Anxiety symptoms are associated with smaller insular and orbitofrontal cortex volumes in late-life depression.
ABSTRACT: BACKGROUND:Increasing understanding of the neural correlates of anxiety symptoms in late-life depression (LLD) could inform the development of more targeted and effective treatments. METHODS:Grey matter volume (GMV) was assessed with volumetric magnetic resonance imaging in a sample of 113 adults ?60 years with MDD using the following regions of interest: amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. RESULTS:After controlling for demographic (age, sex, education) and clinical variables (antidepressant use, anxiolytic use, duration of illness, medical comorbidity, cognitive functioning), greater severity of anxiety symptoms was associated with lower GMV bilaterally in the insula, F(1,102) = 6.63, p?=?0.01, and OFC, F(1,102) = 8.35, p?=?0.005. By contrast, depressive symptom severity was significantly associated with lower bilateral insula volumes, F(1,102) = 6.43, p?=?0.01, but not OFC volumes, F(1,102) = 5.37, p?=?0.02. LIMITATIONS:Limitations include (1) the relatively mild nature of anxiety symptoms in our sample; (2) the cross-sectional research design, which prohibits inferences of directionality; (3) the relatively homogenous demographic of the sample, and (4) the exclusion of participants with significant psychiatric comorbidity, suicidality, or cognitive impairment. CONCLUSIONS:Decreased OFC volumes may serve as a unique biomarker of anxiety symptoms in LLD. Future longitudinal and clinical studies with long-term follow up and more diverse samples will help further elucidate the biological, psychological, and social factors affecting associations between anxiety and brain morphology in LLD.
Project description:Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances.
Project description:<h4>Background</h4>The anterior insula cortex is considered to be both the structural and functional link between experience, affect, and behaviour. Magnetic resonance imaging (MRI) studies have shown changes in anterior insula gray matter volume (GMV) in psychosis, bipolar, depression and anxiety disorders in older patients, but few studies have investigated insula GMV changes in young people. This study examined the relationship between anterior insula GMV, clinical symptom severity and neuropsychological performance in a heterogeneous cohort of young people presenting for mental health care.<h4>Methods</h4>Participants with a primary diagnosis of depression (n?=?43), bipolar disorder (n?=?38), psychosis (n?=?32), anxiety disorder (n?=?12) or healthy controls (n?=?39) underwent structural MRI scanning, and volumetric segmentation of the bilateral anterior insula cortex was performed using the FreeSurfer application. Statistical analysis examined the linear and quadratic correlations between anterior insula GMV and participants' performance in a battery of clinical and neuropsychological assessments.<h4>Results</h4>Compared to healthy participants, patients had significantly reduced GMV in the left anterior insula (t?=?2.05, p?=?.042) which correlated with reduced performance on a neuropsychological task of attentional set-shifting (??=?.32, p?=?.016). Changes in right anterior insula GMV was correlated with increased symptom severity (r?=?.29, p?=?.006) and more positive symptoms (r?=?.32, p?=?.002).<h4>Conclusions</h4>By using the novel approach of examining a heterogeneous cohort of young depression, anxiety, bipolar and psychosis patients together, this study has demonstrated that insula GMV changes are associated with neurocognitive deficits and clinical symptoms in such young patients.
Project description:Adults with a history of depression show distinct patterns of grey matter volume (GMV) in frontal cortical (e.g., prefrontal cortex, orbitofrontal cortex) and limbic (e.g., anterior cingulate, amygdala, hippocampus, dorsal striatum) structures, regions relevant to the processing and regulation of reward, which is impaired in the context of depression. However, it is unclear whether these GMV associations with depression precede depressive disorder onset or whether GMV is related to early emerging symptoms or familial depression. To address these questions, we used voxel-based morphometry (VBM) to examine GMV in 85 community-dwelling children (M = 11.12 years, SD = 0.63 years) screened for current and lifetime depression. Associations between children's depressive symptoms (self- and mother-report of children's symptoms), children's maternal depression history, and GMV were examined. Although maternal depression history was unrelated to children's GMV, child GMV in the orbitofrontal cortex (OFC) was negatively related to children's self-reported depressive symptoms, using both a priori ROI and whole-brain analyses. Moderated regression analyses indicated that girls' GMV was negatively related to girls' depressive symptoms (as indexed by both self- and mother-report of girls' symptoms), whereas boys' symptoms were positively related to GMV. Our findings suggest that brain morphology in the OFC, a region with functional roles in processes relevant to depressive symptoms (i.e., reward-based learning and reward processing), is associated with early depressive symptoms prior to the development of clinically significant depression.
