Borderline personality disorder (BPD) and major depressive disorder (MDD) are both associated with abnormalities in the regulation of emotion, with BPD being highly comorbid with MDD. Disorder-specific dysfunctions in BPD, however, have hardly been addressed, hence the lack of knowledge pertaining to the specificity of emotion processing deficits and their commonality with MDD. 24 healthy comparison subjects, 21 patients with MDD, and 13 patients with comorbid BPD and MDD (BPD + MDD group) were studied using functional MRI. The subjects were required to perform an emotional interference task that entailed categorizing facial affect while ignoring words that labeled the emotional contents of the external stimuli. Collapsing across emotional face types, we observed that participants with BPD + MDD uniquely displayed a greater involvement of the visual areas and the cerebellum. During emotional conflict processing, on the other hand, the lateral prefrontal cortex (LPFC) appeared to be affected in both patient groups. In comparison to the HC, the MDD group showed differences also in the posterior medial frontal cortex (pMFC) and the inferior parietal lobule (IPL). Thus, our data indicate dysfunctionality in the neural circuitry responsible for emotional conflict control in both disorders. The enhanced visual cortex activation in BPD + MDD suggests the visual system's hyperresponsiveness to faces at an early perceptual level. Not being associated with co-occurring depression, this effect in BPD + MDD appears to represent specific personality traits such as disturbed reactivity toward emotionally expressive facial stimuli.

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.

Adequate emotional control is essential for mental health. Deficiencies in emotion regulation are evident in many psychiatric disorders, including depression. Patients with depression show, for instance, disrupted neural emotion regulation in cognitive regulation regions such as lateral and medial prefrontal cortices. Since depressed individuals tend to attribute positive events to external circumstances and negative events to themselves, modifying this non-self-serving attributional style may represent a promising regulation strategy. Spontaneous causal attributions are generally processed in medial brain structures, particularly the precuneus. However, so far no study has investigated neural correlates of instructed causal attributions (e.g. instructing a person to intentionally relate positive events to the self) and their potential to regulate emotions. The current study therefore aimed to examine how instructed causal attributions of positive and negative events affect the emotional experience of depressed individuals as well as its neural bases. For this purpose pictures of sad and happy faces were presented to 26 patients with a lifetime major depression (MDD) and 26 healthy controls (HC) during fMRI. Participants should respond naturally ("view") or imagine that the person on the picture was sad/happy because of them ("internal attribution") or because something else happened ("external attribution"). Trait attributional style and depressive symptoms were assessed with questionnaires to examine potential influential factors on emotion regulation ability. Results revealed that patients compared to controls show a non-self-serving trait attributional style (i.e. more external attributions of positive events and more internal attributions of negative events). Intriguingly, when instructed to apply specific causal attributions during the emotion regulation task, patients and controls were similarly able to regulate positive and negative emotions. Regulating emotions through instructed attributions (internal/external attribution>view) generally engaged the precuneus, which was correlated with patients' trait attributional style (i.e. more precuneus activation during external>view was linked to a general tendency to relate positive events to external sources). Up-regulating happiness through internal (compared to external) attributions recruited the parahippocampal gyrus only in controls. The down-regulation of sadness (external>internal attribution), in contrast, engaged the superior frontal gyrus only in patients. Superior frontal gyrus activation thereby correlated with depression severity, which implies a greater need of cognitive resources for a successful regulation in more severely depressed. Patients and controls did not differ in activation in brain regions related to cognitive emotion regulation or attribution. However, results point to a disturbed processing of positive emotions in depression. Interestingly, increased precuneus resting-state connectivity with emotion regulation brain regions (inferior parietal lobule, middle frontal gyrus) was linked to healthier attributions (i.e. external attributions of negative events) in patients and controls. Adequate neural communication between these regions therefore seem to facilitate an adaptive trait attributional style. Findings of this study emphasize that despite patients' dysfunctional trait attributional style, explicitly applying causal attributions effectively regulates emotions. Future research should examine the efficacy of instructed attributions in reducing negative affect and anhedonia in depressed patients, for instance by means of attribution trainings during psychotherapy.