Brain structural alterations associated with young women with subthreshold depression.
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ABSTRACT: Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD.
Project description:ObjectiveNeuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years.MethodHigh-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes.ResultsAdolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial-prefrontal gray matter volume.ConclusionSubthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal-striatal-limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial-prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.
Project description:Attentional bias toward negative stimuli has been observed in major depression disorders (MDDs). Imaging studies suggest the engagement of fronto-limbic regions like amygdala, anterior cingulate cortex (ACC), and lateral prefrontal cortex, is related to negatively biased attention. However, neural correlates of attentional bias for negative stimuli in individuals with subthreshold depression (SubD), that is individuals who have clinically relevant depressive symptoms but do not fulfill the criteria for MDD, remain unclear. Here, we used functional neuroimaging and the dot-probe task to elucidate the neural substrates of negatively biased attention among individuals with SubD. Behavioral results found that individuals with SubD allocated more attention toward negative stimuli relative to neutral stimuli, which were not observed among non-depressed controls (NCs). Imaging results found greater amygdala and rostral ACC activity in attentional bias toward negative stimuli among participants with SubD compared to NCs; Additionally, participants with SubD showed reduced engagement of bilateral inferior frontal gyrus compared with NCs in the attentional processing of negative stimuli. Together, these results suggest that alteration of fronto-limbic systems relative to controls, known to be related to negative detection and attentional control, is associated with negatively biased attention in individuals with SubD.
Project description:Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1-6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or develop in early childhood prior to reading onset. Further studies using larger sample sizes and longitudinal analyses are needed in order to determine whether the identified structural alterations may be utilized as structural markers for the early identification of children at risk, which may prevent the negative clinical, social and psychological outcome of developmental dyslexia.
Project description:Postpartum depression (PPD) affects approximately 1 in 10 women after childbirth. A thorough understanding of a preexisting vulnerability to PPD will likely aid the early detection and treatment of PPD. Using a within-sample association, the study examined whether the brain's structural and functional alterations predict the onset of depression. 157 euthymic postpartum women were subjected to a multimodal MRI scan within the first 6 days of childbirth and were followed up for 12 weeks. Based on a clinical interview 12 weeks postpartum, participants were classified as mentally healthy or having either PPD or adjustment disorder (AD). Voxel-based morphometry and resting-state functional connectivity comparisons were performed between the three groups. 13.4% of women in our study developed PPD (n = 21) and 12.1% (n = 19) adjustment disorder (AD). The risk factors for PPD were a psychiatric history and the experience and severity of baby blues and the history of premenstrual syndrome. Despite the different risk profiles, no differences between the PPD, AD and control group were apparent based on structural and functional neuroimaging data immediately after childbirth. At 12 weeks postpartum, a significant association was observed between Integrated Local Correlation (LCor) and the Edinburgh Postnatal Depression Score (EPDS). Our findings do not support the notion that the brain's structural and resting-state functional alterations, if present, can be used as an early biomarker of PPD or AD. However, effects may become apparent if continuous measures of symptom severity are chosen.
Project description:Objective: Suicide is the leading cause of death from bipolar disorder (BD). At least 25-50% of the patients with BD will attempt suicide, with suicide rates much higher in women patients than in men. It is crucial to explore the potential neural mechanism underlying suicidality in women with BD, which will lead to understanding and detection of suicidality and prevent death and injury from suicide. Methods: Brain function and structure were measured by amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) in 155 women [30 women with BD and a history of suicidality, 50 women with BD without suicidality, and 75 healthy controls (HC)]. The differences in ALFF and GMV across the BD with suicidality, BD without suicidality, and HC groups were investigated. Results: BD with suicidality showed significantly increased ALFF in the left and right cuneus compared with BD without suicidality and HC groups. Moreover, the GMV in the left lateral prefrontal cortex and left cuneus in BD with suicidality were significantly lower than those in BD without suicidality and HC groups, while the GMV of the right ventral prefrontal cortex was significantly decreased in both BD with and without suicidality groups. Conclusions: This study, combining functional and structural neuroimaging techniques, may help to identify specific pathophysiological changes in women with BD and suicidality. Increased ALFF and less GMV in cuneus might represent the neuroimaging features of suicidality in women with BD. Investigating this potential neuromarker for suicidality in women with BD may lead to the ability to prevent suicidality.
