Differences In Amygdala Volume Research Articles

Amygdala volumes and associations with socio-emotional competencies in preterm youth: cross-sectional and longitudinal data.

Socio-emotional difficulties often result from very preterm (VPT) birth. The amygdala's developmental trajectory, including its nuclei, has been recognized as a significant factor in observed difficulties. This study aims to assess the relationship between amygdala volume and socio-emotional competencies in VPT children and adolescents. Socio-emotional competencies were assessed, and amygdala volumes, including subnuclei, were extracted automatically from structural scans in a cross-sectional cohort of VPT (n = 75) and full-term (FT, n = 41) aged 6-14 years. Group differences in amygdala volumes were assessed using ANCOVA, and associations with socio-emotional competencies were studied using partial least squares correlation (PLSC). In a VPT subgroup, additional longitudinal data with amygdala volumes at term-equivalent age (TEA) were manually extracted, growth rates calculated, and associations with school-age socio-emotional competencies investigated using PLSC. Using cross-sectional data at school-age, amygdala volumes displayed comparable developmental patterns between the VPT and the FT groups. Greater volumes were associated with more emotional regulation difficulties in VPT and lower affect recognition competencies in FT. In the longitudinal VPT subgroup, no significant associations were found between amygdala volume trajectory and socio-emotional competencies. Although our findings suggest typical amygdala development after VPT birth, further research is necessary to elucidate the developmental trajectory of amygdala and the role of resilience factors. In our cohort, amygdala volumes, including subnuclei, displayed comparable developmental trajectories between the very preterm and the full-term groups. Higher amygdala volumes at school-age were associated with higher emotional regulation difficulties in the very-preterm born group, and with lower affect recognition abilities in full-term born children and adolescents. In a subgroup of very-preterm children and adolescents followed from birth to school-age, no significant associations were found between amygdala volumes at term-equivalent age and socio-emotional competencies at school-age.

Abnormal amygdala volume moderates parenting and anxiety symptoms in children and adolescents with anxiety disorder

Anxiety disorders (AD) usually onset in childhood or adolescence and are related to brain development and early experiences during this period. As the hub of the fear circuit, the amygdala plays a crucial role in the development of emotional processing, and abnormalities in its structure and function are associated with anxiety disorders. We aim to uncover the amygdala volume's moderation between parenting and anxiety severity in children and adolescents with AD. 129 children and adolescents with anxiety and 135 age- and sex-matched Health controls (HC) using the publicly available Healthy Brain Network (HBN) dataset were included. Anxiety severity was measured using the Screen for Child Anxiety Related Disorders Self-report (SCARED-SR) and parenting was measured using the Alabama Parenting Questionnaire Self-Report (APQ-SR). We investigated age-related differences in amygdala volume in children and adolescents with anxiety disorders. Further, we examined the role of amygdala volume in moderating the association between parental involvement, particularly the maternal involvement, and anxiety symptoms in this population. We found larger bilateral amygdala in the AD group compared with the HC among the age range of 7–12. And increases in amygdala volume tended to negatively moderate the linear relationships between maternal involvement and anxiety symptoms in the AD group. These findings provide new evidence of abnormal brain alteration in children and adolescents with anxiety and may reflect proactive adaptations of adolescent brain development.

Amygdala enlargement in temporal lobe epilepsy: Histopathology and surgical outcomes.

Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.

Amygdala Volume is Associated with ADHD Risk and Severity Beyond Comorbidities in Adolescents: Clinical Testing of Brain Chart Reference Standards

Understanding atypicalities in ADHD brain correlates is a step towards better understanding ADHD etiology. Efforts to map atypicalities at the level of brain structure have been hindered by the absence of normative reference standards. Recent publication of brain charts allows for assessment of individual variation relative to age- and sex-adjusted reference standards and thus estimation not only of case-control differences but also of intraindividual prediction. Methods. Aim was to examine, whether brain charts can be applied in a sample of adolescents (N = 140, 38% female) to determine whether atypical brain subcortical and total volumes are associated with ADHD at-risk status and severity of parent-rated symptoms, accounting for self-rated anxiety and depression, and parent-rated oppositional defiant disorder (ODD) as well as motion. Results. Smaller bilateral amygdala volume was associated with ADHD at-risk status, beyond effects of comorbidities and motion, and smaller bilateral amygdala volume was associated with inattention and hyperactivity/impulsivity, beyond effects of comorbidities except for ODD symptoms, and motion. Conclusions. Individual differences in amygdala volume meaningfully add to estimating ADHD risk and severity. Conceptually, amygdalar involvement is consistent with behavioral and functional imaging data on atypical reinforcement sensitivity as a marker of ADHD-related risk. Methodologically, results show that brain chart reference standards can be applied to address clinically informative, focused and specific questions.

