DSM-IV Bipolar Disorder Research Articles

Childhood trauma and altered response of retinal neurons as an early risk endophenotype of schizophrenia and mood disorder

BackgroundExposure to childhood trauma may cause several alterations in brain structure and connectivity in adult patients having a major psychiatric disorder. Recent reports have shown that adult patients and young healthy offspring of patients carry similar abnormal retinal response. Because the retina and the brain have the same embryonic origin, the retina gives access to living neuronal tissue that may capture the early neurobiological effect of trauma. ObjectiveEvaluate the association between exposure to childhood trauma and anomalies in cone (photopic) and rod (scotopic) responses assessed by electroretinography (ERG) in children and adolescents at familial risk (FHRs) of psychosis or mood disorders. MethodsERG recordings (n=194) undertaken on 134 offspring (Mage of 1st recording=15.7, 49% females) enrolled in our longitudinal study and born to a parent having DSM-IV schizophrenia, bipolar disorder or major depressive disorder were analyzed using repeated measures linear mixed models and applying multiple comparisons. The scotopic and photopic a- and b-wave latencies and amplitudes were recorded. Five types of childhood trauma were assessed prospectively and retrospectively in FHRs: physical abuse, sexual abuse, emotional abuse, neglect and witnessing domestic violence. ResultsNone of the ERG scotopic or photopic parameters were associated with the global measure of exposure to trauma. However, when analyzing the specific effect of each type of trauma, data suggested that physical abuse in girls would be significantly associated with a prolonged scotopic a-wave latency (p=0.024, ES=0.28) and a trend of association was observed with a prolonged photopic b-wave latency (p=0.099, ES=0.27). ConclusionOur study did not suggest a substantial effect of childhood trauma on previously reported ERG anomalies in the cone and rod response in youth at familial risk of psychosis or mood disorder. Only one type of trauma i.e., physical violence toward the child, could have a specific effect on the cone and rod prolonged latencies in girls. Methodological limitations are discussed for consideration in interpreting the findings.

Family environment and polygenic risk in the bipolar high-risk context.

The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD. Offspring of a parent with BD (oBD; n=266) or no psychiatric disorders (n=174), aged 12-21 at recruitment, participated in the US and Australia. Empirically-derived profiles of FE classified offspring by their perceived levels of familial cohesion, flexibility, and conflict. Offspring BD-PRS were derived from Psychiatric Genomics Consortium BD-GWAS. Lifetime DSM-IV bipolar disorders were derived from the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. We used a novel stepwise approach for latent class modeling with predictors and distal outcomes. Fifty-two offspring were diagnosed with BD. For those with well-functioning FE (two-thirds of the sample), higher BD-PRS tracked positively with liability for BD. However, for those with high-conflict FEs, the relationship between BD-PRS and liability to BD was negative, with highest risk for BD observed with lower BD-PRS. In exploratory analyses, European-ancestry offspring with BDhad elevated history of suicidal ideation in high-conflict FE compared towell-functioning-FE, and of suicide attempt with low-BD-PRS and high-conflictFE. The data suggest that the relationship of BD-PRS and offspring liability for BD differed between well-functioning versus high-conflict FE, potentially in line with a multifactorial liability threshold model and supporting future study of and interventions improving family dynamics.

Genetic Liabilities Differentiating Bipolar Disorder, Schizophrenia, and Major Depressive Disorder, and Phenotypic Heterogeneity in Bipolar Disorder