Project description:Social anxiety is a common problem that usually emerges at puberty, during which great developmental changes occur both in the brain and mental state. However, little is known about the influence of social anxiety on adolescents’ brain and behavior. The present study investigated the neural basis of social anxiety using voxel-based morphometry (VBM) and functional connectivity analysis. Then we investigated whether social anxiety is associated with attention bias. Furthermore, we investigated the neural basis of this association. Finally, longitudinal data was used to test if these biomarkers could predict social anxiety. The results indicated that social anxiety is positively associated with the grey matter volume (GMV) of orbital-frontal cortex (OFC), and the functional connectivity (FC) of OFC-amygdala. Mediation analysis revealed that the relationship between social anxiety and attention avoidance is partly mediated by the FC of OFC-amygdala. Finally, the present study demonstrated a close relationship between FC of the OFC-amygdala, the GMV of the OFC and the individual’s social anxiety one year later. The present study suggested the aberrant structure of OFC and its connectivity with amygdala as the neural underpinning of social anxiety, which might serve as a compensatory mechanism to decrease attention avoidance and promote effective emotion regulation.
Project description:An overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests that the two disorders exhibit similar brain mechanisms. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess the gray matter volume (GMV) and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients.High-resolution T1-weighted images were acquired from 37 non-comorbid MDD patients, 24 non-comorbid SAD patients and 41 healthy controls (HCs). Voxel-based morphometry analysis of the GMV (corrected with a false discovery rate of p<0.001) and vertex-based analysis of cortical thickness (corrected with a clusterwise probability of p<0.001) were performed, and group differences were compared by ANOVA followed by post hoc tests.Relative to the HCs, both the MDD patients and SAD patients showed the following results: GMV reductions in the bilateral orbital frontal cortex (OFC), putamen, and thalamus; cortical thickening in the bilateral medial prefrontal cortex, posterior dorsolateral prefrontal cortex, insular cortex, left temporal pole, and right superior parietal cortex; and cortical thinning in the left lateral OFC and bilateral rostral middle frontal cortex. In addition, MDD patients specifically showed a greater thickness in the left fusiform gyrus and right lateral occipital cortex and a thinner thickness in the bilateral lingual and left cuneus. SAD patients specifically showed a thinner cortical thickness in the right precentral cortex.Our results indicate that MDD and SAD share common patterns of gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience network and dorsal attention network. These consistent structural differences in the two patient groups may contribute to the broad spectrum of emotional, cognitive and behavioral disturbances observed in MDD patients and SAD patients. In addition, we found disorder-specific involvement of the visual processing regions in MDD and the precentral cortex in SAD. These findings provide new evidence regarding the shared and specific neuropathological mechanisms that underlie MDD and SAD.
Project description:Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabilities characterise children with conduct problems and high levels of callous-unemotional traits (CP/HCU) compared with children with conduct problems and low callous-unemotional traits (CP/LCU). We used voxel-based morphometry to study grey matter volume (GMV) in 89 male participants (aged 10-16), 60 of whom exhibited CP. The CP group was subdivided into CP/HCU (n = 29) and CP/LCU (n = 31). Whole-brain and regional GMV were compared across groups (CP vs. typically developing (TD) controls (n = 29); and CP/HCU vs. CP/LCU vs. TD). Whole-brain analyses showed reduced GMV in left middle frontal gyrus in the CP/HCU group compared with TD controls. Region-of-interest analyses showed reduced volume in bilateral orbitofrontal cortex (OFC) in the CP group as a whole compared with TD controls. Reduced volume in left OFC was found to be driven by the CP/HCU group only, with significant reductions relative to both TD controls and the CP/LCU group, and no difference between these latter two groups. Within the CP group left OFC volume was significantly predicted by CU traits, but not conduct disorder symptoms. Reduced right anterior cingulate cortex volume was also found in CP/HCU compared with TD controls. Our results support previous findings indicating that GMV differences in brain regions central to decision-making and empathy are implicated in CP. However, they extend these data to suggest that some of these differences might specifically characterise the subgroup with CP/HCU, with GMV reduction in left OFC differentiating children with CP/HCU from those with CP/LCU.
