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1.
Eur J Neurosci ; 59(12): 3322-3336, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38650167

ABSTRACT

Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict white matter (WM) integrity in emerging mental disorders. Young people (N = 364) accessing early-intervention clinics underwent assessments for chronotype, subjective sleep quality, and diffusion tensor imaging. Using machine learning, we examined whether chronotype or sleep quality (alongside diagnostic and demographic factors) could predict four measures of WM integrity: fractional anisotropy (FA), and radial, axial, and mean diffusivities (RD, AD and MD). We prioritised tracts that showed a univariate association with sleep quality or chronotype and considered predictors identified by ≥80% of machine learning (ML) models as 'important'. The most important predictors of WM integrity were demographics (age, sex and education) and diagnosis (depressive and bipolar disorders). Subjective sleep quality only predicted FA in the perihippocampal cingulum tract, whereas chronotype had limited predictive importance for WM integrity. To further examine links with mood disorders, we conducted a subgroup analysis. In youth with depressive and bipolar disorders, chronotype emerged as an important (often top-ranking) feature, predicting FA in the cingulum (cingulate gyrus), AD in the anterior corona radiata and genu of the corpus callosum, and RD in the corona radiata, anterior corona radiata, and genu of corpus callosum. Subjective quality was not important in this subgroup analysis. In summary, chronotype predicted altered WM integrity in the corona radiata and corpus callosum, whereas subjective sleep quality had a less significant role, suggesting that circadian factors may play a more prominent role in WM integrity in emerging mood disorders.


Subject(s)
Diffusion Tensor Imaging , Sleep Quality , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Male , Female , Adolescent , Diffusion Tensor Imaging/methods , Young Adult , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/physiopathology , Machine Learning , Depressive Disorder/diagnostic imaging , Depressive Disorder/physiopathology , Chronotype
2.
Eur Arch Psychiatry Clin Neurosci ; 273(5): 1139-1149, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35908116

ABSTRACT

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback was found to reduce depressive symptoms. However, no direct comparison of drug-free patients with an active psychotherapy control group is available. The present study compared rt-fMRI neurofeedback with cognitive behavioral therapy, as the standard treatment in patients declining anti-depressants. Twenty adult, drug-free patients with mild or moderate depression were non-randomly assigned either to a course of eight half-hour sessions of neurofeedback targeting the left medial prefrontal cortex (N = 12) or to a 16-session course of cognitive behavioral therapy (N = 8). Montgomery-Asberg Depression Rating Scale was introduced at baseline, mid-treatment, and end-treatment points. In each group, 8 patients each remained in the study to a mid-treatment evaluation and 6 patients each to the study end-point. ANOVA revealed a depression reduction with a significant effect of Time (F(3,6) = 19.0, p < 0.001, η2 = 0.76). A trend to greater improvement in the cognitive behavioral therapy group compared to neurofeedback emerged (Group × Time; p = 0.078). Percent signal change in the region of interest between up- and down-regulation conditions was significantly correlated with session number (Pearson's r = 0.85, p < 0.001) indicating a learning effect. As limitations, small sample size could lead to insufficient power and non-random allocation to selection bias. Both neurofeedback and cognitive behavioral therapy improved mild and moderate depression. Neurofeedback was not superior to cognitive behavioral therapy. Noteworthy, the neurofeedback training course was associated with continuous improvement in the self-regulation skill, without plateau. This study delivers data to plan clinical trials comparing neurofeedback with cognitive behavioral interventions.


