Social withdrawal is a key symptom of depression. The resulting loss of social reinforcement in turn contributes to chronic, recurrent courses of the disease. However, it is not clear whether ...depressed patients have less motivation to socially interact, or whether their skills in doing so are impaired. The current study investigates potential skill deficits in patients with treatment-resistant depression (TRD).
15 TRD patients and 19 age- and sex-matched healthy controls performed the EmpaToM, a paradigm which includes naturalistic video stimuli of either neutral or emotional valence and which differentiates between socio-affective (affective empathy, compassion) and socio-cognitive (theory of mind) skills.
Controlling for the baseline affective state in neutral situations, TRD patients displayed significantly reduced affective empathy towards emotional situations compared to healthy controls. Furthermore, TRD patients were less compassionate in both neutral and emotional situations. In contrast, socio-cognitive skill performances did not differ between patients and healthy controls.
Further studies might explore socio-affective and socio-cognitive skills in TRD patients using socio-affective/-cognitive tasks involving face-to-face social interactions.
Our study revealed a specific socio-affective deficit in TRD patients, while showing intact socio-cognitive skills. Patients were less able to affectively resonate with others (affective empathy) and exhibited generally reduced feelings of compassion. These deficits might interfere with providing and receiving social support. Our study contributes to a better understanding of the underlying causes of social withdrawal and stresses the need to specifically address pervasive socio-affective deficits in psychotherapy of TRD patients.
•The causes of social isolation in treatment-resistant depression are still unclear.•Deficits in specific social skills may contribute to social isolation.•Patients with treatment-resistant depression have impaired socio-affective skills.•These patients' socio-cognitive skills resemble those of healthy controls.•Psychotherapy should address pervasive socio-affective deficits.
Treatment resistant major depression is accompanied with a sizable impact on quality of life with severe consequences for social integrity, individual health and socioeconomic state. In- and ...outpatient care of patients with treatment resistant major depression remains very challenging for both patients and the health system. One reason is the limited knowledge on the etiology of treatment resistance in major depression resulting difficulties developing efficient treatment strategies for this group of severe depressed patients. Therefore, new focuses on research are needed. Biomarkers reliably reflecting neuropathological processes could help to understand the actual mechanisms in treatment resistance. Neurofilament light protein might be a reliable biomarker of axonal damage in the brain. Due to accumulating evidence that major depression is associated with axonal damage, it is our hypothesis that treatment resistant major depression is correlated with persistent axonal damage within circuits processing affective responses. Axonal damage is reflected by increased levels of neurofilament light protein in plasma. To evaluate our hypothesis, neurofilament light protein will be measured in a group of patients with homogeneous symptomatology of treatment resistant major depression.
Deep brain stimulation (DBS) of the supero-lateral medial forebrain bundle (slMFB) is associated with rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Beyond that, ...improvements in social functioning have been reported. However, it is unclear whether social skills, the basis of successful social functioning, are systematically altered following slMFB DBS. Therefore, the current study investigated specific social skills (affective empathy, compassion, and theory of mind) in patients with TRD undergoing slMFB DBS in comparison to healthy subjects. 12 patients with TRD and 12 age- and gender-matched healthy subjects (5 females) performed the EmpaToM, a video-based naturalistic paradigm differentiating between affective empathy, compassion, and theory of mind. Patients were assessed before and three months after DBS onset and compared to an age- and gender-matched sample of healthy controls. All data were analyzed using non-parametric Mann-Whitney U tests. DBS treatment significantly affected patients' affective responsiveness towards emotional versus neutral situations (i.e. affective empathy): While their affective responsiveness was reduced compared to healthy subjects at baseline, they showed normalized affective responsiveness three months after slMFB DBS onset. No effects occurred in other domains with persisting deficits in compassion and intact socio-cognitive skills. Active slMFB DBS resulted in a normalized affective responsiveness in patients with TRD. This specific effect might represent one factor supporting the resumption of social activities after recovery from chronic depression. Considering the small size of this unique sample as well as the explorative nature of this study, future studies are needed to investigate the robustness of these effects.
Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two ...stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT. Sixteen patients suffering from TRD received DBS of the slMFB and were randomized to sham or real stimulation for the duration of 2 months after implantation. Primary outcome measure was mean reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) during 12 months of DBS (timeline analysis). Secondary outcomes were the difference in several clinical measures between sham and real stimulation at 8 weeks and during stimulation phases. MADRS ratings decreased significantly from 29.6 (SD +/- 4) at baseline to 12.9 (SD +/- 9) during 12 months of DBS (mean MADRS, n = 16). All patients reached the response criterion, most patients (n = 10) responded within a week; 50% of patients were classified as remitters after 1 year of stimulation. The most frequent side effect was transient strabismus. Both groups (active/sham) demonstrated an antidepressant micro-lesioning effect but patients had an additional antidepressant effect after initiation of stimulation. Both rapid onset and stability of the antidepressant effects of slMFB-DBS were demonstrated as in our previous pilot study. Given recent experiences from pivotal trials in DBS for MDD, we believe that slow, careful, and adaptive study development is germane. After our exploratory study and a large-scale study, we conducted this gateway trial in order to better inform planning of the latter. Important aspects for the planning of RCTs in the field of DBS for severe and chronic diseases are discussed including meaningful phases of intra-individual and between-group comparisons and timeline instead of single endpoint analyses.
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