Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more... Show moreInsufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received >= two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with >= two anti-depressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the 2 anti-depressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response. Show less
Altered processing of emotional faces due to childhood maltreatment has repeatedly been reported, and may be a key process underlying the intergenerational transmission of maltreatment. The current... Show moreAltered processing of emotional faces due to childhood maltreatment has repeatedly been reported, and may be a key process underlying the intergenerational transmission of maltreatment. The current study is the first to examine the role of neural reactivity to emotional and neutral faces in the transmission of maltreatment, using a multi-generational family design including 171 participants of 51 families of two generations with a large age range (8–69 years). The impact of experienced and perpetrated maltreatment (abuse and neglect) on face processing was examined in association with activation in the amygdala, hippocampus, inferior frontal gyrus (IFG) and insula in response to angry, fearful, happy and neutral faces. Results showed enhanced bilateral amygdala activation in response to fearful faces in older neglected individuals, whereas reduced amygdala activation was found in response to these faces in younger neglected individuals. Furthermore, while experienced abuse was associated with lower IFG activation in younger individuals, experience of neglect was associated with higher IFG activation in this age group, pointing to potentially differential effects of abuse and neglect and significant age effects. Perpetrated abusive and neglectful behavior were not related to neural activation in any of these regions. Hence, no indications for a role of neural reactivity to emotional faces in the intergenerational transmission of maltreatment were found. Show less
Background Psychopathy has repeatedly been linked to disturbed associative learning from aversive events (i.e., threat conditioning). Optimal threat conditioning requires the generation of internal... Show moreBackground Psychopathy has repeatedly been linked to disturbed associative learning from aversive events (i.e., threat conditioning). Optimal threat conditioning requires the generation of internal representations of stimulus–outcome contingencies and the rate with which these may change. Because mental representations are imperfect, there will always be uncertainty about the accuracy of representations in the brain (i.e., representational uncertainty). However, it remains unclear 1) to what extent threat conditioning is susceptible to different types of uncertainty in representations about contingencies during the acquisition phase and 2) how representational uncertainty relates to psychopathic features. Methods A computational model was applied to functional neuroimaging data to estimate uncertainty in representations of contingencies (CoUn) and the rate of change of contingencies (RUn), respectively, from brain activation during the acquisition phase of threat conditioning in 132 adolescents at risk of developing antisocial personality profiles. Next, the associations between these two types of representational uncertainty and psychopathy-related dimensions were examined. Results The left and right amygdala activations were associated with CoUn, while the bilateral insula and the right amygdala were associated with RUn. Different patterns of relationships were found between psychopathic features and each type of uncertainty. Callous-unemotional traits and impulsive-irresponsible traits uniquely predicted increased CoUn, while only impulsive-irresponsible traits predicted increased RUn. Conclusions The findings suggest that 1) the insula and amygdala differ in how these regions are affected by different types of representational uncertainty during threat conditioning and 2) CoUn and RUn have different patterns of relationships with psychopathy-related dimensions. Show less