Alterations of amygdala volume and functional connectivity in migraine patients comorbid with and without depression.

The comorbid relationship between migraine and depression has been well recognized, but its underlying pathophysiology is unclear. Here, we aimed to explore the structural changes of the amygdala and the abnormal functional connectivity of the centromedial amygdala (CMA) in migraineurs with depression. High-resolution T1-weighted and functional magnetic resonance images were acquired from 22 episodic migraineurs with comorbid depression (EMwD), 21 episodic migraineurs without depression (EM), and 17 healthy controls (HC). Voxel-based morphometry and resting-state functional connectivity (rsFC) were applied to examine the intergroup differences in amygdala volume. The bilateral amygdala volume was increased in the EMwD and EM groups compared with the HC group, but there were no differences between the EMwD and EM groups. The right CMA exhibited decreased rsFC in the left dorsolateral prefrontal cortex (DLPFC) in the EMwD group compared with the EM group, while rsFC increased between the CMA and the contralateral DLPFC in the EM group compared with the HC group. In addition, the EM group showed decreased rsFC between the left CMA and the left pallidum compared with the HC group. Enlarged amygdala is an imaging feature of EM and EMwD. The inconsistency of rsFC between CMA and DLPFC between migraineurs with and without depression might indicate that decreased rsFC between CMA and DLPFC is a neuropathologic marker for the comorbidity of migraine and depression. The core regions might be a potential intervention target for the treatment of EMwD in the future.

Maternal perinatal depression and child brain structure at 2-3 years in a South African birth cohort study

Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2–3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6–10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = −74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = −78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.

The Effects of Brain Magnetic Resonance Imaging Indices in the Association of Olfactory Identification and Cognition in Chinese Older Adults.

BackgroundOlfactory identification dysfunction frequently occurs in individuals with cognitive decline; however, a pathological mechanism linking the two has not been discovered. We aimed to study the association between olfactory identification and cognitive function, and determine the effects of brain regions atrophy therein.MethodsA total of 645 individuals (57.5% were female) from the Taizhou Imaging Study, who underwent cognitive and olfactory identification measurements, were included. A subsample of participants underwent brain magnetic resonance imaging (n = 622). Cognition was assessed with a neuropsychological battery. Olfactory identification was measured using a 12-item Sniffin’ Sticks test. Beta and logistic regressions were used to elucidate the association between olfactory identification and cognition, and the effects of brain regions atrophy in this association.ResultsDementia was diagnosed in 41 (6.4%) individuals (mean age = 64.8 years), and mild cognitive impairment (MCI) in 157 (24.3%) individuals (mean age = 64.4 years). Olfactory identification was associated with MMSE and MoCA (both P < 0.001) and specific cognitive domains (memory, executive function, visuospatial function, and language; all P < 0.05). Higher olfactory identification was associated with lower likelihood of MCI and dementia (P < 0.05). The amygdala volume was significantly related to olfactory identification, MMSE, MoCA, and language, and could attenuate the association between olfactory identification and cognitive function.ConclusionThe association between olfactory identification and cognition can be partly attributable to differences in amygdala volume, suggesting that the amygdala could be a shared neural substrate that links olfactory identification and cognitive function. Limitations of this study include that all these results were based on a cross-sectional study.

