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1.
Clin EEG Neurosci ; 52(1): 38-51, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32491928

RESUMO

The human brain is characterized by complex structural, functional connections that integrate unique cognitive characteristics. There is a fundamental hurdle for the evaluation of both structural and functional connections of the brain and the effects in the diagnosis and treatment of neurodegenerative diseases. Currently, there is no clinically specific diagnostic biomarker capable of confirming the diagnosis of major depressive disorder (MDD). Therefore, exploring translational biomarkers of mood disorders based on deep learning (DL) has valuable potential with its recently underlined promising outcomes. In this article, an electroencephalography (EEG)-based diagnosis model for MDD is built through advanced computational neuroscience methodology coupled with a deep convolutional neural network (CNN) approach. EEG recordings are analyzed by modeling 3 different deep CNN structure, namely, ResNet-50, MobileNet, Inception-v3, in order to dichotomize MDD patients and healthy controls. EEG data are collected for 4 main frequency bands (Δ, θ, α, and ß, accompanying spatial resolution with location information by collecting data from 19 electrodes. Following the pre-processing step, different DL architectures were employed to underline discrimination performance by comparing classification accuracies. The classification performance of models based on location data, MobileNet architecture generated 89.33% and 92.66% classification accuracy. As to the frequency bands, delta frequency band outperformed compared to other bands with 90.22% predictive accuracy and area under curve (AUC) value of 0.9 for ResNet-50 architecture. The main contribution of the study is the delineation of distinctive spatial and temporal features using various DL architectures to dichotomize 46 MDD subjects from 46 healthy subjects. Exploring translational biomarkers of mood disorders based on DL perspective is the main focus of this study and, though it is challenging, with its promising potential to improve our understanding of the psychiatric disorders, computational methods are highly worthy for the diagnosis process and valuable in terms of both speed and accuracy compared with classical approaches.


Assuntos
Encéfalo/fisiopatologia , Aprendizado Profundo , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia , Adulto , Interfaces Cérebro-Computador/psicologia , Diagnóstico por Computador/métodos , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação
2.
Sci Rep ; 10(1): 17057, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051528

RESUMO

Electroconvulsive therapy (ECT) is a highly effective neuromodulatory intervention for treatment-resistant major depressive disorder (MDD). Presently, however, understanding of its neurophysiological effects remains incomplete. In the present study, we utilised resting-state electroencephalography (RS-EEG) to explore changes in functional connectivity, network topology, and spectral power elicited by an acute open-label course of ECT in a cohort of 23 patients with treatment-resistant MDD. RS-EEG was recorded prior to commencement of ECT and again within 48 h following each patient's final treatment session. Our results show that ECT was able to enhance connectivity within lower (delta and theta) frequency bands across subnetworks largely confined to fronto-central channels, while, conversely, more widespread subnetworks of reduced connectivity emerged within faster (alpha and beta) bands following treatment. Graph-based topological analyses revealed changes in measures of functional segregation (clustering coefficient), integration (characteristic path length), and small-world architecture following ECT. Finally, post-treatment enhancement of delta and theta spectral power was observed, which showed a positive association with the number of ECT sessions received. Overall, our findings indicate that RS-EEG can provide a sensitive measure of dynamic neural activity following ECT and highlight network-based analyses as a promising avenue for furthering mechanistic understanding of the effects of convulsive therapies.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Eletroconvulsoterapia/métodos , Rede Nervosa/fisiologia , Adulto , Encéfalo/fisiopatologia , Estudos de Coortes , Conectoma/métodos , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/terapia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Resultado do Tratamento
3.
Sci Rep ; 10(1): 15391, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958845

