Stephanie Salcedo

Empirically supported psychosocial interventions for bipolar disorder: Current state of the research

OBJECTIVES Bipolar disorder requires psychiatric medications, but even guideline-concordant treatment fails to bring many patients to remission or keep them euthymic. To address this gap, researchers have developed adjunctive psychotherapies. The purpose of this paper is to critically review the evidence for the efficacy of manualized psychosocial interventions for bipolar disorder. METHODS We conducted a search of the literature to examine recent (2007-present), randomized controlled studies of the following psychotherapy interventions for bipolar disorder: psychoeducation (PE), cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy (IPSRT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and family therapies such as family focused therapy (FFT). RESULTS All of the psychotherapy interventions appear to be effective in reducing depressive symptoms. Psychoeducation and CBT are associated with increased time to mood episode relapse or recurrence. MBCT has demonstrated a particular effectiveness in improving depressive and anxiety symptoms. Online psychotherapy interventions, programs combining one or more psychotherapy interventions, and targeted interventions centering on particular symptoms have been the focus of recent, randomized controlled studies in bipolar disorder. CONCLUSIONS Psychotherapy interventions for the treatment of bipolar disorder have substantial evidence for efficacy. The next challenge will to disseminate these psychotherapies into the community.

Dopamine in the medial amygdala network mediates human bonding

Significance Early life bonding in humans has critical long-term implications for health, productivity, and well-being in society. Nonetheless, neural mechanisms of bonding are typically studied in rodents, and no studies to date had examined the neurochemistry of human social affiliation. This study utilizes a state-of-the-art technology to demonstrate that human maternal bonding is associated with striatal dopamine function and the recruitment of a cortico–striatal–amygdala brain network that supports affiliation. The simultaneous probing of neurochemical responses and whole-brain network function in mothers watching their infants provides a unique observation into an “affiliating brain.” These results advance the mechanistic understanding of human social bonding and promote basic and clinical research in social neuroscience, development, and psychopathology. Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers’ dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the “medial amygdala network”) that supports social functioning. We also measured the mothers’ behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother’s infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

Baseline disability and poor functioning in Bipolar disorder predict worse outcomes: Results from the Bipolar CHOICE study

OBJECTIVE To examine the effects of treatment on functioning impairments and quality of life and assess baseline functioning and employment status as predictors of treatment response in symptomatic individuals from the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (Bipolar CHOICE) study. METHOD Bipolar CHOICE was an 11-site, 6-month randomized effectiveness study comparing lithium to quetiapine, each with adjunctive personalized treatments (APTs). We examined post hoc (1) the effects of treatment on functioning, (2) how changes in functioning differed between treatment responders and nonresponders, and (3) whether functioning and employment status mediated treatment response in 482 participants with DSM-IV-TR bipolar I or II disorder from September 2010 to September 2013. RESULTS Treatment was associated with significant improvements in functioning and quality of life, regardless of treatment group (P values < .0001). Responders showed greater improvements in quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire P values < .05) and functioning (Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool P values < .05) than nonresponders. Unemployed or disabled participants at baseline had significantly greater illness severity at baseline than employed participants (P values < .05). Over the study duration, employed participants reported greater improvements in physical health and quality of life in leisure activities than both unemployed and disabled participants (P values < .05). Individuals who saw greater improvement in functioning and quality of life tended to show greater improvements in depressive and anxiety symptoms (P values ≤ .0001), as well as overall illness severity (P values < .001). Early (8 weeks) and very early (4 weeks) clinical changes in mood symptoms predicted changes in functioning and quality of life at 6 months (P values < .001). CONCLUSIONS Prior disability status was associated with a worse treatment response and prospective illness course. Results implicate functioning and employment status as important markers of illness severity and likelihood of recovery in bipolar disorder, suggesting that interventions that target functional impairment may improve outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

Psychotherapy use in bipolar disorder: Association with functioning and illness severity.

Objective: This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. Methods: Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants’ psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups. Results: Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. Conclusions: These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden.

An exploratory study of responses to low-dose lithium in African Americans and Hispanics

OBJECTIVES Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). METHODS LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs. OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. RESULTS African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. CONCLUSIONS African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group.

A Novel Home Sleep Monitoring Device and Brief Sleep Intervention for Bipolar Disorder: Feasibility, Tolerability, and Preliminary Effectiveness

Sleep disturbance is common in bipolar disorder and negatively impacts its course of illness. The purpose of this study is to assess the feasibility and tolerability of a novel EKG-based home sleep monitoring device (M1) as well as a brief (two session) psychosocial sleep intervention for individuals with bipolar disorder. The sleep intervention is individually tailored for patients with insomnia or hypersomnia and extends skills designed for non-psychiatric populations as well as includes specific considerations for sleep disturbance in bipolar disorder. We found that both the M1 device and the sleep intervention were feasible and well tolerated. Participants’ sleep duration improved after the brief sleep intervention, but their sleep was more unstable as measured by the M1. Self-reported sleepiness, sleep quality, and mood symptoms improved; however, only some measures reached statistical significance (i.e., duration of sleep, dysfunction due to sleepiness). These data suggest that the M1 device is a feasible means to obtain objective sleep quality and quantity data in individuals with bipolar disorder. A brief sleep intervention may be helpful in improving sleep in a bipolar population at risk for substantial sleep disturbance, but larger, longitudinal studies are warranted.

