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1.
Acta Psychiatr Scand ; 150(2): 91-104, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38643982

RESUMO

INTRODUCTION: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. METHODS: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. RESULTS: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). CONCLUSIONS: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples.


Assuntos
Transtorno Bipolar , Compostos de Lítio , Fenótipo , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/classificação , Transtorno Bipolar/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Análise por Conglomerados , Compostos de Lítio/farmacologia , Compostos de Lítio/uso terapêutico , Antimaníacos/uso terapêutico , Antimaníacos/farmacologia
2.
J Psychiatr Res ; 174: 326-331, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692162

RESUMO

There is limited information on the association between participants' clinical status or trajectories and missing data in electronic monitoring studies of bipolar disorder (BD). We collected self-ratings scales and sensor data in 145 adults with BD. Using a new metric, Missing Data Ratio (MDR), we assessed missing self-rating data and sensor data monitoring activity and sleep. Missing data were lowest for participants in the midst of a depressive episode, intermediate for participants with subsyndromal symptoms, and highest for participants who were euthymic. Over a mean ± SD follow-up of 246 ± 181 days, missing data remained unchanged for participants whose clinical status did not change throughout the study (i.e., those who entered the study in a depressive episode and did not improve, or those who entered the study euthymic and remained euthymic). Conversely, when participants' clinical status changed during the study (e.g., those who entered the study euthymic and experienced the occurrence of a depressive episode), missing data for self-rating scales increased, but not for sensor data. Overall missing data were associated with participants' clinical status and its changes, suggesting that these are not missing at random.


Assuntos
Transtorno Bipolar , Humanos , Transtorno Bipolar/epidemiologia , Adulto , Feminino , Masculino , Estudos Longitudinais , Pessoa de Meia-Idade , Adulto Jovem , Autorrelato
3.
J Affect Disord ; 351: 49-57, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280568

RESUMO

INTRODUCTION: Mnemonic discrimination (MD), the ability to discriminate new stimuli from similar memories, putatively involves dentate gyrus pattern separation. Since lithium may normalize dentate gyrus functioning in lithium-responsive bipolar disorder (BD), we hypothesized that lithium treatment would be associated with better MD in lithium-responsive BD patients. METHODS: BD patients (N = 69; NResponders = 16 [23 %]) performed the Continuous Visual Memory Test (CVMT), which requires discriminating between novel and previously seen images. Before testing, all patients had prophylactic lithium responsiveness assessed over ≥1 year of therapy (with the Alda Score), although only thirty-eight patients were actively prescribed lithium at time of testing (55 %; 12/16 responders, 26/53 nonresponders). We then used computational modelling to extract patient-specific MD indices. Linear models were used to test how (A) lithium treatment, (B) lithium responsiveness via the continuous Alda score, and (C) their interaction, affected MD. RESULTS: Superior MD performance was associated with lithium treatment exclusively in lithium-responsive patients (Lithium x AldaScore ß = 0.257 [SE 0.078], p = 0.002). Consistent with prior literature, increased age was associated with worse MD (ß = -0.03 [SE 0.01], p = 0.005). LIMITATIONS: Secondary pilot analysis of retrospectively collected data in a cross-sectional design limits generalizability. CONCLUSION: Our study is the first to examine MD performance in BD. Lithium is associated with better MD performance only in lithium responders, potentially due to lithium's effects on dentate gyrus granule cell excitability. Our results may influence the development of behavioural probes for dentate gyrus neuronal hyperexcitability in BD.


Assuntos
Transtorno Bipolar , Lítio , Humanos , Lítio/uso terapêutico , Lítio/farmacologia , Transtorno Bipolar/tratamento farmacológico , Projetos Piloto , Estudos Retrospectivos , Estudos Transversais , Compostos de Lítio/uso terapêutico
4.
Nat Commun ; 14(1): 8488, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123557

RESUMO

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer's brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.


Assuntos
Acesso à Informação , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Metabolômica/métodos , Biblioteca Gênica , Análise por Conglomerados
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