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1.
J Affect Disord ; 302: 50-57, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35074460

RESUMO

BACKGROUND: Bipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I). METHODS: Forty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann-Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P < 0.001, cluster-level P < 0.05). RESULTS: Compared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P < 0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P < 0.05, GRF corrected). CONCLUSIONS: BP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.


Assuntos
Transtorno Bipolar , Córtex Cerebelar , Substância Cinzenta , Transtorno Bipolar/patologia , Transtorno Bipolar/fisiopatologia , Córtex Cerebelar/patologia , Córtex Cerebelar/fisiopatologia , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos
2.
Schizophr Bull ; 48(1): 56-68, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34409449

RESUMO

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.


Assuntos
Transtorno Bipolar/classificação , Transtorno Bipolar/fisiopatologia , Transtornos Psicóticos/classificação , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/classificação , Esquizofrenia/fisiopatologia , Adulto , Biomarcadores , Análise por Conglomerados , Conjuntos de Dados como Assunto , Eletroencefalografia , Endofenótipos , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Inibição Psicológica , Estudos Longitudinais , Masculino , Desempenho Psicomotor/fisiologia , Movimentos Sacádicos/fisiologia
3.
Schizophr Bull ; 48(1): 37-46, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34499169

RESUMO

BACKGROUND: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. METHODS: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. RESULTS: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). CONCLUSIONS: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.


Assuntos
Transtornos Psicóticos Afetivos/sangue , Fator Ativador de Células B/sangue , Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Esquizofrenia/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Transtornos Psicóticos Afetivos/fisiopatologia , Transtorno Bipolar/fisiopatologia , Estudos Transversais , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/fisiopatologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-34929323

RESUMO

INTRODUCTION: Women with bipolar disorder (BD) present a high prevalence of polycystic ovary syndrome (PCOS) and other reproductive disorders even before diagnosis or treatment of the disease. Postulations on the potential molecular mechanisms of comorbid PCOS in women with BD remain limited to influence of medications and need further extension. OBJECTIVES: This review focuses on evidence suggesting that common metabolic and immune disorders may play an important role in the development of BD and PCOS. RESULTS: The literature covered in this review suggests that metabolic and immune disorders, including the dysfunction of the hypothalamic-pituitary-adrenal axis, chronic inflammatory state, gut microbial alterations, adipokine alterations and circadian rhythm disturbance, are observed in patients with BD and PCOS. Such disorders may be responsible for the increased prevalence of PCOS in the BD population and indicate a susceptibility gene overlap between the two diseases. Current evidence supports postulations of common metabolic and immune disorders as endophenotype in BD as well as in PCOS. CONCLUSIONS: Metabolic and immune disorders may be responsible for the comorbid PCOS in the BD population. The identification of hallmark metabolic and immune features common to these two diseases will contribute to the clarification of the effect of BD on the reproductive endocrine function and development of symptomatic treatments targeting the biomarkers of the two diseases.


Assuntos
Transtorno Bipolar , Comorbidade , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Síndrome do Ovário Policístico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Ritmo Circadiano/fisiologia , Feminino , Humanos , Doenças do Sistema Imunitário/complicações , Doenças Metabólicas/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia
5.
PLoS One ; 16(12): e0262129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972188

RESUMO

BACKGROUND: Bipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice. METHODS: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017. RESULTS: In total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes. CONCLUSIONS: In Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.


