RESUMO
Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[18F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I. [18F]MNI-659 PET data were acquired from 25 patients with BD-I and 27 age- and sex-matched healthy controls. Patients with BD-I had significantly lower PDE10A availability than controls in the executive (F = 8.86; P = 0.005) and sensorimotor (F = 6.13; P = 0.017) subregions of the striatum. Lower PDE10A availability in the executive subregion was significantly associated with a higher frequency of mood episodes in patients with BD-I (r = -0.546; P = 0.007). This study provides the first evidence of altered PDE10A availability in patients with BD-I. Lower PDE10A availability in the executive subregion of the striatum is associated with an increased recurrence risk, suggesting that PDE10A may prevent BD-I relapse. Further studies are required to elucidate the role of PDE10A in BD-I pathophysiology and explore its potential as a treatment target.
Assuntos
Transtorno Bipolar , Diester Fosfórico Hidrolases , Tomografia por Emissão de Pósitrons , Recidiva , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Masculino , Feminino , Adulto , Diester Fosfórico Hidrolases/metabolismo , Estudos de Casos e Controles , Pessoa de Meia-Idade , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Adulto Jovem , Ftalimidas , QuinazolinonasRESUMO
Introduction: Lithium is a gold-standard agent for bipolar disorder (BD) and can affect the size, structure and/or function of thyroid gland with long-term exposure. Thyroid ultrasound can detect structural thyroid abnormalities, but it is under-reported with few prior studies in lithium users. The study aimed to evaluate thyroid volume and echogenicity in lithium users with BD and healthy participants, and explores its association with clinical variables and thyroid functions. Method: This was an observational study with 102 participants in total. Study group consisted of 52 clinically-stable (HAM-D ≤ 13, YMRS <8) follow-up patients with DSM-5 BD on lithium maintenance. Healthy controls (HC) comprised 50 participants with no illness in self and family. Assessments included NIMH Life-chart, IGLSI typical/atypical scale, lithium response scale (LRS) and CGI-BP. Fasting venous sample was taken for thyroid functions, Anti-TPO antibodies and serum lithium. Thyroid ultrasonography was also conducted. Results: Mean age of cases was 39.42 ± 12.62 years, with 42.3% females, which was comparable to HC. Median duration of illness was 10.5 years (Q1-Q3 = 6-19 years), with median lithium exposure for 4.5 years (Q1-Q3:2.2-7.75), and serum lithium 0.67 mmol/L (SD:0.31). Thyroid volume was significantly higher for cases than HC (10.67 ± 5.46 mL vs 4.30 ± 2.06 mL; p < 0.001). Relative to HC, serum TSH was higher in cases (p = 0.018), while anti-TPO positivity was comparable (14.0% vs 3.85%, p = 0.089). Thyroid nodules were more frequent in male cases (p = 0.013) compared to male controls.Thyroid volume did not show association with serum TSH (p = 0.277) and lithium response (p = 0.36). Conclusion: Findings indicate a uniform enlargement of thyroid gland in lithium users with BD. Thyroid volume did not show association with thyroid functions and lithium response, however prospective studies may give better insight about their trajectories over time.
Assuntos
Transtorno Bipolar , Glândula Tireoide , Ultrassonografia , Humanos , Masculino , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/diagnóstico por imagem , Feminino , Adulto , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Compostos de Lítio/administração & dosagem , Compostos de Lítio/farmacologia , Antimaníacos/administração & dosagem , Antimaníacos/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Lítio/administração & dosagemRESUMO
AIMS: The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period. METHODS: We utilized 1H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC. RESULTS: Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (p = 0.004; p = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (p = 0.03). No significant alterations were found in depressed group between baseline and follow-up. CONCLUSION: This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.
