Models describing the neural correlates of biased emotion processing in depression have focused on increased activation of anterior cingulate and amygdala and decreased activation of striatum and ...dorsolateral prefrontal cortex. However, neuroimaging studies investigating emotion processing in depression have reported inconsistent results. This meta-analysis integrates these findings and examines whether emotional valence modulates such abnormalities. A systematic literature search identified 26 whole-brain and 18 region-of-interest studies. Peak coordinates and effect sizes were combined in an innovative parametric meta-analysis. Opposing effects were observed in the amygdala, striatum, parahippocampal, cerebellar, fusiform and anterior cingulate cortex, with depressed subjects displaying hyperactivation for negative stimuli and hypoactivation for positive stimuli. Anterior cingulate activity was also modulated by facial versus non-facial stimuli, in addition to emotional valence. Depressed subjects also showed reduced activity in left dorsolateral prefrontal cortex for negative stimuli and increased activity in orbitofrontal cortex for positive stimuli. Emotional valence is a moderator of neural abnormalities in depression, and therefore a critical feature to consider in models of emotional dysfunction in depression.
Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive ...disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
Childhood maltreatment, including abuse and neglect, may have sustained effects on the integrity and functioning of the brain, alter neurophysiological responsivity later in life, and predispose ...individuals toward psychiatric conditions involving socioaffective disturbances. This meta-analysis aims to quantify associations between self-reported childhood maltreatment and brain function in response to socioaffective cues in adults. Seventeen functional magnetic resonance imaging studies reporting on data from 848 individuals examined with the Childhood Trauma Questionnaire were included in a meta-analysis of whole-brain findings, or a review of region of interest findings. The spatial consistency of peak activations associated with maltreatment exposure was tested using activation likelihood estimation, using a threshold of p < .05 corrected for multiple comparisons. Adults exposed to childhood maltreatment showed significantly increased activation in the left superior frontal gyrus and left middle temporal gyrus, and decreased activation in the left superior parietal lobule and the left hippocampus. Although hyperresponsivity to socioaffective cues in the amygdala and ventral anterior cingulate cortex in correlation with maltreatment severity is a replicated finding in region of interest studies, null results are reported as well. The findings suggest that childhood maltreatment has sustained effects on brain function into adulthood, and highlight potential mechanisms for conveying vulnerability to development of psychopathology.
Taking the perspective of somebody else (Theory of Mind; ToM) is an essential human ability depending on a large cerebral network comprising prefrontal and temporo-parietal regions. Recently, ToM was ...suggested to consist of two processes: (1) self-perspective inhibition and (2) belief reasoning. Moreover, it has been hypothesized that self-perspective inhibition may build upon basic motor response inhibition. This study tested both hypotheses for the first time using functional Magnetic Resonance Imaging (fMRI), through administering both a ToM and a stop-signal paradigm in the same subjects. Both self-perspective and motor response inhibition yielded bilateral inferior frontal gyrus (IFG) activation, suggesting a common inhibitory mechanism, while belief reasoning was mediated by the superior temporal gyrus (STG) and temporo-parietal junction (TPJ). Thus, we provide neurobiological evidence for a subdivision of ToM into self-perspective inhibition and belief reasoning. Furthermore, evidence for partially shared neural mechanisms for inhibition in complex social situations and basic motor response inhibition was found.
► ToM can be subdivided into self-perspective inhibition and belief reasoning. ► Self-perspective inhibition is mediated by the bilateral IFG. ► Belief reasoning is mediated by the left STG, TPJ and MTG. ► Self-inhibition and response inhibition build upon similar neural mechanisms.
Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. ...Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2–3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2–3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation.
•MRI data are challenging to acquire in the early years of life.•Paediatric MRI without sedation is feasible in sub-Saharan Africa, with 77% success.•The Drakenstein Child Health study has novel MRI data of South African children.•Morphological features of the cortex associate with neurocognitive development.•Structure-cognition relationships in heteromodal association regions at 2–3 years.
Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and ...genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Evidence suggests that psychopathology is associated with an advanced brain ageing process, typically mapped using machine learning models that predict an individual's age based on structural ...neuroimaging data. The brain predicted age difference (brain-PAD) captures the deviation of brain age from chronological age. Substantial heterogeneity between studies has introduced uncertainty regarding the magnitude of the brain-PAD in adult psychopathology. The present meta-analysis aimed to quantify structural MRI-based brain-PAD in adult psychotic and mood disorders, while addressing possible sources of heterogeneity related to diagnosis subtypes, segmentation method, age and sex. Clinical factors influencing brain ageing in axis 1 psychiatric disorders were systematically reviewed. Thirty-three studies were included for review. A random-effects meta-analysis revealed a brain-PAD of +3.12 (standard error = 0.49) years in psychotic disorders (n = 16 studies), +2.04 (0.10) years in bipolar disorder (n = 5), and +0.90 (0.20) years in major depression (n = 7). An exploratory meta-analysis found a brain-PAD of +1.57 (0.67) in first episode psychosis (n = 4), which was smaller than that observed in psychosis and schizophrenia (n = 10, +3.87 (0.61)). Patient mean age significantly explained heterogeneity in effect size estimates in psychotic disorders, but not mood disorders. The systematic review determined that clinical factors, such as higher symptom severity, may be associated with a larger brain-PAD in psychopathology. In conclusion, larger structural MRI-based brain-PAD was confirmed in adult psychopathology. Preliminary evidence was obtained that brain ageing is greater in those with prolonged duration of psychotic disorders. Accentuated brain ageing may underlie the cognitive difficulties experienced by some patients, and may be progressive in nature.
•Machine learning models can accurately predict brain age from brain imaging data.•This meta-analysis found advanced brain ageing in psychotic and mood disorders.•Brain ageing may possibly advance with prolonged duration of psychotic disorders.•Symptom severity of psychopathology is associated with advanced brain ageing.
Neuroimaging genomics is a relatively new field focused on integrating genomic and imaging data in order to investigate the mechanisms underlying brain phenotypes and neuropsychiatric disorders. ...While early work in neuroimaging genomics focused on mapping the associations of candidate gene variants with neuroimaging measures in small cohorts, the lack of reproducible results inspired better-powered and unbiased large-scale approaches. Notably, genome-wide association studies (GWAS) of brain imaging in thousands of individuals around the world have led to a range of promising findings. Extensions of such approaches are now addressing epigenetics, gene-gene epistasis, and gene-environment interactions, not only in brain structure, but also in brain function. Complementary developments in systems biology might facilitate the translation of findings from basic neuroscience and neuroimaging genomics to clinical practice. Here, we review recent approaches in neuroimaging genomics-we highlight the latest discoveries, discuss advantages and limitations of current approaches, and consider directions by which the field can move forward to shed light on brain disorders.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with ...MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking ...as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2-3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6-10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = -74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = -78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.
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