Smaller Amygdala Volumes Research Articles

Subclinical post-traumatic stress symptomology and brain structure in youth with chronic headaches

Background/aimsPost-traumatic stress symptoms (PTSS) and chronic pain often co-occur at high rates in youth. PTSS may alter brain structure thereby contributing to headache chronicity. This study examined whether PTSS and altered limbic circuitry were associated with headache frequency in youth. MethodsThirty youth aged 10–18 years with chronic headaches and 30 age- and sex-matched controls underwent a 3T MRI scan. Volumes of the hippocampus and amygdala were obtained from T1-weighted images. Mean fractional anisotropy (FA, an index of white matter structure) axial and radial diffusivity values of the cingulum and uncinate fasciculus were extracted from diffusion-weighted images. Youth reported on their headaches daily, for one-month, and self-reported pubertal status, emotion regulation, adverse childhood experiences (ACEs) and PTSS using validated measures. Volumes of the hippocampus and amygdala and diffusivity values of the cingulum and uncinate were compared between patients and controls. Hierarchical linear regressions were used to examine the association between PTSS, subcortical volumes and/or diffusivity values and headache frequency. ResultsMean FA values of the cingulum were higher in patients compared to controls (P = 0.02, Cohen’s d = 0.69). Greater PTSS (P = 0.04), smaller amygdala volumes (P = 0.01) and lower FA of the cingulum (P = 0.04) were associated with greater headache frequency, after accounting for age, puberty, pain duration, emotion regulation, and ACEs (Adjusted R2 ≥ 0.15). Headache frequency was associated with increases in radial diffusivity (P = 0.002, Adjusted R2 = 0.59), as opposed to axial diffusivity (n.s.). ConclusionsPTSS, smaller amygdalar volume, and poorer cingulum structural connectivity were associated with headache frequency in youth, and may underlie headache chronicity.

Childhood trauma and amygdala nuclei volumes in youth at risk for mental illness.

Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth. Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure. Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment. The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.

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.

Smaller left hippocampal subfield CA1 volume is associated with reported childhood physical and/or sexual abuse in major depression: A pilot study

BackgroundSmaller hippocampal volumes are reported in adults with major depressive disorder (MDD) and in reported childhood abuse. The hippocampus is a complex structure with distinct functional subfields. We sought to examine the effect of MDD diagnosis and childhood abuse on hippocampal subfields. MethodsForty-one MDD participants (17 reported abuse and 24 did not) and 46 healthy volunteers (HV) (2 reported abuse) underwent T1- weighted structural magnetic resonance imaging (MRI) and clinical characterization in a retrospective design. A subfield segmentation program was used to measure the whole and subfield hippocampal volumes. Linear mixed-effects models were fitted for group comparisons. ResultsNo main effect of diagnosis interaction effect between diagnosis and subfield region was observed. However, a comparison of abused MDD vs. HVs showed a group by region interaction. A significant interaction between childhood abuse and region was observed. Effects were confined to the left side of the brain, and post hoc, exploratory region-specific tests indicated smaller left CA1 volume in abused MDD compared with non-abused MDD. In addition, smaller amygdala volume was found in all MDD compared with HVs. LimitationsWe did not have a sample of healthy volunteers with reported childhood abuse. ConclusionsThe diagnosis of pure MDD may not be sufficient to exert effects on hippocampal volumes, indicating the importance of taking into account childhood trauma in studies on psychopathological mechanisms. Left CA1 might be the hippocampal subfield most relevant to reported childhood abuse. Smaller amygdala volume may be related to MDD diagnosis independent of childhood abuse.

