Amygdala Volume Research Articles

Amygdala volume and depression symptoms in young adolescents who use cannabis

IntroductionBoth cannabis use and depressive symptomology increase in prevalence throughout adolescence. Concurrently, the brain is undergoing neurodevelopment in important limbic regions, such as the amygdala. Prior research indicates the amygdala may also be related to cannabis use and depressive symptoms. We aimed to investigate the effects of adolescent cannabis use on amygdala volumes as well as the interaction of cannabis use and amygdala morphometry on depressive symptoms in youth. MethodTwo-hundred-twenty-four participants (ages 12–15), balanced by sex assigned at birth, were selected from a sub-sample of the Adolescent Brain Cognitive Development (ABCD) Study based on hair toxicology and self-report measures of cannabis use. Participants positive for cannabinoids in hair and/or self-reported cannabis use were demographically matched to youth with no self-reported or confirmed cannabis use. The guardians of these youth reported depression symptoms on the Child Behavioral Checklist. Linear mixed effect models were run investigating cannabis use group on amygdala volumes bilaterally, controlling for whole brain volume and random effects of scanner type. Additional analyses examined cannabis group status and bilateral amygdala volume on depression symptoms. ResultsCannabis use was not significantly associated with amygdala volume but was associated with increased depressive symptoms (p<0.01). Cannabis group interacted with amygdala volume, such that individuals with smaller volumes had increased depressive symptoms within the cannabis group (p’s<0.01–0.02). ConclusionAberrations in amygdala volume based on cannabis use were not found in early adolescence; however, more depressive symptoms were related to cannabis group. Youth who use cannabis and have smaller amygdala volumes were at increased risk for depressive symptomology, suggesting potential neurovulnerabilities to cannabis use.

Amygdala and hippocampal substructure volumes and their association with improvement in mood symptoms in patients with mood disorders undergoing electroconvulsive therapy

Electroconvulsive therapy (ECT) demonstrates favorable outcomes in the management of severe depressive disorders. ECT has been consistently associated with volumetric increases in the amygdala and hippocampus. However, the underlying mechanisms of these structural changes and their association to clinical improvement remains unclear. In this cross-sectional structural MRI study, we assessed the difference in amygdala subnuclei and hippocampus subfields in n = 37 patients with either unipolar or bipolar disorder immediately after eighth ECT sessions compared to (n = 40) demographically matched patients in partial remission who did not receive ECT (NoECT group). Relative to NoECT, the ECT group showed significantly larger bilateral amygdala volumes post-treatment, with the effect originating from the lateral, basal, and paralaminar nuclei and the left corticoamydaloid transition area. No significant group differences were observed for the hippocampal or cortical volumes. ECT was associated with a significant decrease in depressive symptoms. However, there were no significant correlations between amygdala subnuclei volumes and symptom improvement. Our study corroborates previous reports on increased amygdalae volumes following ECT and further identifies the subnuclei driving this effect. However, the therapeutic effect of ECT does not seem to be directly related to structural changes in the amygdala.

Comparing Automated Subcortical Volume Estimation Methods; Amygdala Volumes Estimated by FSL and FreeSurfer Have Poor Consistency.

Subcortical volumes are a promising source of biomarkers and features in biosignatures, and automated methods facilitate extracting them in large, phenotypically rich datasets. However, while extensive research has verified that the automated methods produce volumes that are similar to those generated by expert annotation, the consistency of methods with each other is understudied. Using data from the UK Biobank, we compare the estimates of subcortical volumes produced by two popular software suites: FSL and FreeSurfer. Although most subcortical volumes exhibit good to excellent consistency across the methods, the tools produce diverging estimates of amygdalar volume. Through simulation, we show that this poor consistency can lead to conflicting results, where one but not the other tool suggests statistical significance, or where both tools suggest a significant relationship but in opposite directions. Considering these issues, we discuss several ways in which care should be taken when reporting on relationships involving amygdalar volume.

The gut-brain axis in individuals with alcohol use disorder: Anexploratory study of associations among clinical symptoms, brain morphometry, and the gut microbiome.

Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD. We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

Global left frontal cortex connectivity attenuates the adverse effect of brain atrophy on global cognition in non-dementia participants

Aim: To investigate whether higher global left frontal cortex (gLFC) connectivity, a potential neural substrate of cognitive reserve (CR), mitigates the impact of brain atrophy on cognition in non-dementia participants. Methods: A total of 43 clinically diagnostic normal controls (NC), 63 subjective cognitive decline (SCD) and 30 mild cognitive impairment (MCI) were recruited, who underwent resting-state fMRI and structural MRI scans. The gLFC connectivity was defined as the average positive functional connectivity between the left frontal cortex and each voxel in the gray matter. Hippocampus, parahippocampal gyrus, and amygdala volume volumes/intracranial volume ratio (HpVR, PhgVR, and AmyVR) values were computed as measures of brain atrophy. In general linear analysis, interaction term gLFC connectivity × brain atrophy on global cognition performance were tested, which were repeated in women and men separately. The Trial registration number is NCT03370744. Results: Significant interaction effects of HpVR * gLFC connectivity (P = 0.031) and PhgVR * gLFC connectivity (P = 0.006) were observed, while AmyVR * gLFC connectivity (P = 0.088) showed a marginal significance. After accounting for APOE ε4 carrying status or diagnosis based on amyloidosis, the significant results still existed. In separate analysis, the significant interaction effects of HpVR * gLFC connectivity (P = 0.004), PhgVR * gLFC connectivity (P = 0.017), and AmyVR * gLFC connectivity (P = 0.027) were only observed in men, not in women. Conclusion: The gLFC connectivity is associated with greater resilience against the adverse effect of specified brain atrophy on global cognition, which is more effective in men.

The neural substrates of social cognition deficits in newly diagnosed multiple sclerosis patients.

Cognitive and affective symptoms in multiple sclerosis (MS) can be independently impaired and have different pathways of progression. Cognitive alterations have been described since the earliest MS stages; by contrast, the social cognition (SC) domain has never been investigated in the first year from MS diagnosis. We aimed to evaluate SC and unravel its neural bases in newly diagnosed MS patients. Seventy MS patients underwent at diagnosis a 3 T-MRI and a neuropsychological/SC assessment (median time between diagnosis and MRI/cognitive evaluation = 0 months). We tested two matched reference samples: 31 relapsing-remitting MS patients with longer course (mean ± SD disease duration = 7.0 ± 4.5 years) and 38 healthy controls (HCs). Cortical thicknesses (CTh) and volumes of brain regions were calculated. Newly diagnosed MS patients performed significantly lower than HCs in facial emotion recognition (global: p < 0.001; happiness: p = 0.041, anger: p = 0.007; fear: p < 0.001; disgust: p = 0.004) and theory of mind (p = 0.005), while no difference was found between newly diagnosed and longer MS patients. Compared to lower performers, higher performers in facial emotion recognition showed greater volume of amygdala (p = 0.032) and caudate (p = 0.036); higher performers in theory of mind showed greater CTh in lingual gyrus (p = 0.006), cuneus (p = 0.024), isthmus cingulate (p = 0.038), greater volumes of putamen (p = 0.016), pallidum (p = 0.029), and amygdala (p = 0.032); patients with higher empathy showed lower cuneus CTh (p = 0.042) and putamen volume (p = 0.007). SC deficits are present in MS patients since the time of diagnosis and remain persistent along the disease course. Specific basal, limbic, and occipital areas play a significant role in the pathogenesis of these alterations.

Comparison of detailed brain volume measurements in schizophrenia with healthy individuals

Aims: This study aims to provide insights into the preliminary and definitive diagnosis, treatment modalities, and elucidation of the underlying pathophysiological mechanisms of schizophrenia, alongside ongoing research efforts. Methods: This retrospective study examined a cohort of 31 patients (17 male, 14 female) diagnosed with schizophrenia according to the criteria specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM V) at the Psychiatry Clinic of the University Hospital. The healthy control group, comprising 31 individuals (17 male, 14 female), was selected from archived records at the same hospital, with sociodemographic characteristics matching those of the patient group. High-resolution T1-weighted MRI images of the individuals were analyzed using the VolBrain AssemblyNet program. Results: It has been observed that the volumes of various brain structures, including white matter (WM), gray matter (GM), subcortical GM, cortical GM, WM+GM, IC, total cerebrum, right cerebrum, left cerebrum, cerebrum WM, cerebrum GM, are significantly reduced (p&lt;0.05) in patients diagnosed with schizophrenia compared to healthy controls. Additionally, volumes of cerebellar WM, GM, vermis, brainstem, accumbens, hippocampus, thalamus, ventral diencephalon (DC), amygdala, and basal forebrain were found to be decreased in schizophrenia patients compared to healthy controls. Conversely, volumes of the pallidum, caudate, putamen, inferior lateral ventricle, lateral ventricle, third ventricle, fourth ventricle, and CSF were observed to be increased. Conclusion: These findings underscore the widespread nature of neuroanatomical alterations in schizophrenia and highlight the importance of understanding these changes for elucidating the disorder's pathophysiology and developing targeted therapeutic interventions. Further research is warranted to explore the interplay of genetic, developmental, and environmental factors in schizophrenia.