Project description:The unique neuroanatomical underpinnings of internalizing symptoms and impulsivity during childhood are not well understood. In this study, we examined associations of brain structure with anxiety, depression, and impulsivity in children and adolescents. Participants were 7- to 21-year-olds (N?=?328) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study who completed high-resolution, 3-Tesla, T1-weighted MRI and self-report measures of anxiety, depression, and/or impulsivity. Cortical thickness and surface area were examined across cortical regions-of-interest (ROIs), and exploratory whole-brain analyses were also conducted. Gray matter volume (GMV) was examined in subcortical ROIs. When considered separately, higher depressive symptoms and impulsivity were each significantly associated with reduced cortical thickness in ventromedial PFC/medial OFC, but when considered simultaneously, only depressive symptoms remained significant. Higher impulsivity, but not depressive symptoms, was associated with reduced cortical thickness in the frontal pole, rostral middle frontal gyrus, and pars orbitalis. No differences were found for regional surface area. Higher depressive symptoms, but not impulsivity, were significantly associated with smaller hippocampal GMV and larger pallidal GMV. There were no significant associations between anxiety symptoms and brain structure. Depressive symptoms and impulsivity may be linked with cortical thinning in overlapping and distinct regions during childhood and adolescence.
Project description:Although oxytocin (OXT) plays an important role in secure attachment formation with a primary caregiver, which is impaired in many children with childhood maltreatment (CM), epigenetic regulation in response to CM is a key factor in brain development during childhood. To address this issue, we first investigated differences in salivary DNA methylation of the oxytocin receptor (OXTR) between CM and Non-CM groups of Japanese children (CM: n?=?44; Non-CM: n?=?41) and its impact on brain structures in subgroup analysis using brain imaging and full clinical data (CM: n?=?24; Non-CM: n?=?31). As a result, we observed that the CM group showed higher CpG 5,6 methylation than did the Non-CM group and confirmed negative correlations of gray matter volume (GMV) in the left orbitofrontal cortex (OFC) with CpG 5,6 methylation. In addition, the CM group showed significantly lower GMV in the left OFC than did the Non-CM group. Furthermore, as a result of examining the relationship between GMV in the left OFC and psychiatric symptoms in CM, we observed a negative association with insecure attachment style and also confirmed the mediation effect of left-OFC GMV reduction on the relationship between OXTR methylation and insecure attachment style. These results suggest that any modulation of the oxytocin signaling pathway induced by OXTR hypermethylation at CpG 5,6 leads to atypical development of the left OFC, resulting in distorted attachment formation in children with CM.
Project description:The phenotype and genotype of antisocial behavior among females are different from those among males. Previous studies have documented structural brain alterations in males with antisocial behavior, yet little is known about the neural correlates of female antisocial behavior. The present study examined young women who had presented conduct disorder (CDW) prior to age 15 to determine whether brain abnormalities are present in adulthood and whether the observed abnormalities are associated with comorbid disorders or maltreatment that typically characterize this population. Using magnetic resonance imaging and voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who presented CD by midadolescence and 25 healthy women (HW), age, on average, 23 years. Participants completed structured, validated interviews to diagnose mental disorders, and validated questionnaires to document physical and sexual abuse. Relative to HW, CDW presented increased GMV in the left superior temporal gyrus that was associated with past alcohol and drug dependence, current use of alcohol and drugs, and current anxiety and depression symptoms and maltreatment. Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and anterior cingulate cortex that was associated with past comorbid disorders, current alcohol and drugs use, current anxiety and depression symptoms, and maltreatment. The CDW also presented reduced total GMV that was associated with past comorbid disorders and current anxiety/depression symptoms. Alterations of brain structure were observed among young adult females with prior CD, relative to HW, all of which were associated with internalizing and externalizing disorders and maltreatment that typically accompany CD.
Project description:Background: Symptoms of anxiety are present not only in panic disorder or other anxiety disorders, but are highly prevalent in the general population. Despite increasing biological research on anxiety disorders, there is little research on understanding subclinical or sub-threshold symptoms relating to anxiety in non-clinical community samples, which could give clues to factors relating to resilience or compensatory changes. Aims:This study focused on brain structural correlates of subclinical anxiety/agoraphobia symptoms from a multi-center imaging study. Methods: We obtained high-resolution structural T1 MRI scans of 409 healthy young participants and used the CAT12 toolbox for voxel-based morphometry (VBM) analysis. Subjects provided self-ratings of anxiety using the SCL-90-R, from which we used the phobia subscale, covering anxiety symptoms related to those of panic and agoraphobia spectrum. Results: We found significant (p < 0.05, FDR-corrected) correlations (mostly positive) of cortical volume with symptom severity, including the right lingual gyrus and calcarine sulcus, as well as left calcarine sulcus, superior, middle, and inferior temporal gyri. Uncorrected exploratory analysis also revealed positive correlations with GMV in orbitofrontal cortex, precuneus, and insula. Conclusions: Our findings show brain structural associations of subclinical symptoms of anxiety, which overlap with those seen in panic disorder or agoraphobia. This is consistent with a dimensional model of anxiety, which is reflected not only functionally but also on the structural level.