RESUMO

Postpartum depression (PPD), a main cause of maternal suicide, is an important issue in perinatal mental health. Recently, cerebral diffusion tensor imaging (DTI) studies have shown reduced fractional anisotropy (FA) in major depressive disorder (MDD) patients. There are, however, no reports using diffusion kurtosis imaging (DKI) for evaluation of PPD. This was a Japanese single-institutional prospective study from 2016 to 2019 to examine the pathophysiological changes in the brain of PPD patients using DKI. The DKI data from 3.0 T MRI of patients one month after delivery were analyzed; the patients were examined for PPD by a psychiatrist. The mean kurtosis (MK), FA and mean diffusivity (MD) were calculated from the DKI data and compared between PPD and non-PPD groups using tract-based spatial statistics analysis. Of the 75 patients analyzed, eight patients (10.7%) were diagnosed as having PPD. In the PPD group, FA values in the white matter and thalamus were significantly lower and MD values in the white matter and putamen were significantly higher. The area with significant differences in MD value was more extensive (40.8%) than the area with significant differences in FA value (6.5%). These findings may reflect pathophysiological differences of PPD compared with MDD.


Assuntos
Depressão Pós-Parto/diagnóstico por imagem , Depressão Pós-Parto/fisiopatologia , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Anisotropia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Paridade/fisiologia , Estudos Prospectivos , Putamen/diagnóstico por imagem , Putamen/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia
4.
Life Sci ; 262: 118501, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991880

RESUMO

AIMS: Major depressive disorder, as a destructive mental health disorder, is a major contributor to disability and death. Numerous studies have illustrated that activation of inflammation and fluctuating immune reactions play a crucial role in the physiopathology of depression. The effectiveness of antidepressants is affected by the intensity of the inflammatory response. Thus, we aim to reveal the correlation of inflammatory factors and depression. MAIN METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ™)-based proteomics was applied to verify the quantitation of target proteins in the PFC of chronic social defeat stress (CSDS) model mice. Ingenuity pathway analysis (IPA) was performed to explore related pathways, and the involvement of molecules was validated by western blotting and real time-quantitative polymerase chain reaction (RT-qPCR). KEY FINDINGS: According to the IPA results, CSDS-susceptible mice and CSDS-resilient mice both exhibited alterations of the inflammasome pathway in the PFC. Compared with control mice, susceptible mice subjected to CSDS showed an increased ATP-activated purinergic receptor P2X7 (also known as P2RX7) protein level. Nevertheless, the expression levels of cysteinyl aspartate-specific protease 1 (Caspase 1) and apoptosis-associated speck-like protein containing a CARD (ASC) were reduced in CSDS mice, and downregulation of interleukin-1ß (IL-1ß) was found in susceptible mice. Moreover, no significant difference was found in nuclear factor-κB levels among the three groups. SIGNIFICANCE: CSDS administration leads to dysfunctions of key molecules in the inflammasome pathway, promoting depressive-like behaviors in mice.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Inflamassomos/metabolismo , Proteômica , Estresse Psicológico/fisiopatologia , Animais , Comportamento Animal/fisiologia , Depressão/fisiopatologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Resiliência Psicológica
5.
Proc Natl Acad Sci U S A ; 117(40): 25138-25149, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958675

RESUMO

Major depressive disorder emerges from the complex interactions of biological systems that span genes and molecules through cells, networks, and behavior. Establishing how neurobiological processes coalesce to contribute to depression requires a multiscale approach, encompassing measures of brain structure and function as well as genetic and cell-specific transcriptional data. Here, we examine anatomical (cortical thickness) and functional (functional variability, global brain connectivity) correlates of depression and negative affect across three population-imaging datasets: UK Biobank, Brain Genomics Superstruct Project, and Enhancing NeuroImaging through Meta Analysis (ENIGMA; combined n ≥ 23,723). Integrative analyses incorporate measures of cortical gene expression, postmortem patient transcriptional data, depression genome-wide association study (GWAS), and single-cell gene transcription. Neuroimaging correlates of depression and negative affect were consistent across three independent datasets. Linking ex vivo gene down-regulation with in vivo neuroimaging, we find that transcriptional correlates of depression imaging phenotypes track gene down-regulation in postmortem cortical samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data reveal somatostatin interneurons and astrocytes to be consistent cell associates of depression, through both in vivo imaging and ex vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS-derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multiscale approaches, the transcriptional correlates of depression-linked brain function and structure were enriched for disorder-relevant molecular pathways. These findings bridge levels to connect specific genes, cell classes, and biological pathways to in vivo imaging correlates of depression.