Quantitative cellular pathology of the amygdala in temporal lobe epilepsy and correlation with magnetic resonance imaging volumetry, tissue microstructure, and sudden unexpected death in epilepsy risk factors.

Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction. Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR-pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal-associated apnea. We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule-associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6-235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency. Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.

The amygdala volume moderates the relationship between childhood maltreatment and callous-unemotional traits in adolescents with conduct disorder.

CU traits, characterized by shallow affect, lack of fear, and absence of remorse, have been moderately associated with childhood maltreatment in a recent meta-analysis. However, the potential impact of brain structures remains undetermined. This paper examines the relationship between callous-unemotional (CU) traits, childhood maltreatment, and amygdala volumes. In this study, we used a region-of-interest (ROI) analysis to explore the interaction between the volumes of the amygdala, childhood maltreatment, and the manifestation of CU traits in adolescents diagnosed with conduct disorder (CD, N = 67), along with a comparison group of healthy-control youths (HCs, N = 89). The ROI analysis revealed no significant group differences in the bilateral amygdalar volumes. Significant positive correlation was discovered between all forms of child maltreatment (except for physical neglect) and CU traits across subjects. But the interaction of physical abuse and amygdala volumes was only significant within CD patients. Notably, a sensitivity analysis suggested that gender significantly influences these findings. These results contribute critical insights into the etiology of CU traits, emphasizing the need for customized clinical assessment tools and intervention strategies.

Prenatal Maternal Psychological Distress During the COVID-19 Pandemic and Newborn Brain Development

Elevated maternal psychological distress during pregnancy is associated with altered fetal brain development. During the COVID-19 pandemic, prenatal maternal psychological distress more than doubled. To examine the association of the pandemic and rising maternal psychological distress with brain growth in newborns using quantitative 3-dimensional volumetric magnetic resonance imaging (MRI). This prospective cross-sectional study recruited mother-infant dyads at Children's National Hospital, Washington, DC, during the COVID-19 pandemic (June 1, 2020, to June 30, 2022) into a longitudinal infant brain development study and compared them with an existing normative healthy cohort (recruited March 1, 2014, to December 31, 2019). Exclusion criteria included multiple gestation pregnancy, known or suspected congenital infection, documented chromosomal abnormalities, or any maternal contraindication to MRI, as well as prenatal COVID-19 exposure. Infants with structural brain abnormalities or a postnatal confirmation of a genetic syndrome were excluded. Psychological distress during COVID-19 pandemic. Prenatal maternal mental health was evaluated using the Spielberger State-Trait Anxiety Inventory and the Perceived Stress Scale. Neonates underwent nonsedated brain MRI. An ordinary least squares linear regression model was used to measure the differences in regional brain volumes of neonates born before vs during the pandemic with and without exposure to elevated prenatal maternal psychological distress after adjustment for neonatal sex and gestational age at MRI and maternal age and educational level. A total of 159 mother-infant dyads were included in the analysis: 103 before and 56 during the pandemic (median gestational age of infants, 39.6 [IQR, 38.4-40.4] weeks; median maternal age, 34.5 [IQR, 31.0-37.0] years). Eighty-three infants (52.2%) were female. Among the mothers, 130 (81.8%) had a college degree and 87 (54.7%) had a graduate degree. Forty-four mothers (27.7%) identified as Asian, Hispanic, or multiracial; 27 (17.0%), as Black; and 88 (55.3%), as White. Scores on anxiety and stress measures were significantly increased in the pandemic cohort. Infants of mothers with elevated maternal distress showed median reductions in white matter (-0.36 [95% CI, -0.61 to -0.11] cm3; Q < .001), right hippocampal (-0.35 [95% CI, -0.65 to -0.06] cm3; Q = .04), and left amygdala (-0.49 [95% CI, -0.84 to -0.13] cm3; Q = .03) volumes compared with infants of mothers with low distress levels. After adjusting for the cohort effect of the pandemic, elevated trait anxiety remained significantly associated with decreased left amygdalar volumes (-0.71 [95% CI, -1.12 to -0.29]; Q < .001). In this cross-sectional study of maternal-infant dyads prior to and during the COVID-19 pandemic, regional neonatal brain volumes were associated with elevated maternal psychological distress.