Assuntos
Ácido Aspártico , Transtorno Bipolar , Ácido Glutâmico , Glutamina , Córtex Pré-Frontal , Espectroscopia de Prótons por Ressonância Magnética , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Transtorno Bipolar/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/diagnóstico por imagem , Masculino , Feminino , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Glutamina/metabolismo , Ácido Glutâmico/metabolismo , Pessoa de Meia-Idade , Seguimentos , Creatina/metabolismo , Adulto Jovem , Fosfocreatina/metabolismoRESUMO
Brain network hubs are highly connected brain regions serving as important relay stations for information integration. Recent studies have linked mental disorders to impaired hub function. Provincial hubs mainly integrate information within their own brain network, while connector hubs share information between different brain networks. This study used a novel time-varying analysis to investigate whether hubs aberrantly follow the trajectory of other brain networks than their own. The aim was to characterize brain hub functioning in clinically remitted bipolar patients. We analyzed resting-state functional magnetic resonance imaging data from 96 euthymic individuals with bipolar disorder and 61 healthy control individuals. We characterized different hub qualities within the somatomotor network. We found that the somatomotor network comprised mainly provincial hubs in healthy controls. Conversely, in bipolar disorder patients, hubs in the primary somatosensory cortex displayed weaker provincial and stronger connector hub function. Furthermore, hubs in bipolar disorder showed weaker allegiances with their own brain network and followed the trajectories of the limbic, salience, dorsal attention, and frontoparietal network. We suggest that these hub aberrancies contribute to previously shown functional connectivity alterations in bipolar disorder and may thus constitute the neural substrate to persistently impaired sensory integration despite clinical remission.
Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Rede Nervosa , Córtex Somatossensorial , Humanos , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Masculino , Feminino , Adulto , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Conectoma , Pessoa de Meia-Idade , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Humanos , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Feminino , Masculino , Adulto , Imageamento por Ressonância Magnética/métodos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Estudos Transversais , Pessoa de Meia-Idade , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Conectoma/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Análise Multivariada , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Mapeamento Encefálico/métodosRESUMO
OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-â ). METHODS: From August 2013 and August 2019, a total of 155 BD-â patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-â , which are part of the alerting and orienting network.
Assuntos
Atenção , Transtorno Bipolar , Canais de Cálcio Tipo L , Genótipo , Humanos , Adulto , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Masculino , Feminino , Canais de Cálcio Tipo L/genética , Imageamento por Ressonância Magnética , Córtex Cerebral/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Identifying white matter (WM) microstructural similarities and differences between major depressive disorder (MDD) and bipolar disorder (BD) is an important way to understand the potential neuropathological mechanism in emotional disorders. Numerous diffusion tensor imaging (DTI) studies over recent decades have confirmed the presence of WM anomalies in these two affective disorders, but the results were inconsistent. This study aimed to determine the statistical consistency of DTI findings for BD and MDD by using the coordinate-based meta-analysis (CBMA) approach. METHODS: We performed a systematic search of tract-based spatial statistics (TBSS) studies comparing MDD or BD with healthy controls (HC) as of June 30, 2024. The seed-based d-mapping (SDM) was applied to investigate fractional anisotropy (FA) changes. Meta-regression was then used to analyze the potential correlations between demographics and neuroimaging alterations. RESULTS: Regional FA reductions in the body of the corpus callosum (CC) were identified in both of these two diseases. Besides, MDD patients also exhibited decreased FA in the genu and splenium of the CC, as well as the left anterior thalamic projections (ATP), while BD patients showed FA reduction in the left median network, and cingulum in addition to the CC. CONCLUSIONS: The results highlighted that altered integrity in the body of CC served as the shared basis of MDD and BD, and distinct microstructural WM abnormalities also existed, which might induce the various clinical manifestations of these two affective disorders. The study was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42022301929.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Imagem de Tensor de Difusão , Substância Branca , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologiaRESUMO
BACKGROUND: Bipolar disorder (BD) is often misidentified as unipolar depression (UD) during its early stages, typically until the onset of the first manic episode. This study aimed to explore both shared and unique neurostructural changes in patients who transitioned from UD to BD during follow-up, as compared to those with UD. METHODS: This study utilized high-resolution structural magnetic resonance imaging (MRI) to collect brain data from individuals initially diagnosed with UD. During the average 3-year follow-up, 24 of the UD patients converted to BD (cBD). For comparison, the study included 48 demographically matched UD patients who did not convert and 48 healthy controls. The MRI data underwent preprocessing using FreeSurfer, followed by surface-based morphometry (SBM) analysis to identify cortical thickness (CT), surface area (SA), and cortical volume (CV) among groups. RESULTS: The SBM analysis identified shared neurostructural characteristics between the cBD and UD groups, specifically thinner CT in the right precentral cortex compared to controls. Unique to the cBD group, there was a greater SA in the right inferior parietal cortex compared to the UD group. Furthermore, no significant correlations were observed between cortical morphological measures and cognitive performance and clinical features in the cBD and UD groups. LIMITATIONS: The sample size is relatively small. CONCLUSIONS: Our findings suggest that while cBD and UD exhibit some common alterations in cortical macrostructure, numerous distinct differences are also present. These differences offer valuable insights into the neuropathological underpinnings that distinguish these two conditions.
Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Feminino , Masculino , Adulto , Seguimentos , Estudos Prospectivos , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Casos e ControlesRESUMO
BACKGROUND: The widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. METHODS: This study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. RESULTS: Model constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = - 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. CONCLUSIONS: This study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.
Assuntos
Transtorno Bipolar , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Transtorno Bipolar/psicologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Feminino , Masculino , Adulto , Fatores de Risco , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Suicídio/psicologia , Pessoa de Meia-Idade , Tentativa de Suicídio/psicologia , Descanso/fisiologia , Adulto JovemRESUMO
BACKGROUND: Bipolar disorder I (BD-I) is a heterogeneous disorder with a high prevalence of comorbid anxiety. The aim of this study was to investigate whether anxiety and mania symptoms define distinct subgroups within BD-I and to explore potential differences in functional network characteristics between these subgroups. METHODS: Subgroups were identified using scores from clinical anxiety and mania scales. After dimension reduction of these scores, data-driven clustering analysis with cross-validation was employed to reveal the existence of subgroups. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were pre-processed using fMRIPrep. After parcellation and network construction, global and regional graph theoretical measures were calculated per subgroup. RESULTS: Clustering results revealed that, based on anxiety symptomatology, subjects fell into two distinct subgroups, whereas mania symptoms divided subjects into four unique subgroups. These subgroups varied notably on several symptom scales. Network assortativity was significantly associated with anxiety subgroups. Post-hoc pairwise comparisons did not reveal significant global functional network differences between the anxiety subgroups or between mania subgroups. Regional network differences between clinical subgroups were especially apparent for strength and degree in the temporal and frontal lobes. LIMITATIONS: Small sample size of some subgroups is a limitation of this study as is the categorical rather than continuous representation of anxiety and mania symptoms. CONCLUSIONS: BD-I populations may be stratified into robust subgroups based on anxiety and mania symptoms, showing differences in functional network connectivity. Our findings highlight new avenues of research for investigating heterogeneity in psychiatric populations.
Assuntos
Ansiedade , Transtorno Bipolar , Imageamento por Ressonância Magnética , Mania , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Masculino , Feminino , Adulto , Mania/diagnóstico por imagem , Mania/fisiopatologia , Ansiedade/psicologia , Ansiedade/fisiopatologia , Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto Jovem , Pessoa de Meia-Idade , Análise por Conglomerados , Mapeamento Encefálico/métodosRESUMO
BACKGROUND: Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs. METHODS: A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD. RESULTS: BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the default mode network. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities. LIMITATIONS: Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings. CONCLUSIONS: The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention.