Assuntos
Transtorno Bipolar/fisiopatologia , Mania/fisiopatologia , Adolescente , Adulto , Afeto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Transtorno Bipolar/complicações , Índice de Massa Corporal , Comorbidade , Feminino , Indicadores Básicos de Saúde , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Transtornos da Personalidade/complicações , Prevalência , Estudos Retrospectivos , Risco , Transtornos Relacionados ao Uso de Substâncias/complicações , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
6.
Sci Rep ; 11(1): 22007, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759276

RESUMO

Default mode network (DMN) is a set of functional brain structures coherently activated when individuals are in resting-state. In this study, we constructed multi-frequency band resting-state EEG-based DMN functional network models for major psychiatric disorders to easily compare their pathophysiological characteristics. Phase-locking values (PLVs) were evaluated to quantify functional connectivity; global and nodal clustering coefficients (CCs) were evaluated to quantify global and local connectivity patterns of DMN nodes, respectively. DMNs of patients with post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder, major depressive disorder (MDD), bipolar disorder, schizophrenia (SZ), mild cognitive impairment (MCI), and Alzheimer's disease (AD) were constructed relative to their demographically-matched healthy control groups. Overall DMN patterns were then visualized and compared with each other. In global CCs, SZ and AD showed hyper-clustering in the theta band; OCD, MCI, and AD showed hypo-clustering in the low-alpha band; OCD and MDD showed hypo-clustering and hyper-clustering in low-beta, and high-beta bands, respectively. In local CCs, disease-specific patterns were observed. In the PLVs, lowered theta-band functional connectivity between the left lingual gyrus and the left hippocampus was frequently observed. Our comprehensive comparisons suggest EEG-based DMN as a useful vehicle for understanding altered brain networks of major psychiatric disorders.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Rede Nervosa/fisiopatologia , Doença de Alzheimer/fisiopatologia , Transtorno Bipolar/fisiopatologia , Mapeamento Encefálico , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno de Pânico/fisiopatologia , Esquizofrenia/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
7.
Sci Rep ; 11(1): 22426, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789827

RESUMO

Current criteria for depression are imprecise and do not accurately characterize its distinct clinical presentations. As a result, its diagnosis lacks clinical utility in both treatment and research settings. Data-driven efforts to refine criteria have typically focused on a limited set of symptoms that do not reflect the disorder's heterogeneity. By contrast, clinicians often write about patients in depth, creating descriptions that may better characterize depression. However, clinical text is not commonly used to this end. Here we show that clinically relevant depressive subtypes can be derived from unstructured electronic health records. Five subtypes were identified amongst 18,314 patients with depression treated at a large mental healthcare provider by using unsupervised machine learning: severe-typical, psychotic, mild-typical, agitated, and anergic-apathetic. Subtypes were used to place patients in groups for validation; groups were found to be associated with future outcomes and characteristics that were consistent with the subtypes. These associations suggest that these categorizations are actionable due to their validity with respect to disease prognosis. Moreover, they were derived with automated techniques that might theoretically be widely implemented, allowing for future analyses in more varied populations and settings. Additional research, especially with respect to treatment response, may prove useful in further evaluation.


Assuntos
Depressão/classificação , Depressão/fisiopatologia , Transtorno Depressivo/classificação , Transtorno Depressivo/fisiopatologia , Registros Eletrônicos de Saúde , Adolescente , Adulto , Idoso , Transtorno Bipolar/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/fisiopatologia , Estudos Retrospectivos , Aprendizado de Máquina não Supervisionado , Adulto Jovem
8.
Expert Opin Investig Drugs ; 30(11): 1081-1087, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34844484

RESUMO

INTRODUCTION: The quest toward more effective treatments for bipolar disorder (BD) solicits novel drugs and further research on the underpinning neurobiology. The present review aims to critically appraise the existing evidence about the pharmacological treatment of BD toward the development of novel treatment avenues. AREAS COVERED: The present review appraises animal and human studies concerning both the currently available psychotropic drugs, and the general medicine drugs which may represent a path toward the development of novel drugs for BD. PubMed and Scopus were last accessed on February 20th, 2021 for records indexed upon inception relevant to the pharmacological treatment of BD. Immune-modulating agents, anti-inflammatory agents, and glutamate antagonists represent the most intriguing potential targets for the development of new drugs for BD, thus receiving critical appraisal in the present text. EXPERT OPINION: Regardless of the neurobiological pathways worthy of investigation toward the development of experimental drugs for BD, several unmet needs need to be addressed first. In particular, several biomarkers are altered in BD. However, it is the opinion herein expressed by the authors that it remains uncertain what comes first, that is peripheral changes or the disease.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Drogas em Investigação/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores/metabolismo , Transtorno Bipolar/fisiopatologia , Desenvolvimento de Medicamentos , Drogas em Investigação/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Humanos , /farmacologia
9.
J Psychiatry Neurosci ; 46(5): E559-E567, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34625488

