Left Amygdala Volume Research Articles

Prospective Longitudinal Analysis of Amygdala Volumes and Association with Mood and Memory Outcomes in Brain Tumor Patients

<h3>Purpose/Objective(s)</h3> The amygdala, a deep gray matter structure comprised of several nuclei with different functional connectivity, plays a key role in emotional processing and memory. We analyzed volume change of the amygdala and respective nuclei after brain RT using quantitative brain MRI, and association with mood and memory outcomes. <h3>Materials/Methods</h3> On a prospective trial, primary brain tumor patients (n=63) receiving fractionated RT underwent volumetric brain MRI and mood and memory testing (Beck Depression Inventory [BDI]; Beck Anxiety Inventory [BAI]; Brief Visuospatial Memory Test [BVMT] Total/Delayed Recall; Hopkins Verbal Learning Test [HVLT] Total/Delayed Recall) at baseline, 3, 6, and 12 months post RT. Amygdala and 8 nuclei (lateral [L], basal [B], central [C], medial [M], cortical [CO], accessory basal [AB], corticoamygdaloid transition [CA], paralaminar [PL]) were autosegmented bilaterally with validated methods. Tumor/surgical cavity/edema were censored. Nuclei with "higher order" cortical connectivity (CA, B, AB) were grouped. Linear mixed effects models assessed longitudinal change in amygdala volumes and association with dose, controlling for time and subject-specific effects. Amygdala volume change from baseline to 3 and 6 months was dichotomized by the median (low vs high atrophy). Wilcoxon rank sum tests assessed association between volume change and cognitive scores. <h3>Results</h3> We found atrophy over time in combined (p=0.001), right (p=0.001), and left (p<0.05) amygdala. Atrophy was noted bilaterally in CA (left p=0.023, right p=0.003), B (left p=0.024, right p=0.006) and AB nuclei (left p=0.016, right p=0.005), which are higher order nuclei. Higher RT dose was associated with atrophy in combined (p=0.037), left (0.011) and right (0.002) amygdala volumes. Left higher order nuclei atrophy was inversely associated with change in BDI scores from baseline to 6 months (p=0.025). Similarly, right higher order nuclei atrophy was inversely associated with change in BDI scores from baseline to 3 months (p=0.04). BAI scores at 6 months were higher in the low atrophy group for combined amygdala volume (p=0.038). Right higher order nuclei volume change from baseline to 3 months was associated with BVMT total (p=0.009) and delayed (p=0.007) recall at 6 months, and change in BVMT total (p=0.041) from baseline to 6 months; higher scores were found in patients with less volume loss. There were no significant associations on HVLT. <h3>Conclusion</h3> The amygdala and its subregions exhibit dose-dependent volume loss after brain RT. Certain subregions, particularly higher order nuclei with more cortical connectivity, are more susceptible. Atrophy within higher order nuclei appears associated with depression and anxiety symptoms, and decline in visuospatial but not verbal memory. Future cognitive-sparing efforts should consider this amygdala subregion.

Maternal adverse childhood experiences and infant subcortical brain volume

BackgroundA large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age. MethodsThe sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ). ResultsMultivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (β = -0.220, t(79) = -2.661, p = .009, R2= 0.494, and right (β = −0.167, t(79) = -2.043, p = .044, R2= 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (β = .232, p = .040, R2= 0.094, and β = −0.337, p = .022, R2= 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]). ConclusionsMaternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.

Treatment with morning blue light increases left amygdala volume and sleep duration among individuals with posttraumatic stress disorder.