Assuntos
Transtorno Bipolar , Encéfalo , Endofenótipos , Família , Imageamento por Ressonância Magnética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/genética , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologiaRESUMO
OBJECTIVE: We aimed to compare retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness in bipolar disorder (BD) and major depressive disorder (MDD). METHOD: The study included thirty MDD, thirty-two BD participants in depressive episode, and thirty-seven controls matched according to age, gender, body mass index (BMI), and smoking status. Optic coherence tomography (OCT) measurements were performed for both participants and controls. The RNFL and GCC thickness were measured and recorded automatically by a spectral OCT device. Participants were also subjected to Hamilton Depression Rating Scale (HAM-D). RESULTS: RNFL superior thickness was significantly lower in BD participants, compared to the MDD participants and controls (p = 0.001). GCC inferior (p = 0.022) and inferonasal (p = 0.005) thickness were detected lower in BD group, compared to the control groups. In the BD group, HAM-D scores were negatively correlated with RNFL-temporal (p = 0.049, r= -0.357), GCC inferotemporal (p = 0.02, r= -0.416) and superotemporal thickness (p = 0.002, r= -0.546). CONCLUSIONS: RNFL thickness were lower in BD participants compared to the MDD and controls and, GCC thickness were lower in BD participants compared to the controls. Our findings support the hypothesis that neurodegeneration is part of the pathogenesis of BD. Future research are needed to confirm the lack of RNFL thickness in MDD, which could have immediate therapeutic consequences as well as implications for distinguishing BD from MDD.
RNFL thickness is lower in BD participants compared to the MDD and controls.GCC thickness were lower in BD participants compared to the controls.HAM-D scores are negatively correlated with RNFL temporal and, GCC inferotemporal and superotemporal thickness.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Feminino , Masculino , Adulto , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Tomografia de Coerência Óptica/métodos , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Pessoa de Meia-Idade , Diagnóstico Diferencial , Retina/patologia , Retina/diagnóstico por imagemRESUMO
INTRODUCTION: Anomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. METHODS: Participants included 113 youth, 13-20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. RESULTS: ROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. CONCLUSION: We found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.
Assuntos
Transtorno Bipolar , Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Adolescente , Circulação Cerebrovascular/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Adulto Jovem , Encéfalo/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Endotélio Vascular/diagnóstico por imagem , Hiperemia/fisiopatologia , Hiperemia/diagnóstico por imagemRESUMO
Electroconvulsive therapy (ECT) demonstrates favorable outcomes in the management of severe depressive disorders. ECT has been consistently associated with volumetric increases in the amygdala and hippocampus. However, the underlying mechanisms of these structural changes and their association to clinical improvement remains unclear. In this cross-sectional structural MRI study, we assessed the difference in amygdala subnuclei and hippocampus subfields in n = 37 patients with either unipolar or bipolar disorder immediately after eighth ECT sessions compared to (n = 40) demographically matched patients in partial remission who did not receive ECT (NoECT group). Relative to NoECT, the ECT group showed significantly larger bilateral amygdala volumes post-treatment, with the effect originating from the lateral, basal, and paralaminar nuclei and the left corticoamydaloid transition area. No significant group differences were observed for the hippocampal or cortical volumes. ECT was associated with a significant decrease in depressive symptoms. However, there were no significant correlations between amygdala subnuclei volumes and symptom improvement. Our study corroborates previous reports on increased amygdalae volumes following ECT and further identifies the subnuclei driving this effect. However, the therapeutic effect of ECT does not seem to be directly related to structural changes in the amygdala.
Assuntos
Tonsila do Cerebelo , Eletroconvulsoterapia , Hipocampo , Imageamento por Ressonância Magnética , Transtornos do Humor , Humanos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Transtornos do Humor/terapia , Transtornos do Humor/diagnóstico por imagem , Transtornos do Humor/psicologia , Resultado do Tratamento , Idoso , Transtorno Bipolar/terapia , Transtorno Bipolar/diagnóstico por imagemRESUMO
