Introduction: Vitamin D inadequacy or deficiency (VDID) has been reported in a high percentage of otherwise healthy individuals. Factors that may contribute to the high prevalence of VDID in people with mental disorders include diet low in vitamin D, poor sunlight exposure, decrease in cutaneous vitamin D synthesis, intake of certain medications, poor mobility, excessive alcohol intake, and tobacco smoking. VDID has been correlated to a host of adverse conditions, including rickets, osteoporosis, osteomalacia, muscle diseases, depression, cognitive dysfunction, and even certain cancers. Objectives: The purpose of this study was to report the prevalence and correlates of vitamin D inadequacy in a sample of 290 psychiatric patients admitted to inpatient or day hospital treatment at the University of Siena Medical Center. Methods: We retrospectively evaluated the prevalence of VDID in 290 psychiatric inpatients' medical records during the year 2017 and evaluated the correlates of VDID in patients with mental illness. Results: Two hundred and seventy two out of two hundred and ninety patients (94%) showed VDID. Physical activity and regular diet were positively correlated with vitamin D levels whereas age, tobacco smoking, PTH, alkaline phosphatase levels were negatively correlated. Statistically significant differences were found among smokers and non-smokers in all study groups. Conclusions: VDID was highly prevalent in our sample. In addition to vitamin D supplementation, psychosocial intervention able to promote and help sustain physical activity, appropriate diet, quitting smoking and sensible sun exposure to prevent and treat VDID in patients with mental health should be implemented, tested, and introduced in our clinical practice.

Brain-derived neurotrophic factor (BDNF) is critical for neuroplasticity, synaptic transmission, and neuronal survival. Studies have implicated it in the pathophysiology of depression, as its expression is significantly reduced in brain areas such as the prefrontal cortex and hippocampus in patients with depression. Our narrative review focuses on the relationship between BDNF, ketamine, and esketamine, specifically by summarizing human studies investigating BDNF variations in patients treated with these two drugs. BDNF plays a pivotal role in neuroplasticity and neurotrophic mechanisms that can be enhanced by traditional antidepressants, which have been shown to increase BDNF levels both peripherally and in targeted brain regions. Ketamine and its S-enantiomer, esketamine, exert both rapid and sustained antidepressant effects through activation of glutamate-related pathways, with neurotrophic effects involving BDNF, as demonstrated in experimental studies. However, clinical findings have shown mixed results, with most indicating an increase in plasma BDNF in patients treated with intravenous ketamine, although some studies contradict these findings. In addition to this, there are few studies of BDNF and esketamine. Currently, the limited number of studies suggests the need for further research, including larger sample sizes and investigations of BDNF and intranasal esketamine, which has been approved by several regulatory agencies for the treatment of treatment-resistant depression.

(1) Background: Previous literature reported in both subjects with Borderline personality disorder (BPD) and Bipolar disorder (BD) higher levels of autistic traits, linked to a greater suicidality risk. The aim of this study was to evaluate and compare the presence of autistic traits in a sample of individuals with BD or BPD, with a specific focus on suicidality. (2) Methods: We recruited two clinical samples of subjects (BPD and BD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the AdAS Spectrum, the RRS and, for evaluating suicidality, the MOODS-SR. (3) Results: The CTL group showed significantly lower scores of both BD and BPD on AdAS Spectrum, RRS, and suicidality scores. BPD subjects showed significantly lower scores than BD ones in most of AdAS Spectrum domain scores. Correlation and regression analyses highlighted specific patterns of association among AdAS Spectrum domains, RRS, and suicidality in each clinical group. (4) Conclusions: Both BPD and BD individuals show greater levels of autistic traits, which seem to be distributed in a continuum featuring the highest levels among BD subjects. In both disorders, higher autistic traits were linked to suicidal tendencies, although with different patterns of association between BD and BPD subjects.

Over the past two decades, immune–inflammatory dysregulation has emerged as a central paradigm in the biology of mood disorders. Patients with major depression (MDD) and bipolar disorder (BD) frequently display low-grade systemic inflammation. Elevated C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) identify clinically relevant subgroups of patients characterized by greater severity, cognitive impairment, and poor treatment response. Changes in the gut microbiota and disruptions of the blood–brain barrier (BBB) act as important gateways through which systemic immune activity can influence the brain. At the intracellular level, pattern-recognition receptors activate convergent hubs including NF-κB, JAK/STAT, and MAPK cascades, while the NLRP3 inflammasome integrates mitochondrial dysfunction and oxidative stress with IL-1β release and pyroptosis. These pathways converge on glial dysregulation, impaired BDNF/TrkB signaling, and kynurenine pathway (KP) alterations, fostering excitotoxicity and synaptic deficits. Translational studies demonstrate that elevated CRP and IL-6 predict poor antidepressant outcomes. Anti-inflammatory agents such as infliximab and celecoxib show efficacy in specific subgroups of patients. Emerging multi-omics approaches identify immuno-metabolic biotypes, supporting the rationale for biomarker-guided stratification. These findings define an ‘inflammatory biotype’ of mood disorders and highlight the need for biomarkers and precision-based trials to guide treatment.

SUMMARY. Aim. To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. Methods. Medline and Cochrane Library searches were searched using the keywords ‘trazodone’ AND ‘depression’, to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. Results. Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. Discussion. Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. Conclusions. Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.