RESUMO

BACKGROUND: Adolescents with bipolar disorder have high rates of cannabis use, and cannabis use is associated with increased symptom severity and treatment resistance in bipolar disorder. Studies have identified anomalous resting-state functional connectivity among reward networks in bipolar disorder and cannabis use independently, but have yet to examine their convergence. METHODS: Participants included 134 adolescents, aged 13 to 20 years: 40 with bipolar disorder and lifetime cannabis use, 31 with bipolar disorder and no history of cannabis use, and 63 healthy controls without lifetime cannabis use. We used a seed-to-voxel analysis to assess the restingstate functional connectivity of the amygdala, the nucleus accumbens and the orbitofrontal cortex, regions implicated in bipolar disorder and cannabis use. We used a generalized linear model to explore bivariate correlations for each seed, controlling for age and sex. RESULTS: We found 3 significant clusters. Resting-state functional connectivity between the left nucleus accumbens seed and the left superior parietal lobe was negative in adolescents with bipolar disorder and no history of cannabis use, and positive in healthy controls. Resting-state functional connectivity between the right orbitofrontal cortex seed and the right lateral occipital cortex was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in healthy controls and adolescents with bipolar disorder and no history of cannabis use. Resting-state functional connectivity between the right orbitofrontal cortex seed and right occipital pole was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in adolescents with bipolar disorder and no history of cannabis use. LIMITATIONS: The study did not include a cannabis-using control group. CONCLUSION: This study provides preliminary evidence of cannabis-related differences in functional reward circuits in adolescents with bipolar disorder. Further studies are necessary to evaluate whether the present findings reflect consequences of or predisposition to cannabis use.


Assuntos
Transtorno Bipolar/fisiopatologia , Cannabis , Uso da Maconha , Vias Neurais , Descanso , Recompensa , Adolescente , Tonsila do Cerebelo/fisiopatologia , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia , Núcleo Accumbens/fisiopatologia , Córtex Pré-Frontal/fisiopatologia
10.
Genes (Basel) ; 12(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34680877

RESUMO

Suicide in Bipolar Disorder (BD) is a relevant clinical concern. Genetics may shape the individual risk for suicide behavior in BD, together with known clinical factors. The lack of consistent replication in BD may be associated with its multigenetic component. In the present contribution we analyzed a sample of BD individuals (from STEP-BD database) to identify the genetic variants potentially associated with three different suicide-related phenotypes: (1) a feeling that the life was not worth living; (2) fantasies about committing a violent suicide; (3) previous attempted suicide. The sample under analysis included 1115 BD individuals. None of the SNPs reached genome-wide significance. However, a trend of association was evidenced for rs2767403, an intron variant of AOPEP gene, in association with phenotype #1 (p = 5.977 × 10-6). The molecular pathway analysis showed a significant enrichment in all the investigated phenotypes on pathways related to post synaptic signaling, neurotransmission and neurodevelopment. Further, NOTCH signaling or the γ-aminobutyric acid (GABA)-ergic signaling were found to be associated with specific suicide-related phenotypes. The present investigation contributes to the hypothesis that the genetic architecture of suicide behaviors in BD is related to alteration of entire pathways rather than single genes. In particular, our molecular pathway analysis points on some specific molecular events that could be the focus of further research in this field.