Understanding the origins of clinical heterogeneity in bipolar disorder (BD) will inform new approaches to stratification and studies of underlying mechanisms. To identify components of genetic liability that are shared between BD, schizophrenia, and major depressive disorder (MDD) and those that differentiate each disorder from the others and to examine associations between heterogeneity for key BD symptoms and each component. Using data from the Bipolar Disorder Research Network in the United Kingdom, components of liability were identified by applying genomic structural equation modeling to genome-wide association studies of schizophrenia, BD, and MDD. Polygenic risk scores (PRS) representing each component were tested for association with symptoms in an independent BD data set. Adults with DSM-IV BD or schizoaffective disorder, bipolar type, were included. Data were collected from January 2000 to December 2013, and data were analyzed from June 2020 to February 2022. PRS representing the components of liability were tested for association with mania and depression, psychosis, and mood incongruence of psychosis in participants with BD, measured using the Bipolar Affective Disorder Dimensional Scale. Of 4429 included participants, 3012 (68.0%) were female, and the mean (SD) age was 46.2 (12.3) years. Mania and psychosis were associated with the shared liability component (mania β = 0.29; 95% CI, 0.23-0.34; P = 3.04 × 10-25; psychosis β = 0.05; 95% CI, 0.04-0.07; P = 2.33 × 10-13) and the components that differentiate each of schizophrenia (mania β = 0.08; 95% CI, 0.03-0.14; P = .002; psychosis β = 0.03; 95% CI, 0.01-0.04; P = 1.0 × 10-4) and BD (mania β = 0.14; 95% CI, 0.09-0.20; P = 1.99 × 10-7; psychosis β = 0.02; 95% CI, 0.01-0.03; P = .006) from the other disorders. The BD differentiating component was associated with mania independently of effects on psychosis (β = 0.14; 95% CI, 0.08-0.20; P = 4.32 × 10-6) but not with psychosis independently of mania. Conversely, the schizophrenia differentiating component was associated with psychosis independently of effects on mania (β = 0.01; 95% CI, 0.003-0.03; P = .02), but not with mania independently of psychosis. Mood incongruence of psychosis was associated only with the schizophrenia differentiating component (β = 0.03; 95% CI, 0.01-0.05; P = .005). Depression was associated with higher MDD differentiating component (β = 0.07; 95% CI, 0.01-0.12; P = .01) but lower BD differentiating component (β = -0.11; 95% CI, -0.17 to -0.06; P = 7.06 × 10-5). In this study of BD, clinical heterogeneity reflected the burden of liability to BD and the contribution of alleles that have differentiating effects on risk for other disorders; mania, psychosis, and depression were associated with the components of genetic liability differentiating BD, MDD, and schizophrenia, respectively. Understanding the basis of this etiological heterogeneity will be critical for identifying the different pathophysiological processes underlying BD, stratifying patients, and developing precision therapeutics.

Comorbid Eating Disorders in a Sample of Youth With Bipolar Disorder: Elevated Burden of Dimensional and Categorical Psychopathology.

Objective: There is growing recognition of the importance of comorbid eating disorders (ED) among individuals with bipolar disorder (BD). However, most studies on this topic have focused on adult samples, and little is known regarding comorbid ED among youth with BD.Methods: The sample included 197 youth with DSM-IV BD (BD-I, BD-II, or BD-NOS [not otherwise specified]), aged 13-20 years and recruited from a subspecialized clinic within a tertiary academic health sciences center from 2009 to 2017. Univariate analyses examined demographic and clinical variables among participants with versus without lifetime DSM-IV ED. Variables significant at P < .10 were entered into a backward stepwise regression.Results: Fifty-six participants (28.4%) had lifetime DSM-IV ED (3.6% anorexia nervosa, 8.1% bulimia nervosa, 16.8% ED not otherwise specified). Significant correlates of lifetime ED were female sex (P < .001), BD-II subtype (P = .03), suicidal ideation (P = .006), suicide attempts (P = .004), non-suicidal self-injury (P < .001), sexual abuse (P = .02), cigarette smoking (P = .001), anxiety disorders (P = .004), posttraumatic stress disorder (P = .004), substance use disorders (P = .006), history of individual therapy (P = .01), and family history of anxiety (P = .01). Significant correlates of no lifetime ED were BD-I subtype (P < .001) and lifetime lithium use (P = .01). The ED group had significantly more severe lifetime depression (P < .001) and significantly more self-reported affective lability (P < .001) and borderline personality traits (P < .001). In multivariate analysis, the most robust predictors of lifetime ED were female sex (odds ratio [OR] = 4.61, P = .004), BD-I subtype (OR = 0.21, P = .03), cigarette smoking (OR = 2.78, P = .02), individual therapy (OR = 3.92, P = .03), family history of anxiety (OR = 2.86, P = .02), and borderline personality traits (OR = 1.01, P = .009).Conclusions: ED are common among youth with BD and associated with adverse clinical characteristics, many of which converge with prior adult literature. Future studies evaluating specific ED subtypes are warranted, as are treatment studies targeting comorbid ED in youth with BD.

Dimensions of Formal Thought Disorder and Their Relation to Gray- and White Matter Brain Structure in Affective and Psychotic Disorders.