AMYLOID-β IS ASSOCIATED WITH THINNER CORTEX IN COGNITIVELY NORMAL OLDEST-OLD INDIVIDUALS

Background: Previous autopsy studies have demonstrated a high prevalence of widespread Alzheimer's disease (AD) pathology in individuals without dementia at high ages (>85y), which has raised doubts on the relationship of amyloid-β (Aβ) with dementia. In younger elderly (60-80y) without cognitive impairment, Aβ accumulation has been associated with subtle cognitive changes and cortical thinning. However, it remains unclear whether Aβ accumulation in oldest-old individuals with normal cognition is associated with changes in brain structure and cognitive functioning. We studied this using data from the EMIF-AD 90+ study. Methods: We selected 61 cognitively normal (CN) individuals from the EMIF-AD 90+ study, with available amyloid positron emission tomography (PET), and structural magnetic resonance imaging (MRI). Visual rating of the amyloid PET scan was used to classify the subjects as CN Aβ- (n=34) or CN Aβ+ (n=27). Cognitive performance on the Logical Delayed Memory test and MMSE were compared between groups. Subcortical volumes and cortical thickness measures in each ROI of FreeSurfer's Desikan-Killany atlas were calculated from 3T 3D-T1 images, and compared between groups using general linear models with Bonferroni correction and adjusted for age, and sex. Results: The individuals had a mean age of 93 years (range 88-102y), and 44% were rated as Aβ+. CN Aβ+ individuals had lower, but non-significant, memory scores and worse MMSE scores compared to the Aβ- group (Table1). Moreover, compared to the Aβ- group, CN individuals with Aβ+ showed thinner parahippocampal, rostral anterior cingulate, medial orbitofrontal, fusiform, superior temporal cortex, and smaller amygdala volume (pBonferroni

On a continuum to anxiety disorders: Adolescents at parental risk for anxiety show smaller rostral anterior cingulate cortex and insula thickness

BackgroundHaving a parent with an anxiety disorder increases the risk of anxiety symptoms and anxiety disorders during the lifespan. Moreover, childhood and adolescence anxiety disorders and symptoms have been linked to a range of brain structure abnormalities. However, to date, no study has investigated brain anatomy in adolescents at high risk based on parental anxiety disorders and in adolescents with an anxiety disorder but without any treatment or therapy. MethodsAnatomical images from magnetic resonance imaging of 68 adolescents with anxiety disorders without any treatment (N = 20), at risk for anxiety because of their parents’ anxiety disorders (N = 21), and comparison youths (N = 27), were analyzed using Freesurfer. ResultsCompared to comparison group, smaller cortical thickness of the rostral anterior cingulate cortex and of the insula was observed in anxious and at-risk groups; smaller amygdala volume was observed in the anxious group only. LimitationsThe age range studied is large (10 to 17 years old). Moreover, this study is cross-sectional. Since adolescence is one of the biggest periods of cerebral reorganization, longitudinal follow-up of these youths would be necessary. ConclusionsSmaller rostral anterior cingulate cortex and insula cortical thickness appear to be cerebral markers of the risk of developing an anxiety disorder in adolescence. The reduction of the amygdala volume seems to be linked to the onset of the disorder.

Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery

BackgroundSurgery or multiple procedural interventions in extremely preterm neonates influence neurodevelopmental outcome and may be associated with long-term changes in somatosensory function or pain response. MethodsThis observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102, 60% female) and term-born controls (TC; n=48) aged 18–20 yr from the UK EPICure cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation included: quantitative sensory testing (thenar eminence, chest wall); clinical pain history; questionnaires (intelligence quotient; pain catastrophising; anxiety); and structural brain imaging. ResultsReduced thermal threshold sensitivity in EP vs TC participants persisted at age 18–20 yr. Sex-dependent effects varied with stimulus intensity and were enhanced by neonatal surgery, with reduced threshold sensitivity in EP surgery males but increased sensitivity to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent differences in thermal sensitivity correlated with smaller amygdala volume (P<0.05) but not current intelligence quotient. While generalised decreased sensitivity encompassed mechanical and thermal modalities in EP surgery males, a mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal scars in males and females. More EP participants reported moderate–severe recurrent pain (22/101 vs 4/48; χ2=0.04) and increased pain intensity correlated with higher anxiety and pain catastrophising. ConclusionsAfter preterm birth and neonatal surgery, different patterns of generalised and local scar-related alterations in somatosensory function persist into early adulthood. Sex-dependent changes in generalised sensitivity may reflect central modulation by affective circuits. Early life experience and sex/gender should be considered when evaluating somatosensory function, pain experience, or future chronic pain risk.

