Amygdala Gray Matter Volume Research Articles

Challenges in replication: Does amygdala gray matter volume relate to social network size?

In this work, we tried to replicate and extend prior research on the relationship between social network size and the volume of the amygdala. We focused on the earliest evidence for this relationship (Bickart et al., Nature Neuroscience 14(2), 163–164, 2011) and another methodologically unique study that often is cited as a replication (Kanai et al., Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327–1334, 2012). Despite their tight link in the literature, we argue that Kanai et al. (Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327–1334, 2012) is not a replication of Bickart et al. Nature Neuroscience 14(2), 163–164 (2011), because it uses different morphometric measurements. We collected data from 128 participants on a 7-Tesla MRI and examined variations in gray matter volume (GMV) in the amygdala and its nuclei. We found inconclusive support for a correlation between measures of real-world social network and amygdala GMV, with small effect sizes and only anecdotal evidence for a positive relationship. We found support for the absence of a correlation between measures of online social network and amygdala GMV. We discuss different challenges faced in replication attempts for small effects, as initially reported in these two studies, and suggest that the results would be most helpful in the context of estimation and future meta-analytical efforts. Our findings underscore the value of a narrow approach in replication of brain-behavior relationships, one that is focused enough to investigate the specifics of what is measured. This approach can provide a complementary perspective to the more popular “thematic” alternative, in which conclusions are often broader but where conclusions may become disconnected from the evidence.

Network dysfunction of sadness facial expression processing and morphometry in euthymic bipolar disorder

Facial emotion recognition (FER), including sadness, is altered in bipolar disorder (BD). However, the relationship between this impairment and the brain structure in BD is relatively unexplored. Furthermore, its association with clinical variables and with the subtypes of BD remains to be clarified. Twenty euthymic patients with BD type I (BD-I), 28 BD type II (BD-II), and 45 healthy controls completed a FER test and a 3D-T1-weighted magnetic resonance imaging. Gray matter volume (GMV) of the cortico-limbic regions implicated in emotional processing was estimated and their relationship with FER performance was investigated using network analysis. Patients with BD-I had worse total and sadness-related FER performance relative to the other groups. Total FER performance was significantly negatively associated with illness duration and positively associated with global functioning in patients with BD-I. Sadness-related FER performance was also significantly negatively associated with the number of previous manic episodes. Network analysis showed a reduced association of the GMV of the frontal–insular–occipital areas in patients with BD-I, with a greater edge strength between sadness-related FER performance and amygdala GMV relative to controls. Our results suggest that FER performance, particularly for facial sadness, may be distinctively impaired in patients with BD-I. The pattern of reduced interrelationship in the frontal–insular–occipital regions and a stronger positive relationship between facial sadness recognition and the amygdala GMV in BD may reflect altered cortical modulation of limbic structures that ultimately predisposes to emotional dysregulation. Future longitudinal studies investigating the effect of mood state on FER performance in BD are warranted.

Brain structure underlying the empathizing-systemizing difference in children with autism spectrum disorder.

Behavioral research has shown that children with autism spectrum disorder (ASD) havea higher empathizing-systemizing difference(D score) than normal children. However, there is no research about the neuroanatomical mechanisms of the empathizing-systemizing difference in children with ASD. Participants comprised 41 children with ASD and 39 typically developing (TD) children aged 6‒12years. Empathizing-systemizing difference was estimated using the D score from the Chinese version of Children's Empathy Quotient and Systemizing Quotient. We quantified brain morphometry, including global and regional brain volumes and surface-based cortical measures (cortical thickness, surface area, and gyrification) via structural magnetic resonance imaging. We found that the D score was significantly negatively associated with amygdala gray matter volume [β = -0.16; 95% confidence interval (CI): -0.30, -0.02; P value = 0.030] in children with ASD. There was a significantly negative association between D score and gyrification in the left lateral occipital cortex (LOC) in children with ASD (B = -0.10; SE = 0.03; cluster-wise P value = 0.006) and a significantly positive association between D score and gyrification in the right fusiform in TD children (B = 0.10; SE = 0.03; cluster-wise P value = 0.022). Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume (β = 0.19; 95% CI 0.04, 0.35; P value = 0.013) and left LOC gyrification (β = 0.11; 95% CI 0.05, 0.17; P value = 0.001) but not in right fusiform gyrification (β = 0.08; 95% CI -0.02, 0.17; P value = 0.105). Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing-systemizing difference in children with ASD but not in TD children. Large-scale neuroimaging studies are necessary to test the replicability of our findings.