BackgroundPosttraumatic stress disorder (PTSD) is associated with numerous cognitive, affective, and psychophysiological outcomes, including problems with sleep and circadian rhythms. We tested the effectiveness of a daily morning blue-light exposure treatment (BLT) versus a matched amber light treatment (ALT) to regulate sleep in individuals diagnosed with PTSD. Moreover, PTSD is also associated with reliable findings on structural neuroimaging scans, including reduced amygdala volumes and other differences in cortical gray matter volume (GMV) that may be indicative of underlying neurobehavioral dysfunctions. We examined the effect of BLT versus ALT on GMV and its association with sleep outcomes.MethodsSeventy-six individuals (25 male; 51 female) meeting DSM-V criteria for PTSD (Age = 31.45 years, SD = 8.83) completed sleep assessments and structural neuroimaging scans, followed by random assignment one of two light groups, including BLT (469 nm; n = 39) or placebo ALT (578 nm; n = 37) light therapy daily for 30-min over 6-weeks. Participants wore a wrist actigraph for the duration of the study. After treatment, participants returned to complete sleep assessments and a structural neuroimaging scan. Neuroimaging data were analyzed using the Computational Anatomy Toolbox (CAT12) and Voxel-Based Morphometry (VBM) modules within the Statistical Parametric Mapping (SPM12) software.ResultsThe BLT condition produced significant increases in total time in bed and total sleep time from actigraphy compared to the ALT condition, while ALT improved wake after sleep onset and sleep efficiency compared to BLT. Additionally, BLT led to an increase in left amygdala volume compared to ALT but did not affect hypothesized medial prefrontal regions. Finally, within group correlations showed that improvements in sleep quality and nightmare severity were correlated with increases in left amygdala volume over the course of treatment for the BLT group but not the ALT group.ConclusionIn individuals with PTSD, daily exposure to morning blue light treatment was associated with improvements in objective sleep duration and increased volume of the left amygdala compared to amber placebo light treatment, and changes in amygdala volume correlated with subjective improvement in sleep. These findings suggest that daily morning BLT may provide an important non-pharmacologic adjunctive approach for facilitating sleep and neurobehavioral recovery from PTSD.

Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer’s Disease in a Thai Population

Background: Mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are common in older adults. Much recent work has implicated the connection between the gut and the brain via bidirectional communication of the gastrointestinal tract and the central nervous system through biochemical signaling. Altered gut microbiota composition has shown controversial results based on geographic location, age, diet, physical activity, psychological status, underlying diseases, medication, and drug use. Objectives: This study aimed to investigate the relationships of gut microbiota with MCI and AD. Methods: 16S metagenome profiles from stool collection of participant groups (normal; n = 20, MCI; n = 12, AD; n = 20) were analyzed. The diagnosis of cognitive conditions was made by standard criteria consisting of clinical interviews, physical examinations, cognitive assessments, laboratory examinations, and neuroimaging by both structural neuroimaging and amyloid positron emission tomography scans. Correlations between medical factors with food frequency and the fecal microbiome were elucidated. Results: A significant difference at the operational taxonomic unit level was observed. The significantly higher abundance of bacteria in nondementia patients belonged to the Clostridiales order, including Clostridium sensu stricto 1 (p < 0.0001), Fusicatenibacter (p = 0.0007), Lachnospiraceae (p = 0.001), Agathobacter (p = 0.021), and Fecalibacterium (p < 0.0001). In contrast, Escherichia-Shigella (p = 0.0002), Bacteroides (p = 0.0014), Holdemanella (p < 0.0001), Romboutsia (p = 0.001), and Megamonas (p = 0.047) were the dominant genera in the AD group. Left and right hippocampus and right amygdala volumes were significantly decreased in the AD group (p < 0.001) and significantly correlated with the groups of bacteria that were significantly different between groups. Conclusion: There was a relationship between the composition of the gut microbiome and neurodegenerative disorders, including MCI and AD. Reduction of Clostridiaceae and increases in Enterobacteriaceae and Bacteroides were associated with persons with MCI and AD, consistent with previous studies. The altered gut microbiome could be potentially targeted for the early diagnosis of dementia and the reduction of AD risk.

Brain Anatomy in Boys with Conduct Disorder: Differences Among Aggression Subtypes.

