Deep brain stimulation of the supero-lateral branch of the medial forebrain bundle does not lead to changes in personality in patients suffering from severe depression.

BACKGROUND: Reports of changes in patients' social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients' self-ratings of personality are valid. METHODS: TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS). Personality was measured with the NEO-Five-Factor Inventory (NEO-FFI), depression severity with Hamilton (HDRS), and Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Personality dimensions did not change with slMFB-DBS compared with baseline. Extraversion was negatively correlated with HDRS28 (r = -0.48, p < 0.05) and MADRS (r = -0.45, p < 0.05) at t2. Inter-rater reliability was high for the NEO-FFI at baseline (Cronbach's α = 0.74) and at t4 (α = 0.65). Extraversion [t(29) = -5.20; p < 0.001] and openness to experience [t(29) = -6.96; p < 0.001] differed statistically significant from the normative sample, and did not predict the antidepressant response. CONCLUSIONS: slMFB-DBS was not associated with a change in personality. The severity of depression was associated with extraversion. Personality of TRD patients differed from the healthy population and did not change with response, indicating a possible scar effect. Self-ratings of personality seem valid to assess personality during TRD.

Impaired socio-affective, but intact socio-cognitive skills in patients with treatment-resistant, recurrent depression.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. LIMITATIONS: Further studies might explore socio-affective and socio-cognitive skills in TRD patients using socio-affective/-cognitive tasks involving face-to-face social interactions. CONCLUSION: 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.

Treatment resistance in major depression is correlated with increased plasma levels of neurofilament light protein reflecting axonal damage.

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.