Male-specific, replicable and functional roles of genetic variants and cerebral gray matter volumes in ADHD: a gene-wide association study across KTN1 and a region-wide functional validation across brain

Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10–5 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10–22 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010 < p ≤ 0.013). The ADHD-risk alleles also significantly reduced some cortical (right superior temporal pole, right rectus) and cerebellar but increased other cortical (0.007 ≤ p ≤ 0.050) GMVs. To conclude, we identified a set of replicable and functional risk KTN1 alleles for ADHD, specifically in males. KTN1 may play a critical role in the pathogenesis of ADHD, and the reduction of specific cortical and subcortical, including amygdalar but not basal ganglia or hippocampal, GMVs may serve as a neural marker of the genetic effects.

Subcortical structures associated with childhood trauma and perceived stress in schizophrenia.

Childhood trauma influences the clinical features of schizophrenia. In this study, we examined how childhood trauma and perceived stress are associated with clinical manifestations and subcortical gray matter volumes (GMVs) in patients with schizophrenia. We recruited 127 patients with schizophrenia and 83 healthy controls for assessment of early childhood trauma, perceived stress, and clinical symptoms. With structural brain imaging, we identified the GMVs of subcortical structures and examined the relationships between childhood trauma, perceived stress, clinical symptoms, and subcortical GMVs. Compared to controls, patients with schizophrenia showed higher levels of childhood trauma and perceived stress. Patients with schizophrenia showed significantly smaller amygdala and hippocampus GMVs as well as total cortical GMVs than age-matched controls. Childhood trauma score was significantly correlated with the severity of clinical symptoms, depression, perceived stress, and amygdala GMVs. Perceived stress was significantly correlated with clinical symptoms, depression, and hippocampus and amygdala GMVs. Further, the association between childhood trauma (emotional neglect) and stress coping ability was mediated by right amygdala GMV in patients with schizophrenia. Patients with schizophrenia had more exposure to early-life trauma and poorer stress coping. Both childhood trauma and perceived stress were associated with smaller amygdala volumes. The relationship between early-life trauma and perceived stress was mediated by right amygdala GMV in patients with schizophrenia. These findings together suggest the long-term effects of childhood trauma on perceived stress and the subcortical volumetric correlates of the effects in schizophrenia.

Startle Latency as a Potential Marker for Amygdala-Mediated Hyperarousal

BackgroundFear-related disorders are characterized by hyperexcitability in reflexive circuits and maladaptive associative learning mechanisms. The startle reflex is suited to investigate both processes, either by probing it under baseline conditions or by deriving it in fear conditioning studies. In anxiety research, the amplitude of the fear-potentiated startle has been shown to be influenced by amygdalar circuits and has typically been the readout of interest. In schizophrenia research, prolonged startle peak latency under neutral conditions is an established readout, thought to reflect impaired processing speed. We therefore explored whether startle latency is an informative readout for human anxiety research. MethodsWe investigated potential similarities and differences of startle peak latency and amplitude derived from a classical fear conditioning task in a sample of 206 participants with varying severity levels of anxiety disorders and healthy control subjects. We first reduced startle response to stable components and regressed individual amygdala gray matter volumes onto the resulting startle measures. We then probed time, stimulus, and group effects of startle latency. ResultsWe showed that startle latency and startle amplitude were 2 largely uncorrelated measures; startle latency, but not amplitude, showed a sex-specific association with gray matter volume of the amygdala; startle latencies showed a fear-dependent task modulation; and patients with fear-related disorders displayed shorter startle latencies throughout the fear learning task. ConclusionsThese data provide support for the notion that probing startle latencies under threat may engage amygdala-modulated threat processing, making them a complementary marker for human anxiety research.

Gut Microbiome Diversity and Abundance Correlate with Gray Matter Volume (GMV) in Older Adults with Depression.

Growing evidence supports the concept that bidirectional brain–gut microbiome interactions play an important mechanistic role in aging, as well as in various neuropsychiatric conditions including depression. Gray matter volume (GMV) deficits in limbic regions are widely observed in geriatric depression (GD). We therefore aimed to explore correlations between gut microbial measures and GMV within these regions in GD. Sixteen older adults (>60 years) with GD (37.5% female; mean age, 70.6 (SD = 5.7) years) were included in the study and underwent high-resolution T1-weighted structural MRI scanning and stool sample collection. GMV was extracted from bilateral regions of interest (ROI: hippocampus, amygdala, nucleus accumbens) and a control region (pericalcarine). Fecal microbiota composition and diversity were assessed by 16S ribosomal RNA gene sequencing. There were significant positive associations between alpha diversity measures and GMV in both hippocampus and nucleus accumbens. Additionally, significant positive associations were present between hippocampal GMV and the abundance of genera Family_XIII_AD3011_group, unclassified Ruminococcaceae, and Oscillibacter, as well as between amygdala GMV and the genera Lachnospiraceae_NK4A136_group and Oscillibacter. Gut microbiome may reflect brain health in geriatric depression. Future studies with larger samples and the experimental manipulation of gut microbiome may clarify the relationship between microbiome measures and neuroplasticity.