Aggression is a core feature of conduct disorder (CD), but the motivation, execution of aggression may vary. A deeper understanding of the neural substrates of aggressive behaviours is critical for effective clinical intervention. Seventy-six Boys with CD (50 with impulsive aggression (I-CD) and 26 with premeditated aggression (P-CD)) and 69 healthy controls (HCs) underwent a structural MRI scan and behavioural assessments. Whole-brain analyses revealed that, compared to HCs, the I-CD group showed significant cortical thinning in the right frontal cortex, while the P-CD group demonstrated significant folding deficits in the bilateral superior parietal cortex. Both types of aggression negatively correlated with the left amygdala volume, albeit in different ways. The present results demonstrated that the complex nature of aggression relies on differentiated anatomical substrates, highlighting the importance of exploring differential circuit-targeted interventions for CD patients.

Left amygdala structure mediates longitudinal associations between exposure to threat and long-term psychiatric symptomatology in youth.

Traumatic experiences during childhood can have profound effects on stress sensitive brain structures (e.g., amygdala and hippocampus) and the emergence of psychiatric symptoms. Recent theoretical and empirical work has delineated dimensions of trauma (i.e., threat and deprivation) as having distinct neural and behavioral effects, although there are few longitudinal examinations. A sample of 243 children and adolescents were followed for three time points, with each assessment approximately 1 year apart (ages 9–15 years at Time 1; 120 males). Participants or their caregiver reported on youths' threat exposure, perceived stress (Time 1), underwent a T1‐weighted structural high‐resolution MRI scan (Time 2), and documented their subsequent psychiatric symptoms later in development (Time 3). The primary findings indicate that left amygdala volume, in particular, mediated the longitudinal association between threat exposure and subsequent internalizing and externalizing symptomatology. Greater threat exposure related to reduced left amygdala volume, which in turn differentially predicted internalizing and externalizing symptoms. Decreased bilateral hippocampal volume was related to subsequently elevated internalizing symptoms. These findings suggest that the left amygdala is highly threat‐sensitive and that stress‐related alterations may partially explain elevated psychopathology in stress‐exposed adolescents. Uncovering potential subclinical and/or preclinical predictive biomarkers is essential to understanding the emergence, progression, and eventual targeted treatment of psychopathology following trauma exposure.

Mothers' Attachment Representations and Children's Brain Structure.

Ample research demonstrates that parents’ experience-based mental representations of attachment—cognitive models of close relationships—relate to their children’s social-emotional development. However, no research to date has examined how parents’ attachment representations relate to another crucial domain of children’s development: brain development. The present study is the first to integrate the separate literatures on attachment and developmental social cognitive neuroscience to examine the link between mothers’ attachment representations and 3- to 8-year-old children’s brain structure. We hypothesized that mothers’ attachment representations would relate to individual differences in children’s brain structures involved in stress regulation—specifically, amygdala and hippocampal volumes—in part via mothers’ responses to children’s distress. We assessed 52 mothers’ attachment representations (secure base script knowledge on the Attachment Script Assessment and self-reported attachment avoidance and anxiety on the Experiences in Close Relationships scale) and children’s brain structure. Mothers’ secure base script knowledge was significantly related to children’s smaller left amygdala volume but was unrelated to hippocampal volume; we found no indirect links via maternal responses to children’s distress. Exploratory analyses showed associations between mothers’ attachment representations and white matter and thalamus volumes. Together, these preliminary results suggest that mothers’ attachment representations may be linked to the development of children’s neural circuitry related to stress regulation.

Racism May Weaken the Brain-Behavior Association among African American Children: The Case of Amygdala Volume-Emotion Regulation Link

