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.

Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. Methods: A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. Results: Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms—especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. Conclusions: High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies—such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms—may support more individualized and safer treatment strategies.

Violence against women impacts a minimum of 35% of the global female population, encompassing sexual, physical, and psychological forms. Perpetrators of this violence include partners, family members, or strangers. Its ramifications are substantial, evident in the prevalence of chronic pain reported by between 48% and 84% of women who have experienced abuse, with an odds ratio of 2.08. Notably associated diagnoses include pelvic/vaginal pain, fibromyalgia, irritable bowel syndrome/bowel symptoms, abdominal pain, migraine/headache, and back and neck pain. These diagnoses significantly limit a woman’s ability to participate in daily activities, such as exercising or working, leading to genuine disability. Despite substantial evidence, the precise cause and etiology of these conditions remain unclear. Adhering to the bio-psycho-social model, it is conceivable that chronic pain in victims of violence cannot be attributed to a single factor alone, but rather to a combination of all three: biological, psychological, and social factors. Uncovering these factors could have significant clinical and legal implications. On one hand, it would be possible to conduct screenings to avoid developing chronic pain. and guide individuals toward the correct treatment. On the other hand, victims could seek compensation for chronic pain resulting from violence. Considering the limited knowledge about the causes of chronic pain and the absence of tools to identify risk factors or a set of tests for evaluating victims of violence, the goal of the research described in this project protocol is to pinpoint the specific contributing factors for chronic pain due to violence victimization. Additionally, it aims to devise a comprehensive protocol for assessing these factors in forensic science.

The COVID-19 pandemic has deeply affected adolescents’ psychosocial development, increasing vulnerability to distress and risk behaviors. This study examined whether aggression mediates the association between COVID-19–related stress and deviant behavior. A cross-sectional survey was conducted with 638 adolescents and young adults (M = 18.8, SD = 3.51) from central Italy. Participants completed standardized self-report measures on COVID-related stress, aggression, and deviance. Analyses included Spearman correlations, regression models, and mediation testing. Social isolation was positively associated with aggression, whereas fear of COVID was negatively associated with aggression. Only physical aggression was significantly linked to deviant behavior. Mediation analysis showed that physical aggression partially mediated the relationship between COVID-19 stress and deviance: social isolation predicted higher physical aggression (β = 0.38, p < .001), which was associated with deviance (β = 0.07, p < .001); the indirect effect was significant (β = 0.027, p = .002). Fear of contagion showed a small but significant negative indirect effect (β = –0.006, p = .022). Social isolation increased risk, whereas fear of contagion appeared to have a potential protective function.

Anxiety symptoms are highly prevalent in major depressive disorder (MDD) and are associated with greater severity, functional impairment, and poorer treatment outcomes. Bupropion is widely used in clinical practice and is generally considered to have a favorable tolerability profile, but its effects on comorbid anxiety remain uncertain. We conducted a PRISMA-guided systematic review of randomized controlled trials, pooled analyses, and open-label comparative studies evaluating bupropion in adults with MDD and clinically significant anxiety symptoms. Searches of PubMed, Scopus and Web of Science were performed through August 2025. Outcomes included validated measures of anxiety and depressive symptoms and reported tolerability. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence was evaluated using GRADE. Six studies (n ≈ 3700) met inclusion criteria. Anxiety was a predefined secondary outcome in some trials and a post hoc or exploratory measure in others. Across designs, bupropion was generally associated with improvements in anxiety and depressive symptoms on secondary or exploratory anxiety measures. In pooled patient-level analyses, SSRIs showed a modest advantage over bupropion in patients with high baseline anxiety, whereas individual randomized and open-label studies found no significant between-group differences. None of the included studies reported a clear signal of anxiety worsening with bupropion on the anxiety measures used. Tolerability findings indicated a lower risk of sexual dysfunction with bupropion compared with SSRIs, while insomnia occurred more frequently but was generally manageable. Low-certainty evidence suggests that bupropion may provide clinically relevant improvement in anxiety symptoms in adults with MDD, with generally comparable efficacy to SSRIs in most presentations but a modest SSRI advantage in highly anxious subgroups. Interpretation should consider that anxiety outcomes were often secondary or exploratory and that several studies were at risk of bias. Well-designed randomized trials with anxiety as a primary endpoint are needed.