Subject(s)
Cognitive Behavioral Therapy , Depressive Disorder , Adult , Humans , Pilot Projects , Magnetic Resonance Imaging/methods , Depression/diagnostic imaging , Depression/therapy , Depressive Disorder/diagnostic imaging , Depressive Disorder/therapy , Cognitive Behavioral Therapy/methods
3.
J Ultrasound Med ; 42(3): 687-699, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36047031

ABSTRACT

BACKGROUND: Transcranial sonography (TCS) is an available and noninvasive neuroimaging method that has been found to reduce the echogenicity of the brainstem raphe (BR) in patients with depression. Applying the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we performed a meta-analysis of the diagnostic accuracy of TCS. METHODS: A systematic search was conducted in PubMed, EMBASE, The Cochrane Library, and Web of Science. The databases were searched from inception to December 2021. The quality of the included literature was assessed using the QUADAS-2. Heterogeneity analysis was performed. A summary receiver operating characteristic (SROC) curve was generated to evaluate the diagnostic accuracy of TCS. RESULTS: We included 12 studies with 809 patients. The pooled sensitivity was 0.66 (95% confidence interval [CI]: 0.61-0.71), and the specificity was 0.84 (95% CI: 0.80-0.87). The combined positive likelihood ratio (LR) was 3.84 (95% CI: 2.68-5.51), the negative LR was 0.41 (95% CI: 0.29-0.57), and the diagnostic odds ratio (DOR) was 11.45 (95% CI: 5.57-23.02). The area under the curve (AUC) of the plotted SROC curve was 0.86 (95% CI: 0.83-0.89). The meta-regression and subgroup analyses found no source of heterogeneity. CONCLUSION: TCS has high potential and efficacy in diagnosing depression and may be a reasonable test to perform clinically for the assessment of depression.


Subject(s)
Depressive Disorder , Humans , Ultrasonography , ROC Curve , Area Under Curve , Depressive Disorder/diagnostic imaging , Sensitivity and Specificity
4.
J Neurophysiol ; 127(1): 146-149, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34879212

ABSTRACT

Adolescence is a developmental period associated with major neural reorganization and the onset of many psychological disorders. Depression in particular is prevalent and impairing in adolescents and rates have been rising in recent years. Recent advances in the neurobiology of adolescent depression contribute to a better understanding of functional connectivity among neural networks and represent a promising start for determining biomarkers of depression and potential areas of intervention.


Subject(s)
Brain/physiopathology , Connectome , Depression/physiopathology , Depressive Disorder/physiopathology , Nerve Net/physiopathology , Adolescent , Brain/diagnostic imaging , Depression/diagnostic imaging , Depressive Disorder/diagnostic imaging , Humans , Nerve Net/diagnostic imaging
5.
Bipolar Disord ; 24(5): 474-498, 2022 08.
Article in English | MEDLINE | ID: mdl-35060259

ABSTRACT

OBJECTIVES: Magnetic resonance imaging (MRI) studies comparing bipolar and unipolar depression characterize pathophysiological differences between these conditions. However, it is difficult to interpret the current literature due to differences in MRI modalities, analysis methods, and study designs. METHODS: We conducted a systematic review of publications using MRI to compare individuals with bipolar and unipolar depression. We grouped studies according to MRI modality and task design. Within the discussion, we critically evaluated and summarized the functional MRI research and then further complemented these findings by reviewing the structural MRI literature. RESULTS: We identified 88 MRI publications comparing participants with bipolar depression and unipolar depressive disorder. Compared to individuals with unipolar depression, participants with bipolar disorder exhibited heightened function, increased within network connectivity, and reduced grey matter volume in salience and central executive network brain regions. Group differences in default mode network function were less consistent but more closely associated with depressive symptoms in participants with unipolar depression but distractibility in bipolar depression. CONCLUSIONS: When comparing mood disorder groups, the neuroimaging evidence suggests that individuals with bipolar disorder are more influenced by emotional and sensory processing when responding to their environment. In contrast, depressive symptoms and neurofunctional response to emotional stimuli were more closely associated with reduced central executive function and less adaptive cognitive control of emotionally oriented brain regions in unipolar depression. Researchers now need to replicate and refine network-level trends in these heterogeneous mood disorders and further characterize MRI markers associated with early disease onset, progression, and recovery.