Introduction: The amygdala has a central core role in regulating emotions. However, less is known about the racial/ethnic variation in the relevance of amygdala volume for emotion regulation of US children. According to the Minorities’ Diminished Returns (MDRs) phenomenon, due to racism, segregation, and social stratification (rather than innate differences due to genetics), some of the individual-level individual social determinants, could lose some of their relevance for African American (in comparison to White) children. Purpose: Conceptualizing race as a social factor that reflects structural racism and discrimination and building on the MDRs framework, we explored racial variation in the magnitude of the association between amygdala volume and emotion regulation/impulsivity of US children. Methods: For this cross-sectional study, we used baseline data which included behavioral, social, and structural magnetic resonance imaging (MRI) data of 6030 US children ages 9-10. Data came from the Adolescent Brain Cognitive Development (ABCD) study. The primary outcomes were positive and negative urgency. These were measured using Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking, Positive Urgency, and Impulsive Behavior Scale (UPPS-SS) UPPS-SS. The independent variables were right and left amygdala volume. The covariates were age, sex, parental education, household income, parental marital status, neighborhood socioeconomic status, and ethnicity. Race was the moderator. Results: Children with larger amygdala volumes had lower positive and negative urgency. The correlations between amygdala volume and positive and negative urgency were modified by race. For White children, children had better emotion regulation when they had a large amygdala. For African American children, positive and negative urgency did not show an association with amygdala size. Conclusions: The results can be explained by the Minorities’ Diminished Returns (MDRs) hypothesis. In line with MDRs and as a result of structural and interpersonal inequalities, such as school segregation, the amygdala-emotion regulation seen for White children does not replicate for African American children. For White children, however, in the absence of higher-level social determinants, amygdala size correlates with emotion regulation. The brainbehavior link is weaker for African American children whose lives are less predictable and affected by experiences of racial discrimination. Unequal effects of equal resources across racial groups are due to racism and discrimination, not biological innate differences such as genetics.

Differences in subcortical brain volumes among patients with schizophrenia and bipolar disorder and healthy controls.

Background:Patients with schizophrenia and bipolar disorder have an overlapping polygenic architecture and clinical similarities, although the 2 disorders are distinct diagnoses with clinical dissimilarities. It remains unclear whether there are specific differences in subcortical volumes between schizophrenia and bipolar disorder, and whether the subcortical differences are affected by any clinical characteristics. We investigated differences in subcortical volumes bilaterally among patients with schizophrenia, patients with bipolar disorder and healthy controls. We also investigated the influences of clinical characteristics on specific subcortical volumes in these patient groups.Methods:We collected 3 T T1-weighted MRI brain scans from 413 participants (157 with schizophrenia, 51 with bipolar disorder and 205 controls) with a single scanner at a single institute. We used FreeSurfer version 6.0 for processing the T1-weighted images to segment the following subcortical brain volumes: thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens. Differences in the 7 subcortical volumes were investigated among the groups. We also evaluated correlations between subcortical volumes and clinical variables in these patient groups.Results:Of 7 subcortical regions, patients with schizophrenia had significantly smaller volumes in the left thalamus (Cohen d = −0.29, p = 5.83 × 10−3), bilateral hippocampi (left, d = −0.36, p = 8.85 × 10−4; right, d = −0.41, p = 1.15 × 10−4) and left amygdala (d = −0.31, p = 4.02 × 10−3) than controls. Compared with controls, patients with bipolar disorder had bilateral reductions only in the hippocampal volumes (left, d = −0.52, p = 1.12 × 10−3; right, d = −0.58, p = 0.30 × 10−4). We also found that patients with schizophrenia had significantly smaller volumes in the bilateral amygdalae (left, d = −0.43, p = 4.22 × 10−3; right, d = −0.45, p = 4.56 × 10−3) than patients with bipolar disorder. We did not find any significant volumetric differences in the other 6 subcortical structures between patient groups (p > 0.05). Smaller left amygdalar volumes were significantly correlated with younger onset age only in patients with schizophrenia (r = 0.22, p = 5.78 × 10−3).Limitations:We did not evaluate the differences in subcortical volumes between patients stratified based on clinical bipolar disorder subtype and a history of psychotic episodes because our sample size of patients with bipolar disorder was limited.Conclusion:Our findings suggest that volumetric differences in the amygdala between patients with schizophrenia and those with bipolar disorder may be a putative biomarker for distinguishing 2 clinically similar diagnoses.

