Darren William Roddy

Background: The impact of depression on brain aging remains unclear, but both have been linked to stressful life events. Shared biological pathways may underlie structural brain changes. Clarifying these relationships could advance understanding of underlying mechanisms and inform treatment approaches. Methods: Structural MRI scans of 190 participants (controls, n = 110, clinically diagnosed with major depressive disorder [MDD], n = 80), from the REDEEM dataset, were input into three pretrained brain age prediction models: brainageR, DeepBrainNet, and pyment. Prediction accuracy was compared in controls to identify the optimal model. DeepBrainNet demonstrated the highest accuracy and was selected for subsequent analysis. Brain-predicted age difference (brain-PAD) was calculated as predicted age minus chronological age. Linear regression examined the effects of MDD diagnosis, childhood maltreatment, and cortisol awakening response on brain-PAD. Results: Depressed participants reported greater childhood maltreatment but a similar cortisol awakening response. An Age × Group interaction ( β = 0.34, 95% CI: 0.15–0.53, p < 0.001) indicated older adults with MDD exhibited greater positive deviations from normative brain age predictions, suggesting nonuniform brain aging across the lifespan. Cortisol awakening response showed a negative association with brain-PAD ( β = −0.01, 95% CI: −0.01 to −0.00, p = 0.041), indicating higher HPA-axis reactivity was linked to younger-appearing brains. Females showed lower brain-PAD than males, reflecting younger-appearing brains. Conclusions: MDD was associated with age-dependent differences in brain-PAD. The protective association between cortisol awakening response and brain age highlights the importance of integrating stress biomarkers to better understand neural aging mechanisms in depression.

This study investigated associations between bullying victimization and brain development using longitudinal structural MRI data from the IMAGEN cohort (n = 2094; 1009 females) across three time points (∼14, ∼19, and ∼22 years). A data-driven analysis revealed that higher bullying victimization was significantly associated with accelerated volumetric growth in subcortical and limbic regions, including the putamen (β = 0.12, 95% CI: 0.10–0.15), amygdala (β = 0.07, 95% CI: 0.05–0.09), hippocampus (β = 0.06, 95% CI: 0.04–0.08), and anterior cingulate cortex (caudal: β = 0.05, 95% CI: 0.03–0.07; rostral: β = 0.06, 95% CI: 0.04–0.08). In contrast, bullying victimization was also significantly associated with reduced volumetric growth in the cerebellum (β = −0.09, 95% CI: −0.11 to −0.07), entorhinal cortex (β = −0.10, 95% CI: −0.13 to −0.07), and insula (β = −0.08, 95% CI: −0.11 to −0.06). Exploratory analyses indicated that females exhibited more pronounced changes in emotional processing regions, while males showed greater changes in motor and sensory areas. Overall, the findings indicate that bullying victimization is associated with widespread structural differences in brain development from adolescence to early adulthood, with sex-specific trajectories.

Early life adversity, defined as exposure to stressful events during childhood, is a significant risk factor for the development of psychiatric disorders. Diffusion tensor imaging studies employing tract-based spatial statistics have shown microstructural abnormalities in white matter among individuals exposed to early life adversity; however, robust conclusions are yet to be drawn. This systematic review synthesizes findings of previous tract-based spatial statistics studies to identify the white matter alterations in adult brains exposed to early life adversity, in papers with methodological consistency. The literature search (April 2024) was conducted to identify tract-based spatial statistics studies that compared diffusion metrics between adults exposed to early life adversity and adults not. Embase, Pubmed, and PsycInfo were searched, retrieving 2458 articles. Following deduplication, 1739 titles and/or abstracts were screened. 1699 articles were excluded, and 40 full texts were reviewed. Seven articles, reporting on 764 subjects, met the inclusion criteria and were included in the narrative synthesis. Compared to controls, adults exposed to early life adversity showed lower fractional anisotropy values in white matter tracts of the limbic and visual processing systems, specifically the anterior thalamic radiation, inferior longitudinal fasciculus, corona radiata, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum bundle. This systematic review highlights that early life adversity may underlie emotional dysregulation and contribute to an increased risk of psychopathology in later life and explores the potential neurobiological mechanisms that underpin these structural changes. Understanding these associations is crucial for developing targeted interventions aimed at mitigating the long-term impact of early life adversity.

