Correction of depression-associated circadian rhythm abnormalities is associated with lithium response in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%-40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. METHODS: In secondary analyses of a multi-center, prospective, trial of lithium for BD, we examined the relationship between circadian rhythms and therapeutic response to lithium. Using standardized instruments, we measured morningness, diurnal changes in mood, sleep, and energy (circadian rhythm disturbances) in a cross-sectional study of 386 BD subjects with varying lithium exposure histories. Next, we tracked symptoms of depression and mania prospectively over 12 weeks in a subset of 88 BD patients initiating treatment with lithium. Total, circadian, and affective mood symptoms were scored separately and analyzed. RESULTS: Subjects with no prior lithium exposure had the most circadian disruption, while patients stable on lithium monotherapy had the least. Patients who were stable on lithium with another drug or unstable on lithium showed intermediate levels of disruption. Treatment with lithium for 12 weeks yielded significant reductions in total and affective depression symptoms. Lithium responders (Li-Rs) showed improvement in circadian symptoms of depression, but non-responders did not. There was no difference between Li-Rs and nonresponders in affective, circadian, or total symptoms of mania. CONCLUSIONS: Exposure to lithium is associated with reduced circadian disruption. Lithium response at 12 weeks was selectively associated with the reduction of circadian depressive symptoms. We conclude that stabilization of circadian rhythms may be an important feature of lithium's therapeutic effects. CLINICAL TRIALS REGISTRY: NCT0127253.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

Clinical predictors of non-response to lithium treatment in the Pharmacogenomics of Bipolar Disorder (PGBD) study.

BACKGROUND: Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. METHODS: The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. RESULTS: A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. CONCLUSIONS: In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.

Parenting With and Beyond Cancer: A Photo-Elicitation Study.

The purpose of this study was to understand the occupational performance of parents with cancer and to understand if photo-elicitation would provide new insights into these experiences. In a semi-structured photo-elicitation interview, 36 participants living with and beyond cancer who had children under 18 years old shared and discussed photographs related to their parenting experiences. Transcribed interviews were analyzed using thematic analysis. Two main themes were identified. Parents shared how they (a) managed daily responsibilities and (b) maintained connection with their family. Across all types, stages and phases of the cancer continuum parents shared experiences related to maintaining child and family responsibilities and maintaining connection with their children. Photo-elicitation was an efficient and effective method to gather rich data from parents living with cancer. The results emphasize the clinical utility of using photo-elicitation to understand the occupational performance of parents throughout the cancer continuum of care.

Understanding the daily activities of parents with cancer through picturesThe purpose of this study was to understand the experiences of parents living with and beyond cancer. We used pictures taken by parents about their daily life to guide interviews to see if this approach would provide new insights into their daily experiences. Thirty-six parents with a cancer diagnosis (both mothers and fathers) who had children under 18 years of age participated in interviews. Interviews were analyzed using qualitative methods. Parents shared how they managed daily responsibilities and stayed connected with their family while living with and beyond cancer. Discussing the parents' pictures during the interviews gave researchers a deeper understanding of their experiences living with cancer. The study sample consisted of primarily non-Hispanic White, well-educated parents. Therefore, the results may only be applicable to this specific population.

A 7 Tesla Amygdalar-Hippocampal Shape Analysis of Lithium Response in Bipolar Disorder.

Research to discover clinically useful predictors of lithium response in patients with bipolar disorder has largely found them to be elusive. We demonstrate here that detailed neuroimaging may have the potential to fill this important gap in mood disorder therapeutics. Lithium treatment and bipolar disorder have both been shown to affect anatomy of the hippocampi and amygdalae but there is no consensus on the nature of their effects. We aimed to investigate structural surface anatomy changes in amygdala and hippocampus correlated with treatment response in bipolar disorder. Patients with bipolar disorder (N = 14) underwent lithium treatment, were classified by response status at acute and long-term time points, and scanned with 7 Tesla structural MRI. Large Deformation Diffeomorphic Metric Mapping was applied to detect local differences in hippocampal and amygdalar anatomy between lithium responders and non-responders. Anatomy was also compared to 21 healthy comparison participants. A patch of the ventral surface of the left hippocampus was found to be significantly atrophied in non-responders as compared to responders at the acute time point and was associated at a trend-level with long-term response status. We did not detect an association between response status and surface anatomy of the right hippocampus or amygdala. To the best of our knowledge, this is the first shape analysis of hippocampus and amygdala in bipolar disorder using 7 Tesla MRI. These results can inform future work investigating possible neuroimaging predictors of lithium response in bipolar disorder.