Hippocampus and amygdala volumes are reduced in patients with schizoaffective disorder

We aimed to examine the hippocampus and amygdala volumes in patients with schizoaffective disorder with the notion that schizoaffective disorder has strong resemblance of clinical presentation with schizophrenia and bipolar disorder and that there have been studies on regions of interest volumes in patients with schizophrenia and bipolar disorder but not in patients with schizoaffective disorder. Eighteen patients with schizoaffective disorder and nineteen healthy controls were included into the study. Hippocampus and amygdala volumes were examined by using the MRI. Both hippocampus and amygdala volumes were statistically significantly reduced in patients with schizoaffective disorder compared to those of the healthy control comparisons (p<0.001 for the hippocampus and p<0.001 for the amygdala). In summary, our findings of the present study suggest that patients with schizoaffective disorder seem to have smaller volumes of the hippocampus and amygdala regions and that our results were in accordance with those obtained both in patients with schizophrenia and bipolar disorder, considering that schizoaffective disorder might have neuroanatomic similarities with both schizophrenia and bipolar disorder. Beacuse of some limitations aforementioned especially age, it is required to replicate our present results in this patient group.

Beyond the hippocampus: Amygdala and memory functioning in older adults

BackgroundMedial temporal lobe atrophy has been linked to decline in neuropsychological measures of explicit memory function. While the hippocampus has long been identified as a critical structure in learning and memory processes, less is known about contributions of the amygdala to these functions. We sought to investigate the relationship between amygdala volume and memory functioning in a clinical sample of older adults with and without cognitive impairment. MethodsA serial clinical sample of older adults that underwent neuropsychological assessment at an outpatient neurology clinic was selected for retrospective chart review. Patients were included in the study if they completed a comprehensive neuropsychological assessment within six months of a structural magnetic resonance imaging scan. Regional brain volumes were quantified using Neuroreader® software. Associations between bilateral hippocampal and amygdala volumes and memory scores, derived from immediate and delayed recall conditions of a verbal story learning task and a visual design reconstruction task, were examined using mixed-effects general linear models, controlling for total intracranial volume, scanner model, age, sex and education. Partial correlation coefficients, adjusted for these covariates, were calculated to estimate the strength of the association between volumes and memory scores. ResultsA total of 68 (39 F, 29 M) participants were included in the analyses, with a mean (SD) adjusted age of 80.1 (6.0) and educational level of 15.9 (2.5) years. Controlling for age, sex, education, and total intracranial volume, greater amygdala volumes were associated with better verbal and visual memory performance, with effect sizes comparable to hippocampal volume. No significant lateralized effects were observed. Partial correlation coefficients ranged from 0.47 to 0.33 (p<.001). ConclusionThese findings contribute to a growing body of knowledge identifying the amygdala as a target for further research in memory functioning. This highlights the importance of considering the broader functioning of the limbic system in which multiple subcortical structures contribute to memory processes and decline in older adults.

A Mendelian randomization study of the entire phenome to explore the causal links between epilepsy.

The causes and triggering factors of epilepsy are still unknown. The results of genome-wide association studies can be utilized for a phenome-wide association study using Mendelian randomization (MR) to identify potential risk factors for epilepsy. This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p<1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2weeks (p=0.042), blood uridine (p=0.003), blood propionylcarnitine (p=0.041), and free cholesterol (p=0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p>0.05). Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.

Sodium signal intensity of CSF using 1H-guided 23Na-MRI as a potential noninvasive biomarker in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and mnestic deficits. The pathophysiology of AD is not fully understood, which renders the development of accurate tools for early diagnosis and effective therapies exceedingly difficult. In this study, we investigated the use of 23Na-MRI to measure the relative sodium signal intensities (rSSIs) in CSF in patients with AD and healthy controls. We prospectively recruited 11 patients with biomarker-diagnosed early-stage AD, as well as 12 cognitively healthy age-matched controls. All participants underwent 23Na-MRI to measure rSSI. Statistical analyses were performed to compare CSF sodium signal intensities between groups and to evaluate the specificity and sensitivity of the rSSI in the diagnosis of AD. RSSIs in CSF were significantly higher in AD patients (mean=68.6%±7.7%) compared to healthy controls (mean=56.9%±5.5%) (p<.001). There was also a significant negative correlation between rSSI in CSF and hippocampus and amygdala volumes (r=-.54 and -.49, p<.05) as well as a positive correlation with total CSF volumes (r=.81, p<.05). Receiver operating characteristic analysis showed high diagnostic accuracy for rSSI in discriminating between AD patients and healthy controls (area under the curve=.94). Our study provides evidence that rSSI in CSF is increased in AD patients in comparison to healthy controls. rSSI may serve as a potential marker for early detection and monitoring of disease progression. Larger, longitudinal studies are needed to confirm our findings and to investigate the association between rSSI in CSF and the severity of cognitive impairment.