Factorial dimensions and neurobiological underpinnings of formal thought disorders (FTD) have been extensively investigated in schizophrenia spectrum disorders (SSD). However, FTD are also highly prevalent in other disorders. Still, there is a lack of knowledge about transdiagnostic, structural brain correlates of FTD. In N = 1071 patients suffering from DSM-IV major depressive disorder, bipolar disorder, or SSD, we calculated a psychopathological factor model of FTD based on the SAPS and SANS scales. We tested the association of FTD dimensions with 3 T MRI measured gray matter volume (GMV) and white matter fractional anisotropy (FA) using regression and interaction models in SPM12. We performed post hoc confirmatory analyses in diagnostically equally distributed, age- and sex-matched sub-samples to test whether results were driven by diagnostic categories. Cross-validation (explorative and confirmatory) factor analyses revealed three psychopathological FTD factors: disorganization, emptiness, and incoherence. Disorganization was negatively correlated with a GMV cluster comprising parts of the middle occipital and angular gyri and positively with FA in the right posterior cingulum bundle and inferior longitudinal fascicle. Emptiness was negatively associated with left hippocampus and thalamus GMV. Incoherence was negatively associated with FA in bilateral anterior thalamic radiation, and positively with the hippocampal part of the right cingulum bundle. None of the gray or white matter associations interacted with diagnosis. Our results provide a refined mapping of cross-disorder FTD phenotype dimensions. For the first time, we demonstrated that their neuroanatomical signatures are associated with language-related gray and white matter structures independent of diagnosis.

Childhood Trauma May Increase Risk of Psychosis and Mood Disorder in Genetically High-risk Children and Adolescents by Enhancing the Accumulation of Risk Indicators.

Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk. We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring. Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58). Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.

Childhood adversities and the comorbidity between mood and general medical disorders in adults: Results from the WHO World Mental Health Survey Portugal

ObjectiveChildhood adversities have been linked to poor health outcomes in adults, including both mood and general medical disorders. Here we tested the hypothesis that childhood adversities specifically increase the risk of comorbidity between mood and general medical disorders, rather than increasing the risk of either one independently. MethodsMood disorders (DSM-IV major depressive, dysthymic and bipolar disorders), childhood adversities and general medical disorders were assessed in 2060 adults in the WHO World Mental Health Survey Portugal. Discrete-time survival analyses were used to investigate the association between mood disorders and subsequent first-onset general medical disorders and between general medical disorders and subsequent first-onset mood disorders, in adults. Discrete-time survival and multinomial regression analyses were used to test the influence of childhood adversities on the comorbidity between mood disorders and general medical disorders. Anxiety disorders were used as a psychiatric control. ResultsAdult-onset mood disorders were found to precede the onset of diabetes (OR:1.8; 95% CI:1.2–2.9), arthritis (OR:1.6; 95% CI:1.1–2.3) and seasonal allergies (OR:1.6; 95% CI:1.1–2.5) while adult-onset hypertension was found to precede the onset of mood disorders (OR:1.7; 95% CI:1.2–2.6). Maladaptive family functioning (abuse, neglect and parental maladjustment), was associated with mood disorders (OR:1.5; 95% CI:1.2–1.9), hypertension (OR:1.4; 95% CI:1.1–1.7), arthritis (OR:1.3; 95% CI:1.0–1.6) and seasonal allergies (OR:1.5; 95% CI:1.1–2.0) in adulthood. Finally, the effect of maladaptive family functioning in predicting comorbid mood disorders and arthritis significantly differed from its effect in predicting only arthritis (p ​= ​0.01), which was not observed for other comorbidities. Maladaptive family functioning further predicted comorbid anxiety disorders and hypertension. ConclusionChildhood adversities may be a specific risk factor for comorbid mood disorders and arthritis in adults.

The functional impairment of different subtypes and occupational states in euthymic patients with bipolar disorder

BackgroundThe aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients.MethodsA total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively.ResultsEmployed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups.ConclusionEmployed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.

Physical activity and childhood trauma experiences in patients with schizophrenia or bipolar disorders

Background Physical activity promotes resilience and reduces stress. Here we aimed to clarify the impact of physical activity and childhood trauma experiences on current mood and cognitive function in patients with schizophrenia (SZ) or bipolar disorders (BD). Methods Three-hundred-and-six patients with DSM-IV schizophrenia (SZ) or bipolar disorder (BD) were included in the study. Diagnoses were assessed using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Physical activity was measured as hours spent on any regular physical activity per week. All patients underwent a neuropsychological test battery. History of Childhood trauma was assessed using the Childhood Trauma Questionnaire and mood symptoms were assessed with the Inventory of Depressive Symptoms. Results Patients with childhood trauma who were physically inactive (˂90 min per week) had the most severe clinical profile, characterised by the highest depressive symptoms (p ˂ 0.001) and lowest performance on working memory tasks (p ˂ 0.001). Among patients with childhood trauma, those who were physically active (≥90 min per week) had better working memory performance than physically inactive patients (p = 0.02). Discussion A history of childhood trauma was associated with poorer working memory and more depressive symptoms only in patients who were physically inactive, suggesting a possible protective factor of physical activity in severe mental disorder.

Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): A Randomized, Double-Blind, Placebo-Controlled Trial.

To assess the efficacy and safety of citalopram in the acute and maintenance phases of bipolar depression in a randomized, double-blind, placebo-controlled trial. Between 2007 and 2014, 119 subjects with acute major depressive episodes diagnosed with DSM-IV bipolar disorder, type I or type II, were randomized blindly to citalopram or placebo, added to standard mood stabilizers. They were followed for 6 weeks for acute efficacy (primary outcome) and up to 1 year for maintenance efficacy (secondary outcome) using scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mania Rating Scale of the Schedule for Affective Disorders and Schizophrenia (MRS-SADS). The study was powered for a clinically meaningful effect size. Mean ± SD MADRS scores changed from a baseline value of 27.4 ± 9.1 to 13.1 ± 8.4 at the end of the acute phase for citalopram versus a change from 27.4 ± 7.3 to 15.2 ± 9.9 for placebo, a clinically and statistically nonsignificant difference. Maintenance efficacy also was not better with citalopram than with placebo. Acute manic/hypomanic episodes were similar in both groups, and subjects with type II illness did not have better outcomes than subjects with type I illness. In maintenance treatment, MRS-SADS scores were greater overall, especially in subjects with a rapid-cycling illness course, with citalopram versus placebo. Citalopram, added to standard mood stabilizers, did not have clinically meaningful benefit versus placebo for either acute or maintenance treatment of bipolar depression. Acute mania did not worsen with citalopram, but maintenance treatment led to worsened manic symptoms, especially in subjects with a rapid-cycling course. ClinicalTrials.gov identifier: NCT00562861.

9.2 CORRELATES, COURSE, AND OUTCOMES OF INCREASED ENERGY IN YOUTH WITH BIPOLAR DISORDER

The conceptualization of bipolar disorder (BD) has recently changed such that, in the DSM-5, diagnosing BD now requires the presence of increased energy as a gate A criterion for hypo/mania. This change has resulted in some conflicting reactions in the field. The current study assesses whether there are differences between youth with DSM-IV BD who endorsed increased energy, and those who did not, during their baseline worst lifetime mood episode. The longitudinal trajectories of increased energy as a symptom, mental health symptomatology, and clinical outcomes, are also analyzed.

The influence of borderline personality traits on clinical outcomes in bipolar disorder.

Systematic reviews suggest comorbid borderline personality disorder is present in approximately 20% of individuals who have bipolar disorder, but current diagnostic systems demonstrate a move towards dimensional rather than categorical approaches to classifying personality pathology. We aimed to examine the presence and severity of borderline personality traits in bipolar I and bipolar II disorder, and to explore associations between the presence/severity of borderline personality traits and clinical outcomes in bipolar disorder. Borderline personality traits were measured in 1447 individuals with DSM-IV bipolar disorder (1008 bipolar I disorder and 439 bipolar II disorder) using the Borderline Evaluation of Severity over Time (BEST) questionnaire. Lifetime clinical outcomes were assessed via Schedules for Clinical Assessment in Neuropsychiatry (SCAN) semi-structured interview and clinical case notes. Borderline personality traits were common in both bipolar disorder groups, with 86.2% participants reporting at least one trait. These included traits that overlap with (eg mood instability) and those that are distinct from the symptoms of bipolar disorder (eg fear of abandonment). Borderline personality traits were significantly more frequent and more severe in bipolar II disorder compared to bipolar I disorder. More severe borderline traits, and even the presence of a single borderline personality trait, were significantly associated with younger age of bipolar disorder onset and higher prevalence of lifetime alcohol misuse in both bipolar disorder groups. The presence of comorbid borderline personality traits should be considered in the management of all patients with bipolar disorder irrespective of whether criteria for a categorical borderline personality disorder diagnosis are met.

Childhood Trauma Is Nominally Associated With Elevated Cortisol Metabolism in Severe Mental Disorder.

