Exploring Clinical Correlates of Metacognition in Bipolar Disorders Using Moderation Analyses: The Role of Antipsychotics.
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SUBMITTER: Roux P
PROVIDER: S-EPMC8509459 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.ResultsWe found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.ConclusionsTaken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
| S-EPMC10705597 | biostudies-literature
Project description:OBJECTIVES:Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS:Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ? 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS:Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS:This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.
| S-EPMC6296224 | biostudies-literature
Project description:Theoretical models of bipolar disorders (BD) posit core deficits in reward system function. However, specifying which among the multiple reward system's neurobehavioral processes are abnormal in BD is necessary to develop appropriately targeted interventions. Research on probabilistic-reinforcement learning deficits in BD is limited, particularly during adolescence, a period of significant neurodevelopmental changes in the reward system. The present study investigated probabilistic-reinforcement learning, using a probabilistic selection task (PST), and its correlates, using self-reported reward/threat sensitivities and cognitive tasks, in 104 adolescents with and without BD. Compared with healthy peers, adolescents with BD were less likely to persist with their choices based on prior positive feedback (i.e., lower win-stay rates) in the PST's acquisition phase. Across groups, a greater win-stay rate appeared to be a more efficient learning strategy-associated with fewer acquisition trials and better testing phase performance. Win-stay rates were also related to verbal learning indices, but not self-reported reward/threat sensitivities. Finally, lower win-stay rates had significant incremental validity in predicting a BD diagnosis, after accounting for effects of current symptoms, reward sensitivities, verbal learning, and IQ. The present findings support multiple dysfunctional processes of the reward system in adolescent BD that require additional examinations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
| S-EPMC6242350 | biostudies-literature
Project description:ImportanceBipolar disorder (BD) is a debilitating mental illness associated with high costs to diagnosed individuals and society. Within the past 2 decades, increasing numbers of children and adolescents have been diagnosed as having BD. While functional magnetic resonance imaging (fMRI) studies have begun to investigate the neural mechanisms underlying BD, few have directly compared differences in youths with BD and adults with BD (hereafter BD-youths and BD-adults, respectively).ObjectiveTo test the hypothesis that BD-youths (<18 years old) would show greater convergence of amygdala hyperactivation and prefrontal cortical hypoactivation vs BD-adults.Data sourcesPubMed and PsycINFO databases were searched on July 17, 2013, for original, task-related coordinate-based fMRI articles.Study selectionIn total, 21 pediatric studies, 73 adult studies, and 2 studies containing distinct pediatric and adult groups within the same study met inclusion criteria for our ALE analyses.Data extraction and synthesisCoordinates of significant between-group differences were extracted from each published study. Recent improvements in GingerALE software were used to perform direct comparisons of pediatric and adult fMRI findings. We conducted activation likelihood estimation (ALE) meta-analyses directly comparing the voxelwise convergence of fMRI findings in BD-youths vs BD-adults, both relative to healthy control (HC) participants.ResultsAnalyses of emotional face recognition fMRI studies showed significantly greater convergence of amygdala hyperactivation among BD-youths than BD-adults. More broadly, analyses of fMRI studies using emotional stimuli showed significantly greater convergence of hyperactivation among BD-youths than BD-adults in the inferior frontal gyrus and precuneus. In contrast, analyses of fMRI studies using nonemotional cognitive tasks and analyses aggregating emotional and nonemotional tasks showed significantly greater convergence of hypoactivation among BD-youths than BD-adults in the anterior cingulate cortex.Conclusions and relevanceOur data suggest that amygdala, prefrontal, and visual system hyperactivation is important in the emotional dysfunction present in BD-youths, as well as that anterior cingulate cortex hypoactivation is relevant to the cognitive deficits in BD-youths. Future studies are required to determine if the developmental fMRI differences between BD-youths and BD-adults identified by our ALE meta-analyses are useful as brain-based diagnostic or treatment markers of BD, including either longitudinal neuroimaging studies of BD-youths as they become adults or cross-sectional imaging studies directly comparing BD-youths with BD-adults.
| S-EPMC4545589 | biostudies-literature
Project description:Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.