The utility of PHQ-9 and CGI-S in measurement-based care for predicting suicidal ideation and behaviors.

BACKGROUND: Measurement-based care (MBC) has emerged as an effective strategy for improving outcomes in patients with mood disorders. Suicide is a particularly devastating outcome of mood disorders. Using data from a new MBC program from the National Network of Depression Centers (NNDC), we examined whether capturing a patient-rated symptom measure, the patient health questionnaire (PHQ-9), along with a provider-rated global functioning measure, the clinical global impression scale (CGI-S), improves identification of patients at risk of suicide over using either measure alone. METHODS: A total of 126 adults with mood disorders from nine sites in the NNDC completed the PHQ-9 and CGI-S and had at least one subsequent visit where they completed the Columbia-suicide severity rating scale (C-SSRS). The PHQ-9 (≥10) and CGI-S (≥4) were dichotomized at commonly accepted severity thresholds. Associations of the PHQ-9 and CGI-S with suicidal ideation or behavior were examined using Firth's logistic regression to accommodate small samples while controlling for age, sex, race, and diagnosis. RESULTS: Patients who scored higher on only the PHQ-9 or CGI-S were not significantly more likely to experience subsequent suicidal ideation or behaviors. However, patients who scored higher on both the PHQ-9 and CGI-S were significantly more likely to experience suicidal ideation (OR = 4.70, p = 0.0005) and suicidal behaviors (OR = 25.38, p = 0.0003). DISCUSSION: Information from both patient and clinician-rated measures was better able to identify patients with mood disorders at risk for suicidal ideation and behaviors. Using both together may help reduce the risk of suicide by identifying those patients at greatest risk and allowing for more targeted interventions.

The association between lithium use and neurocognitive performance in patients with bipolar disorder.

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1-5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1-5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

Effectiveness of the Adolescent Depression Awareness Program (ADAP) on Depression Literacy and Mental Health Treatment.

BACKGROUND: Analysis of data from a NIMH-supported study was conducted to evaluate the effectiveness of the Adolescent Depression Awareness Program (ADAP) in promoting depression literacy and help-seeking behavior. METHODS: Eighteen Pennsylvania schools were matched on size, sex, race, test scores, median income, and free/reduced lunch status. Schools randomized to the intervention implemented ADAP as a compulsory part of the schools health curriculum, while control schools collected study measures. RESULTS: Post-randomization analysis revealed no significant differences by sex on the pre-assessments between intervention and control schools. In the intervention schools, a total of 1427 students received ADAP. Written parental consent and adolescent assent was obtained from 33.7% students. The online REDCap survey was completed by 41.78% of the consenting students. The Adolescent Depression Knowledge Questionnaire (ADKQ) findings suggest that ADAP significantly improved depression knowledge (Est. =1.07, SE =.25, p < .001), compared to those in the control group. ADAP was found to facilitate help-seeking behavior by student report in those participating in the REDCap survey 4 months following the ADAP curriculum. CONCLUSIONS: Results of the survey suggests that ADAP facilitates help-seeking behaviors in teens. This study supports the efficacy of a teacher delivered school-based universal prevention program, ADAP, on depression literacy.

Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Mobile technology for medication adherence in people with mood disorders: A systematic review.

BACKGROUND: Medication non-adherence is a critical challenge for many patients diagnosed with mood disorders (Goodwin and Jamison, 1990). There is a need for alternative strategies that improve adherence among patients with mood disorders that are cost-effective, able to reach large patient populations, easy to implement, and that allow for communication with patients outside of in-person visits. Technology-based approaches to promote medication adherence are increasingly being explored to address this need. The aim of this paper is to provide a systematic review of the use of mobile technologies to improve medication adherence in patients with mood disorders. METHODS: A total of nine articles were identified as describing mobile technology targeting medication adherence in mood disorder populations. RESULTS: Results showed overall satisfaction and feasibility of mobile technology, and reduction in mood symptoms; however, few examined effectiveness of mobile technology improving medication adherence through randomized control trials. LIMITATIONS: Given the limited number of studies, further research is needed to determine long term effectiveness. CONCLUSIONS: Mobile technologies has the potential to improve medication adherence and can be further utilized for symptom tracking, side effects tracking, direct links to prescription refills, and provide patients with greater ownership over their treatment progress.