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1.
Adv Exp Med Biol ; 1180: 59-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784957

RESUMO

Neuroimaging shed light on the understanding of psychopathological mechanisms underlying major depressive disorder, despite its inconsistent findings. Noninvasive neuroimaging studies have indicated that various behavioral deficits in major depressive disorder are implicated with structural and functional abnormalities in specific brain regions. Moreover, disrupted brain morphological and functional properties may map out the underlying pathways from genetic and environmental factors to the prognosis of depression. Molecular neuroimaging studies have also provided novel method to probe transmitters and metabolites in brain regions rather than simply measuring brain morphological changes. Recent advanced neuroimaging approaches (e.g., pattern recognition) provides great opportunity to probe neuroimaging biomarkers that may contributes to improving diagnostic accuracy and predicting treatment outcomes. In this chapter, we conclude neuroimaging studies in the research field of depression from psychopathological, molecular, genetic/environmental, diagnostic, and therapeutic perspectives.


Assuntos
Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem , Biomarcadores , Humanos
2.
Adv Exp Med Biol ; 1192: 159-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31705495

RESUMO

This chapter presents an overview of accumulating neuroimaging data with emphasis on translational potential. The subject will be described in the context of three disease states, i.e., schizophrenia, bipolar disorder, and major depressive disorder, and for three clinical goals, i.e., disease risk assessment, subtyping, and treatment decision.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem , Psiquiatria , Esquizofrenia/diagnóstico por imagem , Biomarcadores , Tomada de Decisão Clínica , Humanos , Imagem por Ressonância Magnética , Medição de Risco
3.
Int J Neural Syst ; 29(7): 1950005, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387489

RESUMO

Although electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder (MDD), the mechanism underlying the therapeutic efficacy and side effects of ECT remains poorly understood. Here, we investigated alterations in the cortical morphological measurements including cortical thickness (CT), surface area (SA), and local gyrification index (LGI) in 23 MDD patients before and after ECT. Furthermore, multivariate pattern analysis using linear support vector machine (SVM) was applied to investigate whether the changed morphological measurements can be effective indicators for therapeutic efficacy of ECT. Surface-based morphometry (SBM) analysis found significantly increased vertex-wise and regional cortical thickness (CT) and surface area (SA) in widespread regions, mainly located in the left insula (INS) and left fusiform gyrus, as well as hypergyrification in the left middle temporal gyrus (MTG) in MDD patients after ECT. Partial correlational analyses identified associations between the morphological properties and depressive symptom scores and impaired memory scores. Moreover, SVM result showed that the changed morphological measurements were effective to classify the MDD patients before and after ECT. Our findings suggested that ECT may enhance cortical neuroplasticity to facilitate neurogenesis to remit depressive symptoms and to impair delayed memory. These findings indicated that the cortical morphometry is a good index for therapeutic efficacy of ECT.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Máquina de Vetores de Suporte , Adulto , Transtorno Depressivo Maior/psicologia , Eletroconvulsoterapia/tendências , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Máquina de Vetores de Suporte/tendências
5.
Dev Psychopathol ; 31(3): 1037-1052, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064610

RESUMO

Aberrant face emotion processing has been demonstrated in youth with and at a familial risk for bipolar and major depressive disorders. However, the neurobiological factors related to emotion processing that underlie resilience from youth-onset mood disorders are not well understood. Functional magnetic resonance imaging data during an implicit emotion processing task were collected at baseline from a sample of 50 youth, ages 8-17, who were healthy but also familially at high risk for either bipolar disorder or major depressive disorder, and 24 healthy controls with no family history of psychopathology (HCL). Participants were reevaluated 3 years later and classified into three groups for analysis: high-risk youth who converted to a psychiatric diagnosis (CVT; N = 23), high-risk youth who were resilient from developing any psychopathology (RES; N = 27), and HCL youth (N = 24) who remained healthy at follow-up. For happy > calm faces, the CVT and RES groups had significantly lower activation in the left inferior parietal lobe (IPL), while the RES group had lower activation in the right supramarginal gyrus. For fear > calm faces, the RES group had lower activation in the right precuneus and inferior frontal gyrus (IFG) compared to the CVT group. Connectivity analyses revealed the RES group exhibited higher left IPL connectivity with visual cortical regions for happy > calm faces, and higher IFG connectivity with frontal, temporal, and limbic regions for fear > calm faces. These connectivities were correlated with improvements in prosocial behaviors and global functioning. Our findings suggest that differential activation and connectivity in the IPL, IFG, and precuneus in response to emotional stimuli may represent distinct resilience and risk markers for youth-onset mood disorders.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções/fisiologia , Expressão Facial , Resiliência Psicológica , Adolescente , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Encéfalo/fisiopatologia , Criança , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética/métodos , Masculino
6.
Brain Stimul ; 12(5): 1197-1204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105027