Assuntos
Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Transtorno Depressivo Maior/genética , Regulação da Expressão Gênica/genética , Somatostatina/genética , Astrócitos/metabolismo , Astrócitos/patologia , Autopsia , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Feminino , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Interneurônios/metabolismo , Interneurônios/patologia , Masculino , Herança Multifatorial/genética , Neuroimagem/métodos , Transdução de Sinais/genética , Análise de Célula Única/métodos
6.
PLoS One ; 15(9): e0238726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915846

RESUMO

BACKGROUND: There are no reliable and validated objective biomarkers for the assessment of depression severity. We aimed to investigate the association between depression severity and timing-related speech features using speech recognition technology. METHOD: Patients with major depressive disorder (MDD), those with bipolar disorder (BP), and healthy controls (HC) were asked to engage in a non-structured interview with research psychologists. Using automated speech recognition technology, we measured three timing-related speech features: speech rate, pause time, and response time. The severity of depression was assessed using the Hamilton Depression Rating Scale 17-item version (HAMD-17). We conducted the current study to answer the following questions: 1) Are there differences in speech features among MDD, BP, and HC? 2) Do speech features correlate with depression severity? 3) Do changes in speech features correlate with within-subject changes in depression severity? RESULTS: We collected 1058 data sets from 241 individuals for the study (97 MDD, 68 BP, and 76 HC). There were significant differences in speech features among groups; depressed patients showed slower speech rate, longer pause time, and longer response time than HC. All timing-related speech features showed significant associations with HAMD-17 total scores. Longitudinal changes in speech rate correlated with changes in HAMD-17 total scores. CONCLUSIONS: Depressed individuals showed longer response time, longer pause time, and slower speech rate than healthy individuals, all of which were suggestive of psychomotor retardation. Our study suggests that speech features could be used as objective biomarkers for the assessment of depression severity.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Fala , Inteligência Artificial , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
7.
PLoS Comput Biol ; 16(9): e1008162, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32997653

RESUMO

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.


Assuntos
Transtorno da Personalidade Borderline , Tomada de Decisões/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Aprendizado Social/fisiologia , Anedonia , Teorema de Bayes , Transtorno da Personalidade Borderline/fisiopatologia , Transtorno da Personalidade Borderline/psicologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Humanos , Modelos Psicológicos , Recompensa , Análise e Desempenho de Tarefas
8.
Sci Rep ; 10(1): 12870, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32733056

RESUMO

Literature suggests that neurobiological factors such as brain structure play an important role in linking social stress with depression in adolescence. We aimed to examine the role of subcortical volumetric alteration in the association between peer problems as one type of social stress and adolescent depression. We hypothesized that there would be indirect effects of peer problems on adolescent depression through subcortical volumetric alteration. Seventy eight adolescents with major depressive disorder (MDD) (age mean [SD] = 14.9 ± 1.5, 56 girls) and 47 healthy controls [14.3 ± 1.4, 26 girls]) participated in this study. High-resolution structural T1 images were collected using the Siemens 3T MR scanner. Subcortical volumes were segmented using the Freesurfer 6.0 package. Peer problems were assessed using the Peer-Victimization Scale and the Bullying-Behavior Scale. There was a significant indirect effect of peer problems on adolescent depression through nucleus accumbens (NAcc) volume alteration, but not through the amygdala and hippocampal volumes. This result supported our model, which stated that peer problems have indirect effects through subcortical volumetric alteration (i.e., increased NAcc volume) on adolescent depression. Our finding suggests that altered NAcc volume may serve as a pathway, through which peer problems as one type of social stressor contribute to adolescent depression.