Anxiety–Amygdala Associations: Novel Insights From the First Longitudinal Study of Autistic Youth With Distinct Anxiety

In the current issue of Biological Psychiatry, Andrews et al. ( 1 Andrews D.S. Aksman L. Kerns C.M. Lee J.K. Winder-Patel B.M. Harvey D.J. et al. Association of amygdala development with different forms of anxiety in autism spectrum disorder. Biol Psychiatry. 2022; 91: 977-987 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar ) offer novel and important insights into how the amygdala is associated with anxiety in autism. Despite much theoretical rationale for a role of the amygdala in anxiety in individuals diagnosed with autism spectrum disorder (ASD) ( 1 Andrews D.S. Aksman L. Kerns C.M. Lee J.K. Winder-Patel B.M. Harvey D.J. et al. Association of amygdala development with different forms of anxiety in autism spectrum disorder. Biol Psychiatry. 2022; 91: 977-987 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar , 2 Yarger H.A. Nordahl C.W. Redcay E. Examining associations between amygdala volumes and anxiety symptoms in autism spectrum disorder [published online ahead of print Oct 21]. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021; PubMed Google Scholar , 3 Herrington J.D. Maddox B.B. Kerns C.M. Rump K. Worley J.A. Bush J.C. et al. Amygdala volume differences in autism spectrum disorder are related to anxiety. J Autism Dev Disord. 2017; 47: 3682-3691 Crossref PubMed Scopus (41) Google Scholar , 4 Juranek J. Filipek P.A. Berenji G.R. Modahl C. Osann K. Spence M.A. Association between amygdala volume and anxiety level: Magnetic resonance imaging (MRI) study in autistic children. J Child Neurol. 2006; 21: 1051-1058 Crossref PubMed Scopus (94) Google Scholar , 5 Yarger H.A. Redcay E. A conceptual model of risk and protective factors associated with internalizing symptoms in autism spectrum disorder: A scoping review, synthesis, and call for more research. Dev Psychopathol. 2020; 32: 1254-1272 Crossref PubMed Scopus (5) Google Scholar ), previous empirical studies have yielded mixed results on the magnitude (or presence), direction, and laterality of the association between anxiety and amygdala volumes. Measurement of anxiety has varied across studies, with differing assessment tools, as well as the use of dimensional versus categorical approaches to evaluating the presence of anxiety. In addition, recent research ( 2 Yarger H.A. Nordahl C.W. Redcay E. Examining associations between amygdala volumes and anxiety symptoms in autism spectrum disorder [published online ahead of print Oct 21]. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021; PubMed Google Scholar , 6 Kerns C.M. Winder-Patel B. Iosif A.M. Nordahl C.W. Heath B. Solomon M. et al. Clinically significant anxiety in children with autism spectrum disorder and varied intellectual functioning. J Clin Child Adolesc Psychol. 2021; 50: 780-795 Crossref PubMed Scopus (32) Google Scholar ) has argued that traditional, “DSM” anxiety disorders as operationalized in the DSM-5 ( 7 American Psychiatric A. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association, Washington, D.C.2013 Crossref Google Scholar ) (e.g., generalized anxiety disorder, separation anxiety, specific phobia, and social phobia—referred to as “DSM anxiety” in the remainder of the commentary) do not capture all types of anxiety that individuals with ASD experience ( 6 Kerns C.M. Winder-Patel B. Iosif A.M. Nordahl C.W. Heath B. Solomon M. et al. Clinically significant anxiety in children with autism spectrum disorder and varied intellectual functioning. J Clin Child Adolesc Psychol. 2021; 50: 780-795 Crossref PubMed Scopus (32) Google Scholar ). Instead, researchers have posited that individuals with ASD experience “distinct anxiety,” which includes anxieties such as idiosyncratic fears (e.g., fears of toilets), social anxiety without the fear of evaluation by others (required criterion for diagnosis of DSM social anxiety), or fear of change. The diverse methods used to assess anxiety and the failure to evaluate the presence of anxiety experienced specifically by those with ASD (i.e., distinct anxiety) may be contributing to these mixed results. Andrews et al. ( 1 Andrews D.S. Aksman L. Kerns C.M. Lee J.K. Winder-Patel B.M. Harvey D.J. et al. Association of amygdala development with different forms of anxiety in autism spectrum disorder. Biol Psychiatry. 2022; 91: 977-987 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar ) address these limitations in the first published study to investigate and report associations between amygdala volumes and DSM anxiety and distinct anxiety in autistic youth and, notably, is the first to look at developmental trajectories in amygdala growth over time with relation to distinct and DSM anxiety in autistic youth. SEE CORRESPONDING ARTICLE ON PAGE 977 SEE CORRESPONDING ARTICLE ON PAGE 977 Association of Amygdala Development With Different Forms of Anxiety in Autism Spectrum DisorderBiological PsychiatryVol. 91Issue 11PreviewThe amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism. Full-Text PDF

Individual differences in amygdala volumes predict changes in functional connectivity between subcortical and cognitive control networks throughout adolescence

Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.

