosis. Methods: We searched the most relevant medical databases and included studies reporting original data on possible biomarkers of TRD. The keywords "treatment resistant depression" or "TRD" matched with "biomarker," "inflammation," "hormone," "cytokine" or "biological marker" were entered in PubMed, ISI Web of Knowledge and SCOPUS databases. Articles were included if they included a comparison with healthy controls (HC). Results: Of the 1878 papers identified, 35 were included in the present study. Higher plasma levels of IL-6 and TNF-α were detected in TRD patients compared to HC. While only a few studies on cortisol have been found, four papers showed elevated levels of C-reactive protein among these patients and four articles focused on immunological cells. Altered kynurenine metabolism in TRD patients was reported in two studies, while contrasting results were found with regard to BDNF. Conclusion: Only a few biological alterations correlate with TRD. TNF-α seems to be the most relevant biomarker to discriminate TRD patients from both HC and treatment-responsive MDD patients. Moreover, several discrepancies among studies have been found, due to methodological differences and the lack of a standardized diagnostic definition of TRD.

The Efficacy of Psychoeducational Family Intervention for Major Depression: Study Protocol of a Randomized Controlled Trial.

This study aims to assess the efficacy of a psychoeducational family intervention (PFI) to reduce the severity of depressive symptoms and to improve psychosocial functioning and to increase social contacts in a sample of patients with major depressive disorder (MDD). The degree to which PFI will reduce patients' relapses, hospitalizations, and self-stigmatization and will improve their quality of life will also be assessed. Other secondary outcomes include the improvement of relatives' coping strategies, family burden, expressed emotions and quality of life. This non-profit, unfunded, national, multicentric randomized controlled trial with blinded outcome assessments will be carried out in 24 Italian university outpatient units. Families will be assessed at baseline and at 6, 12, and 24 months post-randomization. Our working hypothesis is that the PFIs will reduce the patients' severity of depressive symptoms, their relapses, and their hospitalizations, and that they will improve their psychosocial functioning and quality of life. We expect these results to be maintained after 12 and 24 months, albeit with a reduction in magnitude. The sample will consist of 384 patients randomized at a 1:1 ratio and stratified according to center, age, gender, and educational level.

Can Brain-Derived Neurotrophic Factor Be Considered a Biomarker for Bipolar Disorder? An Analysis of the Current Evidence.

Brain-derived neurotrophic factor (BDNF) plays a key role in brain development, contributing to neuronal survival and neuroplasticity. Previous works have found that BDNF is involved in several neurological or psychiatric diseases. In this review, we aimed to collect all available data on BDNF and bipolar disorder (BD) and assess if BDNF could be considered a biomarker for BD. We searched the most relevant medical databases and included studies reporting original data on BDNF circulating levels or Val66Met polymorphism. Only articles including a direct comparison with healthy controls (HC) and patients diagnosed with BD according to international classification systems were included. Of the 2430 identified articles, 29 were included in the present review. Results of the present review show a reduction in BDNF circulating levels during acute phases of BD compared to HC, which increase after effective therapy of the disorders. The Val66Met polymorphism was related to features usually associated with worse outcomes. High heterogeneity has been observed regarding sample size, clinical differences of included patients, and data analysis approaches, reducing comparisons among studies. Although more studies are needed, BDNF seems to be a promising biomarker for BD.