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising intervention for major depression. However, its clinical effects are heterogeneous. We investigated, in a subsample of the randomized, clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECT-TDCS), whether the volumes of left and right prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were associated with prefrontal tDCS response. METHODS: Baseline structural T1 weighted MRI data were analyzed from 52 patients (15 males). Patients were randomized to the following conditions: escitalopram 20 mg/day, bifrontal tDCS (2 mA, 30min, 22 sessions), or placebo. Antidepressant outcomes were assessed over a treatment period of 10 weeks. Voxel-based gray matter volumes of PFC and ACC were determined using state-of-the-art parcellation approaches. RESULTS: According to our a priori hypothesis, in the left dorsal PFC, larger gray matter volumes were associated with depression improvement in the tDCS group (n = 15) compared to sham (n = 21) (Cohen's d = 0.3, 95% confidence interval [0.01; 0.6], p = 0.04). Neither right PFC nor ACC volumes were associated with depression improvement. Exploratory analyses of distinct PFC subregions were performed, but no area was associated with tDCS response after correction for multiple comparisons. CONCLUSION: Left PFC baseline gray matter volume was associated with tDCS antidepressant effects. This brain region and its subdivisions should be investigated further as a potential neurobiological predictor for prefrontal tDCS treatment in depression and might be correlated with tDCS antidepressant mechanisms of action.


Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Substância Cinzenta/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Resultado do Tratamento
7.
Neuroimage Clin ; 22: 101796, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30935858

RESUMO

BACKGROUND: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy. OBJECTIVE: Here, we attempted to replicate the procedure followed in the Drysdale et al. study and their findings in a different clinical population and a more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study? METHODS: We followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling. RESULTS AND CONCLUSION: As in the original study, we found extremely high canonical correlations between functional connectivity and clinical symptoms, and an optimal three-cluster solution. However, neither canonical correlations nor clusters were statistically significant. On the basis of our extensive evaluations of the analysis methodology used and within the limits of comparison of our sample relative to the sample used in Drysdale et al., we argue that the evidence for the existence of the distinct resting state connectivity-based subtypes of depression should be interpreted with caution.


Assuntos
Encéfalo/fisiopatologia , Conectoma/métodos , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Aprendizado de Máquina , Adulto , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
8.
Transl Psychiatry ; 9(1): 127, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944309

RESUMO

Treatment outcomes for major depressive disorder (MDD) need to be improved. Presently, no clinically relevant tools have been established for stratifying subgroups or predicting outcomes. This literature review sought to investigate factors closely linked to outcome and summarize existing and novel strategies for improvement. The results show that early recognition and treatment are crucial, as duration of untreated depression correlates with worse outcomes. Early improvement is associated with response and remission, while comorbidities prolong course of illness. Potential biomarkers have been explored, including hippocampal volumes, neuronal activity of the anterior cingulate cortex, and levels of brain-derived neurotrophic factor (BDNF) and central and peripheral inflammatory markers (e.g., translocator protein (TSPO), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor alpha (TNFα)). However, their integration into routine clinical care has not yet been fully elucidated, and more research is needed in this regard. Genetic findings suggest that testing for CYP450 isoenzyme activity may improve treatment outcomes. Strategies such as managing risk factors, improving clinical trial methodology, and designing structured step-by-step treatments are also beneficial. Finally, drawing on existing guidelines, we outline a sequential treatment optimization paradigm for selecting first-, second-, and third-line treatments for acute and chronically ill patients. Well-established treatments such as electroconvulsive therapy (ECT) are clinically relevant for treatment-resistant populations, and novel transcranial stimulation methods such as theta-burst stimulation (TBS) and magnetic seizure therapy (MST) have shown promising results. Novel rapid-acting antidepressants, such as ketamine, may also constitute a paradigm shift in treatment optimization for MDD.