BACKGROUND: Functional Magnetic Resonance Imaging (fMRI) has shown brain activity alterations in individuals with a history of attempted suicide (SA) who are diagnosed with depression disorder (DD) or bipolar disorder (BD). However, patterns of spontaneous brain activity and their genetic correlations need further investigation. METHODS: A voxel-based meta-analysis of 19 studies including 26 datasets, involving 742 patients with a history of SA and 978 controls (both nonsuicidal patients and healthy controls) was conducted. We examined fMRI changes in SA patients and analyzed the association between these changes and gene expression profiles using data from the Allen Human Brain Atlas by partial least squares regression analysis. RESULTS: SA patients demonstrated increased spontaneous brain activity in several brain regions including the bilateral inferior temporal gyrus, hippocampus, fusiform gyrus, and right insula, and decreased activity in areas like the bilateral paracentral lobule and inferior frontal gyrus. Additionally, 5,077 genes were identified, exhibiting expression patterns associated with SA-related fMRI alterations. Functional enrichment analyses demonstrated that these SA-related genes were enriched for biological functions including glutamatergic synapse and mitochondrial structure. Concurrently, specific expression analyses showed that these genes were specifically expressed in the brain tissue, in neurons cells, and during early developmental periods. CONCLUSION: Our findings suggest a neurobiological basis for fMRI abnormalities in SA patients with DD or BD, potentially guiding future genetic and therapeutic research.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Tentativa de Suicídio , Adulto , Feminino , Humanos , Masculino , Transtorno Bipolar/genética , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Expressão Gênica , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto JovemRESUMO
Schizophrenia (SZ) and bipolar disorder (BD) are characterized by major symptomatic, cognitive, and neuroanatomical changes. Recent studies have used optical coherence tomography (OCT) to investigate retinal changes in SZ and BD, but their unique and shared changes require further evaluation. Articles were identified using PubMed and Google Scholar. 39 studies met the inclusion criteria. Diagnostic groups were proband (SZ/BD combined), SZ, BD, and healthy control (HC) eyes. Meta-analyses utilized fixed and random effects models when appropriate, and publication bias was corrected using trim-and-fill analysis ("meta" package in R). Results are reported as standardized mean differences with 95% CIs. Data from 3145 patient eyes (1956 SZ, 1189 BD) and 3135 HC eyes were included. Studies identified thinning of the peripapillary retinal nerve fiber layer (pRNFL, overall and in 2 subregions), m-Retina (overall and all subregions), mGCL-IPL, mIPL, and mRPE in SZ patients. BD showed thinning of the pRNFL (overall and in each subregion), pGCC, and macular Retina (in 5 subregions), but no changes in thickness or volume for the total retina. Neither SZ nor BD patients demonstrated significant changes in the fovea, mRNFL, mGCL, mGCC, mINL, mOPL, mONL, or choroid thicknesses. Moderating effects of age, illness duration, and smoking on retinal structures were identified. This meta-analysis builds upon previous literature in this field by incorporating recent OCT studies and examining both peripapillary and macular retinal regions with respect to psychotic disorders. Overall, this meta-analysis demonstrated both peripapillary and macular structural retinal abnormalities in people with SZ or BD compared with HCs.
Assuntos
Transtorno Bipolar , Esquizofrenia , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/patologia , Retina/diagnóstico por imagem , Retina/patologia , Retina/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Esquizofrenia/patologia , Tomografia de Coerência ÓpticaRESUMO
Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at increased risk of developing psychopathology. Structural brain alterations have been found in child and adolescent offspring of patients with bipolar disorder and schizophrenia, but the developmental trajectories of brain anatomy in this high-familial-risk population are still unclear. 300 T1-weighted scans were obtained of 187 offspring of at least one parent diagnosed with bipolar disorder (n=80) or schizophrenia (n=53) and offspring of parents without severe mental illness (n=54). The age range was 8 to 23 years old; 113 offspring underwent two scans. Global brain measures and regional cortical thickness and surface area were computed. A generalized additive mixed model was used to capture non-linear age trajectories. Offspring of parents with schizophrenia had smaller total brain volume than offspring of parents with bipolar disorder (d=-0.20, p=0.004) and control offspring (d=-0.22, p=0.005) and lower mean cortical thickness than control offspring (d=-0.23, p<0.001). Offspring of parents with schizophrenia showed differential age trajectories of mean cortical thickness and cerebral white matter volume compared with control offspring (both p's=0.003). Regionally, offspring of parents with schizophrenia had a significantly different trajectory of cortical thickness in the middle temporal gyrus versus control offspring (p<0.001) and bipolar disorder offspring (p=0.001), which was no longer significant after correcting for mean cortical thickness. These findings suggest that particularly familial high risk of schizophrenia is related to reductions and deviating developmental trajectories of global brain structure measures, which were not driven by specific regions.
