Search

Background: Stress and trauma significantly contribute to various psychiatric disorders, including schizophrenia. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, particularly abnormal cortisol secretion, is implicated in schizophrenia's pathophysiology. Salivary cortisol, a convenient measure, provides insights into HPA axis activity. This systematic review and meta-analysis assess salivary cortisol levels in individuals with schizophrenia compared to healthy controls, evaluating its potential as a biomarker for schizophrenia. Aim: To assess the differences in salivary cortisol levels at baseline and in response to stress between patients with schizophrenia and healthy controls, determining the reliability of salivary cortisol as a biomarker for schizophrenia. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. We searched MEDLINE/PubMed, Cochrane Central, and EMBASE for human studies on schizophrenia and controls published from January 1, 2013, to July 1, 2023, reporting baseline or post-stress salivary cortisol levels. Exclusions were non-human studies, non-specific schizophrenia diagnoses, or missing cortisol data. Two reviewers independently extracted data and appraised quality, resolving discrepancies by consensus. Due to significant heterogeneity (I² = 94 % for baseline, 75 % for stress response), a random effects model was used. Results: Nineteen studies were initially selected, with twelve excluded due to non-specific schizophrenia diagnoses and missing cortisol data. The final meta-analysis included seven studies with 507 schizophrenia patients and 175 healthy controls. Key findings include: Baseline cortisol levels: No significant difference in baseline salivary cortisol levels between schizophrenia patients and healthy controls (pooled estimate: −0.02, 95 % CI: −0.47–0.42). Cortisol response to stress: No significant difference in post-stress cortisol levels between the two groups (pooled estimate: 0.03, 95 % CI: −1.84–1.79). Study variability: High variability across studies due to differences in design, patient characteristics, and cortisol measurement techniques. Despite some evidence of altered cortisol dynamics in schizophrenia, high variability in methodologies and confounding factors like medication use and psychosocial stressors complicate definitive conclusions. Conclusion: The review underscores the potential of cortisol as a biomarker for stress response; however, its use in diagnosing schizophrenia remains inconclusive. Individual variability and methodological differences limit the diagnostic accuracy of salivary cortisol. Future research with larger sample sizes, uniform methodologies, and comprehensive control for confounding variables is essential to elucidate the role of salivary cortisol in schizophrenia and its potential clinical applications.

Background Inflammation is increasingly recognised as a fundamental component of the pathophysiology of major depressive disorder (MDD), with a variety of inflammatory biomarkers playing pivotal roles. These markers are closely linked to both the severity of symptoms and the responsiveness to treatments in MDD. Aims This scoping review aims to explore the scientific literature investigating the complex relationships between inflammatory biomarkers and depression, by identifying new studies and critical issues in current research. Method Following the PRISMA Extension for Scoping Reviews guidelines, we systematically searched databases including PubMed, Scopus, PsycINFO, Open Grey and Cochrane Library. Our search focused on articles published from 1 January 2020 to 1 May 2024. We included studies evaluating inflammatory biomarkers in adult patients with MDD, utilising observational and randomised controlled trial designs, and review studies. Results Our analysis examined 44 studies on the complex interplay between inflammation and its multiple effects on MDD. Significant associations between specific inflammatory biomarkers and depression severity were found, requiring cautious interpretation. We also highlight several methodological limitations in the current studies, which warrant caution in directly applying these findings to clinical practice. However, identified methodologies show potential for using these biomarkers as diagnostic tools or therapeutic targets, including anti-inflammatory interventions. Conclusions The findings emphasise the need for sophisticated, integrative research to understand inflammation's role in MDD. Future studies should identify specific biomarker panels for diagnosing depression and bridging peripheral biomarker measurements with central neuroinflammatory processes, leading to better diagnostic and treatment strategies.

In the STAR*D study, the efficacy of treatments for major depression was examined. It was found that, while many responded to the initial antidepressant treatment, only 30% of participants achieved complete remission. Concerning treatment resistance in depression, there is a recent distinction emerging between treatment-resistant depression (TRD) and difficult-to-treat depression (DTD). Historically, TRD and DTD have been conflated, but it is essential to recognize them as separate entities. While TRD is characterized by a patient’s inadequate response to two or more consecutive antidepressant treatments given for an adequate duration and dosage without achieving acceptable therapeutic effects, DTD describes a clinical category where patients do not achieve full symptom control despite various therapeutic approaches. The recent shift in perspective proposes a more integrated approach for DTD, encompassing psychosocial, biological, and interactive factors. This multifactorial model calls for a multidisciplinary therapeutic intervention, not restricted to pharmacological treatments but also including psychotherapy, neurostimulation, and social interventions. Informing professionals and the general public about the significance of this new approach could mitigate the stigma associated with depression and enhance the quality of care. The future challenge will involve a deeper clinical understanding of DTD and its optimal management by refining available treatments.

Aims and method Accumulating evidence suggests that early life trauma (ELT) initiates and perpetuates a cycle of depression, leading to challenges in management and achieving remission. This scoping review aimed to examine the intricate relationship between ELT and difficult-to-treat depression (DTD). An extensive literature search from 1 January 2013 to 21 October 2023 was conducted using the Cochrane Library, PubMed, Scopus, PsycINFO and OpenGrey. Results Our review identified scientific literature illustrating the multifaceted link between ELT and DTD, highlighting the dual impact of ELT on therapeutic resistance and clinical complexity. Clinical implications This complexity hampers management of patients with DTD, who are characterised by limited pharmacological responsiveness and heightened relapse risk. While exploring the ELT–DTD nexus, the review revealed a paucity of literature on the impact of ELT within DTD. Findings underscore the profound link between ELT and DTD, which is essential for comprehensive understanding and effective management. Tailoring treatments to address ELT could enhance therapeutic outcomes for patients with DTD. Future studies should use larger samples and well-defined diagnostic criteria and explore varied therapeutic approaches.