Assuntos
Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Eletroconvulsoterapia/métodos , Estudo de Associação Genômica Ampla , Humanos , Neuroimagem , Guias de Prática Clínica como Assunto , Psicoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Lancet Psychiatry ; 6(4): 318-326, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30904126

RESUMO

BACKGROUND: Childhood maltreatment is a leading environmental risk factor for an unfavourable course of disease in major depressive disorder. Both maltreatment and major depressive disorder are associated with similar brain structural alterations suggesting that brain structural changes could mediate the adverse influence of maltreatment on clinical outcome in major depressive disorder. However, longitudinal studies have not been able to confirm this hypothesis. We therefore aimed to clarify the relationship between childhood trauma, brain structural alterations, and depression relapse in a longitudinal design. METHODS: We recruited participants at the Department of Psychiatry, University of Münster, Germany, from the Münster Neuroimage Cohort for whom 2-year longitudinal clinical data were available. Baseline data acquisition comprised clinical assessments, structural MRI, and retrospective assessment of the extent of childhood maltreatment experiences using the Childhood Trauma Questionnaire. Clinical follow-up assessments were conducted in all participants 2 years after initial recruitment. FINDINGS: Initial recruitment was March 21, 2010-Jan 29, 2016; follow-up reassessment Sept 7, 2012-March 9, 2018. 110 patients with major depressive disorder participated in this study. 35 patients were relapse-free, whereas 75 patients had experienced depression relapse within the 2-year follow-up period. Childhood maltreatment was significantly associated with depression relapse during follow-up (odds ratio [OR] 1·035, 95% CI 1·001-1·070; p=0·045). Both previous childhood maltreatment experiences and future depression relapse were associated with reduced cortical surface area (OR 0·996, 95% CI 0·994-0·999; p=0·001), primarily in the right insula at baseline (r=-0·219, p=0·023). Insular surface area was shown to mediate the association between maltreatment and future depression relapse (indirect effect: coefficient 0·0128, SE 0·0081, 95% CI 0·0024-0·0333). INTERPRETATION: Early life stress has a detrimental effect on brain structure, which increases the risk of unfavourable disease courses in major depression. Clinical and translational research should explore the role of childhood maltreatment as causing a potential clinically and biologically distinct subtype of major depressive disorder. FUNDING: The German Research Foundation, the Interdisciplinary Centre for Clinical Research, and the Deanery of the Medical Faculty of the University of Münster.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Adolescente , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Recidiva , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
10.
Transl Psychiatry ; 9(1): 116, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30877271

RESUMO

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.


Assuntos
Citalopram/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo/fisiopatologia , Rede Nervosa/fisiopatologia , Administração Intravenosa , Adulto , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/efeitos dos fármacos , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Escalas de Graduação Psiquiátrica , Inibidores de Captação de Serotonina/administração & dosagem , Adulto Jovem
11.
J Affect Disord ; 251: 78-85, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30909161

RESUMO

BACKGROUND: Major depressive disorder (MDD) has been assumed to be associated with aberrant brain connectivity. However, research suggests that brain connectivity abnormalities should not be restricted to extrinsic white matter connectivity, but may also impact on intrinsic gray matter connectivity. Therefore, our study aimed to investigate the intrinsic gray-matter connectivity in MDD. METHODS: The participants were 16 first-episode, drug-naïve patients with MDD and 16 healthy controls matched on age and gender. All participants were scanned by 3.0T structural magnetic resonance imaging. Global and local intrinsic gray-matter connectivity were measured based on surface-based geodesic distances, including mean coritical separation distances (MSDs), perimeter function, and radius function. RESULTS: MDD patients had significantly lower MSDs in the left postcentral gyrus and higher MSDs in the left superior parietal cortex. Marginally significant correlation was observed between MSDs in the left postcentral gyrus and symptoms of depression. Compared with healthy controls, depressed subjects had abnormal local intrinsic gray-matter connectivity in the left postcentral gyrus, the left transverse temporal gyrus, the right lingual gyrus, the right lateral occipital cortex, and the right superior frontal gyrus. Furthermore, local intrinsic gray matter connections of these brain areas were associated with some symptoms of depression. LIMITATIONS: The small sample size limited the interpretability of our potential conclusions. CONCLUSION: Aberrant intrinsic gray-matter connectivity was observed in depressed subjects, indicating abnormal intrinsic wiring cost of brain architecture. This might help explain the aberrant topological properties of brain functional connectivity and provide insights into the vulnerability of MDD.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Substância Cinzenta/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Encefalopatias/fisiopatologia , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Lobo Occipital/fisiopatologia , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Substância Branca/patologia
12.
Depress Anxiety ; 36(5): 433-441, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30900329