Assuntos
Transtorno Depressivo Maior , Imagem por Ressonância Magnética , Núcleo Accumbens , Estresse Psicológico , Adolescente , Criança , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiopatologia , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/fisiopatologia
9.
JAMA Netw Open ; 3(8): e207434, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32809030

RESUMO

Importance: There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are very limited data on the association of MST with suicidality directly. It is important to explore the potential of MST as a viable treatment alternative to electroconvulsive therapy for suicidality. Objective: To determine the association of MST with suicidality in patients with treatment-resistant major depressive disorder. Design, Setting, and Participants: This nonrandomized controlled trial took place at a single tertiary care psychiatric facility in Canada. It followed an open-label study design with consecutive treatment cohorts. Consecutive groupings of 67 patients with treatment-resistant major depressive disorder and with baseline suicidality present were treated for up to 24 treatments. The study was run from February 2012 through June 2019. Patients were followed up for 6 months at the end of the treatment period. This post hoc secondary analysis of the trial was performed from January to November 2019. Interventions: MST was delivered at 100% stimulator output over the prefrontal cortex with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency, for a maximum of 24 sessions. Main Outcomes and Measures: Remission from suicidality was measured as an end point score of 0 on the Beck Scale for Suicidal Ideation. A linear mixed model was used to assess the trajectory of Beck Scale for Suicidal Ideation scores. Results: A total of 67 patients (mean [SD] age, 46.3 [13.6] years; 40 women [60.0%]) received a mean (SD) of 19.5 (5.1) MST treatments. The overall number of patients achieving remission was 32 (47.8%). Sixteen patients (55.2%) receiving low-frequency MST achieved remission, as well as 12 patients (54.5%) in the moderate-frequency group, and 4 patients (25.0%) in the high-frequency group. The linear mixed model revealed an association of time with Beck Scale for Suicidal Ideation scores (F8,293.95 = 5.73; P < .001). Conclusions and Relevance: These findings suggest that MST may be an effective treatment for suicidality, and sensitivity analysis shows this may be particularly so at low and moderate frequencies. Future studies should directly compare MST with electroconvulsive therapy for treating suicidality and should evaluate MST as a treatment for suicidality across mental disorders. Trial Registration: ClinicalTrials.gov Identifier: NCT01596608.


Assuntos
Transtorno Depressivo Maior , Terapia de Campo Magnético , Ideação Suicida , Adulto , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Psychiatry Res ; 291: 113287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32763548

RESUMO

Transcranial magnetic stimulation (TMS) can be used to evaluate the effects of pharmacological interventions. The aim of this study was to assess the impact of the selective serotonin reuptake inhibitor, sertraline, and the atypical antipsychotic drugs quetiapine and olanzapine, on cortical excitability in unmedicated patients with major depressive disorder (MDD). The study included 45 medication-free MDD patients diagnosed according to DSM V. They were divided randomly into three groups who received a single oral dose of one of the three drugs sertraline (50 mg), quetiapine (100 mg) and olanzapine (10 mg). Psychological evaluation was conducted using the Mini-Mental State Examination (MMSE) and Beck Depression Inventory Scale (BDI). Resting and active motor thresholds (rMT and aMT) together with contralateral and ipsilateral cortical silent periods (cSP, and iSP) were measured for each participant before and at the time of maximum concentration of drug intake. There was significant increase in excitability of motor cortex after sertraline without changes in GABAB neurotransmission. Quetiapine and olanzapine potentiated inhibitory GABAB neurotransmission (prolongation of cSP); olanzapine additionally prolonged the iSP. Thus TMS can differentiate between the impact of different psychotropic drugs on excitatory and inhibitory transmission in motor cortex.


Assuntos
Antipsicóticos/uso terapêutico , Excitabilidade Cortical/efeitos dos fármacos , Transtorno Depressivo Maior/fisiopatologia , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Estimulação Magnética Transcraniana/efeitos dos fármacos , Adulto , Antipsicóticos/farmacologia , Excitabilidade Cortical/fisiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Estimulação Magnética Transcraniana/psicologia , Adulto Jovem
11.
Am J Psychiatry ; 177(8): 671-685, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32741287