Charting the human amygdala development across childhood and adolescence: Manual and automatic segmentation

The developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the ‘gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (http://deepneuro.bnu.edu.cn/?p=163). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves between manual tracing and the automatic methods (except FSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate amygdala structure at school age, calling for next generation tools.

Parsing differences in amygdala volume among individuals with and without social and generalized anxiety disorders across the lifespan

Structural differences in the amygdala (AMG) are implicated in anxiety and observed among individuals with generalized (GAD) and social anxiety (SAD) disorders. Findings have been mixed, perhaps because studies rarely examine differences between GAD and SAD, test comorbidity, or examine age-related differences. We tested AMG volume differences among a sample of adults and youth with/without SAD and GAD. Participants (N = 242; ages 7–60 years) completed an MRI scan, diagnostic interviews, and anxiety symptom measures. Groups were formed from diagnostic interviews: 1) Typically developing (TD; n = 91); 2) GAD (n = 53); 3) SAD (n = 35); and 4) comorbid SAD/GAD (n = 63). We used analysis of covariance with a bonferroni correction to examine group differences in AMG volume. The SAD and comorbid SAD/GAD groups exhibited increased bilateral AMG volume compared to the TD group. GAD and TD groups did not differ from each other in AMG size. The SAD, but not the comorbid SAD/GAD group, displayed greater right AMG size relative to the GAD group. SAD and comorbid SAD/GAD groups did not differ from the GAD group in left AMG volume. SAD and SAD/GAD groups did not exhibit different bilateral AMG size. Linear regression analyses demonstrated that greater social anxiety but not generalized anxiety symptom severity was associated with enlarged AMG volume. Age was not associated with AMG volume and nor did age moderate any group or symptom effects. Future longitudinal studies should examine whether larger AMG volume is a unique biomarker for SAD across the lifespan.

Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion-based subsegmentation and a high-risk design.

Amygdala abnormalities are widely documented in bipolar spectrum disorders (BSD). Amygdala volume typically is measured after BSD onset; thus, it is not known whether amygdala abnormalities predict BSD risk or relate to the disorder. Additionally, past literature often treated the amygdala as a homogeneous structure, and did not consider its distinct subnuclei and their differential connectivity to other brain regions. To address these issues, we used a behavioral high‐risk design and diffusion‐based subsegmentation to examine amygdala subnuclei among medication‐free individuals with, and at risk for, BSD. The behavioral high‐risk design (N = 114) included low‐risk (N = 37), high‐risk (N = 47), and BSD groups (N = 30). Diffusion‐based subsegmentation of the amygdala was conducted to determine whether amygdala volume differences related to particular subnuclei. Individuals with a BSD diagnosis showed greater whole, bilateral amygdala volume compared to Low‐Risk individuals. Examination of subnuclei revealed that the BSD group had larger volumes compared to the High‐Risk group in both the left medial and central subnuclei, and showed larger volume in the right lateral subnucleus compared to the Low‐Risk group. Within the BSD group, specific amygdala subnuclei volumes related to time since first episode onset and number of lifetime episodes. Taken together, whole amygdala volume analyses replicated past findings of enlargement in BSD, but did not detect abnormalities in the high‐risk group. Examination of subnuclei volumes detected differences in volume between the high‐risk and BSD groups that were missed in the whole amygdala volume. Results have implications for understanding amygdala abnormalities among individuals with, and at risk for, a BSD.

Effects of Childhood Adversity on the Volumes of the Amygdala Subnuclei and Hippocampal Subfields in Major Depressive Disorder: High-Field Magnetic Resonance Imaging Study

Reductions in total hippocampus volume have frequently been reported in Magnetic Resonance Imaging (MRI) studies in major depressive disorder (MDD), while total amygdala volume differences have been inconsistent. Childhood maltreatment is an important risk factor for MDD in adulthood and may affect hippocampus and amygdala volumes. Here we compared the volumes of amygdala subnuclei and hippocampal subfields in MDD and controls and examined their relationship with childhood maltreatment.