Altered centromedial amygdala functional connectivity in adults is associated with childhood emotional abuse and predicts levels of depression and anxiety

BackgroundChildhood maltreatment is significantly associated with greater occurrence of mental disorders in adulthood such as depression and anxiety. As a key node of the limbic system, the amygdala is engaged in emotional processing and regulation and is dysfunctional in many psychiatric disorders. The present study aimed at exploring the association between childhood maltreatment and amygdala-based functional networks and their potential contributions to depression and anxiety. MethodsTotally 90 Chinese healthy volunteers participated in a resting-state fMRI experiment. Levels of childhood maltreatment experience were assessed using the Childhood Trauma Questionnaire (CTQ-SF) as well as levels of depression and anxiety. Associations between CTQ-SF scores and bilateral amygdala gray matter volume and resting-state functional connectivity (RSFC) of the amygdala and selected regions of interest were analyzed using multiple regression analyses with sex and age as covariates. A subsequent moderation analysis was performed to identify whether associations were predictive of depression and anxiety levels. ResultsChildhood maltreatment was significantly negatively associated with RSFC between left amygdala and anterior insula. Further sub-region analyses revealed that this negative association only occurred for the left centromedial amygdala subregion, which subsequently moderated the relationship between levels of childhood emotional abuse and depression / anxiety. LimitationsNo psychiatric patients were involved and specific neural associations with different childhood maltreatment subtypes need to be examined in future studies. ConclusionThe present findings provide evidence for altered RSFC of centromedial amygdala and the anterior insula associated with childhood maltreatment and which moderate levels of depression and anxiety in adulthood.

Neuroanatomical Correlates of Perceived Stress Controllability in Adolescents and Emerging Adults.

Stressful life events predict changes in brain structure and increases in psychopathology, but not everyone is equally affected by life stress. The learned helplessness theory posits that perceiving life stressors as uncontrollable leads to depression. Evidence supports this theory for youth, but the impact of perceived control diverges based on stressor type: perceived lack of control over dependent (self-generated) stressors is associated with greater depression symptoms when controlling for the frequency of stress exposure, but perceived control over independent (non-self-generated) stressors is not. However, it is unknown how perceived control over these stressor types is associated with brain structure. We tested whether perceived lack of control over dependent and independent life stressors, controlling for stressor exposure, is associated with gray matter (GM) in a priori regions of interest (ROIs; mPFC, hippocampus, amygdala) and across the cortex in a sample of 108 adolescents and emerging adults ages 14-22. There were no associations across the full sample between perceived control over either stressor type and GM in the ROIs. However, less perceived control over dependent stressors was associated with greater amygdala gray matter volume in female youth and greater medial prefrontal cortex thickness in male youth. Furthermore, whole-cortex analyses revealed less perceived control over dependent stressors was associated with greater GM thickness in cortical regions involved in cognitive and emotional regulation. Thus, appraisals of control have distinct associations with brain morphology while controlling for stressor frequency, highlighting the importance of differentiating between these aspects of the stress experience in future research.

Brain structure, psychosocial, and physical health in acute and chronic back pain: a UK Biobank study.

Brain structure, psychosocial, and physical factors underpin back pain conditions; however, less is known about how these factors differ based on pain duration and location. We examined, cross-sectionally, 11,106 individuals from the UK Biobank who (1) were pain-free (n = 5616), (2) had acute back pain (n = 1746), (3) had chronic localised back pain (CBP; n = 1872), or (4) had chronic back pain and additional chronic pain sites (CWP; n = 1872). We found differences in structural brain measures in the chronic pain groups alone. Both CBP and CWP groups had lower primary somatosensory cortex {CBP mean difference (MD) (95% confidence interval [CI]): -250 (-393, -107) mm3, P < 0.001; CWP: -170 (-313, -27)mm3, P = 0.011} and higher caudate gray matter volumes (CBP: 127 [38,216]mm3, P = 0.001; CWP: 122 [33,210]mm3, P = 0.002) compared with pain-free controls. The CBP group also had a lower primary motor cortex volume (-215 [-382, -50]mm3, P = 0.005), whereas the CWP group had a lower amygdala gray matter volume (-27 [-52, -3]mm3, P = 0.021) compared with pain-free controls. Differences in gray matter volumes in some regions may be moderated by sex and body mass index. Psychosocial factors and body mass index differed between all groups and affected those with widespread pain the most (all, P < 0.001), whereas grip strength was only compromised in individuals with widespread pain (-1.0 [-1.4, -0.5] kg, P < 0.001) compared with pain-free controls. Longitudinal research is necessary to confirm these interactions to determine the process of pain development in relation to assessed variables and covariates. However, our results suggest that categorised pain duration and the number of pain sites warrant consideration when assessing markers of brain structure, psychosocial, and physical health.