RESUMO

Major depressive disorder is a remarkably common and often severe psychiatric disorder associated with high levels of morbidity and mortality. Patients with major depression are prone to several comorbid psychiatric conditions, including posttraumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, and medical conditions, including cardiovascular disease, diabetes, stroke, cancer, which, coupled with the risk of suicide, result in a shortened life expectancy. The goal of this review is to provide an overview of our current understanding of major depression, from pathophysiology to treatment. In spite of decades of research, relatively little is known about its pathogenesis, other than that risk is largely defined by a combination of ill-defined genetic and environmental factors. Although we know that female sex, a history of childhood maltreatment, and family history as well as more recent stressors are risk factors, precisely how these environmental influences interact with genetic vulnerability remains obscure. In recent years, considerable advances have been made in beginning to understand the genetic substrates that underlie disease vulnerability, and the interaction of genes, early-life adversity, and the epigenome in influencing gene expression is now being intensively studied. The role of inflammation and other immune system dysfunction in the pathogenesis of major depression is also being intensively investigated. Brain imaging studies have provided a firmer understanding of the circuitry involved in major depression, providing potential new therapeutic targets. Despite a broad armamentarium for major depression, including antidepressants, evidence-based psychotherapies, nonpharmacological somatic treatments, and a host of augmentation strategies, a sizable percentage of patients remain nonresponsive or poorly responsive to available treatments. Investigational agents with novel mechanisms of action are under active study. Personalized medicine in psychiatry provides the hope of escape from the current standard trial-and-error approach to treatment, moving to a more refined method that augurs a new era for patients and clinicians alike.


Assuntos
Transtorno Depressivo Maior , Gerenciamento Clínico , Comorbidade , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Interação Gene-Ambiente , Humanos , Neuroimagem/métodos , Medicina de Precisão/tendências , Fatores de Risco
12.
Psychiatry Res Neuroimaging ; 304: 111149, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32738725

RESUMO

Notwithstanding being the object of a growing field of clinical research, the investigation of the dynamic resting-state functional connectivity alterations in psychiatric illnesses is still in its early days. Current research on major depressive disorder (MDD) and bipolar disorder (BD) has evidenced abnormal resting-state functional connectivity (rsFC), especially in regions subserving emotional processing and regulation such as the amygdala. However, dynamic changes in functional connectivity within the amygdalar subregions in distinguishing BD and MDD has not yet been fully understood. In this paper, we aim at analyzing the patterns characterizing dynamic FC (dFC) in the right amygdala to investigate the differences between similarly depressed BD and MDD. A number of 40 BD patients, 61 MDD patients and 63 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) at rest. Using the right-amygdala as seed region, we compared the dFC within three subdivisions, namely, laterobasal (LB), centromedial (CM) and superficial (SF) between all the groups. To do so, one-way ANOVA followed by post-hoc t-tests were employed. Compared to HCs, patients with BD had a decreased dFC between right LB and the left postcentral gyrus as well as an increased dFC between right CM and the right cerebellum.Compared to BD patients, patients with MDD showed a decreased dFC between right CM and the cerebellum and an increased dFC between right LB and the left postcentral gyrus. These findings present initial evidence that abnormal patterns of the right-amygdalar subregions shared by BD and MDD supports the differential pathophysiology of these disorders.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia
13.
Psychiatry Res Neuroimaging ; 303: 111134, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32652482

RESUMO

Major depressive disorder (MDD) is characterized by heterogeneous clinical performance and neurocognitive impairment. It is important to explore the correlation between global functioning and regional homogeneity (ReHo)/amplitude of low-frequency fluctuation (ALFF) values in MDD patients. 67 first-episode, drug naïve MDD patients and 69 healthy subjects were enrolled in the study. The MATRICS Consensus Cognitive Battery (MCCB) and the Functioning Assessment Short Test (FAST) were used to assess functional impairment in patients. Brain activity was assessed using ReHo and ALFF measurements. The relationship between the clinical features and altered brain function was evaluated using correlation analysis. There were significant differences in the ReHo and ALFF values between MDD patients and healthy subjects. The reduction in ReHo in the left calcarine/lingual gyrus/cuneus was negatively correlated with occupational functioning and the total FAST scores. The reduction in ALFF in the right calcarine/lingual gyrus was positively correlated with the verbal learning aspects of the MCCB. These findings suggest that the altered brain function in the default mode network (DMN) may be related to functional impairments in patients with first-episode, drug naïve major depressive disorder.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
J Fr Ophtalmol ; 43(7): 586-597, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32631695