Objectives: Compassion is the emotion that motivates people to relieve the physical, emotional, or mental pains of others. Engaging in compassionate behaviour has been found to enhance psychological wellness and resilience. However, constant displays of compassionate behaviour can lead to burnout particularly for healthcare workers who inherently practise compassion day to day. This burnout can be relieved by Compassion focused meditation. The aim of this review is to identify neuroplastic changes in the brain associated with meditation, with a focus on compassion and compassion related meditation. Methods: Based on PRISMA guidelines, we conducted a scoping review of studies which described neuroplastic effects of meditation, focusing on compassion-based training. Studies were excluded if they (i) included multiple meditation practices or (ii) included participant populations with psychiatric/neuropsychiatric history (except anxiety or depression) or (iii) included exclusively ageing populations. Results: The results of the reviewed studies showed various neurological changes in regions of the brain as a result of compassion based training. These regions include amygdala, the anterior insula, medial prefrontal cortex, medial orbitofrontal cortex and structures within the dopamine system. Conclusion: This review highlights that compassion-based training could lead to neuroplastic changes which interconnect to enhance overall well-being, resilience and compassionate care among health-care professionals. However, further work is required to establish conclusive evidence of its sustained benefit and cost-effectiveness, as well as its utility in a healthcare setting.

Early life adversity, defined as exposure to stressful events during childhood, is a significant risk factor for the development of psychiatric disorders. Diffusion tensor imaging studies employing tract-based spatial statistics have shown microstructural abnormalities in white matter among individuals exposed to early life adversity; however, robust conclusions are yet to be drawn. This systematic review synthesizes findings of previous tract-based spatial statistics studies to identify the white matter alterations in adult brains exposed to early life adversity, in papers with methodological consistency. The literature search (April 2024) was conducted to identify tract-based spatial statistics studies that compared diffusion metrics between adults exposed to early life adversity and adults not. Embase, Pubmed, and PsycInfo were searched, retrieving 2458 articles. Following deduplication, 1739 titles and/or abstracts were screened. 1699 articles were excluded, and 40 full texts were reviewed. Seven articles, reporting on 764 subjects, met the inclusion criteria and were included in the narrative synthesis. Compared to controls, adults exposed to early life adversity showed lower fractional anisotropy values in white matter tracts of the limbic and visual processing systems, specifically the anterior thalamic radiation, inferior longitudinal fasciculus, corona radiata, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum bundle. This systematic review highlights that early life adversity may underlie emotional dysregulation and contribute to an increased risk of psychopathology in later life and explores the potential neurobiological mechanisms that underpin these structural changes. Understanding these associations is crucial for developing targeted interventions aimed at mitigating the long-term impact of early life adversity.

This study investigated associations between bullying victimization and brain development using longitudinal structural MRI data from the IMAGEN cohort (n = 2,094; 1,009 females) across three time points (∼14, ∼19, and ∼22 years). A data-driven analysis revealed that higher bullying victimization was significantly associated with accelerated volumetric growth in subcortical and limbic regions, including the putamen (β = 0.12, 95% CI: 0.10–0.15), amygdala (β = 0.07, 95% CI: 0.05–0.09), hippocampus (β = 0.06, 95% CI: 0.04– 0.08), and anterior cingulate cortex (caudal: β = 0.05, 95% CI: 0.03–0.07; rostral: β = 0.06, 95% CI: 0.04–0.08). In contrast, bullying victimization was also significantly associated with reduced volumetric growth in the cerebellum (β = –0.09, 95% CI: –0.11 to –0.07), entorhinal cortex (β = –0.10, 95% CI: –0.13 to –0.07), and insula (β = –0.08, 95% CI: –0.11 to –0.06).Exploratory analyses indicated that females exhibited more pronounced changes in emotional processing regions, while males showed greater changes in motor and sensory areas. Overall, the findings indicate that bullying victimization is associated with widespread structural differences in brain development from adolescence to early adulthood, with sex-specific trajectories.