Project description:Adolescent-onset major depressive disorder (MDD) is associated with an increased risk of recurrent depressive episodes, suicidal behaviors, and psychiatric morbidity throughout the lifespan. The objective of the present study was to investigate brain structural and functional changes in adolescent patients with MDD. Furthermore, we aimed to clarify the influence of early-life stress on brain function and structure. The study investigated adolescent patients with severe MDD (n=20, mean age=16.0, range=15-18 years) and a control sample of matched healthy adolescents (n=21, mean age=16.6, range=15-18 years). Functional MRI data were obtained using a face-matching paradigm to investigate emotion processing. Structural MRI data were analyzed using voxel-based morphometry (VBM). In line with previous studies on adult MDD, adolescent patients showed elevated amygdala activity to negative and reduced amygdala activity to positive emotional stimuli. Furthermore, MDD patients showed smaller hippocampal volumes compared to healthy adolescents. Higher levels of childhood maltreatment were associated with smaller hippocampal volumes in both depressed patients and healthy controls, whereby no associations between amygdala reactivity and childhood maltreatment were found. Our results suggest that hippocampal alterations in youth MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.
Project description:IntroductionThe interplay between influential factors and the incidence of subthreshold depression (SD) in young adults remains poorly understood.ObjectivesThis study sought to understand the dietary habits, gut microbiota composition, etc. among individuals with SD in young adults and to investigate their association with SD occurrence.MethodsEmploying a cross-sectional approach, 178 individuals with SD, aged 18-32 years, were matched with 114 healthy counterparts. SD status was evaluated using the Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Beck Depression Inventory 2nd version (BDI-II), the 17-item Hamilton Rating Scales of Depression (HAMD-17), and Pittsburgh Sleep Quality Index (PSQI). Metagenomic sequencing was utilized to identify fecal microbial profiles. Dietary patterns were discerned via factor analysis of a 25-item food frequency questionnaire (FFQ). Logistic regression analysis and mediation analysis were performed to explore the potential links between gut microbiota, dietary patterns, and incident SD.ResultsData on dietary habits were available for 292 participants (mean [SD] age, 22.1 [2.9] years; 216 [73.9 %] female). Logistic regression analysis revealed that dietary patterns Ⅰ (odds ratio [OR], 0.34; 95 % CI, 0.15-0.75) and IV (OR, 0.39; 95 % CI, 0.17-0.86 and OR, 0.39; 95 % CI, 0.18-0.84) were associated with reduced risk of SD. Distinct microbial profiles were observed in young adults with SD, marked by increased microbial diversity and taxonomic alterations. Moreover, mediation analysis suggested Veillonella atypica as a potential mediator linking SDS or BDI-II scores with a healthy dietary pattern rich in bean products, coarse grains, nuts, fruits, mushrooms, and potatoes (β = 0.25, 95 % CI: 0.02-0.78 and β = 0.18, 95 % CI: 0.01-0.54).ConclusionsOur findings highlight the complex interplay between dietary patterns, gut microbiota, and the risk of developing SD in young adults, underscoring the potential for dietary interventions and microbiome modulation in mental health promotion.