MR-assisted PET motion correction in simultaneous PET/MRI studies of dementia subjects: MR-Assisted PET Motion correction

Subject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners.

Diagnostic Accuracy of the CASI-4R Psychosis Subscale for Children Evaluated in Pediatric Outpatient Clinics

Diagnostic accuracy of the Diagnostic and Statistical Manual of Mental Disorders–oriented Child and Adolescent Symptom Inventory (CASI-4R) Psychotic Symptoms scale was tested using receiver operating characteristic analyses to identify clinically significant psychotic symptoms. Participants were new outpatients (N = 700), ages 6.0 to 12.9 years (M = 9.7, SD = 1.8) at 9 child outpatient mental health clinics, who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) Study baseline assessment. Because LAMS undersampled participants with low mania scores by design, present analyses weighted low scorers to produce unbiased estimates. Psychotic symptoms, operationally defined as a score of 3 or more for hallucinations or 4 or more for delusions based on the Schedule for Affective Disorders and Schizophrenia (K-SADS) psychosis items, occurred in 7% of youth. K-SADS diagnoses for those identified with psychotic symptoms above threshold included major depressive disorder, bipolar spectrum disorder, attention deficit/hyperactivity disorder, posttraumatic stress disorder, psychotic disorders, and autism spectrum disorder. The optimal psychosis screening cut score (maximizing sensitivity and specificity) was 2.75+ (corresponding diagnostic likelihood ratio [DiLR] = 4.29) for the parent version and 3.50+ (DiLR = 5.67) for the teacher version. The Area under the Curve for parent and teacher report was .83 and .74 (both p < .001). Parent report performed significantly better than teacher report for identifying psychotic symptoms above threshold (p = .03). The CASI-4R Psychosis subscale (J) appears clinically useful for identifying psychotic symptoms in children because of its brevity and accuracy.

An Efficient Approach to Perform MR-assisted PET Data Optimization in Simultaneous PET/MR Neuroimaging Studies

A main advantage of PET is that it provides quantitative measures of the radiotracer concentration, but its accuracy is confounded by factors including attenuation, subject motion, and limited spatial resolution. Using the information from one simultaneously acquired morphologic MR sequence with embedded navigators for MR motion correction (MC), we propose an efficient method, MR-assisted PET data optimization (MaPET), for attenuation correction (AC), PET MC, and anatomy-aided reconstruction. Methods: For AC, voxelwise linear attenuation coefficient maps were generated using an SPM8-based method on the MR volume. The embedded navigators were used to derive head motion estimates for event-based PET MC. The anatomy provided by the MR volume was incorporated into the PET image reconstruction using a kernel-based method. Region-based analyses were performed to assess the quality of images generated through various stages of PET data optimization. Results: The optimized PET images reconstructed with MaPET were superior in image quality to images reconstructed using only AC, with high signal-to-noise ratio and low coefficient of variation (5.08 and 0.229 in a composite cortical region compared with 3.12 and 0.570, P < 10−4 for both comparisons). The optimized images were also shown using the Cohen’s d metric to achieve a greater effect size in distinguishing cortical regions with hypometabolism from regions of preserved metabolism. Conclusion: We have shown that the spatiotemporally correlated data acquired using a single MR sequence can be used for PET attenuation, motion, and partial-volume effects corrections and that the MaPET method may enable more accurate assessment of pathologic changes in dementia and other brain disorders.

Diagnostic Efficiency of the Child and Adolescent Symptom Inventory (CASI-4R) Depression Subscale for Identifying Youth Mood Disorders

This study examined the diagnostic and clinical utility of the Child and Adolescent Symptom Inventory–4 R (CASI-4 R) Depressive and Dysthymia subscale for detecting mood disorders in youth (ages 6–12; M = 9.37) visiting outpatient mental health clinics. Secondary analyses (N = 700) utilized baseline data from the Longitudinal Assessment of Manic Symptoms study. Semistructured interviews with youth participants and their parents/caregivers determined psychiatric diagnoses. Caregivers and teachers completed the CASI-4 R. CASI-4 R depressive symptom severity and symptom count scores each predicted mood disorder diagnoses. Both caregiver scores (symptom severity and symptom count) of the CASI-4 R subscale significantly identified youth mood disorders (areas under the curve [AUCs] = .78–.79, ps < .001). The symptom severity version showed a small but significant advantage. Teacher symptom severity report did not significantly predict mood disorder diagnosis (AUC = .56, p > .05), whereas the teacher symptom count report corresponded to a small effect size (AUC = .61, p < .05). The CASI-4 R Depression scale showed strong incrememental validity even controlling for the other CASI-4 R scales. Caregiver subscale cutoff scores were calculated to assist in ruling in (diagnostic likelihood ratio [DLR] = 3.73) or ruling out (DLR = 0.18) presence of a mood disorder. The CASI-4 R Depressive subscale caregiver report can help identify youth mood disorders, and using DLRs may help improve diagnostic accuracy.