•Sample comprised cross-diagnostic bipolar/schizophrenia-spectrum disorder patients.•Patients were clustered based on cognitive variables and compared to controls.•Subgroups were Globally Impaired, ...Selectively Impaired and Superior/Near-Normal.•Alternative cognitive measure scores mostly consistent with clustering variables.•Suggests cognitive subgroups were not artefacts of the measures used to define them.
Cognitive heterogeneity in schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) has been explored using clustering analyses. However, the resulting subgroups have not been cognitively validated beyond measures used as clustering variables themselves. We compared the emergent cross-diagnostic subgroups of SSD and BD patients on measures used to classify them, and also across a range of alternative cognitive measures assessing some of the same constructs.
Domain scores from the Matrics Consensus Cognitive Battery were used in a cross-diagnostic clustering analysis of 86 patients with SSD (n = 45) and BD (n = 41). The emergent subgroups were then compared to each other and healthy controls (n = 76) on these and alternative measures of these domains, as well as on premorbid IQ, global cognition and a proxy of cognitive decline.
A three-cluster solution was most appropriate, with subgroups labelled as Globally Impaired, Selectively Impaired, and Superior/Near-Normal relative to controls. With the exception of processing speed performance, the subgroups were generally differentiated on the cognitive domain scores used as clustering variables. Differences in cognitive performance among these subgroups were not always statistically significant when compared on the alternative cognitive measures. There was evidence of global cognitive impairment and putative cognitive decline in the two cognitively impaired subgroups.
For clustering analysis, sample size was relatively small.
The overall pattern of findings tentatively suggest that emergent cross-diagnostic cognitive subgroups are not artefacts of the measures used to define them, but may represent the outcome of different cognitive trajectories.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite advances in the treatment of bipolar disorder (BD), most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, ...many patients continue to experience neurocognitive dysfunction, reduced daytime activity levels, and sleep disturbances. This 8-week, randomized, placebo-controlled pilot study evaluated the feasibility, safety and preliminary efficacy of the wake-promoting drug, modafinil (Provigil
), on neurocognitive functioning, daytime sleepiness, and sleep quality in affectively-stable BD patients.
Twelve individuals with affectively-stable BD were recruited and randomized to a flexible dose of modafinil (100 to 200 mg/day) or placebo, adjunctive to a therapeutic dose of a mood stabilizer. Weekly in-person visits tracked sleep quality and daytime sleepiness as well as side effects and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8.
No serious adverse events were reported. Newly emergent side effects in the modafinil group included heart palpitations, itching, fatigue, and decreased energy. Two patients discontinued modafinil owing to side effects and one of these patients withdrew from the study. One patient discontinued placebo and was withdrawn from the study. Preliminary evaluations of clinical efficacy showed a marginally significant interaction between treatment group and time in two cognitive domains (speed of processing and verbal learning), indicating greater improvement in the modafinil group versus placebo. Additionally, there was a marginally significant effect of treatment group on daytime sleepiness, suggesting lower daytime sleepiness in the modafinil group versus placebo. Counterintuitively, we found a significant treatment group by time interaction effect on sleep quality, suggesting greater improvement in sleep quality in the placebo group versus the modafinil group.
Results suggest that modafinil is a relatively safe medication for affectively-stable BD patients when given with adjunctive mood stabilizers. Results are suggestive of cognitive benefit and improved daytime sleepiness, but worse sleep quality in those patients prescribed modafinil. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot.
ClinicalTrials.gov, identifier NCT01965925.
First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, ...following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting "pseudospecificity."
•BDNF levels are elevated in association with low mood in perimenopausal depression.•Perimenopausal depression BDNF pattern differs from that in major depression (MDD).•BDNF in perimenopausal ...depression resembles premenstrual dysphoric disorder pattern.•Inflammation and cycle phase do not predict mood in perimenopausal depression.•Hormonally-linked mood disorders may have different biomarker profiles than MDD.
Previous work implicates high pro-inflammatory biomarkers in mood disturbance and low brain-derived neurotrophic factor (BDNF) levels in major depression. However, in hormonally-sensitive premenstrual dysphoric disorder (PMDD), BDNF levels are higher when mood is worse. Perimenopausal depression has not been studied to date. We evaluated whether BDNF and inflammatory cytokines predict mood symptoms across the menstrual cycle in hormonally-sensitive perimenopausal depression symptoms.
Data from 49 time points derived from mid-to-late follicular phase M/L-FP and peri‑menstrual assessments of 14 perimenopausal women ages 38–52 with ovulatory menstrual cycles 24–35 days long across 1–2 cycles for mood symptoms, BDNF levels, cytokines, gonadal steroids. Depression was assessed with Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI); irritability with Kellner Symptom Questionnaire Anger-Hostility subscale (SQ); overall psychological distress with Profile of Mood States (POMS). Mixed models were run on dependent measures of MADRS (primary endpoint) and other mood outcomes (BDI, POMS, SQ) with independent variables of interest (each biomarker, cycle phase), controlling for cycle number and participant.
