The inability to inhibit certain behaviors is a key feature of impulsivity, which is often present in people with a substance use disorder. However, the findings on impulsivity in people with alcohol ...dependence (AD) are inconsistent, possibly because of the frequent co-occurrence of depression/anxiety (D/A) and its influence on impulsivity. In the current study, we aimed to distinguish response inhibition impairments in AD from possible response inhibition effects associated with D/A.
AD patients (n = 31) with high D/A co-morbidity were compared to patients with D/A only (n = 18) and healthy controls (HCs; n = 16) using the Stop Signal Task (SST) during functional magnetic resonance imaging (fMRI). Correlation analyses were performed between activated brain areas, behavioral data and addiction and D/A characteristics.
The three groups did not differ on response inhibition performance. However, AD severity, but not D/A severity, was positively associated with decreased response inhibition. During the SST, AD patients showed hyperactivity in the putamen and thalamus compared with D/A patients and HCs. Thalamus activation was negatively associated with AD duration. In addition, AD patients showed hypoactivity in the supplementary motor area (SMA) compared with HCs. SMA activity within HCs was negatively correlated with depressive symptom severity. Discussion In general, AD patients were not more impulsive than D/A patients or HCs but they did reveal inhibition impairments with increasing AD severity. A shift from cortical to subcortical engagement in AD patients during response inhibition may represent an alternative strategy, which decreased with longer drinking history, suggesting the presence of an AD-specific endophenotype.
Background Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We ...investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT). Methods Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well. Results We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys ( pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls ( pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation. Limitations Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses. Conclusion Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning.
•Connectivity analyses complemented with a metric exploring switching in brain activity.•Lower insula-salience connectivity predicts insufficient antidepressant response.•This same insula region is ...activated less when switching from task to a rest.•This could be a potential biomarkers for predicting future antidepressant response.
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 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 antidepressants 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 antidepressant 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.
Depression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of ...emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients.
An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.
Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.
We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.
Aims/hypothesis In addition to nephropathy, retinopathy and peripheral neuropathy, a microvascular complication of type 1 diabetes that may be tentatively referred to as 'diabetic encephalopathy' has ...gained increasing attention. There is growing evidence that lowered cognitive performance in patients with type 1 diabetes is related to chronic hyperglycaemia rather than recurrent episodes of severe hypoglycaemia, as previously speculated. The aim of our study was to use magnetic resonance imaging (MRI) to establish whether long-term hyperglycaemia, resulting in advanced retinopathy, contributes to structural changes in the brain (reduced grey matter). Subjects, materials and methods We applied voxel-based morphometry on magnetic resonance images to compare grey matter density (GMD) between three groups of participants. GMD is used as a marker of cortical atrophy. We compared 13 type 1 diabetic patients with a microvascular complication (i.e. proliferative retinopathy) with 18 type 1 diabetic patients who did not have retinopathy in order to assess the effects of microvascular changes on GMD. Both patient groups were compared with 21 healthy control subjects to assess the effect of diabetes in itself. Results Patients with diabetic retinopathy showed reduced GMD in the right inferior frontal gyrus and right occipital lobe compared both with patients without retinopathy and with healthy controls (p<0.05). Conclusions/interpretation Our data show that patients with type 1 diabetes, who, as a consequence of chronic hyperglycaemia, had developed advanced retinopathy, also showed increased focal cortical atrophy on brain MRI.
Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to ...degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD.
In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by (123)IFP-CIT SPECT tracer binding to the dopamine transporter (DaT).
Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients.
These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.
The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of ...suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10
) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.
Anxiety disorders are associated with substantial functional limitations but the course of functioning following symptom remission remains largely unknown.
Using data from the Netherlands Study of ...Depression and Anxiety (NESDA), we examined the 2-year trajectories of functioning in participants with chronic (n = 586) or remitting anxiety disorders (n = 385) and in healthy controls (n = 585). In participants with remitting anxiety disorders, we identified predictors of functioning from among sociodemographic, clinical and vulnerability variables. Data were analysed using linear mixed models (LMMs). Functioning was assessed with the World Health Organization Disability Assessment Schedule II (WHO DAS II).
At baseline, participants with remitting anxiety disorders functioned significantly better than those with chronic anxiety disorders, but significantly worse than controls. In both anxiety disorder groups, most impairment was reported in social functioning, occupational functioning and cognition. During the follow-up, functioning improved in both groups, probably due to treatments received. Participants who achieved symptom remission experienced moderate improvements in social functioning and cognition but not in occupational functioning. Of those who remitted, 45.8% reported functioning scores similar to healthy controls whereas 28.5% still functioned at the level of those with chronic anxiety disorders. Worse functioning was predicted by severe anxiety disorders, use of psychological treatment, co-morbid depressive disorders and maladaptive personality traits.
In anxiety disorders, symptom remission is accompanied by improvements in functioning but significant functional impairments may persist because of co-morbid disorders, lower functioning prior to the onset of the anxiety disorder or residual subthreshold anxiety symptoms.
Obsessive–compulsive disorder (OCD) is a clinically heterogeneous disorder characterized by multiple, temporally stable symptom dimensions. Preliminary functional neuroimaging studies suggest that ...these symptom dimensions may have distinct neural substrates. Whole-brain voxel-based morphometry was used to examine the common and distinct neuroanatomical (structural) substrates of the major symptom dimensions of OCD. First, we compared 55 medication-free patients with OCD and 50 age-matched healthy control subjects. Multiple regression analyses were then used to examine the relationship between global and regional grey matter (GM) and white matter (WM) volumes and symptom dimension scores within the patient group. OCD patients showed decreased GM volume in left lateral orbitofrontal (BA47), left inferior frontal (BA44/45), left dorsolateral prefrontal (BA9) and right medial prefrontal (BA10) cortices and decreased bilateral prefrontal WM volume. Scores on the ‘symmetry/ordering’ dimension were negatively correlated with ‘global’ GM and WM volumes. Scores on the ‘contamination/washing’ dimension were negatively correlated with ‘regional’ GM volume in bilateral caudate nucleus and WM volume in right parietal region. Scores on the ‘harm/checking’ dimension were negatively correlated with regional GM and WM volume in bilateral temporal lobes. Scores on the ‘symmetry/ordering’ dimension were negatively correlated with regional GM volume in right motor cortex, left insula and left parietal cortex and positively correlated with bilateral temporal GM and WM volume. The results remained significant after controlling for age, sex, educational level, overall illness severity, global WM and GM volumes and excluding patients with comorbid depression. The reported symptom dimension-specific GM and WM alterations support the hypothesis that OCD is an etiologically heterogeneous disorder, with both overlapping and distinct neural correlates across symptom dimensions. These results have clear implications for the current neuroanatomical model of OCD and call for a substantial revision of such model which takes into account the heterogeneity of the disorder.
Objective
To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of ...gaining important novel insights into the underlying neurobiological mechanisms mediating DID.
Methods
This study included 32 female patients with DID and 43 matched healthy controls. Between‐group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex‐wise approach. Whole‐brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization.
Results
Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found.
Conclusions
In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization.
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