Subject(s)
Bipolar Disorder , Depressive Disorder , Bipolar Disorder/diagnosis , Depression , Depressive Disorder/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy
6.
Hum Brain Mapp ; 42(11): 3656-3666, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33932251

ABSTRACT

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never-treated first-episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel-based morphometry derived from T1-weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never-treated first-episode patients with depression (N = 195). The brain-predicted age difference (brain-PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age-, gender-, educational level-matched HCs in Dataset 1. Overall, patients presented higher brain-PAD scores suggesting patients with depression having an "older" brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data-driven method and significant correlation between brain-PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage-dependent phenomenon in depression.


Subject(s)
Aging, Premature , Depressive Disorder , Disease Progression , Gray Matter , Adolescent , Adult , Age Factors , Aging, Premature/diagnostic imaging , Aging, Premature/etiology , Aging, Premature/pathology , Child , Depressive Disorder/complications , Depressive Disorder/diagnostic imaging , Depressive Disorder/pathology , Female , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Models, Theoretical , Young Adult
7.
Hum Brain Mapp ; 42(6): 1617-1625, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33296139

ABSTRACT

Depressive symptoms are common in patients with first-episode psychosis. However, the neural mechanisms underlying the comorbid depression in schizophrenia are still unknown. The main purpose of this study was to characterize the structural abnormalities of first-episodes drug-naïve (FEDN) schizophrenia comorbid with depression by utilizing both volume-based and surface-based morphometric measurements. Forty-two patients with FEDN schizophrenia and 29 healthy controls were recruited. The 24-item Hamilton Depression Rating Scale (HAMD-24) was administrated to divide all patients into depressive patients (DP) and non-depressive patients (NDP). Compared with NDP, DP had a significantly larger volume and surface area in the left isthmus cingulate cortex and also had a greater volume in the left posterior cingulate cortex. Correlation analysis showed that HAMD total score was positively correlated with the surface area of the left isthmus cingulate and gray matter volume of the left isthmus cingulate cortex. In addition, gray matter volume of the left isthmus cingulate was also correlated with the PANSS general psychopathology or total score. The findings suggest that prominent structural abnormalities of gray matter are mainly concentrated on the cingulate cortex in FEDN schizophrenia patients comorbid with depression, which may contribute to depressive symptoms and psychopathological symptoms.


Subject(s)
Depression/pathology , Depressive Disorder/pathology , Gyrus Cinguli/pathology , Schizophrenia/pathology , Adolescent , Adult , Comorbidity , Depression/diagnostic imaging , Depression/epidemiology , Depressive Disorder/diagnostic imaging , Depressive Disorder/epidemiology , Female , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Schizophrenia/diagnostic imaging , Schizophrenia/epidemiology , Young Adult
8.
Hum Brain Mapp ; 42(11): 3547-3560, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33955106

ABSTRACT

To make adaptive decisions under uncertainty, individuals need to actively monitor the discrepancy between expected outcomes and actual outcomes, known as prediction errors. Reward-based learning deficits have been shown in both depression and schizophrenia patients. For this study, we compiled studies that investigated prediction error processing in depression and schizophrenia patients and performed a series of meta-analyses. In both groups, positive t-maps of prediction error tend to yield striatum activity across studies. The analysis of negative t-maps of prediction error revealed two large clusters within the right superior and inferior frontal lobes in schizophrenia and the medial prefrontal cortex and bilateral insula in depression. The concordant posterior cingulate activity was observed in both patient groups, more prominent in the depression group and absent in the healthy control group. These findings suggest a possible role in dopamine-rich areas associated with the encoding of prediction errors in depression and schizophrenia.


Subject(s)
Anticipation, Psychological/physiology , Brain Mapping , Depressive Disorder/physiopathology , Gyrus Cinguli/physiopathology , Insular Cortex/physiopathology , Prefrontal Cortex/physiopathology , Schizophrenia/physiopathology , Depressive Disorder/diagnostic imaging , Gyrus Cinguli/diagnostic imaging , Humans , Insular Cortex/diagnostic imaging , Magnetic Resonance Imaging , Prefrontal Cortex/diagnostic imaging , Schizophrenia/diagnostic imaging
9.
Psychosom Med ; 83(7): 707-714, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34117157

ABSTRACT

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.


