Background: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated... Show moreBackground: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. Methods: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS-, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. Results: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS- patients (p = .015)-part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS- or controls in resting-state functional connectivity of the salience or basal ganglia networks. Conclusions: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research. Show less
Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of... Show moreAnxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders. Show less
Bas-Hoogendam, J.M.; Steenbergen, H. van; Blackford, J.U.; Tissier, R.L.M.; Wee, N.J.A. van der; Westenberg, P.M. 2019
Background Social anxiety disorder (SAD) is an incapacitating disorder running in families. Previous work associated social fearfulness with a failure to habituate, but the habituation response to... Show moreBackground Social anxiety disorder (SAD) is an incapacitating disorder running in families. Previous work associated social fearfulness with a failure to habituate, but the habituation response to neutral faces has, as of yet, not been investigated in patients with SAD and their family members concurrently. Here, we examined whether impaired habituation to neutral faces is a putative neurobiological endophenotype of SAD by using data from the multiplex and multigenerational Leiden Family Lab study on SAD. Methods Participants (n = 110; age, 9.2 - 61.5 years) performed a habituation paradigm involving neutral faces, as these are strong social stimuli with an ambiguous meaning. We used functional magnetic resonance imaging data to investigate whether brain activation related to habituation was associated with the level of social anxiety within the families. Furthermore, the heritability of the neural habituation response was estimated. Results Our data revealed a relationship between impaired habituation to neutral faces and social anxiety in the right hippocampus and right amygdala. In addition, our data indicated that this habituation response displayed moderate - to-moderately high heritability in the right hippocampus. Conclusion The present results provide support for altered habituation as a candidate SAD endophenotype; impaired neural habitation cosegregrated with the disorder within families and was heritable. These findings shed light on the genetic susceptibility to SAD. Show less
Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment (Ud) is... Show moreBackground: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment (Ud) is another transdiagnostic risk factor that may be relevant to explain differences in patient characteristics within diagnostic classifications. Objective: In the current study, we examined unique relations of resting-state functional connectivity (RSFC) with Ud and GPF. Method: RSFC data were collected from a mixed group of adolescents (N = 74) with and without psychiatric disorder, as part of the Emotional Pathways' Imaging Study in Clinical Adolescents (EPISCA) study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and dorsal anterior cingulate cortex (dACC) and with amygdala-medial frontal connectivity were examined. Results: Ud was positively associated with greater functional connectivity between the left amygdala and the left lateral occipital cortex, precuneus, and superior parietal lobule. Furthermore, Ud was negatively associated with left amygdala-medial frontal cortex connectivity. GPF was not significantly associated with dACC or amygdala connectivity. Conclusions: Atypical amygdala connectivity may reflect a vulnerability factor rather than a biomarker of psychopathology. The unique association of Ud and amygdala RSFC, adjusted for a GPF, across participants with and without various classifications of psychopathology illustrates that dimensional approaches based on the AAI may complement psychiatric classifications in clinical research and practice. Show less
The current study examined the effects of oxytocin administration on the response to infant crying in individuals with secure or insecure attachment representations as assessed with the Adult... Show moreThe current study examined the effects of oxytocin administration on the response to infant crying in individuals with secure or insecure attachment representations as assessed with the Adult Attachment Interview. We measured feelings of irritation and the use of excessive force as indicated by grip strength using a handgrip dynamometer during exposure to infant crying in 42 women without children who were administered intranasal oxytocin or a placebo. In addition, amygdala responses to infant crying and control sounds were measured with functional magnetic resonance imaging (fMRI). The effects of oxytocin on reactivity to crying were moderated by attachment security. Oxytocin decreased the use of excessive handgrip force and amygdala reactivity in response to crying in individuals with insecure attachment representations. Our findings indicate that insecure individuals, who show emotional, behavioral, and neural hyperreactivity to crying, benefit the most from intranasal oxytocin. Show less
Aghajani, M.; Veer, I.M.; Hoof, M.J. van; Rombouts, S.A.R.B.; Wee, N.J. van der; Vermeiren, R.R.J.M. 2016