Smaller amygdala volume and increased neuroticism predict anxiety symptoms in healthy subjects: A volumetric approach using manual tracing

Volume reductions in the amygdala (AMY) have been found in patients with anxiety disorders, but findings are mixed in subclinical participants with high trait anxiety scores, in whom both reductions and increases in AMY volume have been identified. One potential reason for such discrepancies could be the employment of different methods to determine the AMY volume (i.e., manual tracing in psychiatric research vs. automated methods), in non-patient research. In addition to trait anxiety, smaller AMY volume has also been linked to neuroticism, a personality trait consistently linked to increased vulnerability to anxiety. However, it is not clear how AMY volume and neuroticism together may contribute to anxiety symptoms in healthy functioning. These issues were investigated in a sample of 46 healthy participants who underwent anatomical MRI scanning and completed questionnaires measuring trait anxiety and neuroticism. AMY volume was assessed using manual tracing, based on anatomical landmarks identified in each participant's anatomical image. First, smaller left AMY volume was linked to higher levels of neuroticism (p = .013) and trait anxiety (p = .024), which in turn were positively correlated with each other. Moreover, AMY volume had a significant indirect effect on trait anxiety through neuroticism (ab = − .009, 95% CI [− .019, − .002]). This effect was not bidirectional, as trait anxiety did not predict AMY volume through neuroticism. Collectively, these findings provide support for a brain-personality-symptom framework of understanding affective dysregulation, which may help inform the development of prevention and intervention paradigms targeting preservation of AMY volume and reduction of neuroticism, to protect against anxiety symptoms.

Abnormal relationships between local and global brain measures in subjects at clinical high risk for psychosis: a pilot study.

We examined whether abnormal volumes of several brain regions as well as their mutual associations that have been observed in patients with schizophrenia, are also present in individuals at clinical high-risk (CHR) for developing psychosis. 3T magnetic resonance imaging was acquired in 19 CHR and 20 age- and handedness-matched controls. Volumes were measured for the body and temporal horns of the lateral ventricles, hippocampus and amygdala as well as total brain, cortical gray matter, white matter, and subcortical gray matter volumes. Relationships between volumes as well as correlations between volumes and cognitive and clinical measures were explored. Ratios of lateral ventricular volume to total brain volume and temporal horn volume to total brain volume were calculated. Volumetric abnormalities were lateralized to the left hemisphere. Volumes of the left temporal horn, and marginally, of the body of the left lateral ventricle were larger, while left amygdala but not hippocampal volume was significantly smaller in CHR participants compared to controls. Total brain volume was also significantly smaller and the ratio of the temporal horn/total brain volume was significantly higher in CHR than in controls. White matter volume correlated positively with higher verbal fluency score while temporal horn volume correlated positively with a greater number of perseverative errors. Together with the finding of larger temporal horns and smaller amygdala volumes in the left hemisphere, these results indicate that the ratio of temporal horns volume to brain volume is abnormal in CHR compared to controls. These abnormalities present in CHR individuals may constitute the biological basis for at least some of the CHR syndrome.

HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes.

Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42.5) to study the relations with lifetime MDD diagnosis, cortisol awakening response, and dexamethasone suppression test (DST) levels (subsample N=1472) and hippocampal and amygdala volume (3T MR images; subsample N=225). Additionally, gene by childhood maltreatment (CM) interactions were investigated. Gene-wide significant results were found for dexamethasone suppression (CYP11A1, CYP17A1, POU1F1, AKR1D1), hippocampal volume (CYP17A1, CYP11A1, HSD3B2, PROP1, AVPRA1, SRD5A1), amygdala volume (POMC, CRH, HSD3B2), and lifetime MDD diagnosis (FKBP5 and CRH), all permutation p-values<0.05. Interactions with CM were found for several genes; the strongest interactions were found for NR3C2, where the minor allele of SNP rs17581262 was related to smaller hippocampal volume, smaller amygdala volume, higher DST levels, and higher odds of MDD diagnosis only in participants with CM. As hypothesized, several HPA-axis genes are associated with stress-related endophenotypes including cortisol response and reduced brain volumes. Furthermore, we found a pleiotropic interaction between CM and the mineralocorticoid receptor gene, suggesting that this gene plays an important moderating role in stress and stress-related disorders.