RESUMO

Major depressive disorder, bipolar disorder and schizophrenia are currently among the most common psychiatric disorders, known to constitute a serious public health issue in terms of morbidity, mortality and functional handicap. Their pathophysiology is still unclear, but there is now increasing evidence supporting the existence of abnormalities of neurotransmission. As the retina is an extension of the central nervous system, it may be an interesting site of study which might provide a better understanding of the pathophysiology of psychiatric disorders. Several studies have demonstrated retinal abnormalities, with abnormal cone and rod responses on electroretinography (ERG), suggesting a process of functional neuronal loss, structurally supported by a decrease in the retinal nerve fiber layer thickness (RNFL) on optical coherence tomography (OCT), which suggests involvement of the molecular signal pathways of neurotransmission. These tests could be useful tools for diagnosing and monitoring psychiatric disorders. This article is an overview of the literature on retinal abnormalities observed in patients with major depressive disorder, bipolar disorder or schizophrenia, and discusses how they could be pathophysiologic markers.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Retina/diagnóstico por imagem , Retina/fisiologia , Esquizofrenia/fisiopatologia , Acuidade Visual/fisiologia , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/patologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/patologia , Eletrorretinografia , Humanos , Fibras Nervosas/patologia , Fibras Nervosas/fisiologia , Retina/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/fisiologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/patologia , Tomografia de Coerência Óptica
15.
PLoS One ; 15(7): e0235272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628698

RESUMO

BACKGROUND: Recent studies have uncovered a peculiar finding: that the strength and dimensionality of depression symptoms' inter-relationships vary systematically across study samples with different average levels of depression severity. Our aim was to examine whether this phenomenon is driven by the proportion of non-affected subjects in the sample. METHODS: Cross-sectional data from the "Cohort Study on Substance Use Risk Factors" was analyzed. Self-reported depression symptoms were assessed via the Major Depressive Inventory. Symptom data were analyzed via polychoric correlations, principal component analysis, confirmatory factor analysis, Mokken scale analysis, and network analysis. Analyses were carried out across 22 subsamples containing increasingly higher proportions of non-depressed participants. Results were examined as a function of the proportion of non-depressed participants. RESULTS: A strong influence of the proportion of non-depressed participants was uncovered: the higher the proportion, the stronger the symptom correlations, higher their tendency towards unidimensionality, better their scalability, and higher the network edge strengths. Comparing the depressed sample with the general population sample, the average symptom correlation increased from 0.29 to 0.51; variance explained by the first eigenvalue increased from 0.36 to 0.56; fit measures from confirmatory one-factor analysis increased from 0.81 to 0.97; the H coefficient of scalability increased from 0.26 to 0.48; and the median network edge increased from 0.00 to 0.07. CONCLUSIONS: Results of psychometric analyses vary substantially as a function of the proportion of non-depressed participants in the sample being studied. This provides a possible explanation for the lack of reproducibility of previous psychometric studies.


Assuntos
Depressão/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Psicometria/estatística & dados numéricos , Adolescente , Estudos Transversais , Depressão/diagnóstico , Depressão/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Amostragem , Autorrelato , Índice de Gravidade de Doença , Suíça/epidemiologia , Adulto Jovem
16.
J Consult Clin Psychol ; 88(8): 786-797, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32700956