Subject(s)
Brain , Depressive Disorder , Anxiety/diagnostic imaging , Arousal , Brain/diagnostic imaging , Brain Mapping , Constipation/diagnostic imaging , Depressive Disorder/diagnostic imaging , Humans , Magnetic Resonance Imaging , Thalamus/diagnostic imaging
10.
Hum Brain Mapp ; 41(1): 241-255, 2020 01.
Article in English | MEDLINE | ID: mdl-31571370

ABSTRACT

Previous structural and functional neuroimaging studies have implicated distributed brain regions and networks in depression. However, there are no robust imaging biomarkers that are specific to depression, which may be due to clinical heterogeneity and neurobiological complexity. A dimensional approach and fusion of imaging modalities may yield a more coherent view of the neuronal correlates of depression. We used linked independent component analysis to fuse cortical macrostructure (thickness, area, gray matter density), white matter diffusion properties and resting-state functional magnetic resonance imaging default mode network amplitude in patients with a history of depression (n = 170) and controls (n = 71). We used univariate and machine learning approaches to assess the relationship between age, sex, case-control status, and symptom loads for depression and anxiety with the resulting brain components. Univariate analyses revealed strong associations between age and sex with mainly global but also regional specific brain components, with varying degrees of multimodal involvement. In contrast, there were no significant associations with case-control status, nor symptom loads for depression and anxiety with the brain components, nor any interaction effects with age and sex. Machine learning revealed low model performance for classifying patients from controls and predicting symptom loads for depression and anxiety, but high age prediction accuracy. Multimodal fusion of brain imaging data alone may not be sufficient for dissecting the clinical and neurobiological heterogeneity of depression. Precise clinical stratification and methods for brain phenotyping at the individual level based on large training samples may be needed to parse the neuroanatomy of depression.


Subject(s)
Anxiety/diagnostic imaging , Depression/diagnostic imaging , Depressive Disorder/diagnostic imaging , Machine Learning , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Adult , Age Factors , Anxiety/pathology , Anxiety/physiopathology , Case-Control Studies , Depression/pathology , Depression/physiopathology , Depressive Disorder/pathology , Depressive Disorder/physiopathology , Female , Functional Neuroimaging/methods , Humans , Male , Middle Aged , Multimodal Imaging , Sex Factors
11.
J Neurosci Res ; 98(6): 1150-1161, 2020 06.
Article in English | MEDLINE | ID: mdl-32090389

ABSTRACT

Adults with autism spectrum disorder (ASD) experience high rates of depression and anxiety, and some evidence suggests mindfulness-based stress reduction (MBSR) is effective in reducing these symptoms. However, the neural mechanisms of symptom alleviation, and benefit of MBSR beyond education/support groups are unknown. Maladaptive forms of self-reflection are linked to ASD, depression, and anxiety. In this pilot study, we hypothesized (a) MBSR would reduce depression and anxiety in adults with ASD and (b) a mechanism of symptom alleviation would be increased blood oxygen level-dependent signal in neural self-reflection hubs. Twenty-eight adults were randomly assigned to an 8-week MBSR group (n = 15) or a support group (n = 13) that met for the same amount of time with relaxation education materials. Based on previous self-reflection literature in ASD, regions of interest (ROIs) were middle cingulate cortex (MCC) and ventromedial prefrontal cortex (vmPFC). Only the MBSR group demonstrated significant reductions in depression, and neither group significantly changed in anxiety. Only the MBSR group increased activity of right MCC during self-reflection, and the increase correlated with depression alleviation. There were no changes in vmPFC for the MBSR group or either ROI for the support/education group. Seed-to-voxel connectivity analysis revealed that only the MBSR group increased functional connectivity between right MCC and pre/postcentral gyrus, suggesting MBSR may increase primary sensorimotor input to higher order cognitive brain regions. Taken together, MBSR may be effective for reducing depression in adults with ASD, and the neural mechanism may be increasing frontal circuit involvement during self-directed thought.