Project description:Some brain abnormalities persist at the remission phase, that is, the state-independent abnormalities, which may be one of the reasons for the high recurrence of major depressive disorder (MDD). Hence, it is of great significance to identify state-independent abnormalities of MDD through longitudinal investigation. Ninety-nine MDD patients and 118 healthy controls (HCs) received diffusion tensor imaging scanning at baseline. After 6-month antidepressant treatment, 68 patients received a second scan, among which 59 patients achieved full clinical remission. Differences in whole-brain structural connectivity (SC) between patients with MDD at baseline and HCs were estimated by two-sample t-tests. Masked with significantly changed SCs in MDD, two-sample t-tests were conducted between the remitted MDD subgroup at follow-up and HCs, and paired t-tests were implemented to compare the differences of SC in the remitted MDD subgroup before and after treatment. Significantly decreased SC between the right insula and the anterior temporal cortex (ATC), between the right ATC and the posterior temporal cortex (PTC), between the left ATC and the auditory cortex as well as increased connectivity between the right posterior cingulate cortex (PCC) and the left medial parietal cortex (MPC) were observed in the MDD group compared with the HC group at baseline (p < 0.05, FDR corrected). The decreased connectivity between the right insula and the ATC and increased connectivity between the right PCC and the left MPC persisted in the remitted MDD subgroup at follow-up (p < 0.05, FDR corrected). The decreased SC between the right insula and the ATC and increased SC between the right PCC and left MPC showed state-independent characters, which may be implicated in the sustained negative attention bias and motor retardation in MDD. In contrast, the decreased SC between the right ATC and the PTC and between the left ATC and the auditory cortex seemed to be state-dependent.
Project description:Accumulating studies have highlighted the links between stress-related networks and the HPA axis for emotion regulation and proved the mapping associations between altered structural and functional networks (called SC-FC coupling) in depression. However, the signatures of SC-FC coupling in subthreshold depression (StD) individuals and their relationships with HPA axis reactivity, as well as the predictive power of these combinations for discriminating StD, remain unclear. This cross-sectional study enrolled 160 adults, including 117 StD and 43 healthy controls (HC). The propensity score matching method was applied for match-pair analysis between StD and HC. Herein, we measured depression level, cortisol level, and brain imaging outcomes. The functional MRI and diffusion tensor imaging methods were employed to acquire the network SC-FC couplings and topological attributes. Support vector machine models were employed to discriminate StD from HC. Herein, 43 pairs were matched, but four participants were excluded due to over-threshold head motion, leaving 41 participants in each group. General linear model results revealed a significant SC-FC coupling increase in the default mode network (DMN) and decrements of global efficiency in DMN and frontoparietal control network (P < 0.05), while the cortisol secretion significantly increased (P < 0.001) in StD individuals. Partial correlation analysis revealed positive associations between DMN coupling and cortisol values (r = 0.298, P = 0.033), and their combination provided greater power for discriminating StD than another single model, with the classification accuracy and AUC value up to 85.71% and 0.894, respectively. In summary, this study clarified the relationship between stress-related network SC-FC coupling and cortisol secretion in influencing depressive symptoms, whose combination would contribute to discriminating subthreshold depressive states in the future.
Project description:BACKGROUND: Altered basal ganglia function has been implicated in the pathophysiology of youth Major Depressive Disorder (MDD). Studies have generally focused on characterizing abnormalities in ventral "affective" corticostriatal loops supporting emotional processes. Recent evidence however, has implicated alterations in functional connectivity of dorsal "cognitive" corticostriatal loops in youth MDD. The contribution of dorsal versus ventral corticostriatal alterations to the pathophysiology of youth MDD remains unclear. METHODS: Twenty-one medication-free patients with moderate-to-severe MDD between the ages of 15 and 24 years old were matched with 21 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging we systematically investigated connectivity of eight dorsal and ventral subdivisions of the striatum. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the depressed and control groups. RESULTS: Depressed youths showed alterations in functional connectivity that were confined to the dorsal corticostriatal circuit. Compared to controls, depressed patients showed increased connectivity between the dorsal caudate nucleus and ventrolateral prefrontal cortex bilaterally. Increased depression severity correlated with the magnitude of dorsal caudate connectivity with the right dorsolateral prefrontal cortex. There were no significant between-group differences in connectivity of ventral striatal regions. CONCLUSIONS: The results provide evidence that alterations in corticostriatal connectivity are evident at the early stages of the illness and are not a result of antidepressant treatment. Increased connectivity between the dorsal caudate, which is usually associated with cognitive processes, and the more affectively related ventrolateral prefrontal cortex may reflect a compensatory mechanism for dysfunctional cognitive-emotional processing in youth depression.