After FDR adjustment, BDNF levels showed consistent significant positive relationships to MADRS (β=0.00053; p = 0.0028), POMS (β=0.00153; p = 0.0394), SQ (β=0.00053; p = 0.0067), and BDI (β=0.00039; p = 0.0231). Cycle phase did not affect this relationship. No other biomarker consistently predicted affective symptom severity.
Small sample size and large number of comparisons.
In women with perimenopausal depression symptoms, BDNF is elevated in association with more severe mood symptomatology, resembling the pattern in hormonally-sensitive PMDD and suggesting a hormonally-sensitive mood disorder biomarker profile distinct from that of major depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background There is evidence that patients with bipolar disorder (BD) score higher on affective temperament ratings compared to healthy controls (HCs). Moreover, unaffected relatives ...demonstrate similar patterns as BD patients suggesting that such temperaments are related to the genetic risk for BD and may serve as endophenotypes for the disorder. It is unknown whether affective temperaments are associated with other core features of BD, such as impairments in neurocognition. This study examined the relationship between affective temperaments and neurocognition in patients with BD and in HCs. Methods Temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) in 64 patients with BD and 109 HCs. Neurocognitive functioning was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Correlational analyses between temperaments and cognition were conducted in BD and HC subjects. Results Data suggest that affective temperaments and neurocognition are correlated. In BD higher ratings of cyclothymia and irritability were associated with better processing speed, working memory, reasoning and problem-solving. In the HC group, increased irritability was related to worse performance on measures of attention and social cognition. Limitations Lack of functional outcome measures to evaluate the impact of temperaments and cognition on psychosocial functioning. It would be useful to test these findings on unaffected relatives of BD patients. Conclusions Cyclothymic and irritable temperaments are correlated with specific aspects of neurocognition in BD. This study is among the few exploring the dimensional relationship between temperaments and cognition in BD, and provides preliminary evidence for future studies investigating the neural and genetic mechanisms underlying the association between these variables.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The U.S. has the highest infant mortality rate among peer countries. Restrictive abortion laws may contribute to poor infant health outcomes. This ecological study investigated the association ...between county-level infant mortality and state-level abortion access legislation in the U.S. from 2014 to 2018.
A multivariable regression analysis with the outcome of county-level infant mortality rates, controlling for the primary exposure of state-level abortion laws, and county-level factors, county-level distance to an abortion facility, and state Medicaid expansion status was performed. Incidence rate ratios and 95% CIs were reported. Analyses were conducted in 2022–2023.
There were 113,397 infant deaths among 19,559,660 live births (infant mortality rate=5.79 deaths/1,000 live births; 95% CI=5.75, 5.82). Black infant mortality rate (10.69/1,000) was more than twice the White infant mortality rate (4.87/1,000). In the multivariable model, increased infant mortality rates were seen in states with ≥8 restrictive laws, with the most restrictive (11–12 laws) having a 16% increased infant mortality level (adjusted incidence rate ratios=1.162; 95% CI=1.103, 1.224). Increased infant mortality rates were associated with increased county-level Black race individuals (adjusted incidence rate ratios=1.031; 95% CI=1.026, 1.037), high school education (adjusted incidence rate ratios=1.018; 95% CI=1.008, 1.029), maternal smoking (adjusted incidence rate ratios=1.025; 95% CI=1.018, 1.033), and inadequate prenatal care (adjusted incidence rate ratios=1.045; 95% CI=1.036, 1.055).
State-level abortion law restrictiveness is associated with higher county-level infant mortality rates. The Supreme Court decision on Dobbs versus Jackson and changes in state laws limiting abortion may affect future infant mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Harmonizing different depression severity scales often requires creation of categorical variables that may decrease the sensitivity of the measure. Our aim was to compare the associations between ...categorical and continuous and harmonized measures of depression and global functioning in a large dataset of older age patients with bipolar disorder (OABD).
In the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) the 17-item Hamilton Depression scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) or the Center for Epidemiological Studies Depression scales (CES-D) was used to assess current depressive symptoms, while the Global Assessment of Functioning (GAF) assessed functional status. Data were harmonized from 8 OABD studies (n = 582). In each subsample, the relationship of depression severity as a continuous and categorical measure was compared to GAF. In the total sample, harmonized ordinal depression categories were compared to GAF.
Effect size and variance explained by the model for the categorical measure in the total sample was higher than both the categorical and continuous measure in the CES-D subsample, higher than the categorical but lower than the continuous measure in the HAM-D subsample, and lower than both the categorical and continuous measures in the MADRS subsample.
All included studies have different inclusion and exclusion criteria, study designs, and differ in aspects of sociodemographic variables.