A berrant connectivity in the cerebellum has been found in psychotic conditions such as schizophrenia corresponding with cognitive and motor deficits found in these conditions. Diffusion differences in the superior cerebellar peduncles, the white matter connecting the cerebellar circuitry to the rest of the brain, have also been found in schizophrenia and high-risk states. However, white matter diffusivity in the peduncles in individuals with sub-threshold psychotic experiences (PEs) but not reaching the threshold for a definitive diagnosis remains unstudied. This study investigates the cerebellar peduncles in adolescents with PEs but no formal psychiatric diagnosis.Sixteen adolescents with PEs and 17 age-matched controls recruited from schools underwent High-Angular-Resolution-Diffusion neuroimaging. Following constrained spherical deconvolution whole-brain tractography, the superior, inferior and middle peduncles were isolated and virtually dissected out using ExploreDTI. Differences for macroscopic and microscopic tract metrics were calculated using one-way between-group analyses of covariance controlling for age, sex and estimated Total Intracranial Volume (eTIV). Multiple comparisons were corrected using Bonferroni correction.A decrease in fractional anisotropy was identified in the right (p = 0.045) and left (p = 0.058) superior cerebellar peduncle; however, this did not survive strict Bonferroni multiple comparison correction. There were no differences in volumes or other diffusion metrics in either the middle or inferior peduncles.Our trend level changes in the superior cerebellar peduncle in a non-clinical sample exhibiting psychotic experiences complement similar but more profound changes previously found in ultra-high-risk individuals and those with psychotic disorders. This suggests that superior cerebellar peduncle circuitry perturbations may occur early along in the psychosis spectrum.

Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p < .00013) with moderate to large effect sizes (.11–.76) throughout all significant subsegments. In this prospective community‐based cohort of school‐age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non‐clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along‐tract analysis of white matter tracts.

Studies of early life stress (ELS) demonstrate the long-lasting effects of acute and chronic stress on developmental trajectories. Such experiences can become biologically consolidated, creating individual vulnerability to psychological and psychiatric issues later in life. The hippocampus, amygdala, and the medial prefrontal cortex are all important limbic structures involved in the processes that undermine mental health. Hyperarousal of the sympathetic nervous system with sustained allostatic load along the Hypothalamic Pituitary Adrenal (HPA) axis and its connections has been theorized as the basis for adult psychopathology following early childhood trauma. In this review we synthesize current understandings and hypotheses concerning the neurobiological link between childhood trauma, the HPA axis, and adult psychiatric illness. We examine the mechanisms at play in the brain of the developing child and discuss how adverse environmental stimuli may become biologically incorporated into the structure and function of the adult brain via a discussion of the neurosequential model of development, sensitive periods and plasticity. The HPA connections and brain areas implicated in ELS and psychopathology are also explored. In a targeted review of HPA activation in mood and psychotic disorders, cortisol is generally elevated across mood and psychotic disorders. However, in bipolar disorder and psychosis patients with previous early life stress, blunted cortisol responses are found to awakening, psychological stressors and physiological manipulation compared to patients without previous early life stress. These attenuated responses occur in bipolar and psychosis patients on a background of increased cortisol turnover. Although cortisol measures are generally raised in depression, the evidence for a different HPA activation profile in those with early life stress is inconclusive. Further research is needed to explore the stress responses commonalities between bipolar disorder and psychosis in those patients with early life stress.