RESUMO

OBJECTIVE: We applied the experimental therapeutics approach to test whether acute treatment outcomes for winter seasonal affective disorder (SAD) are mediated by a cognitive mechanism in cognitive-behavioral therapy (CBT-SAD) versus a chronobiologic mechanism in light therapy (LT). METHOD: Currently depressed adults with major depression, recurrent with seasonal pattern (N = 177; 83.6% female, 92.1% non-Hispanic White, M age = 45.6) were randomized to 6 weeks of LT or group CBT-SAD. SAD symptoms were assessed weekly on the Structured Clinical Interview for the Hamilton Rating Scale for Depression-SAD Version. At pre-, mid-, and posttreatment, participants completed measures of general depressogenic cognitions (Dysfunctional Attitudes Scale; DAS); SAD-specific negative cognitions (Seasonal Beliefs Questionnaire; SBQ); chronotype (Morningness-Eveningness Questionnaire; MEQ); and depressive symptoms (Beck Depression Inventory-Second Edition). RESULTS: Parallel-process growth models showed evidence for hypothesized mechanisms. For SAD-specific negative cognitions (SBQ), both symptom measures showed (1) an effect of treatment group on the slope of the mediator, with CBT-SAD demonstrating greater decreases, and (2) an effect of the slope of the mediator on the slope of the outcome. These effects held for the SBQ but not the broader measure of depressogenic cognitions (DAS). For the chronotype measure (MEQ), treatment assignment affected change, whereby LT was associated with reduced "eveningness," but this was unrelated to change in symptoms. CONCLUSIONS: CBT-SAD promoted decreases in SAD-specific negative cognitions, and these changes were related to decreases in symptoms. Consistent with the theory that LT corrects misaligned circadian rhythms, LT reduced eveningness, but this did not correspond to symptom improvement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior/terapia , Avaliação de Resultados em Cuidados de Saúde , Fototerapia , Transtorno Afetivo Sazonal/terapia , Adulto , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Afetivo Sazonal/fisiopatologia
17.
Adv Pharmacol ; 89: 103-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616204

RESUMO

Depression represents one of the most common and debilitating mental illnesses in the world today. Despite this pressing issue, the majority treatments for depression give patients therapeutic response only approximately half of the time, with many not responding at all. In part, this stagnation has been due to the dominance of the monoamine hypothesis that guides the current approach to understanding and treating depression. While therapies that increase levels of monoamines have been useful, clearly a more complete understanding of the neural circuits and treatments is needed to better help patients. Recent work that exploits the glutamatergic system within the brain has demonstrated a functional role for glutamate in combatting depression. While more research is required to understand the specific glutamatergic pathophysiological mechanisms within depression, emerging clinical work has already demonstrated promising results. Current treatments that target the glutamatergic system, especially NMDA receptor antagonists have already shown efficacy in several clinical trials. In this chapter we briefly introduce a mechanistic basis for a role of glutamate in the pathophysiology of depression. We further review basic and translational studies that describes potential mechanisms and roles for glutamate. A discussion of the first promising NMDA receptor antagonist for depression, ketamine, follows afterward. The development of NMDA receptor antagonists for treatment of depression is chronicled, from initial studies up through the recent FDA approval of intranasal esketamine as well as other newer compounds that have shown recent promise in clinical trials.


Assuntos
Padrões de Prática Médica , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Ácido Glutâmico/uso terapêutico , Humanos , Ketamina/uso terapêutico , Receptores de N-Metil-D-Aspartato/metabolismo
18.
Adv Pharmacol ; 89: 163-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616206

RESUMO

A paradigm shift in the conceptualization of the neurobiology of depression and the serendipitous discovery of ketamine's rapid-acting antidepressant (RAAD) effects has ushered in a new era of innovative research and novel drug development. Since the initial discovery of ketamine's RAAD effects, multiple studies have supported its short-term efficacy for fast-tracked improvements in treatment-resistant depression. Evidence from MRI studies have repeatedly demonstrated functional connectivity alterations in stress- and trauma-related disorders suggesting this may be a viable biomarker of chronic stress pathology (CSP). Human mechanistic studies further support this by coupling functional connectivity to ketamine's RAAD effects including connectivity to glutamate neurotransmission, ketamine to normalized connectivity, and these advantageous normalizations to symptom improvement/ketamine response. This review provides an abridged discussion of the suspected neurobiological underpinnings of ketamine's RAAD effects, highlighting ketamine-induced alterations in prefrontal, striatal, and anterior cingulate cortex functional connectivity in major depressive disorder. We present a model of CSP underscoring the role of synaptic loss and dysconnectivity and discuss how ketamine may be used both as (1) a treatment to restore and normalize these stress-induced neural alterations and (2) a tool to study potential biomarkers of CSP and treatment response. We conclude by noting challenges and future directions including heterogeneity, sex differences, the role of early life stress, and the need for proliferation of new methods, paradigms, and tools that will optimize signal and allow analyses at different levels of complexity, according to the needs of the question at hand, perhaps by thinking hierarchically about both clinical and biological phenotypes.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Ketamina/uso terapêutico , Rede Nervosa/fisiopatologia , Estresse Psicológico/fisiopatologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Doença Crônica , Humanos , Ketamina/farmacologia
19.
Medicine (Baltimore) ; 99(27): e21068, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629736