Association of Amygdala Development With Different Forms of Anxiety in Autism Spectrum Disorder

BackgroundThe 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. MethodsLongitudinal magnetic resonance imaging scans were acquired at up to four time points for 71 autistic and 55 typically developing (TD) children (∼2.5–12 years, 411 time points). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study time 4 (∼8–12 years) using a diagnostic interview tailored to autism: the Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed-effects models were used to test group differences at study time 1 (3.18 years) and time 4 (11.36 years) and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism-distinct anxieties and TD children. ResultsAutistic children with DSM anxiety had significantly larger right amygdala volumes than TD children at both study time 1 (5.10% increase) and time 4 (6.11% increase). Autistic children with autism-distinct anxieties had significantly slower right amygdala growth than TD, autism–no anxiety, and autism–DSM anxiety groups and smaller right amygdala volumes at time 4 than the autism–no anxiety (−8.13% decrease) and autism–DSM anxiety (−12.05% decrease) groups. ConclusionsDisparate amygdala volumes and developmental trajectories between DSM and autism-distinct forms of anxiety suggest different biological underpinnings for these common, co-occurring conditions in autism.

Real-time individual benefit from social interactions before and during the lockdown: the crucial role of personality, neurobiology and genes

Social integration is a major resilience factor for staying healthy. However, the COVID-19-pandemic led to unprecedented restrictions in social life. The consequences of these social lockdowns on momentary well-being are yet not fully understood. We investigated the affective benefit from social interactions in a longitudinal birth cohort. We used two real-time, real-life ecological momentary assessments once before and once during the initial lockdown of the pandemic (N = 70 participants; n~6800 observations) capturing the protective role of social interactions on well-being. Moreover, we used a multimethod approach to analyze ecological assessment data with individual risk and resilience factors, which are promising moderators in the relationship of social behavior, stress reactivity, and affective states (i.e., amygdala volume, neuroticism, polygenic risk for schizophrenia). Social contacts were linked to higher positive affect both during normal times and during the COVID-19-pandemic (beta coefficient = 0.1035), highlighting the beneficial role of social embedding. Interestingly, this relationship was differentially moderated by individual risk and resilience factors. In detail, participants with a larger left amygdala volume (beta coefficient = −0.0793) and higher neuroticism (beta coefficient = −0.0958) exhibited an affective benefit from more social interactions prior to the pandemic. This pattern changed during the pandemic with participants with smaller amygdala volumes and lower neurotic traits showing an affective gain during the pandemic. Moreover, participants with low genetic risk for schizophrenia showed an affective benefit (beta coefficient = −0.0528) from social interactions irrespective of the time point. Our results highlight the protective role of social integration on momentary well-being. Thereby, we offer new insights into how this relationship is differently affected by a person’s neurobiology, personality, and genes under adverse circumstances.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2–5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

Examining Associations Between Amygdala Volumes and Anxiety Symptoms in Autism Spectrum Disorder

BackgroundAnxiety is one of the most common co-occurring conditions in people with autism spectrum disorder. The amygdala has been identified as being associated with anxiety in populations with and without autism, yet associations in autism were based on relatively small or developmentally constrained samples, leaving questions as to whether these results hold at different developmental ages and in a larger, more robust sample. MethodsStructural neuroimaging and parent report of anxiety symptoms of children ages 5–13 years with (n = 123) and without (n = 171) a diagnosis of autism were collected from the University of Maryland and three sites from the Autism Brain Imaging Data Exchange. Standardized residuals for bilateral amygdala volumes were computed adjusting for site, hemispheric volumes, and covariates (age, sex, Full Scale IQ). ResultsClinically significant anxiety symptoms did not differentiate amygdala volumes between groups (i.e., autism and anxiety, autism without anxiety, without autism or anxiety). No significant association between left or right amygdala volumes and anxiety scores was observed among the sample of individuals with autism. Meta-analytic and Bayes factor estimations provided additional support for the null hypothesis. Age, sex, and autism severity did not moderate associations between anxiety and amygdala volumes. ConclusionsNo relation between amygdala volumes and anxiety symptoms in children with autism was observed in the largest sample to investigate this question. We discuss directions for future research to determine whether additional factors including age or method of assessment may contribute to this lack of association.

