Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and serious neurodevelopmental disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Chronic and childhood stress is involved in ADHD development, and ADHD is highly comorbid with anxiety. Similarly, inflammatory diseases and a pro-inflammatory state have been associated with ADHD. However, while several works have studied the relationship between peripheral inflammation and stress in affective disorders such as depression or bipolar disorder, fewer have explored this association in ADHD. In this narrative review we synthetize evidence showing an interplay between stress, anxiety, and immune dysregulation in ADHD, and we discuss the implications of a potential disrupted neuroendocrine stress response in ADHD. Moreover, we highlight confounding factors and limitations of existing studies on this topic and critically debate multidirectional hypotheses that either suggest inflammation, stress, or anxiety as a cause in ADHD pathophysiology or inflammation as a consequence of this disease. Untangling these relationships will have diagnostic, therapeutic and prognostic implications for ADHD patients.

Bipolar disorder (BD) and borderline personality disorder (BPD) are serious and prevalent psychiatric diseases that share common phenomenological characteristics: symptoms (such as anxiety, affective lability or emotion dysregulation), neuroimaging features, risk factors and comorbidities. While several studies have focused on the link between stress and peripheral inflammation in other affective disorders such as anxiety or depression, fewer have explored this relationship in BD and BPD. This review reports on evidence showing an interplay between immune dysregulation, anxiety and stress, and how an altered acute neuroendocrine stress response may exist in these disorders. Moreover, we highlight limitations and confounding factors of these existing studies and discuss multidirectional hypotheses that either suggest inflammation or stress and anxiety as the primum movens in BD and BPD pathophysiology, or inflammation as a consequence of the pathophysiology of these diseases. Untangling these associations and implementing a transdiagnostic approach will have diagnostic, therapeutic and prognostic implications for BD and BPD patients.

Emotion dysregulation (ED), the difficulty in modulating which emotions are felt, and when and how they are expressed or experienced, has been implicated in an array of psychological disorders. Despite potentially different manifestations depending on the disorder, this symptom is emerging as a transdiagnostic construct that can and should be targeted early, given the associations with various maladaptive behaviors as early as childhood and adolescence. As such, our goal was to investigate the psychotherapeutic interventions used to address ED and gauge their effectiveness, safety, and potential mechanisms across various populations. This umbrella systematic review, pre-registered under PROSPERO (registration: CRD42023411452), consolidates evidence from systematic reviews and meta-analyses on psychotherapeutic interventions targeting ED, in accordance with PRISMA guidelines. Our synthesis of quantitative and qualitative evidence from 21 systematic reviews (including 11 meta-analyses) points-with moderate overall risk of bias-to the effectiveness of Dialectical Behavior Therapy and Cognitive Behavioral Therapy in reducing ED in a wide range of adult transdiagnostic psychiatric patients and healthy participants. Similar results have emerged in other less extensively researched methods as well. However, results on adolescents and children are sparse, highlighting the need for additional research to tailor these interventions to the unique challenges of ED in younger populations with diverse externalizing and internalizing disorders. These demonstrated transdiagnostic advantages of psychotherapy for ED underscore the potential for specifically designed interventions that address this issue directly, particularly for high-risk individuals. In these individuals, early interventions targeting transdiagnostic core dimensions may mitigate the emergence of full-blown disorders. Future research on the mediating factors, the durability of intervention effects, and the exploration of understudied interventions and populations may enhance prevention and treatment efficiency, enhancing the quality of life for those affected by varied manifestations of ED.

Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI abnormalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1'233 BD patients). Overall, the quality of the studies included was fair, with a low risk of bias. Heterogeneity in the methods and results of the studies and small sample sizes limit the generalizability of the conclusions. A qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.