The Impact of Worry on Attention to Threat

Prior research has often linked anxiety to attentional vigilance for threat using the dot probe task, which presents probes in spatial locations that were or were not preceded by a putative threat stimulus. The present study investigated the impact of worry on threat vigilance by administering this task during a worry condition and during a mental arithmetic control condition to 56 undergraduate students scoring in the low normal range on a measure of chronic worry. The worry induction was associated with faster responses than arithmetic to probes in the attended location following threat words, indicating the combined influence of worry and threat in facilitating attention. Within the worry condition, responses to probes in the attended location were faster for trials containing threat words than for trials with only neutral words, whereas the converse pattern was observed for responses to probes in the unattended location. This connection between worry states and attentional capture by threat may be central to understanding the impact of hypervigilance on information processing in anxiety and its disorders

Childhood Trauma History Is Linked To Abnormal Brain Connectivity In Major Depression

Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset ( n = 189 patients with MDD, n = 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: ( i ) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], ( ii ) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and ( iii ) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.PEV was supported by the Medical Research Council (grant no. MR/K020706/1) and is a Fellow of MQ: Transforming Mental Health (MQF17_24)

Elevating the field for applying neuroimaging to individual patients in psychiatry

Abstract Although neuroimaging has been widely applied in psychiatry, much of the exuberance in decades past has been tempered by failed replications and a lack of definitive evidence to support the utility of imaging to inform clinical decisions. There are multiple promising ways forward to demonstrate the relevance of neuroimaging for psychiatry at the individual patient level. Ultra-high field magnetic resonance imaging is developing as a sensitive measure of neurometabolic processes of particular relevance that holds promise as a new way to characterize patient abnormalities as well as variability in response to treatment. Neuroimaging may also be particularly suited to the science of brain stimulation interventions in psychiatry given that imaging can both inform brain targeting as well as measure changes in brain circuit communication as a function of how effectively interventions improve symptoms. We argue that a greater focus on individual patient imaging data will pave the way to stronger relevance to clinical care in psychiatry. We also stress the importance of using imaging in symptom-relevant experimental manipulations and how relevance will be best demonstrated by pairing imaging with differential treatment prediction and outcome measurement. The priorities for using brain imaging to inform psychiatry may be shifting, which compels the field to solidify clinical relevance for individual patients over exploratory associations and biomarkers that ultimately fail to replicate

Affective Neural Responses Modulated by Serotonin Transporter Genotype in Clinical Anxiety and Depression

<div><p>Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/L_G carriers showed less activity than their L_A/L_A counterparts in both regions and less activity than S/L_G healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two L_A alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations.</p></div

Demographic and genotypic information for patients and healthy comparison subjects.

<p>Demographic and genotypic information for patients and healthy comparison subjects.</p

5-HTTLPR genotype effects on amygdala activation differentiate patients and healthy comparison subjects.

<p>A) Patients with at least one S or L_G allele (<i>n</i> = 36) showed less amygdala activation than patients with two L_A alleles (<i>n</i> = 14) and than healthy comparison subjects with at least one S or L_G allele (<i>n</i> = 30). This Group x Genotype effect of 5-HTTLPR was observed in amygdala <i>a priori</i> regions of interest (inset) across aversive and neutral valences in anticipation of and response to affective pictures. B) A confirmatory finding in patients (n = 50) indicated a positive association between the number of L_A alleles of the serotonin transporter gene and bilateral activation in the amygdala <i>a priori</i> region of interest (inset). C) A voxelwise regression for patients indicated a positive association between L_A allele number and bilateral amygdala activation (inset) at <i>p</i><0.05, corrected. Y-axes display mean percent signal change averaged over displayed ROIs/clusters. Asterisks on the bar graph indicate significant differences at <i>p</i><0.05. Y-values on coronal images indicate Tailarach and Tournoux coordinates for the AFNI MNI-152 brain used for normalizing. Error bars are mean standard errors.</p

5-HTTLPR genotype effects on anterior insula activation differentiate patients and healthy comparison subjects.

<p>A) Patients with at least one S or L_G allele (<i>n</i> = 36) showed less anterior insula activation than patients with two L_A alleles (<i>n</i> = 14). This Group x Genotype effect of 5-HTTLPR was observed in anterior insula <i>a priori</i> regions of interest (inset) across aversive and neutral valences in anticipation of and response to affective pictures. B) A confirmatory finding in patients (<i>n</i> = 50) indicated a positive association between the number of L_A alleles of the serotonin transporter gene and bilateral activation in anterior insula <i>a priori</i> region of interest (inset). C) A voxelwise regression for patients indicated a positive association between L_A allele number and bilateral anterior insula activation (inset) at <i>p</i><0.05, corrected. Y-axes display mean percent signal change averaged over displayed ROIs/clusters. Asterisks on the bar graph indicate significant differences at <i>p</i><0.05. Y-values on axial images indicate Tailarach and Tournoux coordinates for the AFNI MNI-152 brain used for normalizing. Error bars are mean standard errors.</p

Symptom data for 5-HTTLPR groupings in patients and healthy comparison subjects.

<p>Symptom data for 5-HTTLPR groupings in patients and healthy comparison subjects.</p