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OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions. METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively. RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression. CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.
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ABSTRACT: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.
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Anorexia Nervosa , Transtorno Depressivo Maior , Eletroconvulsoterapia , Estimulação Transcraniana por Corrente Contínua , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Anorexia Nervosa/complicações , Anorexia Nervosa/terapia , Eletroconvulsoterapia/métodos , Depressão/epidemiologia , Depressão/terapia , Estimulação Magnética Transcraniana/métodos , EncéfaloRESUMO
BACKGROUND: The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. AIM: This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. MATERIALS AND METHODS: From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery Åsberg Depression Rating Scale between the Q-ECT and the patient record. RESULTS: A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. CONCLUSIONS: We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.
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Eletroconvulsoterapia , Humanos , Escalas de Graduação Psiquiátrica , Suécia , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to compare the 0.5-millisecond pulse width with broader brief width stimulus and ultrabrief pulse width stimulus in respect to rates of subjective memory impairment and remission 6 months after completion of electroconvulsive therapy (ECT). METHODS: This study used data from the Swedish National Quality Register for ECT. Inclusion criteria were bipolar or unipolar depression with or without psychosis, ECT with unilateral electrode placement, and data on the Montgomery-Åsberg Depression Rating Scale-Self-Assessment and the memory item of the Comprehensive Psychopathological Rating Scale (CPRS-M) before and 6 months after ECT. The primary outcomes were the distributions of patients with a maximum of 10 on the Montgomery-Åsberg Depression Rating Scale-Self-Assessment (remission) and a minimum of 2-step worsening in CPRS-M score according to the ECT pulse widths of <0.5, 0.5, and >0.5 millisecond. RESULT: This study included 312 patients. The distributions of patients with remission or a minimum of 2-step worsening on the CPRS-M 6 months after completion of ECT showed no significant differences between the 3 pulse width groups. Older age was associated with a significantly higher rate of remission 6 months after ECT. CONCLUSIONS: In this cohort of patients, no support was found for the previous research finding of lower rates of subjective memory disturbances 6 months after ultrabrief pulse width ECT in comparison with brief pulse width ECT. Older age was associated with higher remission rate 6 months after ECT. Large randomized studies are required to exclude the possibility of long-term differential effects between pulse widths.
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Depressão/terapia , Eletroconvulsoterapia/métodos , Transtornos da Memória/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Sistema de Registros , SuéciaRESUMO
OBJECTIVES: One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions. METHODS: This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions. RESULTS: Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture. CONCLUSIONS: There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant.
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Eletroconvulsoterapia/efeitos adversos , Fraturas dos Dentes/epidemiologia , Fraturas dos Dentes/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologiaRESUMO
OBJECTIVES: It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups. METHODS: This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups. RESULTS: There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients. CONCLUSIONS: Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.
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Eletroconvulsoterapia , Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores Sexuais , Inquéritos e Questionários , SuéciaRESUMO
Background: Subjective memory deficits are common in depression and during series of treatment with electroconvulsive therapy (ECT). There is a need for feasible assessment of memory deficit. In the Swedish National Quality Register for ECT, patients' subjective memory function is rated by a clinician. Self-ratings would be easier to administer.Objectives: The aim of this study was to analyze the consistency between self-reported and physician estimated subjective memory in depressed patients treated with ECT.Methods: Fifty-two inpatients treated with ECT for major- or bipolar depression were recruited and 41 of them completed the study protocol. Each patient rated their own subjective memory and had it rated in an interview by a physician both before/in the beginning of the ECT series and after the ECT series. The patients' memory was rated and self-rated with the memory item in the Comprehensive Psychopathological Rating Scale (CPRS). We then analyzed correlations, and differences in distributions, between self-reported assessment and physician estimates of patients' subjective memory.Results: The correlations between the self-reported and the physician estimated ratings of subjective memory were 0.699 (p < .01) in baseline ratings and 0.651 (p < .01) in post-treatment ratings. These correlations were relatively high compared to a previous study on self-reported vs. physician estimated CPRS ratings.Conclusions: Based on the results in this study, we propose that patients' self-ratings of subjective memory in association with ECT can be used instead of a physician's rating of patients' subjective memory.
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Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Eletroconvulsoterapia/psicologia , Participação do Paciente/psicologia , Papel do Médico/psicologia , Autorrelato , Adolescente , Adulto , Idoso , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/terapia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/terapia , Autoavaliação Diagnóstica , Eletroconvulsoterapia/métodos , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Autorrelato/normas , Suécia/epidemiologia , Resultado do Tratamento , Adulto JovemAssuntos
Eletroconvulsoterapia , Sistema de Registros , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Eletroconvulsoterapia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Transtorno Depressivo Maior/terapia , Adulto , IdosoRESUMO
Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression.