RESUMO

BACKGROUND: Identifying brain activity patterns that are associated with suicidal ideation (SI) may help to elucidate its pathogenesis and etiology. Suicide poses a significant public health problem, and SI is a risk factor for suicidal behavior. METHODS: Forty-one unmedicated adult participants in a major depressive episode (MDE), 26 with SI on the Beck Scale for Suicidal Ideation and 15 without SI, underwent resting-state functional magnetic resonance imaging scanning. Twenty-one healthy volunteers (HVs) were scanned for secondary analyses. Whole brain analysis of both amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF was performed in MDE subjects to identify regions where activity was associated with SI. RESULTS: Subjects with SI had greater ALFF than those without SI in two clusters: one in the right hippocampus and one in the thalamus and caudate, bilaterally. Multi-voxel pattern analysis distinguished between those with and without SI. Post hoc analysis of the mean ALFF in the hippocampus cluster found it to be associated with a delayed recall on the Buschke memory task. Mean ALFF from the significant clusters was not associated with depression severity and did not differ between MDE and HV groups. DISCUSSION: These results indicate that SI is associated with altered resting-state brain activity. The pattern of elevated activity in the hippocampus may be related to how memories are processed.


Assuntos
Mapeamento Encefálico/métodos , Núcleo Caudado/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Hipocampo/fisiopatologia , Ideação Suicida , Tálamo/fisiopatologia , Adulto , Núcleo Caudado/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Tálamo/diagnóstico por imagem
13.
Brain Connect ; 9(5): 388-398, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30848160

RESUMO

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.


Assuntos
Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Vias Neurais/fisiopatologia , Adolescente , Encéfalo/fisiopatologia , Criança , Simulação por Computador , Transtorno Depressivo Maior/metabolismo , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Sistema Límbico/fisiopatologia , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Vias Neurais/metabolismo , Lobo Parietal/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/fisiopatologia , Prognóstico , Descanso
14.
J Clin Neurosci ; 63: 55-61, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30827879

RESUMO

Occipital bending (OB) describes asymmetry of the occipital lobes where one lobe wraps across the midline, and has been associated with the presence of mood disorders. We evaluated the relationship between OB and major depressive disorder (MDD) in a large population of subjects from the International Study to Predict Optimized Treatment in Depression. MDD patients (n = 231) and healthy controls (n = 68) underwent MRI and neuropsychiatric evaluation, including response or remission to antidepressant medication at baseline and at 8 weeks. Cortical thickness, ventricular volumes and regional grey matter volumes were measured. OB was visually assessed and OB angle measured using a semi-automated method. Correlations with MDD diagnosis, MRI measures and clinical features were tested. Results demonstrated a greater proportion of rightwards OB in MDD compared to control subjects (p = 0.02). There was no difference in the total prevalence of OB (combined left and rightward bending) between MDD and controls. MDD subjects with right OB had greater cortical thickness in three medial occipital regions (cuneus, lingual gyrus and calcarine sulcus) on the left. Lateral ventricular size was 20% lower bilaterally in right OB MDD subjects compared to non-OB MDD subjects. OB was not associated with severity (HDRS-17). Our data suggest the presence of a strong link between greater rightward occipital bending and MDD. Rightward-OB is associated with greater left medial occipital cortical thickness, and with reduced lateral ventricular size. The cause for greater rightward bending in MDD patients is unclear, however our data suggest a developmental aetiology.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Affect Disord ; 250: 178-185, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30856495