| S-EPMC3418516 | biostudies-literature
Project description:Metacognition is impaired in schizophrenia and is an important predictor of functional outcome, but the underlying neuropathology is not clear. Studies have implicated frontal regions and there is also some evidence that the hippocampus might play a pivotal role, but findings are inconsistent. We set out to more comprehensively investigate the neural underpinnings of insight in first-episode psychosis (FEP) using 2 metacognitive measures (the Beck Cognitive Insight Scale [BCIS]) and a perceptual metacognitive accuracy task alongside structural magnetic resonance imaging (MRI). We measured cortical thickness in insula and frontal regions, hippocampal (including subfield) volumes, hippocampal microstructure (using neurite orientation dispersion and density imaging [NODDI]), and fractional anisotropy in fornix. Relative to controls, FEP showed poorer metacognitive accuracy, thinner cortex in frontal regions and lower fornix integrity. In healthy controls (but not FEP), metacognitive accuracy correlated with cortical thickness in frontal cortex and insula. Conversely, in FEP (but not controls), metacognitive accuracy correlated with hippocampal volume and microstructural indices. Subicular hippocampal subregions were particularly implicated. No structural correlates of BCIS were found. These findings suggest that the neural bases of metacognition might differ in FEP: hippocampal (rather than frontal) integrity seems to be critical. Further, the use of objectively measured metacognitive indices seems to be a more powerful method for understanding the neurocircuitry of metacognition in FEP, which has the potential to inform therapeutic strategies and improve outcome in these patients.
| S-EPMC7147593 | biostudies-literature
Project description:BackgroundAtypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.MethodsWe examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.ResultsIn five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.ConclusionAtypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.
| S-EPMC2020469 | biostudies-literature
Project description:BackgroundThis meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder.MethodsTwo categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications.ResultsWe identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P<.0001), relapse of manic symptoms (risk ratio=0.42, P<.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR=2.66, P=.03).ConclusionsLong-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.
| S-EPMC5043645 | biostudies-literature
Project description:Gaussian mixture analysis is frequently used to model the age-at-onset (AAO) in bipolar I disorder and identify homogeneous subsets of patients. This study aimed to examine whether, using admixture analysis of AAO, cross-sectional designs (which cause right truncation), unreliable diagnosis for individuals younger than 10 years old (which causes left truncation) and the selection criterion used for admixture analysis impact the number of identified subsets. A simulation study was performed. Different criteria - the likelihood ratio test (LRT), the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) - were compared using no, left and/or right truncation simulated data. The error rate of each criterion (percentage of erroneous number of detected subsets) was estimated. An application to two real databases, including 2,876 and 1,393 patients, is provided. Without data truncation and regardless of the distribution of AAO, the LRT and the AIC had much higher error rates (12% and 33%, respectively) than the BIC (1%). For a homogeneous population, the error rate increased with the introduction of left truncation. This study shows that the number of subsets identified using admixture analysis may depend on the sample size, the selection criterion, and the study design.
| S-EPMC6877114 | biostudies-literature
Project description:Folate has been implicated in cardiovascular disease with atypical antipsychotic (AAPs) use, and individuals with methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) variants are at greater risk. This study examined the relationship between the MTHFR 677C/T, MTHFR 1298A/C, and COMT Val158Met variants; metabolic syndrome; and lifestyle measures in schizophrenia and bipolar subjects. A total of 237 subjects with bipolar or schizophrenia receiving an antipsychotic for at least 6 months were included in this cross-sectional analysis. Subjects were screened for the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and MTHFR 677C/T, MTHFR 1298A/C, and Val158Met genotypes. In addition, serum folate and homocysteine were measured along with lifestyle factors. The subject's mean age was 44.7 (SD, 11.7) years; 72% were white, and 51% male; 61% were receiving an AAP; the mean body mass index was 32.6 (SD, 8.2) kg/m, and 48% were current smokers. Overall, 41% met metabolic syndrome criteria (n = 98). There were no differences in age, sex, AAP exposure, or body mass index between genotype groups. Metabolic syndrome was related to age, smoking, and the MTHFR 677T and COMT 158Val alleles (? = 34.4, P < 0.0001). In addition, AAP use showed a trend association with metabolic syndrome (? = 3.21, P = 0.07). These data support our previous reports and add more data pointing to folate's role in mediating a link between mental illness and cardiovascular disease. Use of this information clinically may help to reduce the risk for AAP metabolic complications in those whose clinical care necessitates the use of AAPs.
| S-EPMC3622480 | biostudies-literature