ObjectiveIndividuals exposed to childhood trauma display longstanding modifications of the Hypothalamic–Pituitary–Adrenal (HPA) axis, as well as cognitive impairments. Schizophrenia spectrum disorder (SZ) and bipolar disorders (BD) are characterised by higher prevalence of childhood trauma, abnormal HPA axis, and cognitive dysfunction. Elevated cortisol metabolism was recently demonstrated in both disorders. However, it is yet to be established if childhood adversity is associated with cortisol metabolism in this population, and how this may be associated with cognitive function.MethodsOne-hundred-and-fourteen participants with a DSM-IV SZ or BD diagnosis took part in the study. Diagnoses were evaluated by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Estimated cortisol metabolizing activity (5α-reductase and 5β-reductase) was assessed by urinary free cortisol, and metabolites. All patients underwent cognitive assessment and completed the Childhood Trauma Questionnaire.ResultsEstimated 5β-reductase activity was elevated in participant with childhood physical abuse (r = 0.26, p = 0.005). After adjusting for age, sex and diagnosis, physical abuse was still nominally associated with elevated 5β-reductase. Moreover, only high 5α-reductase activity was negatively correlated with working memory and executive performance (r = −0.23, p = 0.01; r = −0.19, p = 0.05, respectively), however this disappeared after adjusting for age, sex and diagnosis. Cortisol metabolism did not mediate the association between childhood trauma and cognitive function.ConclusionsOur study indicates that childhood physical abuse is associated with elevated cortisol metabolism (5β-reductase) in adults with a SZ or BD disorder. However, our study did not support cortisol metabolism as a mediator between childhood trauma experiences and cognitive function within these disorders.

Adverse childhood experiences and postpartum depression in bipolar disorder

BackgroundWomen are particularly vulnerable to recurrence of bipolar disorder (BD) following childbirth. Risk of postpartum psychosis (PP) is especially high, but postpartum depression (PPD) is also common. Adverse childhood experiences (ACEs) have not been associated with PP, but have been associated with PPD in non-bipolar samples. The relationship between ACEs and PPD within BD remains to be investigated. Here, we examined this association in a large, well-defined sample of women with BD. MethodsParticipants were 575 parous women with DSM-IV BD. Lifetime psychopathology, including perinatal, was assessed via semi-structured interview and case-notes. ACEs, assessed via self-report and case-notes, were compared between women with lifetime PPD (n = 368) and those without a lifetime history of perinatal mood episodes (n = 207). ResultsIn univariate analysis exposure to 3 or more ACEs, and to childhood abuse specifically, was significantly associated with PPD (p = 0.026 and 0.041 respectively), but this did not remain significant after adjusting for lifetime number of episodes of depression and parity. Post-hoc analysis revealed more frequent episodes of depression to be associated with both a history of 3 or more ACEs and of childhood abuse. LimitationsLimited range of ACEs assessed and potential recall bias. ConclusionsIncreased frequency of ACEs and particularly childhood abuse was associated with more frequent lifetime episodes of depression, but not specifically episodes with postpartum onset. Understanding factors that mediate the pathway between ACEs and PPD in BD has implications for risk prediction of PPD.

Agitated depression in bipolar disorder.

It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well-characterized bipolar disorder sample. The prevalence of agitation, based on semi-structured interview and medical case-notes, in the most severe depressive episode was estimated in 2925 individuals with DSM-IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models. 32.3% (n=946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P<0.001), poor concentration (OR 1.966, P=0.027), decreased libido (OR 1.960, P<0.001), suicidal ideation (OR 1.861, P<0.001), slowed activity (OR 1.504, P=0.001), and poor appetite (OR 1.297, P=0.029). Over the lifetime illness course, co-morbid panic disorder (OR 2.000, P<0.001), suicide attempt (OR 1.399, P=0.007), and dysphoric mania (OR 1.354, P=0.017) were significantly associated with AD. Agitation accompanied bipolar depression in at least one-third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.