Gray matter volume correlates of adolescent posttraumatic stress disorder: A comparison of manual intervention and automated segmentation in FreeSurfer

Exposure to early life trauma is common and confers risk for psychological disorders in adolescence, including posttraumatic stress disorder (PTSD). Trauma exposure and PTSD are also consistently linked to alterations in gray matter volume (GMV). Despite the quantity of structural neuroimaging research in trauma-exposed populations, little consensus exists amongst research groups on best practices for image processing method and manual editing procedures. The purpose of this report is to evaluate the utility of manual editing of magnetic resonance (MR) images for detecting PTSD-related group differences in GMV. Here, T1-weighted MR images from adolescent girls aged 11–17 were obtained and analyzed. Two datasets were created from the FreeSurfer reconall pipeline, one of which was manually edited by trained research assistants. Gray matter regions of interest were selected and total volume estimates were entered into linear mixed effects models with method (manual edits or automated) as a within-subjects factor and group dummy-coded with PTSD as the reference group. Consistent with prior literature, individuals with PTSD demonstrated reduced GMV of the amygdala compared to trauma-exposed and non-trauma exposed controls, independent of editing method. Our results demonstrate that amygdala GMV reductions in PTSD are robust to certain methodological choices and do not suggest a benefit to the time-intensive manual editing pipeline in FreeSurfer for quantifying PTSD-related GMV.

Differential relationships of PTSD symptom clusters with cortical thickness and grey matter volumes among women with PTSD

Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.

Material hardship, prefrontal cortex-amygdala structure, and internalizing symptoms in children.

Material hardship, or difficulty affording basic resources such as food, housing, utilities, and health care, increases children's risk for internalizing problems. The uncinate fasciculus (UNC) and two of the gray matter regions it connects-the orbitofrontal cortex (OFC) and amygdala-may play important roles in the neural mechanisms underlying these associations. We investigated associations among material hardship, UNC microstructure, OFC and amygdala structure, and internalizing symptoms in children. Participants were 5-9-year-old children (N=94, 61% female) from socioeconomically diverse families. Parents completed questionnaires assessing material hardship and children's internalizing symptoms. High-resolution, T1-weighted magnetic resonance imaging (n=51), and diffusion tensor imaging (n=58) data were acquired. UNC fractional anisotropy (FA), medial OFC surface area, and amygdala gray matter volume were extracted. Greater material hardship was significantly associated with lower UNC FA, smaller amygdala volume, and higher internalizing symptoms in children, after controlling for age, sex, and family income-to-needs ratio. Lower UNC FA significantly mediated the association between material hardship and internalizing symptoms in girls but not boys. These findings are consistent with the notion that material hardship may lead to altered white matter microstructure and gray matter structure in neural networks critical to emotion processing and regulation.

Disruptive Behavior Problems, Callous-Unemotional Traits, and Regional Gray Matter Volume in the Adolescent Brain and Cognitive Development Study