Assuntos
Aminopeptidases/genética , Transtorno Bipolar/genética , Predisposição Genética para Doença , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Adulto , Idoso , Transtorno Bipolar/complicações , Transtorno Bipolar/fisiopatologia , Genoma/genética , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Receptores Notch/genética , Fatores de Risco , Transdução de Sinais/genética , Ácido gama-Aminobutírico/genética
11.
Eur Rev Med Pharmacol Sci ; 25(17): 5483-5489, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34533796

RESUMO

OBJECTIVE: Patients with bipolar disorder (BD) experience a poor quality of life (QoL) and a weak adherence to the therapy due to the various side effects occurring during the pharmacological therapy. To date clinicians have no tools to intervene on such effects, considering them as an unavoidable part of the therapy. This review paves the way for a step forward in the management of patients with BD bridging the therapeutic gap in clinical practice. MATERIALS AND METHODS: We reviewed the literature, searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including bipolar disorder, lithium and valproic acid, inositol role in bipolar disorder, side effects, inositol depletion, supplementation of inositols under lithium treatment, inositol role in metabolism, hypothyroidism, renal and cardiac functionality. In particular, we narrowed the search down to English literature, excluding works before 1980s. Regarding clinical studies, we included case reports and both preclinical and clinical studies, especially only those exhibiting a control group. The outcome of the database search was to highlight the threat of side effects and the relationship with inositol lower levels, paving the way for a step forward in the management of patients with BD. RESULTS: Based on the collected evidence, the combined administration of myo-inositol (myo-ins) and d-chiro-inositol (d-chiro-ins) is strongly recommended in order to restore levels and metabolism of inositols. Previous studies pointed out the beneficial effects of inositols in recovering pathological conditions, like polycystic ovary syndrome (PCOS), hypothyroidism, weight gain, cardiac functionality, being all these conditions related to the depletion of inositols. Furthermore, a controlled dosage of inositols, up to 6 grams/daily, may reduce the side effects caused by lithium therapy, without hindering its central therapeutic role on patients' mood. CONCLUSIONS: Considering the iatrogenic depletion of inositols, the tailored ratio 80:1 in favour of myo-ins, may become a safe and effective strategy to counteract side effects, by providing a large amount of myo-ins and an adequate one of d-chiro-ins. The clinical dosage of inositols used as dietary supplementation is 4 grams/daily, and it may allow the recovery of the side effects and improve patients' QoL, without reducing the central therapeutic effect of the pharmacological therapy.


Assuntos
Antimaníacos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Inositol/administração & dosagem , Antimaníacos/efeitos adversos , Transtorno Bipolar/fisiopatologia , Suplementos Nutricionais , Humanos , Inositol/metabolismo , Compostos de Lítio/administração & dosagem , Compostos de Lítio/efeitos adversos , Adesão à Medicação , Qualidade de Vida , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
12.
Am J Psychiatry ; 178(10): 952-964, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407624

RESUMO

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.


Assuntos
Vias Auditivas/fisiopatologia , Transtorno Bipolar , Eletroencefalografia/métodos , Vias Neurais/fisiopatologia , Transtornos Psicóticos , Estimulação Acústica/métodos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Cognição , Correlação de Dados , Diagnóstico Diferencial , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Técnicas Psicológicas , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Índice de Gravidade de Doença
13.
J Nerv Ment Dis ; 209(8): 578-584, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397758

RESUMO

ABSTRACT: The aim of this study was to investigate the relationship of attachment and coping mechanisms with social functioning in patients with bipolar disorder (BD). Sixty-three patients with BD type I and 63 healthy controls were evaluated. Structured Clinical Interview for DSM-IV Axis I Disorders, Hamilton Depression Rating Scale, Young Mania Rating Scale, Experiences in Close Relationships Questionnaire II, Coping Orientation to Problems Experienced (COPE) inventory, and Social Functioning Scale were used. In the BD group, adaptive coping style scores and attachment avoidance scores were significantly lower than the control group, but mean scores of maladaptive coping styles were higher than the control group. Regression analysis showed that positive reinterpretation and growth, active coping, use of emotional social support, planning, religious activities, and mental disengagement subscales of COPE were significantly associated with social functioning. Psychosocial interventions to strengthen adaptive coping mechanisms may help improve the social functioning in patients with BD.