Nonclinical psychotic-like experiences and schizotypy dimensions: Associations with hippocampal subfield and amygdala volumes.

Schizotypy and psychotic‐like experiences (PLE) form part of the wider psychosis continuum and may have brain structural correlates in nonclinical cohorts. This study aimed to compare the effects of differential schizotypy dimensions, PLE, and their interaction on hippocampal subfields and amygdala volumes in the absence of clinical psychopathology. In a cohort of 367 psychiatrically healthy individuals, we assessed schizotypal traits using the Oxford‐Liverpool Inventory of Life Experiences (O‐LIFE) and PLE using the short form of the Prodromal Questionnaire (PQ‐16). Based on high‐resolution structural MRI scans, we used automated segmentation to estimate volumes of limbic structures. Sex and total intracranial volume (Step 1), PLE and schizotypy dimensions (Step 2), and their interaction terms (Step 3) were entered as regressors for bilateral amygdala and hippocampal subfield volumes in hierarchical multiple linear regression models. Positive schizotypy, but not PLE, was negatively associated with left amygdala and subiculum volumes. O‐LIFE Impulsive Nonconformity, as well as the two‐way interaction between positive schizotypy and PLE, were associated with larger left subiculum volumes. None of the estimators for right hemispheric hippocampal subfield volumes survived correction for multiple comparisons. Our findings support differential associations of hippocampus subfield volumes with trait dimensions rather than PLE, and support overlap and interactions between psychometric positive schizotypy and PLE. In a healthy cohort without current psychosis risk syndromes, the positive association between PLE and hippocampal subfield volume occurred at a high expression of positive schizotypy. Further studies combining stable, transient, and genetic parameters are required.

Stress-induced cortisol response is associated with right amygdala volume in early childhood

Rodent research suggests that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the resulting cortisol stress response can alter the structure of the hippocampus and amygdala. Because early-life changes in brain structure can produce later functional impairment and potentially increase risk for psychiatric disorder, it is critical to understand the relationship between the cortisol stress response and brain structure in early childhood. However, no study to date has characterized the concurrent association between cortisol stress response and hippocampal and amygdala volume in young children. In the present study, 42 young children (Mage = 5.97, SD = 0.76), completed a frustration task and cortisol response to stress was measured. Children also underwent magnetic resonance imaging (MRI), providing structural scans from which their hippocampal and amygdala volumes were extracted. Greater cortisol stress response was associated with reduced right amygdala volume, controlling for whole brain volume, age, sex, and number of cortisol samples. There were no significant associations between cortisol stress response and bilateral hippocampus or left amygdala volumes. The association between right amygdala volume and cortisol stress response raises the non-mutually exclusive possibilities that the function of the HPA axis may shape amygdala structure and/or that amygdala structure may shape HPA axis function. As both cortisol stress response and amygdala volume have been associated with risk for psychopathology, it is possible that the relationship between cortisol stress response and amygdala volume is part of a broader pathway contributing to psychiatric risk.

Brain tissue properties link cardio-vascular risk factors, mood and cognitive performance in the CoLaus|PsyCoLaus epidemiological cohort

Given the controversy about the impact of modifiable risk factors on mood and cognition in ageing, we sought to investigate the associations between cardio-vascular risk, mental health, cognitive performance and brain anatomy in mid- to old age. We analyzed a set of risk factors together with multi-parameter magnetic resonance imaging (MRI) in the CoLaus|PsyCoLaus cohort (n > 1200). Cardio-vascular risk was associated with differences in brain tissue properties – myelin, free tissue water, iron content – and regional brain volumes that we interpret in the context of micro-vascular hypoxic lesions and neurodegeneration. The interaction between clinical subtypes of major depressive disorder and cardio-vascular risk factors showed differential associations with brain structure depending on individuals’ lifetime trajectory. There was a negative correlation between melancholic depression, anxiety and MRI markers of myelin and iron content in the hippocampus and anterior cingulate. Verbal memory and verbal fluency performance were positively correlated with left amygdala volumes. The concomitant analysis of brain morphometry and tissue properties allowed for a neuro-biological interpretation of the link between modifiable risk factors and brain health.