RESUMO

OBJECTIVE: Identification of state-independent and -dependent neural biomarkers may provide insight into the pathophysiology and effective treatment of major depressive disorder (MDD), therefore we aimed to investigate the state-independent and -dependent topological alterations of MDD. METHOD: Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 59 patients with unmedicated first episode current MDD (cMDD), 48 patients with remitted MDD (rMDD) and 60 demographically matched healthy controls (HCs). Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the global and nodal level. RESULTS: At a global level, both patient groups showed decreased normalized clustering coefficient in relative to HCs. On a nodal level, both patient groups showed decreased nodal centrality, predominantly in cortex-mood-regulation brain regions including the dorsolateral prefrontal cortex, posterior parietal cortex and posterior cingulate cortex. By comparison to cMDD patients, rMDD group had a higher nodal centrality in right parahippocampal gyrus. LIMITATIONS: The present study, an exploratory analysis, may require further confirmation with task-based and experimental studies. CONCLUSIONS: Deficits in the topological organization of the whole brain and cortex-mood-regulation brain regions in both rMDD and cMDD represent state-independent biomarkers.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Vias Neurais/diagnóstico por imagem , Adulto Jovem
16.
J Affect Disord ; 245: 1089-1097, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699851

RESUMO

BACKGROUND: Findings regarding brain circuitry abnormalities in suicide attempters (SAs) converge across bipolar disorder (BD) and major depressive disorder (MDD), the most common disorders observed in suicides. These abnormalities appear to be present during adolescence/young adulthood when suicide rates increase steeply, and suicide is a leading cause of death in this age group. Identification of brain circuitry common to adolescent/young adult SAs with BD and MDD is important for generating widely effective early prevention strategies. We examined brain circuitry in SAs in adolescents/young adults across these two disorders. METHODS: Eighty-three participants (ages 14-25 years), 46 with BD (21 SAs) and 37 with MDD (19 SAs), underwent structural and diffusion-weighted magnetic resonance scanning. Whole-brain analyses compared gray matter (GM) volume and white matter (WM) fractional anisotropy (FA) between SAs and non-suicide attempters (NSAs) across and within BD and MDD (p < 0.005). RESULTS: Across and within BD and MDD, SAs showed differences compared to NSAs in ventral prefrontal cortex (PFC) GM volume and fronto-limbic (including uncinate fasciculus (UF)) WM FA. Exploratory analyses showed additional within-disorder differences for BD SAs in dorsolateral PFC (dlPFC) and hippocampus GM volume and UF FA, and for MDD SAs dorsomedial and dlPFC GM and dorsal frontal WM. However, there was no significant interaction between suicide attempt status and diagnosis. LIMITATIONS: Modest sample size. CONCLUSIONS: Common fronto-limbic gray and white matter alterations in adolescent/young adult SAs are potential targets for suicide prevention strategies across mood disorders. Preliminary findings of disorder-specific regional findings could suggest diagnostic-specific optimal targets may exist.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Tentativa de Suicídio , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Anisotropia , Transtorno Bipolar/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética , Feminino , Substância Cinzenta/patologia , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão , Córtex Pré-Frontal/patologia , Adulto Jovem
17.
J Affect Disord ; 245: 1139-1148, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699858

RESUMO

BACKGROUND: Mood disorders are major risk factors for suicidal behavior. While cross-sectional studies implicate frontal systems, data to aid prediction of suicide-related behavior in mood disorders are limited. Longitudinal research on neuroanatomical mechanisms underlying suicide risk may assist in developing targeted interventions. Therefore, we conducted a preliminary study investigating baseline gray and white matter structure and longitudinal structural changes associated with future suicide attempts. METHODS: High-resolution structural magnetic resonance imaging, diffusion tensor imaging, and suicide-related behavioral assessment data for 46 adolescents and young adults with mood disorders [baseline agemean = 18 years; 61% female] were collected at baseline and at follow-up (intervalmean = 3 years). Differences in baseline and longitudinal changes in gray matter volume and white matter fractional anisotropy in frontal systems that distinguished the participants who made future attempts from those who did not were investigated. RESULTS: Seventeen (37%) of participants attempted suicide within the follow-up period. Future attempters (those attempting suicide between their baseline and follow-up assessment), compared to those who did not, showed lower baseline ventral and rostral prefrontal gray matter volume and dorsomedial frontal, anterior limb of the internal capsule, and dorsal cingulum fractional anisotropy, as well as greater decreases over time in ventral and dorsal frontal fractional anisotropy (p < 0.005, uncorrected). LIMITATIONS: Sample size was modest. CONCLUSIONS: Results suggest abnormalities of gray and white matter in frontal systems and differences in developmental changes of frontal white matter may increase risk of suicide-related behavior in youths with mood disorders. Findings provide potential new leads for early intervention and prevention strategies.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Cápsula Interna/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Tentativa de Suicídio , Substância Branca/diagnóstico por imagem , Adolescente , Anisotropia , Transtorno Bipolar/patologia , Estudos Transversais , Transtorno Depressivo Maior/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Substância Cinzenta/patologia , Giro do Cíngulo/patologia , Humanos , Cápsula Interna/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Transtornos do Humor/diagnóstico por imagem , Transtornos do Humor/patologia , Córtex Pré-Frontal/patologia , Ideação Suicida , Substância Branca/patologia , Adulto Jovem
18.
J Affect Disord ; 245: 971-977, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699883