Socioeconomic Status, Amygdala Volume, and Internalizing Symptoms in Children and Adolescents

The associations among socioeconomic disadvantage, amygdala volume, and internalizing symptoms in children and adolescents are unclear and understudied in the extant literature. In this study, we examined associations between socioeconomic status (SES) and amygdala volume by age across childhood and adolescence to test whether socioeconomic disadvantage would be associated with larger amygdala volume at younger ages but with smaller amygdala volume at older ages. We then examined whether SES and amygdala volume were associated with children’s levels of anxiety and depression. Participants were 3- to 21-year-olds from the Pediatric Imaging, Neurocognition, and Genetics study (N = 1,196), which included structural magnetic resonance imaging. A subsample (n = 327; 7–21 years of age) completed self-report measures of anxiety and depression. Lower family income and parental education were significantly associated with smaller amygdala volume in adolescence (13–21 years) but not significantly associated with amygdala volume at younger ages (3–12 years). Lower parental education, but not family income, was significantly associated with higher levels of anxiety and depression, even after accounting for family history of anxiety/depression. Smaller amygdala volume was significantly associated with higher levels of depression, even after accounting for parental education and family history of anxiety/depression. These findings suggest that associations between SES and amygdala structure may vary by age. In addition, smaller amygdala volume may be linked with an increased risk for depression in children and adolescents.

Insular atrophy and diminished disgust reactivity.

Disgust is an emotion that helps us deal with potential contamination (Rozin & Fallon, 1987). It produces a distinctive facial expression (e.g., wrinkled nose) and a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Given the important role that the anterior insula plays in processing and integrating visceral information (Craig, 2009), it is likely to be centrally involved in disgust. Despite this, few studies have examined the link between insular degeneration and the experience, physiology, and expression of disgust. We studied a group that was heterogeneous in terms of insular damage: 84 patients with neurodegenerative diseases (i.e., frontotemporal dementia, corticobasal syndrome, progressive supranuclear palsy, Alzheimer's disease) and 29 controls. Subjects viewed films that elicit high levels of disgust and sadness. Emotional reactivity was assessed using self-report, peripheral physiology, and facial behavior. Regional brain volumes (insula, putamen, pallidum, caudate, and amygdala) were determined from structural MRIs using the FreeSurfer method. Results indicated that smaller insular volumes were associated with reduced disgust responding in self-report and physiological reactivity, but not in facial behavior. In terms of the specificity of these findings, insular volume did not predict sadness reactivity, and disgust reactivity was not predicted by putamen, pallidum, and caudate volumes (lower self-reported disgust was associated with smaller amygdala volume). These findings underscore the central role of the insula in the experience and physiology of disgust. (PsycINFO Database Record

Corticolimbic anatomical characteristics predetermine risk for chronic pain.

SEE TRACEY DOI101093/BRAIN/AWW147 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex-amygdala-accumbens, ventral medial prefrontal cortex-amygdala, and orbitofrontal cortex-amygdala-hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex-amygdala-accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors.