Assuntos
Adaptação Psicológica/fisiologia , Transtorno Bipolar/fisiopatologia , Apego ao Objeto , Interação Social , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Nerv Ment Dis ; 209(8): 609-611, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397761

RESUMO

ABSTRACT: In the working population, bipolar disorder can have a significant negative effect on professional relationships, attendance, functioning, and loss of productivity. In Japan, workers who take a leave due to depressive episodes receive a work-focused intervention program called the "return to work program" during their leave. A 39-year-old Japanese woman with bipolar II disorder took a third sick leave of absence. We recommended her the return to work program of our university hospital. At the beginning of the program, she had a rigid thought process toward her perceptions of her duties in the workplace and at home. Through the program, mindfulness might identify rigidity, group cognitive-behavioral therapy might correct rigidity, and self-analysis might have regained flexibility. In conclusion, a variety of effects of our return to work program might have enabled her thought process to evolve from rigid to flexible, and she showed successful reinstatement.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/reabilitação , Reabilitação Psiquiátrica , Retorno ao Trabalho , Pensamento/fisiologia , Adulto , Feminino , Humanos , Japão
15.
Sci Rep ; 11(1): 16930, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417487

RESUMO

Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Descanso/fisiologia , Adulto , Mapeamento Encefálico , Diagnóstico Diferencial , Feminino , Humanos , Masculino
16.
Curr Top Med Chem ; 21(11): 949-963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34355686

RESUMO

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) have a high prevalence and detrimental socio-economic consequences for the patients and the community. Furthermore, the depressive symptomatology of both disorders is essentially identical, thus rendering the clinical differential diagnosis between the two significantly more difficult considering the concomitant lack of objective biomarkers. Mood disorders are multifactorial disorders the pathophysiology of which includes genetic, epigenetic, neurobiological, neuroimmunological, structural and functional brain alterations, etc. Aberrant genetic variants as well as changed differential expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been implicated in the pathophysiology of MDD and BD. MiRNAs as well as lncRNAs have regulatory and modulating functions on protein-- coding gene expression thus influencing the remodeling of the architecture, neurotransmission, immunomodulation, etc. in the Central Nervous System (CNS) which are essential in the development of psychiatric disorders including MDD and BD. Moreover, both shared and distinct structural, connectivity, task-related and metabolic features have been observed via functional magnetic resonance imaging and magnetic resonance spectroscopy, suggesting the possibility of a dimensional continuum between the two disorders instead of a categorical differentiation. Aberrant connectivity within and between the Default Mode Network, the Salience Network, Executive Network, etc. as well as dysfunctional emotion, cognitive and executive processing have been associated with mood disorders. Therefore, the aim of this review is to explore a more multidimensional framework in the scientific research of mood disorders, including epigenetic and neuroimaging data in order to shape an outline for their translational capacity in clinical practice.


Assuntos
Biomarcadores/análise , Imageamento por Ressonância Magnética/métodos , Transtornos do Humor/diagnóstico , RNA não Traduzido/análise , Biomarcadores/metabolismo , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Regulação da Expressão Gênica , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , MicroRNAs/análise , MicroRNAs/metabolismo , Transtornos do Humor/genética , Transtornos do Humor/fisiopatologia , RNA não Traduzido/metabolismo
17.
Schizophr Bull ; 47(6): 1706-1717, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34254147

RESUMO

OBJECTIVE: Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification. METHODS: A total of 811 participants from 6 sites were included: probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations. RESULTS: When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1. CONCLUSION: These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.