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Biomarcadores , Transtorno Bipolar/metabolismo , Prognóstico , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Transtorno Bipolar/sangue , Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Bipolar/diagnóstico , Quimiocina CCL2/análise , Quimiocina CCL2/sangue , Proteína 1 Semelhante à Quitinase-3/análise , Proteína 1 Semelhante à Quitinase-3/sangue , Citocinas/análise , Feminino , Humanos , Interleucina-8/análise , Interleucina-8/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/análise , Proteínas de Neurofilamentos/sangue , Neuroimunomodulação/imunologia , Neurônios/fisiologia , Estudos Prospectivos , Transtornos Psicóticos/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls. METHOD: Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques. RESULTS: A distinct subgroup (â¼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics. CONCLUSIONS: Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Adulto , Transtorno Bipolar/complicações , Estudos de Casos e Controles , Cognição , Transtornos Cognitivos/complicações , Disfunção Cognitiva , Função Executiva , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Bipolar disorder (BD) is a common chronic psychiatric disorder mainly characterized by episodes of mania, hypomania and depression. The disorder is associated with cognitive impairments and structural brain abnormalities, such as lower cortical volumes in primarily frontal brain regions than healthy controls. Although bipolar disorder types I (BDI) and II (BDII) exhibit different symptoms and severity, previous studies have focused on BDI. Furthermore, the most frequently investigated measure in this population is cortical volume. The aim of our study was to investigate abnormalities in patients with BDI and BDII by simultaneously analyzing cortical volume, thickness and surface area, which yields more information about disease- and symptom-related neurobiology. METHODS: We used MRI to measure cortical volume, thickness and area in patients with BDI and BDII as well as in healthy controls. The large study cohort enabled us to adjust for important confounding factors. RESULTS: We included 81 patients with BDI, 59 with BDII and 85 controls in our analyses. Cortical volume, thickness and surface area abnormalities were present in frontal, temporal and medial occipital regions in patients with BD. Lithium and antiepileptic drug use had an effect on the observed differences in medial occipital regions. Patients with the subtypes BDI and BDII displayed common cortical abnormalities, such as lower volume, thickness and surface area than healthy controls in frontal brain regions but differed in temporal and medial prefrontal regions, where only those with BDI had abnormally low cortical volume and thickness. LIMITATIONS: The group differences can be explained by progressive changes, but also by premorbid conditions. They could also have been influenced by unknown factors, such as social, environmental or genetic factors. CONCLUSION: Our findings suggest diagnosis-related neurobiological differences between the BD subtypes, which could explain distinct symptoms and point to potential biomarkers that could inform the subtype diagnosis of BD.
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Transtorno Bipolar/patologia , Encefalopatias/patologia , Córtex Cerebral/patologia , Adulto , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Distribuição por SexoRESUMO
Higher numbers of manic episodes in bipolar patients has, in cross-sectional studies, been associated with less grey matter volume in prefrontal brain areas. Longitudinal studies are needed to determine if manic episodes set off progressive cortical changes, or if the association is better explained by premorbid brain conditions that increase risk for mania. We followed patients with bipolar disorder type 1 for 6 years. Structural brain magnetic resonance imaging scans were performed at baseline and follow-up. We compared patients who had at least one manic episode between baseline and follow-up (Mania group, n = 13) with those who had no manic episodes (No-Mania group, n = 18). We used measures of cortical volume, thickness, and area to assess grey matter changes between baseline and follow-up. We found significantly decreased frontal cortical volume (dorsolateral prefrontal and inferior frontal cortex) in the Mania group, but no volume changes in the No-Mania group. Our results indicate that volume decrease in frontal brain regions can be attributed to the incidence of manic episodes.
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Transtorno Bipolar/patologia , Lobo Frontal/patologia , Substância Cinzenta/patologia , Adulto , Transtorno Bipolar/psicologia , Encéfalo/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos ProspectivosRESUMO
INTRODUCTION: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737. METHODS: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N = 114) and sex- and age-matched population controls (N = 104). RESULTS: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls. CONCLUSIONS: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.
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Transtorno Bipolar/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/genética , Canais de Cálcio Tipo L/genética , Transtornos Cognitivos/fisiopatologia , Polimorfismo de Nucleotídeo Único , Adulto , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtornos Cognitivos/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Suécia , População Branca/genéticaRESUMO
Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.
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Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Bipolar/tratamento farmacológico , Interleucina-8/líquido cefalorraquidiano , Lítio/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder. METHODS: In total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104). RESULTS: The risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R(2) = 0.17, Q = 0.006) and memory/learning (adjusted R(2) = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R(2) = 0.11, Q = 0.006), visuospatial functions (adjusted R(2) = 0.23, Q = 0.001), and attention/speed (adjusted R(2) = 0.25, Q = 0.001). Results could not be replicated in controls. CONCLUSIONS: The risk variants of the rs35753505 SNP were associated with increased performance in several cognitive domains and IQ, whereas the risk variants of the rs11809911 SNP in LMX1A was associated with reduced IQ and memory/learning.
