Omega-3 fatty acids for inflamed depression - A match/mismatch study.

Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.

Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden.

INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.

Visuospatial ability is associated to 2D laparoscopic simulator performance amongst surgical residents.

Background: The technical skills of a surgeon influence surgical outcome. Testing technical aptitude at point of recruitment of surgical residents is only conducted in a few countries. This study investigated the impact of visuospatial ability (VSA), background factors, and manual dexterity on performance in two different laparoscopic surgical simulators amongst applicants and 1st year surgical residents. Method: Applicants from general surgery, pediatric surgery, and urology were included from seven hospitals in Sweden between 2017 and 2021. Some 73 applicants were invited and 50 completed. Participants filled out a background form, and were tested for manual dexterity, and visuospatial ability. Two laparoscopic simulators were used, one 2D video box trainer and one 3D Virtual Reality Simulator. Results: A significant association was found between the visuospatial ability test and 2D video box laparoscopic performance (95 % CI: 1.028-1.2, p-value <0.01). For every point on the visuospatial test the odds of accomplishing the task increased by 11 %. No association was found between VSA and performance in a laparoscopic VR simulator using 3D vision. No other background factors were associated with performance in the two laparoscopic simulators. Conclusion: Visuospatial ability in applicants to surgical residency positions is associated to performance in a 2D video box trainer. Knowledge of a resident's visuospatial ability can be used to tailor individualized laparoscopic training programs, and in the future might function as a selection tool concerning laparoscopic ability. Key message: Visuospatial ability differs greatly amongst applicants for surgical residency and is associated to laparoscopic simulator performance. Testing applicants' visuospatial ability could possibly be used to tailor individualized laparoscopic training programs or in the future as a selection tool concerning laparoscopic ability.