Specific temperament in patients with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is a neurocutaneous disease, characterized by tumorigenesis and developmental anomalies due to aberrant sonic hedgehog (Shh) signaling. Patients with NBCCS typically appear calm and carefree, suggesting that a specific personality in these patients may be associated with an enhanced hedgehog pathway. Our study aimed to determine the personality type in these patients. We enrolled 14 mentally normal patients with genetically confirmed NBCCS (seven males and seven females; mean age=25.2years) and 20 controls (10 males and 10 females; mean age=27.9years). The patients were assessed with the Japanese version of the Temperament and Character Inventory, based on the seven-dimensional model of temperament and character, and their clinical symptoms were evaluated. The amygdala volumes of six patients with NBCCS were measured using magnetic resonance imaging with image-processing software. Patients with NBCCS scored significantly lower on harm avoidance (0.89) than controls (1.00; P=0.0084). Moreover, patients with NBCCS and developmental malformations such as rib anomalies, who may have experienced Shh signaling enhancement from the prenatal period, scored significantly lower on harm avoidance (0.80 [P=0.0031]). The left amygdala volume was also significantly reduced in patients with NBCCS (P=0.0426). Patients with NBCCS who experienced increased Shh signaling from the prenatal period showed significantly lower harm avoidance related to serotonin. The left amygdala volume was significantly reduced in these patients. Our results indicate that Shh signaling may influence the human personality.

87 Prenatal maternal mental distress impairs newborn amygdala growth and infant neurodevelopment at 18 months

Prenatal maternal mental distress is increasingly associated with adverse outcomes in fetal brain development. However, the association between prenatal maternal mental distress and neonatal brain growth as well as infants’ long-term neurodevelopment remains unclear. This study aims to determine the association between prenatal maternal stress, anxiety, and depression and postnatal brain growth as well as infant neurodevelopmental outcomes at 18 months. We prospectively recruited women with normal pregnancies. Prenatal maternal stress, anxiety, and depression were measured using the Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale, respectively. Neonates were scanned on a 3T MRI scanner with an 8-channel HiRes brain array receive only coil (T2-weighted 3D CUBE sequence; TR/TE: 2500/64.7 ms; flip angle: 90°; resolution: 0.625×0.625×1 mm3). Neonatal brain MR images were segmented into cortical grey matter, white matter, deep grey matter, cerebellum, brainstem, left and right hippocampus and amygdala using Draw-EM pipeline and then manually corrected. Infant neurodevelopment was evaluated using Bayley Scales of Infant and Toddler Development III at 18 months. We studied 116 pregnant women, of which 96 completed mental distress measures twice at different gestational ages (32.0±4.5, 23-40 gestational weeks); 101 newborns underwent postnatal MRI (41.9±1.9, 38-47 gestational weeks); and 87 infants completed neurodevelopmental testing at 18 months. Prenatal maternal anxiety was associated with smaller left and right amygdala volumes in newborns and lower cognitive scores in infants at 18 months. Prenatal maternal stress was also associated with decreased cognitive and motor scores at 18 months. We report that prenatal maternal mental distress is associated with impaired amygdala growth in newborns and delayed cognitive and motor skills in infants at 18 months. Our data suggest maternal mental distress during pregnancy has long-term neurodevelopmental consequences.

