Research reportThe effects of bullying in depression on white matter integrity
Introduction
Depression is associated with abnormal brain integrity. Previous work reveals that lower volumes of the amygdala, anterior cingulate cortex (ACC), and hippocampus are correlated with more severe depressive symptoms [[1], [2], [3]]. Additionally, white matter integrity is reduced in the cingulum bundle, supero-lateral medial forebrain bundle, uncinate fasciculus (UF), and superior longitudinal fasciculus among individuals with elevated symptoms of depression [[4], [5], [6]]. These brain areas generally have large functional implications for stress response, emotional expression, and sensory processing studies [1,7,8], all of which are relevant to mood dysregulation.
While it is clear that depression relates to altered brain signatures, other environmental factors may influence neuroimaging outcomes in this population. In particular, many researchers have postulated that stressful events occurring early in the lifespan also impact brain integrity independent of depression [[9], [10], [11]]. This is especially conceivable considering studies have showed ELS to relate to neural abnormalities both in studies that control for the severity of depression [11,12] and those in a non-clinical population [9,10]. Early life stressors (ELS) affect the neurobiological stress response systems, resulting in an overactive hypothalamic-adrenal-pituitary (HPA) axis and increased vulnerability to develop depression in adulthood [13]. For example, prior work revealed more severe hippocampal atrophy [48] and reduced connectivity within the prefrontal-limbic-thalamic-cerebellar circuitry [11] among ELS-positive (ELS+) individuals with current depression as compared to depressed individuals with no history of ELS.
Less is known about the microstructural integrity of brain white matter among individuals with ELS and depression. Cerebral white matter accounts for more overall brain volume than the cortical and subcortical gray matter [14]. Further, the white matter tracts undergo substantial neurodevelopment during childhood [15] raising the possibility of significant structural and functional damage secondary to ELS.
There is controversy regarding the interaction of ELS and depression on white matter integrity. White matter integrity is often measured with fractional anisotropy (FA), which is a ratio of restricted/unrestricted diffusion. FA is highly impacted by myelination; the less myelinated a white matter tract, the more intercellular space available. With more space available, movement is less anisotropic and results in lower FA. The reverse is true as well; the more densely packed together axons are, the more diffusion of water is restricted and the greater the FA [[16], [17], [18]]. Depression [19] and ELS [9,10] are each associated with lower FA, indicative of reduced white matter microstructure and possibly subsequent reduced connectivity between brain regions [18]. However, studies report increased FA in the rostral cingulum, dorsal cingulum (Ugwu, Amico, Carbadello, Fagan, & Frodl, 2015), uncinate fasciculus, and superior longitudinal fasciculus [12] among adults with depression and a positive history of ELS, and at least one study reported no interdependence between these two factors [5]. Though lower levels of FA are typically thought of as representative of dysfunction, abnormal levels in either direction can indicate dysfunction depending on the brain region [18]. In the case of ELS, higher FA may be indicative of anomalies in the fear network (Ugwu, et al., 2015).
No study has examined the effects of bullying within depression on white matter. Bullying has been strongly related to depression across the life span [[20], [21], [22], [23]]. One study of 2680 adolescents reported that depression was two times more common among individuals with a history of bullying [20]. Further, bullying is common, affecting 24.5% of children in elementary school and 34.1% in middle school [24], with studies showing boys to more likely be both perpetrators and victims of bullying [56,57]. The present study aimed to explore the intersection of bullying as an ELS subtype and depression on neuroimaging markers of white matter microstructural integrity. A total of 186 adults with current depression completed high resolution DTI and self-report measures of emotional health. We hypothesized that individuals with a history of bullying and current depression would exhibit more severe abnormalities in white matter tracts compared to individuals with similar levels of depression but no history of bullying or other forms of ELS.