RESUMO

BACKGROUND: Major depressive disorder (MDD) is accompanied by atypical brain structure affecting grey and white matter from the early stages. Neuroimaging studies of first-episode depression (FED) have provided evidence on this regard, but most of the studies are cross-sectional. The aim of this longitudinal study was to test potential changes in grey matter (GM) and white matter (WM) volumes in FED. METHODS: Thirty-three untreated FED patients (DSM-IV criteria) and 33 healthy controls (HC) underwent a 3T structural magnetic resonance imaging (sMRI) at baseline and after 2 years. Depressive symptoms were assessed at baseline and throughout the study with the 17-item Hamilton Depressive Rating Scale (HDRS-17). Recurrences of FED patients were also collected along the follow-up. To analyze GM and WM differences, whole-brain voxel-based morphometry (VBM, SPM12) was employed (FWE corrected). RESULTS: FED patients showed significant reductions compared to HC in WM volumes of prefrontal cortex (left anterior corona radiata). No differences were found in GM volumes. Full factorial longitudinal analysis of the whole sample revealed no significant effect in GM nor in WM, while the full factorial longitudinal analysis comparing recurrent and non-recurrent patients showed increments in WM volumes of left posterior corona radiata and right posterior thalamic radiation in the recurrent group. LIMITATIONS: Limited sample size, especially in the follow-up. CONCLUSIONS: The present findings provided some new evidence of the role of white matter alterations in the early stages of MDD and in the progression of the illness.


Assuntos
Depressão/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Estudos Transversais , Depressão/patologia , Transtorno Depressivo Maior/patologia , Progressão da Doença , Feminino , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Córtex Pré-Frontal/patologia , Substância Branca/patologia
19.
Transl Psychiatry ; 9(1): 94, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770788

RESUMO

Ultra-high field 7-Tesla (7 T) MRI has the potential to advance our understanding of neuropsychiatric disorders, including major depressive disorder (MDD). To date, few studies have quantified the advantage of resting state functional MRI (fMRI) at 7 T compared to 3-Tesla (3 T). We conducted a series of experiments that demonstrate the improvement in temporal signal-to-noise ratio (TSNR) of a multi-echo multi-band fMRI protocol with ultra-high field 7 T MRI, compared to a similar protocol using 3 T MRI in healthy controls (HC). We also directly tested the enhancement in ultra-high field 7 T fMRI signal power by examining the ventral tegmental area (VTA), a small midbrain structure that is critical to the expected neuropathology of MDD but difficult to discern with standard 3 T MRI. We demonstrate up to 300% improvement in TSNR and resting state functional connectivity coefficients provided by ultra-high field 7 T fMRI compared to 3 T, indicating enhanced power for detection of functional neural architecture. A multi-echo based acquisition protocol and signal denoising pipeline afforded greater gain in signal power compared to classic acquisition and denoising pipelines. Furthermore, ultra-high field fMRI revealed mood-related neurocircuit disturbances in patients with MDD compared to HC, which were not detectable with 3 T fMRI. Ultra-high field 7 T fMRI may provide an effective tool for studying functional neural architecture relevant to MDD and other neuropsychiatric disorders.


Assuntos
Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Adulto , Algoritmos , Estudos de Casos e Controles , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade
20.
Neuroimage ; 189: 700-714, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30716456

RESUMO

Resting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of P < .05 and a height threshold of P < .001) at 50% reproducibility. Together, these results highlight reproducible patterns of functional alterations in MDD and relevant influencing factors, which provides crucial guidance for future neuroimaging studies of this disorder.


Assuntos
Córtex Cerebral/fisiopatologia , Conectoma , Transtorno Depressivo Maior/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto Jovem
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