Decision support models for Alzheimer’s disease and mild cognitive impairment classification based on features extracted from MRI and FDG PET

AbstractBackgroundAccurate diagnosis in early Alzheimers’ disease (AD) and Mild Cognitive Impairment (MCI) is critical for patients to start treatments. In AD and MCI patients, there is a high correlation between brain atrophy and metabolism and physical and cognitive impairments. Here we evaluate the performance of machine learning models for identifying AD and MCI subjects based on features extracted from MR and FDG PET imaging.MethodThe ADNI database was used in this study. 201 AD subjects: 80f(58‐88yo), 121m(56‐90yo); 427 MCI subjects: 163f(56‐90yo), 263m(59‐93yo); and 326 NL subjects: 169f(60‐95yo), 157m(66‐91yo) were included. T1‐weighted MRI and matched F18‐FDG PET scans were processed by PETQuant (CorTechs Labs, San Diego, USA). Segmented brain volumes normalized by intracranial volume and corresponding PET ROI SUV ratios (SUVRs) were calculated. Random Forests algorithm was used in creating machine learning models. One‐third of randomly selected data were used for testing while the rest were used for training. The performance of the models and importance of their features were evaluated.ResultThree models’ performances were evaluated. The first one used both PET SUVRs and MRI‐based volumes, and average model accuracy, recall for identifying AD, MCI and normal were 0.77 and 0.77. The top three features were right isthmus cingulate SUVR, left amygdala volume, and left hippocampus volume. The second model only used MRI, and average accuracy and recall for identifying AD,MCI and normal were 0.77 and 0.76. The top three features were left amygdala volume, left hippocampus volume, and right inferior temporal volume. The third model used PET SUVRs only, and average accuracy and recall were 0.72 and 0.72. The top three features were SUVRs from right isthmus cingulate, left medial‐parietal, and right entorhinal cortex.ConclusionThese models showed a good classification performance among AD, MCI and normal subjects. The model using MRI and PET showed the best performance and was slightly better than using MRI data alone. The MRI model performed better than using the PET data alone. This suggests MRI volumetric measures provide a better classification power than SUVRs extracted from FDG‐PET images.

Perceived control attenuates the relationship between experiences of discrimination and left amygdala volume in older adults

AbstractBackgroundThe medial temporal lobes (MTLs), which exhibit neuropathology in Alzheimer’s disease (AD), are modulated by experience. Animal models of environmental enrichment and chronic stress have shown structural plasticity in the amygdalae and hippocampi. Experiences of discrimination (EoD; e.g., sexism, racism, ageism) are salient chronic psychosocial stressors that affect physical and mental health. Perceived control, one’s perception of environmental and psychological control, may attenuate the impact of EoD by increasing resilience. Although aberrant amygdala activity has been implicated in relation to EoD, research has yet to investigate the structural correlates of EoD.MethodsData from 36 participants (58% female, 55‐86 years, 31% African American) were used to investigate the moderating effect of perceived control on EoD and MTL volume. T1‐weighted MR images were captured on a 3T Philips Achieva scanner and analyzed using FreeSurfer's automatic segmentation protocol. Models were adjusted for age, sex, education, and intracranial volume.ResultsMultiple regression models showed an association between left (t(30) = ‐4.073, p &lt; 0.001) and right (t(30) = ‐2.116, p &lt; 0.05) amygdala, but not hippocampal, volume and EoD scores. Additionally, perceived control significantly interacted with EoD for the left (b = 10.66, t(28) = 2.776, p &lt; 0.01), but not right (b = 2.096, t(28) = 0.514, p &gt; 0.05), amygdala. At lower levels of perceived control, higher EoD (b = ‐108.57, t(28) = ‐4.509, p &lt; 0.001) predicted smaller left amygdala volume. However, EoD (b = ‐11.77, t(28) = ‐0.562, p = 0.58) did not predict left amygdala volume at higher levels of perceived control.ConclusionThis cross‐sectional study of cognitively healthy, older adults, provided evidence that greater EoD was associated with smaller amygdala volumes bilaterally. Further, participants with lower perceived control at higher levels of EoD showed a greater reduction in left, but not right, amygdala volume. This suggests that the interaction between chronic stress and resilience might contribute to neuropathology or reserve of AD‐sensitive regions, specifically in populations that face higher discriminatory experiences. Future studies are needed to examine whether interventions that increase perceived control (resilience) have beneficial effects on neural structure and function.