Subject(s)
Autism Spectrum Disorder/complications , Brain/diagnostic imaging , Depressive Disorder/therapy , Mindfulness/methods , Adolescent , Adult , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/psychology , Depressive Disorder/complications , Depressive Disorder/diagnostic imaging , Depressive Disorder/psychology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pilot Projects , Treatment Outcome , Young Adult
12.
J Psychiatry Neurosci ; 45(6): 406-429, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32726102

ABSTRACT

Background: Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure. Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case-control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions. Results: We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume. Limitations: High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions. Conclusion: Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.


Subject(s)
Anxiety Disorders/pathology , Brain/pathology , Depressive Disorder/pathology , Adult , Anxiety Disorders/diagnostic imaging , Anxiety Disorders/epidemiology , Anxiety Disorders/physiopathology , Brain/diagnostic imaging , Comorbidity , Depressive Disorder/diagnostic imaging , Depressive Disorder/epidemiology , Depressive Disorder/physiopathology , Female , Humans , Male , Middle Aged
13.
Eur Arch Psychiatry Clin Neurosci ; 270(5): 619-631, 2020 Aug.
Article in English | MEDLINE | ID: mdl-30903270

ABSTRACT

Low social integration is commonly described in acutely suicidal individuals. Neural mechanisms underlying low social integration are poorly understood in depressed and suicidal patients. We sought to characterize the neural response to low social integration in acutely suicidal patients. Adult depressed patients within 3 days of a suicide attempt (n = 10), depressed patients with suicidal ideation (n = 9), non-suicidal depressed patients (n = 15), and healthy controls (N = 18) were administered the Cyberball Game while undergoing functional magnetic resonance imaging. We used complementary functional connectivity and region of interest data analysis approaches. There were no group differences in functional connectivity within neural network involving the pain matrix, nor in insula neural activity or the insula during either social inclusion. Superior anterior insula activity exhibited an inverted U-shaped curve across the suicide risk spectrum during social inclusion. Superior insula activity during social inclusion correlated with depression severity and psychological pain. Dorsal anterior cingulate cortex activity during social exclusion correlated with physical pain severity. Neural responses in the anterior insula significantly correlated with depression severity and with psychological pain during social inclusion, whereas dACC activity significantly correlated with physical pain during social exclusion. Recent suicidal behavior seems associated with a distinct neural response to social exclusion independently of presence of depression or suicidal thoughts.


Subject(s)
Brain Mapping , Cerebral Cortex/physiopathology , Depressive Disorder/physiopathology , Social Inclusion , Social Isolation , Suicidal Ideation , Suicide, Attempted , Adolescent , Adult , Cerebral Cortex/diagnostic imaging , Connectome , Depressive Disorder/diagnostic imaging , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Risk Factors , Severity of Illness Index , Young Adult
14.
Int J Mol Sci ; 21(18)2020 Sep 10.
Article in English | MEDLINE | ID: mdl-32927845

ABSTRACT

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (µCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.


Subject(s)
Adverse Childhood Experiences , Bone and Bones/metabolism , Collagen Type I/blood , Depressive Disorder/blood , Osteocalcin/blood , Peptide Fragments/blood , Peptides/blood , Procollagen/blood , Absorptiometry, Photon , Animals , Bone Density , Bone and Bones/diagnostic imaging , Bone and Bones/innervation , Depressive Disorder/diagnostic imaging , Female , Homeostasis , Humans , Male , Mice, Inbred C57BL , Retrospective Studies , X-Ray Microtomography
15.
Psychosom Med ; 81(5): 434-440, 2019 06.
Article in English | MEDLINE | ID: mdl-31008903