RESUMO

BACKGROUND: Alterations in the levels of arginine and its related catabolic products (ie, ornithine, citrulline, and argininosuccinate) in the urea and nitric oxide cycles were reported to play roles in the pathogenesis of major depressive disorder (MDD). The aim of this meta-analysis study is to explore the associations between arginine with its related catabolic products and MDD, and to discuss the possible role of arginine catabolism in the pathoetiology of MDD. METHODS: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The English language literature published in the databases of PubMed, EMBASE, PsycINFO and Web of Science will be systematically searched. Forest plots will be used to estimate the associations between arginine and its related catabolic products with MDD. Subgroup analysis and meta-regression will also be performed to investigate the source of the potential heterogeneity. Sensitivity analysis will be performed to strengthen the results and to investigate whether any single study would have a significant effect on the results of meta-analysis. Publication bias will be tested for using the funnel plot with Begg test and Egger test. The Newcastle-Ottawa Scale will be applied to assess the risk of bias of observational studies. RESULTS: An integrated assessment of arginine with its related catabolic products may contribute to predict the risk of MDD. ETHICS AND DISSEMINATION: The results of associations between arginine with its related catabolic products and MDD will be reported in a peer-reviewed publication. With our findings from this meta-analysis, we hope to provide the most up-to-date evidence for the contributions of arginine and related catabolic products to predict the risk of MDD. SYSTEMATIC REVIEW REGISTRATION: The protocol of current meta-analysis has been registered at the Open Science Framework [Available at: https://doi.org/10.17605/osf.io/7fn59].


Assuntos
Arginina/metabolismo , Transtorno Depressivo Maior/metabolismo , Redes e Vias Metabólicas/fisiologia , Óxido Nítrico/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Humanos , Medição de Risco , Sensibilidade e Especificidade
20.
Psychiatry Res Neuroimaging ; 302: 111109, 2020 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-32480044

RESUMO

There is a growing need for optimizing treatment selection and response prediction in individuals with major depressive disorder (MDD). Prior investigations have shown that changes in electroencephalographic (EEG)-based measures precede symptom improvement and could serve as biomarkers of treatment outcome. One such method is cordance, a computation of regional brain activity based on a combination of absolute and relative resting EEG activity. Specifically, early reduction in prefrontal (PF) and midline right frontal (MRF) theta (4-8Hz) cordance has been shown to predict response to various antidepressants, though replication is required. Thus, this study examined early changes (baseline to week 1) in PF and MRF cordance in 47 MDD patients undergoing antidepressant treatment. Early changes in cordance and in Montgomery Åsberg Depression Rating Scale (MADRS) scores were assessed alone, and in combination, to predict eventual (by week 12) treatment response and remission. Models combining early changes in theta cordance (PF and MRF) and depressive symptoms were most predictive of response to treatment at week 12; remission models (cordance, MADRS, and their combination) were weaker, though provided modest prediction values. These results suggest that antidepressant response may be optimally predicted by combining both EEG and symptom-based measures after one week of treatment.


Assuntos
Antidepressivos/uso terapêutico , Depressão/psicologia , Transtorno Depressivo Maior/tratamento farmacológico , Córtex Pré-Frontal/fisiopatologia , Ritmo Teta , Adulto , Bupropiona/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Eletroencefalografia/métodos , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Resultado do Tratamento
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