Assuntos
Tonsila do Cerebelo/patologia , Transtorno Bipolar/diagnóstico , Disfunção Cognitiva/diagnóstico , Hipocampo/patologia , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Transtorno Bipolar/classificação , Transtorno Bipolar/patologia , Transtorno Bipolar/fisiopatologia , Análise por Conglomerados , Disfunção Cognitiva/classificação , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/classificação , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/classificação , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia
18.
Neural Plast ; 2021: 5560453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194487

RESUMO

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.


Assuntos
Transtorno Bipolar/epidemiologia , Transtornos Cognitivos/epidemiologia , Conectoma , Dislipidemias/epidemiologia , Adolescente , Adulto , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Comorbidade , Rede de Modo Padrão/fisiologia , Feminino , Humanos , Masculino , Neuroimagem , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Máquina de Vetores de Suporte , Adulto Jovem
19.
Drug Des Devel Ther ; 15: 3017-3026, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267503

RESUMO

OBJECTIVE: This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy. LITERATURE SEARCH: A literature search was conducted utilizing PubMed, clinicaltrials.gov, and the manufacturer's website. DATA SYNTHESIS: One phase II trial and two phase III trials evaluating the efficacy and safety of brexanolone were identified. Brexanolone demonstrated efficacy through significantly reduced Hamilton Depression Rating Scale (HAM-D) scores compared to placebo in the treatment of postpartum depression (PPD). Noted adverse effects were somnolence and dizziness, excessive sedation, and loss of consciousness. One published phase II study and the interim results of two phase III trials and one phase II trial on zuranolone were included in this review. Zuranolone, an oral allopregnanolone agonist, is given as a single, 14-day course. A significant reduction in HAM-D scores was demonstrated in patients with major depressive disorder (MDD) at 15 and 28 days compared to placebo. Interim results for zuranolone in PPD and bipolar disorder (BPD) show promising reductions in HAM-D scores. Adverse effects included sedation, dizziness, and headache. PLACE IN THERAPY: Allopregnanolone agonists seem to have a role in PPD when weighing the quick onset of action and potential risks of untreated PPD. The class of medications is limited by the single course for this indication and may fit as a bridge to maintenance therapy with selective serotonin reuptake inhibitors (SSRIs). Brexanolone, specifically, is hindered by the long infusion time, hospitalization associated with administration, and risk evaluation and mitigation strategy program. Zuranolone may also have a role in MDD or BPD, but more data are needed. CONCLUSION: Allopregnanolone agonists present a novel mechanism of action in the treatment of depressive disorders. Clinical trials and interim results support significant reductions in depression scores for brexanolone in PPD, and for zuranolone in PPD, MDD, and BPD.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/tratamento farmacológico , Pregnanolona/agonistas , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Depressão Pós-Parto/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Combinação de Medicamentos , Feminino , Humanos , Gravidez , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pregnanos/farmacologia , Pregnanolona/administração & dosagem , Pregnanolona/efeitos adversos , Pregnanolona/farmacologia , Escalas de Graduação Psiquiátrica , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/farmacologia , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversos , beta-Ciclodextrinas/farmacologia
20.
J Biomed Sci ; 28(1): 45, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112182

RESUMO

Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with a high individual and societal burden. While not all patients display overt markers of elevated inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease, and likely explains the elevated rates of comorbid inflammatory illnesses seen in this population. While individual systems have been intensely studied and targeted, a relative paucity of attention has been given to the interconnecting role of inflammatory signals therein. This review presents an updated overview of some of the most prominent pathophysiologic mechanisms in bipolar disorder, from mitochondrial, endoplasmic reticular, and calcium homeostasis, to purinergic, kynurenic, and hormonal/neurotransmitter signaling, showing inflammation to act as a powerful nexus between these systems. Several areas with a high degree of mechanistic convergence within this paradigm are highlighted to present promising future targets for therapeutic development and screening.


Assuntos
Transtorno Bipolar/fisiopatologia , Inflamação/fisiopatologia , Transdução de Sinais/imunologia , Animais , Transtorno Bipolar/imunologia , Humanos , Camundongos
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