ABSTRACT

OBJECTIVE: Somatic symptoms are prevalent in patients with depression. The centromedial amygdala (CMA) is a key brain region that mediates autonomic and somatic responses. Abnormal function in the CMA may contribute to the development of somatic symptoms in depressed patients. METHODS: We compared the resting-state functional connectivity (RSFC) based on the seed of the left and right CMA between 37 patients with depression and 30 healthy controls. The severity of depressive and somatic symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the 15-item somatic symptom severity scale of the Patient Health Questionnaire (PHQ-15). Correlation analysis was performed to investigate the relationship between the RSFC and clinical variables (HDRS and PHQ-15) in depressed patients. RESULTS: Compared with healthy controls, patients with depression exhibited decreased RSFC between the CMA and insula, and superior temporal gyrus. In addition, functional connectivity between the left CMA and left insula was negatively correlated with PHQ-15 (r = -0.348, p = .037) in depressed patients. No significant relation was found between the RSFC and HDRS in depressed patients. CONCLUSIONS: Functional connectivity between the CMA and insula is reduced in depressive patients, which is associated with the severity of somatic symptoms. Our findings may provide a potential neural substrate to interpret the co-occurrence of depression with somatic symptoms.


Subject(s)
Central Amygdaloid Nucleus/physiopathology , Cerebral Cortex/physiopathology , Connectome , Depressive Disorder/physiopathology , Medically Unexplained Symptoms , Adult , Central Amygdaloid Nucleus/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Depressive Disorder/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Severity of Illness Index
16.
J Psychiatry Neurosci ; 44(4): 223-236, 2019 07 01.
Article in English | MEDLINE | ID: mdl-30840428

ABSTRACT

Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging ­ alone or in combination with other variables ­ can predict the outcomes of various treatment modalities.


Subject(s)
Clinical Protocols , Databases, Factual , Datasets as Topic , Depressive Disorder/diagnostic imaging , Neuroimaging , Canada , Depressive Disorder/therapy , Humans
17.
J Psychiatry Neurosci ; 44(4): 237-245, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30720261

ABSTRACT

Background: Investigating adolescents and young adults may provide a unique opportunity to understand developmental aspects of the neurobiology of depression. During adolescence, a considerable physiologic reorganization of both grey and white matter of the brain takes place, and it has been suggested that differences in grey-matter volumes during adolescence may reflect different maturational processes. Methods: We investigated grey-matter volumes in a comparatively large sample (n = 103) of adolescents and young adults (aged 12 to 27 years), 60 of them with a diagnosis of current depression. Results: Replicating previous studies, we found a clear wholebrain effect of age: the older the participants, the lower their global grey-matter volumes, particularly in the paracingulate and prefrontal cortices. Contrasting depressed and healthy youth in a whole-brain approach, we found greater grey-matter volumes in the dorsolateral prefrontal cortex of those with depression. Furthermore, a region-of-interest analysis indicated lower grey-matter volumes in the hippocampus in participants with depression compared with healthy controls. Limitations: The present study was limited because of a skewed sex distribution, its cross-sectional design and the fact that some participants were taking an antidepressant. Conclusion: During adolescence, restructuring of the brain is characterized by marked decreases in prefrontal grey-matter volumes, interpreted as a correlate of brain maturation. Findings of greater volumes in the prefrontal cortex, particularly in younger adolescents with depression, may suggest that these participants were more prone to delayed brain maturation or increased neuroplasticity. This finding may represent a risk factor for depression or constitute an effect of developing depression.


Subject(s)
Adolescent Development/physiology , Depressive Disorder/pathology , Gray Matter/anatomy & histology , Hippocampus/anatomy & histology , Prefrontal Cortex/anatomy & histology , Adolescent , Adult , Age Factors , Cross-Sectional Studies , Depressive Disorder/diagnostic imaging , Female , Gray Matter/diagnostic imaging , Gray Matter/growth & development , Hippocampus/diagnostic imaging , Hippocampus/growth & development , Humans , Magnetic Resonance Imaging , Male , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/growth & development , Young Adult
18.
Acta Psychiatr Scand ; 140(3): 205-216, 2019 09.
Article in English | MEDLINE | ID: mdl-31265120

ABSTRACT

OBJECTIVE: Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. METHOD: Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. RESULTS: We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. CONCLUSION: The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.