Socioeconomic Disadvantage Moderates the Association of Systemic Inflammation With Amygdala Volume in Adolescents Over a 2-Year Interval: An Exploratory Study

BackgroundResearch has demonstrated an association between elevated systemic inflammation and changes in brain function. Affective areas of the brain involved in processing threat (e.g., amygdala) and reward (e.g., nucleus accumbens) appear to be sensitive to inflammation. Early-life stress, such as experiencing low socioeconomic status (SES), may also potentiate this association, but relevant evidence has come primarily from cross-sectional studies of brain function. It is unclear whether similar associations are present between early-life stress, inflammation, and brain structure, particularly in typically developing populations. MethodsWe recruited and assessed 50 adolescents (31 females/19 males) from the community (mean [SD] age = 15.5 [1.1] years, range = 13.1–17.5 years) and examined in exploratory analyses whether changes in C-reactive protein (ΔCRP) from blood spots predict changes in gray matter volume (ΔGMV) in the bilateral amygdala and nucleus accumbens over a 2-year period. We also investigated whether experiencing early-life stress, operationalized using a comprehensive composite score of SES disadvantage at the family and neighborhood levels, significantly moderated the association between ΔCRP and ΔGMV. ResultsWe found that ΔCRP was negatively associated with Δamygdala GMV (i.e., increasing CRP levels were associated with decreasing amygdala volume; β = −0.84, p = .012). This effect was stronger in youths who experienced greater SES disadvantage (β = −0.56, p = .025). ConclusionsThese findings suggest that increases in systemic inflammation are associated with reductions in amygdala GMV in adolescents, potentially signaling accelerated maturation, and that these neuroimmune processes are compounded in adolescents who experienced greater SES disadvantage. Our findings are consistent with theoretical frameworks of neuroimmune associations and suggest that they may influence adolescent neurodevelopment.

Prenatal SARS-CoV-2 infection results in neurodevelopmental and behavioral outcomes in mice.

Prenatal exposure to viral pathogens has been known to cause the development of neuropsychiatric disorders in adulthood. Furthermore, COVID-19 has been associated with a variety of neurological manifestations, raising the question of whether in utero SARS-CoV-2 exposure can affect neurodevelopment, resulting in long-lasting behavioral and cognitive deficits. Using a human ACE2-knock-in mouse model, we have previously shown that prenatal exposure to SARS-CoV-2 at later stages of development leads to fetal brain infection and gliosis in the hippocampus and cortex. In this study, we aimed to determine whether infection of the fetal brain results in long-term neuroanatomical alterations of the cortex and hippocampus or in any cognitive deficits in adulthood. Here, we show that infected mice developed slower and weighed less in adulthood. We also found altered hippocampal and amygdala volume and aberrant newborn neuron morphology in the hippocampus of adult mice infected in utero. Furthermore, we observed sex-dependent alterations in anxiety-like behavior and locomotion, as well as hippocampal-dependent spatial memory. Taken together, our study reveals long-lasting neurological and cognitive changes as a result of prenatal SARS-CoV-2 infection, identifying a window for early intervention and highlighting the importance of immunization and antiviral intervention in pregnant women.

An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank.

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β = 0.026, pcorr = 0.028) and greater mean cortical thickness in temporal and occipital lobes (β = 0.013 to 0.014, pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (β = -0.013 to -0.022, pcorr<0.05). Results of sensitivity analyses adjusting for birth weight were similar, with an additional association between winter birth and white matter microstructure in the forceps minor and between summer births, greater cingulate thickness and amygdala volume. Further analyses revealed associations between probable depressive phenotypes and a range of neuroimaging measures but a paucity of interactions with seasonality. Our results suggest that seasonality of birth may affect later-life brain structure and play a role in lifetime recurrent Major Depressive Disorder. Due to the small effect sizes observed, and the lack of associations with other mental health traits, further research is required to validate birth season effects in the context of different latitudes, and by co-examining genetic and epigenetic measures to reveal informative biological pathways.

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.

New insights into the effects of type and timing of childhood maltreatment on brain morphometry.

Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.

Faster pace of hippocampal growth mediates the association between perinatal adversity and childhood depression

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children’s subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children’s psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood.