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.

Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis.

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.

Impulsivity is increasingly recognized as a transdiagnostic feature that spans multiple psychiatric disorders, including borderline personality disorder (BPD), bipolar disorder, and substance use disorders. In BPD, impulsive behaviors manifest as substance misuse, risky sexual activity, self-injury, and other maladaptive patterns. This review article updates the clinical and preclinical literature to explore the biological and psychological bases of impulsivity in BPD and considers whether methylphenidate (MPH) can be used as a treatment in this context. Although no medication is specifically approved for BPD, limited evidence from patients with comorbid BPD and attention-deficit/hyperactivity disorder (ADHD) indicates that MPH may reduce impulsivity and improve key symptoms. In addition, real-world data indicate that MPH may be associated with better outcomes and a lower risk of suicidal behaviors in patients with BPD. Nevertheless, such evidence remains scant, particularly among those with a primary diagnosis of BPD without a diagnosis of ADHD. Larger, methodologically rigorous studies are needed to clarify the efficacy and safety of MPH in targeting impulsivity within this population. An improved understanding of dopaminergic mechanisms may eventually shed light on MPH’s therapeutic role in BPD, although current data remain preliminary. Overall, recognizing impulsivity as a core symptom rather than focusing exclusively on diagnostic boundaries may facilitate more tailored and effective interventions for BPD.