Abnormal development pattern of the amygdala and hippocampus from childhood to adulthood with autism

Using magnetic resonance imaging to determine neuropathology in autism spectrum disorders, we report findings on the volume of the amygdala and hippocampus in autistic children. The volumes of amygdala, hippocampus and total brain were obtained by volbrain and their volumes were measured in young people (6.5–27.0 years of age) that comes from ABIDE dataset. Although there was no significant difference in total brain capacity between groups, autistic children (6.5–12.0 years of age) had larger right and left absolute and relative amygdala volumes than the control group. There was no difference in amygdala volume between adolescence (13–19 years old) and adults (20–27 years old). Interestingly, the volume of the amygdala in typical developing children increased significantly from 6.5 to 27 years of age. Thus, amygdala in children with autism was initially small, but no age-related increases were observed in normal developing children. The right absolute hippocampal volume of autistic patients was also larger than that of normal adults, but not after controlling the total brain volume. These cross-sectional findings suggest that abnormal patterns of hippocampal and amygdala development continue into adolescence in autistic patients.

Pain Hypersensitivity is Associated with Increased Amygdala Volume and c-Fos Immunoreactivity in Anophthalmic Mice.

It is well established that early blindness results in brain plasticity and behavioral changes in both humans and animals. However, only a few studies have examined the effects of blindness on pain perception. In these studies, pain hypersensitivity was reported in early, but not late, blind humans. The underlying mechanisms remain unclear, but considering its key role in pain perception and modulation, the amygdala may contribute to this pain hypersensitivity. The first aim of this study was to develop an animal model of early blindness to examine the effects of blindness on pain perception. A mouse cross was therefore developed (ZRDBA mice), in which half of the animals are born sighted and half are born anophthalmic, allowing comparisons between blind and sighted mice with the same genetic background. The second aim of the present study was to examine mechanical and thermal pain thresholds as well as pain behaviors and pain-related c-Fos immunoreactivity induced by the formalin test in the amygdalas of blind and sighted mice. Group differences in amygdala volume were also assessed histologically. Blind mice exhibited lower mechanical and thermal pain thresholds and more pain behaviors during the acute phase of the formalin test, compared with sighted mice. Moreover, pain hypersensitivity during the formalin test was associated with increased c-Fos immunoreactivity in the amygdala. Furthermore, amygdala volume was larger bilaterally in blind compared with sighted mice. These results indicate that congenitally blind mice show pain hypersensitivity like early blind individuals and suggest that this is due in part to plasticity in the amygdala.

Neuroimaging Phenotypes Implicated For GWAS of PTSD Through The PGC And ENIGMA Worldwide Consortia

Here, we present the results of a large-scale neuroimaging-genetics consortium study on PTSD conducted by the Psychiatric Genomic Consortium (PGC) and Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) PTSD Working Group. Hippocampus, hippocampal subfield, and amygdala volume differences are strongly implicated in PTSD, but findings have not always been consistent. Our goal was to characterize these neuroimaging phenotypes for subsequent GWAS. We analyzed neuroimaging and clinical data from 1,868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle) in n=1,868. We assessed 11 hippocampal subfield volumes bilaterally (cornu ammonis 1 (CA1), CA3, CA4, dentate gyrus (DG), fimbria, fissure, hippocampus-amygdala transition area (HATA), molecular layer, parasubiculum, presubiculum, subiculum, and tail) in n=1,398. We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium to assess groups with current PTSD, lifetime PTSD, and current PTSD in participants exposed to childhood trauma. We found that hippocampus and amygdala were smaller in subjects with current PTSD compared to trauma-exposed controls (hippocampus, Cohen’s D=-0.17, p=0.00054; amygdala, D=-0.11, p=0.025). Even though the female-only analysis contained approximately 1,100 fewer subjects than the full sample, the hippocampal results were more significant in females (p=0.00012), and Cohen’s D estimates indicated a stronger effect than in the full sample (D=-0.31 vs. D=-0.17). Current PTSD was associated with smaller subfield volume in the right hippocampal tail (p=0.002, D=0.26) and larger volumes in the right CA1 (p=0.002, D=0.26) in individuals exposed to at least one traumatic event in childhood. Our study is not subject to the biases of meta-analyses of published data, and represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma. The association of PTSD and abnormalities in the CA1 are consistent with its role in contextual fear memory, which is a widely accepted behavioral model for PTSD. The hippocampus and amygdala are crucial for fear processing, episodic and contextual learning and memory, processes related to PTSD symptomatology. This meta-analysis firmly establishes the importance of the hippocampus and amygdala in PTSD, which by itself represents a substantial step forward in identifying the most plausible neuroimaging phenotypes for a GWAS of PTSD.