Associations were only slightly larger for the continuous vs categorical measures of depression scales. Harmonizing different depression scales into ordinal categories for analyses is feasible without losing statistical power.
•Harmonizing different depression severity scales often requires creation of categorical variables.•The creation of categorical variables may decrease the sensitivity of the measure.•Depression severity as continuous and categorical measure was compared to GAF.•Also harmonized ordinal depression categories were compared to GAF.•Associations were slightly larger for the continuous vs categorical measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background We reviewed previous studies comparing schizophrenia patients and healthy subjects for performance on the Iowa Gambling Task (IGT) (a laboratory task designed to measure ...emotion-based decision-making), and found mixed results. We hypothesize that deficits in IGT performance in schizophrenia may be more specifically related to concurrent substance use disorders. To test this hypothesis, we compared schizophrenia patients with (SCZ(+) ) or without (SCZ(−) ) cannabis use disorders, to healthy subjects, on measures of cognition and IGT performance. Methods A comprehensive battery of cognitive tests and the IGT were administered to three groups of subjects: (1) 13 subjects with DSM-IV diagnosis of schizophrenia and no concurrent substance use disorders (mean age: 28 ± 12 (SD); 54% males); (2) 14 subjects with schizophrenia and concurrent cannabis use disorders (mean age: 29 ± 9 (SD); 71% males); and (3) 20 healthy subjects (mean age 33 ± 10 (SD); 60% males). Results Compared to the healthy group, both schizophrenia groups were cognitively more impaired, and did worse on IGT performance. There were no differences between SCZ(+) and SCZ(−) patients on most of the cognitive tests, and IGT performance. Conclusions Schizophrenia patients show widespread impairments in several cognitive domains and emotion-based decision-making. These results are consistent with the evidence that schizophrenia reflects a dorsolateral and orbitofrontal/ventromedial prefrontal cortex dysfunction. More intriguing, it appears that the concurrent abuse of cannabis has no compounding effects on cognition, as well as emotion/affect-based decision-making.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was devised to identify a neurocognitive battery to be used in clinical trials targeting cognition in ...schizophrenia, a process, which resulted in the MATRICS Consensus Cognitive Battery (MCCB). The MCCB has been selected by the United States Food and Drug Administration to be used as the primary outcome measure in registry trials for cognitive agents in schizophrenia. Given the clinical and cognitive overlap between schizophrenia and bipolar disorder (BPD), it is likely that any compound shown to have cognitive benefits in schizophrenia will subsequently be tested in BPD. Unlike the MCCB for schizophrenia, there remains no consensus regarding outcome measures if cognitive trials were to be undertaken in BPD. The utility of the MCCB in BPD has not yet been systematically investigated. We administered the MCCB to 80 bipolar I patients; 37 were strictly euthymic and 43 were symptomatic. We compared their performance with a demographically matched healthy sample (n=148) on seven MCCB domains, and the composite. BPD patients were statistically significantly impaired on five of seven MCCB domains at levels consistent with meta-analytic studies of cognition in BPD. In contrast, patients' performance was less impaired on the Reasoning and Problem-solving and Social Cognition domains, differences that did not survive statistical correction for multiple testing. Symptomatic status only modestly influenced performance. These data suggest that the MCCB, devised for use in schizophrenia, may also represent a useful outcome measure in cognitive trials for BPD. Additional studies should address important psychometric features such as repeatability and potential practice and/or ceiling effects.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Premorbid adjustment problems are shared by schizophrenia and bipolar disorder.•Empirically-derived premorbid adjustment trajectory clusters cut across diagnoses.•Premorbid adjustment trajectories ...in social and academic domains are distinct.•Trajectory clusters differ on childhood neglect history and later symptom severity.
Despite the overlap between schizophrenia and bipolar disorder, neurodevelopmental abnormalities are thought to be associated primarily with schizophrenia. Transdiagnostic and empirical identification of subgroups based on premorbid adjustment (PMA) may enhance understanding of illness trajectories. 160 patients with bipolar I or II disorder (BD; n = 104) or schizophrenia or schizoaffective disorder (SZ; n = 56) were assessed on PMA course from childhood to late adolescence and current symptoms and functioning. A hierarchical cluster analysis was performed using social and academic PMA scores, resulting in three optimal clusters. Cluster 1 (n = 28 SZ, 65 BD) had normal social and academic PMA, the most education, and mildest current symptoms. Cluster 2 (n = 15 SZ, 24 BD) had normal social PMA but an impaired-declining academic course and had a greater proportion of males than Cluster 1. Cluster 3 (n = 13 SZ, 15 BD) had an impaired-stable social PMA and an impaired-declining academic course and the most severe current negative symptoms and childhood trauma. The proportions of SZ and BD diagnoses, current neurocognition, and functioning did not differ between clusters. These findings suggest shared neurodevelopmental abnormalities between SZ and BD, with subgroups exhibiting distinct PMA trajectories that cut across disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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