BackgroundNeurobiological differences linked to socioemotional and cognitive processing are well documented in youths with disruptive behavior disorders (DBDs), especially youths with callous-unemotional (CU) traits. The current study expanded this literature by examining gray matter volume (GMV) differences among youths with DBD with CU traits (DBDCU+), youths with DBD without CU traits (DBD-only), and youths that were typically developing (TD). MethodsData were from the first full sample release of the Adolescent Brain and Cognitive Development Study (mean age = 9.49 years; 49% female). We tested whether the GMVs of 11 regions of interest selected a priori differentiated between our 3 groups: DBDCU+ (n = 288), DBD-only (n = 362), and TD (n = 915). Models accounted for demographic confounders, attention-deficit/hyperactivity disorder, and intracranial volume. We examined two potential moderators of the relationship between GMVs and group membership: sex and clinically significant anxiety (i.e., primary vs. secondary CU traits subtype). ResultsYouths in the DBDCU+ group had lower right amygdala GMV, and youths in the DBD-only group had lower bilateral amygdala GMV relative to TD youths. Youths in the DBDCU+ group had lower bilateral hippocampal GMV, and youths in the DBD-only group had lower left hippocampal GMV relative to TD youths. Youths in the DBDCU+ group evidenced lower left insula GMV relative to TD youths. Finally, youths in the DBD-only group had lower left superior frontal gyrus and lower right caudal anterior cingulate cortex GMVs relative to TD youths. There was no moderation of associations between GMV and group membership by sex. ConclusionsOur findings implicate structural aberrations in both the amygdala and hippocampus in the etiology of DBDs, with minimal evidence for differences based on the presence or absence of CU traits.

How the Social Climate at School is Associated with Students’ Amygdala Gray Matter Volume

How the Social Climate at School is Associated with Students’ Amygdala Gray Matter Volume

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume – with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.

No evidence for morphometric associations of the amygdala and hippocampus with the five-factor model personality traits in relatively healthy young adults.

Despite the important functional role of the amygdala and hippocampus in socioemotional functioning, there have been limited adequately powered studies testing how the structure of these regions relates to putatively relevant personality traits such as neuroticism. Additionally, recent advances in MRI analysis methods provide unprecedented accuracy in measuring these structures and enable segmentation into their substructures. Using the new FreeSurfer amygdala and hippocampus segmentation pipelines with the full Human Connectome Project sample (N = 1105), the current study investigated whether the morphometry of these structures is associated with the five-factor model (FFM) personality traits in a sample of relatively healthy young adults. Drawing from prior findings, the following hypotheses were tested: 1) amygdala and hippocampus gray matter volume would be associated with neuroticism, 2) CA2/3 and dentate gyrus would account for the relationship of the hippocampus with neuroticism, and 3) amygdala gray matter volume would be inversely associated with extraversion. Exploratory analyses were conducted investigating potential associations between all of the FFM traits and the structure of the hippocampus and amygdala and their subregions. Despite some previous positive findings of whole amygdala and hippocampus with personality traits and related psychopathology (e.g., depression), the current results indicated no relationships between the any of the brain regions and the FFM personality traits. Given the large sample and utilization of sophisticated analytic methodology, the current study suggests no association of amygdala and hippocampus morphometry with major domains of personality.

Low left amygdala volume is associated with a longer duration of unipolar depression.

The amygdala plays a crucial role in the pathogenesis of major depressive disorder (MDD). While robust findings support a negative impact of illness duration on hippocampal volume in MDD, morphometric studies of the amygdala have yielded inhomogeneous results. Considering the methodical problems of automatic segmentation methods, a standardized segmentation protocol with proven inter- and intra-rater reliability was employed using high-resolution magnetic resonance imaging. To identify the effect of MDD on amygdala morphometry, 23 unipolar depressed patients who responded to antidepressant medication and 30 age-matched healthy controls (HC) were enrolled. First, gray matter volumes (GMV) of the bilateral amygdala were delineated manually in 3D by three blinded experts using the MultiTracer. The whole brain GMV was determined by using voxel-based morphometry. Second, the differences of the whole brain and the bilateral amygdala GMV values between MDD and HC were calculated with t-statistics. The GMV of the whole brain and the amygdala did not differ between HC and MDD patients. Third, MDD characteristics were correlated with amygdala GMV. Within the normal range, the left amygdala GMV was larger in patients with later onset and smaller in cases of prolonged depression. In line with prior reports of depressed patients responding to antidepressant treatment, amygdala GMV was negatively related to illness duration, suggesting volume loss with disease progression. It remains unclear as to whether the association between illness duration and GMV reduced left amygdala volume indicates a neurotoxic effect of prolonged MDD or is rather a negative predictor of chronic depression.

Amygdala and regional volumes in treatment-resistantversusnontreatment-resistant depression patients

Although treatment-resistant and nontreatment-resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. A whole-brain voxel-based morphometry (VBM) analysis of regional volumes was performed in 125 participants' magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment-resistant depression (TRD), 40 nontreatment-resistant depression (non-TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. TRD patients had higher gray matter (GM) volume in the left and right amygdala than non-TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non-TRD bipolar and non-TRD unipolar patients. An exploratory analysis showed that lithium-treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder

Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adaptable. Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2×2 (group×time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z=3.67, Family-Wise Error corrected p=0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1year after CBT.