Subject(s)
Cerebral Cortex/pathology , Depressive Disorder/pathology , Depressive Disorder/therapy , Electroconvulsive Therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cerebral Cortex/diagnostic imaging , Depressive Disorder/diagnostic imaging , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
19.
Neurocase ; 25(3-4): 75-79, 2019.
Article in English | MEDLINE | ID: mdl-31266394

ABSTRACT

We report a new type of stimulus-bound behavior, denoted forced person-following, which we documented for a patient with hypoxic encephalopathy following a suicide attempt with carbon monoxide poisoning. The patient's brain was damaged in the bilateral frontal, parietal, and temporal lobes and in the basal ganglia. The patient was compelled to follow any person who came into his sight and would continue to do so until the person went out of his sight. The patient also exhibited certain primitive reflexes. The forced person-following exhibited by our patient appears to be a consequence of stimulus-bound behavior due to frontal lobe dysfunction and, to a lesser degree, severe cognitive dysfunctions, e.g., visuospatial deficits, which are related to damage in posterior cortices. The unique behavior exhibited by this patient might contribute to our understanding of innate human behavior.


Subject(s)
Carbon Monoxide Poisoning/complications , Compulsive Behavior/etiology , Depressive Disorder/psychology , Hypoxia, Brain/complications , Suicide, Attempted , Adult , Brain/diagnostic imaging , Carbon Monoxide Poisoning/diagnostic imaging , Carbon Monoxide Poisoning/psychology , Compulsive Behavior/diagnostic imaging , Compulsive Behavior/psychology , Depressive Disorder/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Humans , Hypoxia, Brain/diagnostic imaging , Hypoxia, Brain/psychology , Male
20.
Med Sci Monit ; 25: 1046-1052, 2019 Feb 07.
Article in English | MEDLINE | ID: mdl-30729958

ABSTRACT

BACKGROUND Depression is one of the most important factors affecting quality of life in Parkinson's patients. Most research on Parkinson's disease with depression has focused on neuroimaging, and there have been few quantitative electroencephalogram studies. Sleep is a biomarker for depression; therefore, the aim of this study was to identify differences in quantitative electroencephalograms during sleep in depressed and non-depressed patients with Parkinson's disease. MATERIAL AND METHODS We assessed 38 Parkinson's disease patients (26 depressed patients, 12 non-depressed patients) and 20 normal subjects using the Geriatric Depressive Scale for Depressive Symptoms and quantitative electroencephalogram analysis of amplitude of different frequency bands in different sleep stages using Met-lab software and Fast Fourier Transformation. RESULTS Non-rapid eye moment 2 and the Frontal 4 Electrode amplitude in the delta and theta ranges were progressively and significantly greater in the depressed-Parkinson's disease group (p<0.05) than in the control group. In the depressed Parkinson's disease group, from the comparison of non-rapid eye moment 2 and rapid eye moment, in Frontal 4 the amplitude in the delta ranges of non-rapid eye moment 2 was greater than in the non-depressed group, and in Central 3, Central 4, Occipital 1, and Occipital 2, the amplitudes in the beta ranges of rapid eye moment were greater (p<0.05) than in the non-depressed group. CONCLUSIONS The higher amplitude in theta in frontal areas in NREM2 and the higher amplitude in beta in parietal and occipital lobe areas in REM relative to NREM2 were significantly different in depressed and non-depressed patients with Parkinson's disease.


Subject(s)
Depression/physiopathology , Electroencephalography/methods , Parkinson Disease/physiopathology , Aged , Case-Control Studies , Depression/diagnostic imaging , Depressive Disorder/diagnostic imaging , Female , Humans , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Quality of Life , Sleep/physiology , Sleep Stages , Wakefulness
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