Amygdala Abnormalities in Adults With ADHD

Objective: The suggested neurobiological bases of ADHD focus on the amygdala as a center of emotions processing. Therefore, we hypothesize that patients with ADHD will show an irregular pattern of emotional-related activity of the amygdala region as well as some structural abnormalities. Method: Nine adult patients with ADHD and nine group-matched healthy volunteers were studied using a 1.5-T magnetic resonance imaging (MRI) scanner. Morphometric measurements were obtained manually, and they were later processed and compared. Absolute volumes of several structures and nuclei were calculated with FSL-FIRST. For the functional magnetic resonance examination, a set of two paradigms was prepared, using a block design, incorporating images of the International Affective Picture System (IAPS). The patients were unmedicated at the time of the MRI scan. Results: Negative correlation was found between the right amygdala volume and Barrat’s impulsivity scores (r = −.756, p = .018). The age of patients did not turn out to be a significant factor. No significantly higher activation areas were found in patients with unpleasant content images. For the left amygdala, an Region Of Interest (ROI)-based analysis showed moderately higher level of activation in the patients than in the controls with pleasant content images. Conclusion: Patients with ADHD tend to have smaller amygdala volumes. ADHD patients presented less activation in the area of the left frontal pole than the controls. There was no amygdala activation stated when presenting the pleasant images. Whereas bigger activation of the left amygdala was found in patients while presenting them unpleasant images. These results might suggest that lower emotional processing and less control of impulsivity is associated with dysfunctional amygdala in ADHD patients.

Amygdala volume is reduced in early course schizophrenia

Subcortical structural alterations have been implicated in the neuropathology of schizophrenia. Yet, the extent of anatomical alterations for subcortical structures across illness phases remains unknown. To assess this, magnetic resonance imaging (MRI) was used to examine volume differences of major subcortical structures: thalamus, nucleus accumbens, caudate, putamen, globus pallidus, amygdala and hippocampus. These differences were examined across four groups: (i) healthy comparison subjects (HCS, n=96); (ii) individuals at high risk (HR, n=21) for schizophrenia; (iii) early-course schizophrenia patients (EC-SCZ, n=28); and (iv) chronic schizophrenia patients (C-SCZ, n=20). Raw gray matter volumes and volumetric ratios (volume of specific structure/total gray matter volume) were extracted using automated segmentation tools. EC-SCZ group exhibited smaller bilateral amygdala volumetric ratios, compared to HCS and HR subjects. Findings did not change when corrected for age, level of education and medication use. Amygdala raw volumes did not differ among groups once adjusted for multiple comparisons, but the smaller amygdala volumetric ratio in EC-SCZ survived Bonferroni correction. Other structures were not different across the groups following Bonferroni correction. Smaller amygdala volumes during early illness course may reflect pathophysiologic changes specific to illness development, including disrupted salience processing and acute stress responses.

Neurodevelopmental correlates of proneness to guilt and shame in adolescence and early adulthood

Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15–25) completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain–behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame.

Correlation between amygdala volume and impulsivity in adults with attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurobiological disorder with childhood onset and persistence through adolescence and adulthood. ADHD patients frequently show exaggerated emotional responses. The amygdala plays an important role in emotion processing and in the activation of the frontal lobe. We hypothesised that smaller amygdala volumes in ADHD patients would be associated with less control of impulsivity and emotional instability. We studied nine adult patients with ADHD and nine group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements, which were later processed and compared. Significant negative correlation between the right amygdala volume and Barratt's impulsivity scores was observed (r=-0.756, p=0.018). No correlation was found between impulsivity scores and the volume of the left amygdala. Age was not found to be a contributor of the results. Smaller amygdala volumes have been observed in patients with ADHD. Our results suggest that greater emotional processing and less control of impulsivity are associated with smaller amygdala volumes in ADHD patients. Furthermore, the right amygdala would play a bigger role in impulsivity and behaviour control than the left amygdala. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed.

Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure.

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers’ pregnancy. A significant gender by externalizing behavior interaction revealed that males—but not females—with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction.

Amygdala Volume Changes in Posttraumatic Stress Disorder in a Large Case-Controlled Veterans Group

Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results. To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms. Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use. Durham Veterans Affairs Medical Center, which is located in proximity to major military bases. Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101). Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging. Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms. These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.

Impact of family history and depression on amygdala volume

Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study's purpose was to investigate family history's effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18–65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala without a family history of MDD. These effects had larger right amygdala than healthy controls without MDD family history. These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants, providing a rationale for the inconsistent results in MDD amygdala studies. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.