The relationship between physical activity, clinical and cognitive characteristics and BDNF mRNA levels in patients with severe mental disorders

Background: Here we aimed to clarify the association of physical activity with cognitive function and current mood in severe mental disorders in the most extensive sample to date. Secondly, we aimed to investigate the relationship between physical activity and BDNF mRNA levels.Methods: Three hundred and six patients with a DSM-IV schizophrenia (SZ) or bipolar disorder (BD) spectrum diagnosis were included. Clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV. Depressive symptomatology was measured using the Inventory of Depressive Symptoms (IDS-C) and the Calgary Depression Scale for Schizophrenia (CDSS). All patients underwent neuropsychological assessment. Physical activity was measured as hours spent on any regular physical activity (≥ or ˂90 min) per week. BDNF mRNA was measured in plasma using standardised procedures.Results: Patients with ≥90 min of physical activity per week had fewer depressive symptoms (P ˂0.001, Cohen’s d = 0.48) and performed significantly better on working memory (P ˂ 0.001, d = 0.44) and executive functioning tasks (P ˂ 0.001, d = 0.50) compared to the ˂90-min group. BDNF mRNA was positively associated with physical activity (P = 0.046) and cognitive functioning (P = 0.037).Conclusions: Our study suggests a positive association between self-reported physical activity, cognitive function, mood and BDNF mRNA levels in severe mental disorders.

A 6-Month, Prospective, Randomized Controlled Trial of Customized Adherence Enhancement Versus Bipolar-Specific Educational Control in Poorly Adherent Individuals With Bipolar Disorder.

Nonadherence in bipolar disorder (BD) ranges from 20% to 60%. Customized adherence enhancement (CAE) is a brief, BD-specific approach that targets individual adherence barriers. This prospective, 6-month, randomized controlled trial conducted from October 2012 to July 2017 compared CAE versus a rigorous BD-specific educational program (EDU) on adherence, symptoms, and functional outcomes in poorly adherent individuals. One hundred eighty-four participants with DSM-IV BD were randomized to CAE (n = 92) or EDU (n = 92). Primary outcome was adherence change measured by the Tablets Routine Questionnaire (TRQ) and BD symptoms measured by the Brief Psychiatric Rating Scale. Other outcomes were scores on the Global Assessment of Functioning, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impressions Scale. Assessments were conducted at screening, baseline, 10 weeks, 14 weeks, and 6 months. The sample mean (SD) age was 47.40 (10.46) years; 68.5% were female, and 63.0% were African American. At screening, individuals missed a mean (SD) of 55.15% (28.22%) of prescribed BD drugs within the past week and 48.01% (28.46%) in the past month. Study attrition was < 20%. At 6 months, individuals in CAE had significantly improved past-week (P = .001) and past-month (P = .048) TRQ scores versus those in EDU. Past-week TRQ score improvement remained significant after adjustment for multiple comparisons. There were no treatment arm differences in BPRS scores or other symptoms, possibly related to low symptom baseline values. Baseline-to-6-month comparison showed significantly higher GAF scores (P = .036) for CAE versus EDU. Although both groups used more mental health services at 6 months compared to baseline, increase for CAE was significantly less than that for EDU (P = .046). Whereas both CAE and EDU were associated with improved outcomes, CAE had additional positive effects on adherence, functioning, and mental health resource use compared to EDU. ClinicalTrials.gov identifier: NCT00183495.

The impact of binge eating behavior on lithium- and quetiapine-associated changes in body weight, body mass index, and waist circumference during 6 months of treatment: Findings from the bipolar CHOICE study

Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 = 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p = 0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only, F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating. Bipolar CHOICE was not designed to study anthropometric outcomes. Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach

Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach.Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment.

Attempted suicide and oxytocin-related gene polymorphisms

BackgroundOxytocin may moderate prosocial behaviors, but has also been implicated in negative mental health outcomes. A single-nucleotide polymorphism (SNP) of the oxytocin receptor gene (OXTR), rs53576, and a SNP of the CD38 gene, which regulates oxytocin secretion, rs3796863, have been associated with depression and suicidal ideation. MethodsWe conducted an exploratory study investigating the relationship of these two SNPs to history of suicide attempt. Secondary analyses explored relationships of genotype with sex, diagnosis, history of abuse, depression, suicidal ideation, and attachment and personality traits. Subjects were depressed adults with DSM-IV major depressive disorder (MDD; n = 161) or bipolar disorder (BD; n = 75). ResultsThe A allele of rs53576 was associated with suicide attempt history. A differential effect of rs3796863 genotype on suicide attempt risk was found by diagnosis. In the BD sample, CC and AC genotypes were associated with higher odds of suicide attempt compared to AA, while in the MDD sample, AC subjects were more likely than CC subjects to have made an attempt. LimitationsOur assessment of social sensitivity was limited to measures of attachment style and abuse history and did not differentiate between types of abuse. Plasma oxytocin was not measured. ConclusionsThese findings add to evidence for the involvement of oxytocin in suicide attempts and identify a potential biomarker for differentiating depressed attempters from non-attempters.