Section snippets
Participants
Participants were part of the International Study to Predict Optimized Treatment for Depression (iSPOT-D; [25,26]). Broadly, iSPOT-D is a multisite, international study tasked with investigating pretreatment predictors of interventions for depression. From the total imaging sample of 204 recruited at baseline into the iSPOT-D imaging substudy [26], 192 participants had complete DTI data. Of those 192, 6 were missing ELS data, bringing the sample size of the present analysis to 186 individuals
Results
Overall, 88 people endorsed a history of bullying (4–7: n = 10; 8–12: n = 37; 13–17: n = 41). Table 1 reports demographic results. The ratio of individuals who meet criteria for MDD and endorse bullying in this imaging substudy (47%) aligns well with the rate (45%) from the overall trial sample [37]. Groups by bulling endorsement differed by endorsement of emotional abuse (F(3,196) = 3.435, p = .018), such that there were significantly more individuals who endorsed a history of emotional abuse
Discussion
The results of this study suggest that a history of being bullied in mid to late adolescence imparts a unique effect on white matter integrity beyond the effect of depression. Individuals with depression who had been bullied showed greater FA in the left posterior corona radiata and right medial lemniscus tracts, compared to their non-bullied depressed peers. The direction of this effect contributes to the body of knowledge about the white matter markers of depression and early life stress
Acknowledgements
We acknowledge Brain Resource Ltd as the sponsor for the iSPOT-D study (NCT00693849). We acknowledge the role of A/Prof Anthony Harris and Prof Tim Usherwood as clinical PIs and their role for overseeing the clinical testing and recruitment for the Sydney site for the imaging substudy. We also acknowledge the role of Dr. Claire Day as Global Study coordinator and thank the iSPOT-D Publication Team for their valuable input into this manuscript and to the study overall.
References (59)
- et al.
Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder
J. Affect. Disord.
(2015) - et al.
A review of white matter microstructure alterations of pathways of the reward circuit in depression
J. Affect. Disord.
(2015) - et al.
Impact of early and recent stress on white matter microstructure in major depressive disorder
J. Affect. Disord.
(2018) - et al.
Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies
J. Affect. Disord.
(2012) Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders
Curr. Opin. Neurobiol.
(2001)- et al.
White matter integrity in major depressive disorder: implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms
Psychiatry Res. Neuroimaging
(2016) White matter in learning, cognition and psychiatric disorders
Trends Neurosci.
(2008)- et al.
Diffusion tensor imaging of the brain
Neurotherapeutics
(2007) - et al.
Bullying victimization and adolescent mental health: general and typological effects across sex
J. Crim. Justice
(2013) - et al.
Reliability of the Hamilton Rating Scale for Depression: a meta-analysis over a period of 49years
Psychiatry Res.
(2011)
Early life trauma predicts self-reported levels of depressive and anxiety symptoms in nonclinical community adults: relative contributions of early life stressor types and adult trauma exposure
J. Psychiatry Res.
Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei
Biol. Psychiatry
The measurement of maltreatment: a comparison of approaches
Child Abuse Negl.
False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies
J. Clin. Epidemiol.
White matter correlates of anxiety sensitivity in panic disorder
J. Affect. Disord.
Empirical comparison of diffusion kurtosis imaging and diffusion basis spectrum imaging using the same acquisition in healthy young adults
Front. Neurol.
Altered tract-specific white matter microstructure is related to poorer cognitive performance: the Rotterdam Study
Neurobiol. Aging
White matter integrity and cognitive performance in school-age children: a population-based neuroimaging study
NeuroImage
The International Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment
J. Psychiatric Res.
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
Neuroimage
Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications
Brain Behav. Immun.
A macroscopic view of microstructure: using diffusion-weighted images to infer damage, repair, and plasticity of white matter
Neuroscience
Reduced subgenual cingulate volumes in mood disorders: a meta-analysis
J. Psychiatry Neurosci.: JPN
Untreated depression and hippocampal volume loss
Am. J. Psychiatry
A diffusion tensor imaging study using a voxel-based analysis, region-of-interest method to analyze white matter abnormalities in first-episode, treatment-naive major depressive disorder
J. Neuropsychiatry Clin. Neurosci.
White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology
Neuropsychopharmacology
The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population
Neuropsychiatr. Dis. Treat.
Overlapping and segregated resting‐state functional connectivity in patients with major depressive disorder with and without childhood neglect
Hum. Brain Mapp.
Importance of studying the contributions of early adverse experience to neurobiological findings in depression
Neuropsychopharmacology
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