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Transtorno Bipolar , Cognição/fisiologia , Dopamina/metabolismo , Proteínas com Homeodomínio LIM/genética , Neuregulina-1/genética , Fatores de Transcrição/genética , Adulto , Atenção/fisiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Predisposição Genética para Doença , Humanos , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
BACKGROUND: Bipolar disorder is associated with medical comorbidities that have been linked to systemic inflammatory mechanisms. There is, however, limited evidence supporting a role of neuroinflammation in bipolar disorder. Here we tested whether microglial activation and associated tissue remodelling processes are related to bipolar disorder by analyzing markers in cerebrospinal fluid (CSF) and serum from patients and healthy controls. METHODS: Serum was sampled from euthymic patients with bipolar disorder and healthy controls, and CSF was sampled from a large subset of these individuals. The levels of monocyte chemoattractant protein-1 (MCP-1), YKL-40, soluble cluster of differentiation 14 (sCD14), tissue inhibitor of metalloproteinases-1 (TIMP-1) and tissue inhibitor of metalloproteinases-2 (TIMP-2), were measured, and we adjusted comparisons between patients and controls for confounding factors. RESULTS: We obtained serum samples from 221 patients and 112 controls and CSF samples from 125 patients and 87 controls. We found increased CSF levels of MCP-1 and YKL-40 and increased serum levels of sCD14 and YKL-40 in patients compared with controls; these differences remained after controlling for confounding factors, such as age, sex, smoking, blood-CSF barrier function, acute-phase proteins and body mass index. The CSF levels of MCP-1 and YKL-40 correlated with the serum levels, whereas the differences between patients and controls in CSF levels of MCP-1 and YKL-40 were independent of serum levels. LIMITATIONS: The cross-sectional study design precludes conclusions about causality. CONCLUSION: Our results suggest that both neuroinflammatory and systemic inflammatory processes are involved in the pathophysiology of bipolar disorder. Importantly, markers of immunological processes in the brain were independent of peripheral immunological activity.
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Transtorno Bipolar/imunologia , Microglia/imunologia , Monócitos/imunologia , Adipocinas/sangue , Adipocinas/líquido cefalorraquidiano , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Transtorno Bipolar/sangue , Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Bipolar/tratamento farmacológico , Quimiocina CCL2/sangue , Quimiocina CCL2/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Feminino , Humanos , Lectinas/sangue , Lectinas/líquido cefalorraquidiano , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Psicotrópicos/uso terapêutico , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/líquido cefalorraquidiano , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidor Tecidual de Metaloproteinase-2/líquido cefalorraquidianoRESUMO
Importance: Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. Objective: To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. Design, Setting, and Participants: This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. Main Outcomes and Measures: The primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. Results: Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: ß coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). Conclusions and Relevance: This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.
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Transtorno Depressivo Maior , Eletroconvulsoterapia , Convulsões , Humanos , Eletroconvulsoterapia/métodos , Feminino , Transtorno Depressivo Maior/terapia , Masculino , Pessoa de Meia-Idade , Convulsões/terapia , Adulto , Idoso , Resultado do Tratamento , Suécia , Eletroencefalografia , Estudos de Coortes , Fatores de Tempo , Sistema de RegistrosRESUMO
BACKGROUND: Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process. METHODS: We measured the concentrations of chromogranin B (peptide 439-451) and secretogranin II (peptide 154-165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale. RESULTS: We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease). LIMITATIONS: The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations. CONCLUSION: This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.
Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Secretogranina II/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Cromogranina B/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Cognitive deficits have been documented in patients with bipolar disorder. Further, it has been suggested that the degree and type of cognitive impairment differ between bipolar I and bipolar II disorder, but data is conflicting and remains inconclusive. This study aimed to clarify the suggested differences in cognitive impairment between patients with bipolar I and II disorder in a relatively large, clinically stable sample while controlling for potential confounders. METHODS: 67 patients with bipolar I disorder, 43 with bipolar II disorder, and 86 randomly selected population-based healthy controls were compared. A number of neuropsychological tests were administered, assessing verbal and visual memory and executive functions. Patients were in a stable phase during testing. RESULTS: Patients with bipolar type I and type II were cognitively impaired compared to healthy controls, but there were no statistically significant differences between the two subtypes. The strongest predictor of cognitive impairment within the patient group was current antipsychotic treatment. CONCLUSIONS: The present study suggests that the type and degree of cognitive dysfunction is similar in bipolar I and II patients. Notably, treatment with antipsychotics - but not a history of psychosis - was associated with more severe cognitive impairment. Given that patients with bipolar I disorder are more likely to be on antipsychotic drugs, this might explain why some previous studies have found that patients with type I bipolar disorder are more cognitively impaired than those with type II.
Assuntos
Transtorno Bipolar/psicologia , Transtornos Cognitivos/diagnóstico , Cognição , Função Executiva , Adulto , Antipsicóticos/uso terapêutico , Atenção , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtornos Cognitivos/complicações , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. LIMITATIONS: Retrospective analysis of register data. No comparison group. CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.