Assuntos
Transtorno Bipolar , Encéfalo , Filho de Pais com Deficiência , Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Transtorno Bipolar/genética , Esquizofrenia/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Criança , Masculino , Adolescente , Feminino , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Dinâmica não LinearRESUMO
BACKGROUND: The profiles of cortical gyrification across schizophrenia, bipolar I disorder, and schizoaffective disorder have been studied to a limited extent, report discordant findings, and are rarely compared in the same study. Here we assess gyrification in a large dataset of psychotic disorder probands, categorized according to the DSM-IV. Furthermore, we explore gyrification changes with age across healthy controls and probands. METHODS: Participants were recruited within the Bipolar-Schizophrenia Network of Intermediate Phenotypes study and received T1-MPRAGE and clinical assessment. Gyrification was measured using FreeSurfer 7.1.0. Pairwise t-tests were conducted in R, and age-related gyrification changes were analyzed in MATLAB. P values <0.05 after false discovery rate correction were considered significant. RESULTS: Significant hypogyria in schizophrenia, bipolar disorder, and schizoaffective disorder probands compared to controls was found, with a significant difference bilaterally in the frontal lobe between schizophrenia and bipolar disorder probands. Verbal memory was associated with gyrification in the right frontal and right cingulate cortex in schizophrenia. Age-fitted gyrification curves differed significantly among psychotic disorders and controls. CONCLUSIONS: Findings indicate hypogyria in DSM-IV psychotic disorders compared to controls and suggest differential patterns of gyrification across the different diagnoses. The study extends age related models of gyrification to psychotic disorder probands and supports that age-related differences in gyrification may differ across diagnoses. Fitted gyrification curves among probands categorized by DSM-IV significantly deviate from controls, with the model capturing early hypergyria and later hypogyria in schizophrenia compared to controls; this suggests unique disease and age-related changes in gyrification across psychotic disorders.
Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Fenótipo , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/patologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Transtorno Bipolar/patologia , Transtorno Bipolar/diagnóstico por imagem , Esquizofrenia/patologia , Esquizofrenia/diagnóstico por imagem , Adulto , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologiaRESUMO
BACKGROUND: Cerebral mitochondrial and hemodynamic abnormalities have been implicated in Bipolar Disorder pathophysiology, likely contributing to neurometabolic vulnerability-leading to worsen clinical outcomes and mood instability. To investigate neurometabolic vulnerability in patients with BD, we combined multi-modal quantitative MRI assessment of cerebral oxygenation with acute administration of Methylene Blue, a neurometabolic/hemodynamic modulator acting on cerebral mitochondria. METHODS: Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo. MRI-based measures of Cerebral Blood Flow and Oxygen Extraction Fraction were integrated to compute Cerebral Metabolic Rate of Oxygen in Frontal Lobe, Anterior Cingulate, and Hippocampus-implicated in BD neurometabolic pathophysiology. Inter-daily variation in mood rating was used to assess mood instability. RESULTS: A decrease in global CBF and CMRO2 was observed after acutely administrating MB to all participants. Greater regional CMRO2 reductions were observed after MB, in patients compared to controls in FL (mean = -14.2 ± 19.5 % versus 2.3 ± 14.8 %), ACC (mean = -14.8 ± 23.7 % versus 2.4 ± 15.7 %). The effects on CMRO2 in those regions were primarily driven by patients with longer disease duration and higher mood instability. LIMITATIONS: Sample size; medications potentially impacting on response to MB. CONCLUSIONS: An altered neurometabolic response to MB, a mitochondrial/hemodynamic modulator, was observed in patients, supporting the hypothesis of vulnerability to neurometabolic stress in BD. Integrating quantitative imaging of cerebral oxygen metabolism with a mitochondrial-targeting pharmacological challenge could provide a novel biomarker of neurometabolic and cerebrovascular pathophysiology in BD.
Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Azul de Metileno , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/metabolismo , Transtorno Bipolar/diagnóstico por imagem , Feminino , Masculino , Adulto , Azul de Metileno/farmacologia , Método Simples-Cego , Neuroimagem , Estudos Cross-Over , Pessoa de Meia-Idade , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Giro do Cíngulo/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/diagnóstico por imagem , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacosRESUMO
The urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome's modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome's temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns' spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.