Amygdala Volume Differences in Autism Spectrum Disorder Are Related to Anxiety.

Recent studies suggest that longstanding findings of abnormal amygdala morphology in ASD may be related to symptoms of anxiety. To test this hypothesis, fifty-three children with ASD (mean age = 11.9) underwent structural MRI and were divided into subgroups to compare those with at least one anxiety disorder diagnosis (n = 29) to those without (n = 24) and to a typically developing control group (TDC; n = 37). Groups were matched on age and intellectual level. The ASD and anxiety group showed decreased right amygdala volume (controlled for total brain volume) relative to ASD without anxiety (p = .04) and TDCs (p = .068). Results suggest that youth with ASD and co-occurring anxiety have a distinct neurodevelopmental trajectory.

Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study

ObjectiveIt is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Materials and methodsNineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. ResultsThere was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm3; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10×−4 number of neurons/μm2; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. ConclusionsNeuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala.

Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples.

BackgroundStudies of psychiatric populations have reported associations between childhood adversity and volumes of stress-related brain structures. This meta-analysis investigated these associations in non-clinical samples and therefore independent of the effects of severe mental health difficulties and their treatment.MethodsThe MEDLINE database was searched for magnetic resonance imaging studies measuring brain structure in adults with and without childhood adversity. Fifteen eligible papers (1781 participants) reporting hippocampal volumes and/or amygdala volumes were pooled using a random effects meta-analysis.ResultsThose with childhood adversity had lower hippocampus volumes (hedges g = − 0.15, p = 0.010). Controlling for gender, this difference became less evident (hedges g = − 0.12, p = 0.124). This association differed depending on whether studies included participants with some psychopathology, though this may be due to differences in the type of adversity these studies examined. There was no strong evidence of any differences in amygdala volume.DiscussionChildhood adversity may have only a modest impact on stress-related brain structures in those without significant mental health difficulties.

Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume

The amygdala plays a key role in many affective behaviors and psychiatric disorders that differ between men and women. To test whether human amygdala volume (AV) differs reliably between the sexes, we performed a systematic review and meta-analysis of AVs reported in MRI studies of age-matched healthy male and female groups. Using four search strategies, we identified 46 total studies (58 matched samples) from which we extracted effect sizes for the sex difference in AV. All data were converted to Hedges g values and pooled effect sizes were calculated using a random-effects model. Each dataset was further meta-regressed against study year and average participant age. We found that uncorrected amygdala volume is about 10% larger in males, with pooled sex difference effect sizes of g=0.581 for right amygdala (κ=28, n=2022), 0.666 for left amygdala (κ=28, n=2006), and 0.876 for bilateral amygdala (κ=16, n=1585) volumes (all p values < 0.001). However, this difference is comparable to the sex differences in intracranial volume (ICV; g=1.186, p<.001, 11.9% larger in males, κ=11) and total brain volume (TBV; g=1.278, p<0.001, 11.5% larger in males, κ=15) reported in subsets of the same studies, suggesting the sex difference in AV is a product of larger brain size in males. Among studies reporting AVs normalized for ICV or TBV, sex difference effect sizes were small and not statistically significant: g=0.171 for the right amygdala (p=0.206, κ=13, n=1560); 0.233 for the left amygdala (p=0.092, κ=12, n=1512); and 0.257 for bilateral volume (p=0.131, κ=5, n=1629). These values correspond to less than 0.1% larger corrected right AV and 2.5% larger corrected left AV in males compared to females. In summary, AV is not selectively enhanced in human males, as often claimed. Although we cannot rule out subtle male-female group differences, it is not accurate to refer to the human amygdala as “sexually dimorphic.”