Meredith L. Wallace

Lethal Forethought: Delayed Reward Discounting Differentiates High- and Low-Lethality Suicide Attempts in Old Age

BACKGROUND The decision to commit suicide may be impulsive, but lethal suicidal acts often involve planning and forethought. People who attempt suicide make disadvantageous decisions in other contexts, but nothing is known about the way they decide about the future. Can the willingness to postpone future gratification differentiate between individuals prone to serious, premeditated and less serious, unplanned suicidal acts? METHODS Four groups of depressed participants aged 60 and older made choices between smaller immediate and larger delayed monetary rewards: 15 who had made high-lethality suicide attempts, 14 who had made low-lethality suicide attempts, 12 who seriously contemplated suicide, and 42 people with depression, but no history of suicidal thoughts. The reference group was 31 psychiatrically healthy elders. RESULTS Individuals who had made low-lethality attempts displayed an exaggerated preference for immediate rewards compared with nonsuicidal depressed and healthy control subjects. Those who had carried out high-lethality suicide attempts were more willing to delay future rewards, compared with low-lethality attempters. Better planned suicide attempts were also associated with willingness to wait for larger rewards. These effects were unchanged after accounting for education, global cognitive function, substance use disorders, psychotropic medications, and possible brain injury from attempts. Discount rates were correlated with having debt, but were not significantly associated with income, hopelessness, depressive severity, premorbid IQ, age at first attempt, or choice of violent means. CONCLUSIONS Although clinicians often focus on impulsivity in patients at risk for suicide, these data suggest that identifying biological characteristics and treatments for nonimpulsive suicidal older people may be even more important.

A Novel Approach for Developing and Interpreting Treatment Moderator Profiles in Randomized Clinical Trials

IMPORTANCE Identifying treatment moderators may help mental health practitioners arrive at more precise treatment selection for individual patients and can focus clinical research on subpopulations that differ in treatment response. OBJECTIVE To demonstrate a novel exploratory approach to moderation analysis in randomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS A total of 291 adults from a randomized clinical trial that compared an empirically supported psychotherapy with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy as treatments for depression. MAIN OUTCOMES AND MEASURES We selected 8 relatively independent individual moderators out of 32 possible variables. A combined moderator, M*, was developed as a weighted combination of the 8 selected individual moderators. M* was then used to identify individuals for whom psychotherapy may be preferred to SSRI pharmacotherapy or vice versa. RESULTS Among individual moderators, psychomotor activation had the largest moderator effect size (0.12; 95% CI, <.01 to 0.24). The combined moderator, M*, had a larger moderator effect size than any individual moderator (0.31; 95% CI, 0.15 to 0.46). Although the original analyses demonstrated no overall difference in treatment response, M* divided the study population into 2 subpopulations, with each showing a clinically significant difference in response to psychotherapy vs SSRI pharmacotherapy. CONCLUSIONS AND RELEVANCE Our results suggest that the strongest determinations for personalized treatment selection will likely require simultaneous consideration of multiple moderators, emphasizing the value of the methods presented here. After validation in a randomized clinical trial, a mental health practitioner could input a patients relevant baseline values into a handheld computer programmed with the weights needed to calculate M*. The device could then output the patients M* value and suggested treatment, thereby allowing the mental health practitioner to select the treatment that would offer the greatest likelihood of success for each patient.

Pooled patient-level meta-analysis of children and adults completing a computer-based anxiety intervention targeting attentional bias

Computer-based approaches, such as Attention Bias Modification (ABM), could help improve access to care for anxiety. Study-level meta-analyses of ABM have produced conflicting findings and leave critical questions unresolved regarding ABMs mechanisms of action and clinical potential. We pooled patient-level datasets from randomized controlled trials of children and adults with high-anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was tested as an outcome and a mechanistic mediator and moderator of anxiety reduction. Diagnostic remission and Liebowitz Social Anxiety Scale (LSAS) were clinical outcomes available in enough studies to enable pooling. Per-patient data were obtained on at least one outcome from 13/16 eligible studies [86% of eligible participants; n=778]. Significant main effects of ABM on diagnostic remission (ABM-22.6%, control-10.8%; OR=2.57; p=0.006) and AB (β* (95%CI)=-0.63 (-0.83, -0.42); p<0.00005) were observed. There was no main effect of ABM on LSAS. However, moderator analyses suggested ABM was effective for patients who were younger (≤37y), trained in the lab, and/or assessed by clinicians. Under the same conditions where ABM was effective, mechanistic links between AB and anxiety reduction were supported. Under these specific circumstances, ABM reduces anxiety and acts through its target mechanism, supporting ABMs theoretical basis while simultaneously suggesting clinical indications and refinements to improve its currently limited clinical potential.

Sleep duration is associated with dyslipidemia in patients with bipolar disorder in clinical remission

BACKGROUND The pathways to increased cardiovascular risk in bipolar disorder include health behaviors, psychosocial stress and long-term medication exposure. However, the evidence that the association between cardiovascular risk factors and bipolar disorder remains significant after controlling for these co-factors suggests that additional important risk factors have yet to be identified. Our hypothesis is that disturbances in the sleep-wake cycle are an important and under-recognized pathway through which affective disorders lead to increased cardiovascular risk. METHODS In patients with bipolar disorder type 1 in clinical remission, we: 1) explored whether sleep disturbance predicted the endorsement of NCEP ATP-III criteria for dyslipidemia, independent of other lifestyle factors and 2) tested the association between low HDL (NCEP-ATP III) and sleep duration measured with actigraphy over an eight-day period. RESULTS Median sleep duration is significantly associated with low HDL. The risk of having low HDL increases by 1.23 with every 30 minutes of reduced sleep time. LIMITATIONS Since sleep patterns in patients with bipolar disorder are variable and irregular, it is possible that other sleep characteristics, not present during the span of our study, or the variability itself may be what drives the increased cardiovascular risk. CONCLUSIONS Sleep characteristics of patients with bipolar disorder in clinical remission are associated with cardiovascular risk. More specifically, sleep duration was associated with low HDL. Clinicians should pay special attention to sleep hygiene in treating individuals with bipolar disorder, even when they are in clinical remission.

SEROTONIN TRANSPORTER TRIALLELIC GENOTYPE AND RESPONSE TO CITALOPRAM AND RISPERIDONE IN DEMENTIA WITH BEHAVIORAL SYMPTOMS

The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics are poorly tolerated, and the efficacy of alternative treatments, for example, selective serotonin-reuptake inhibitors (SSRIs), is uncertain. Biomarkers of treatment response may improve this risk/benefit ratio. The length polymorphism of the serotonin transporter promoter gene (5-HTTLPR/SLC6A4) may moderate tolerability of SSRIs and expression of behavioral symptoms in dementia. We assessed the effect of 5-HTTLPR on tolerability and efficacy of citalopram and risperidone in a 12-week randomized controlled trial, which included nondepressed patients with dementia hospitalized for behavioral or psychotic symptoms. Genotypes including the A/G polymorphism of the L allele (rs25531) were determined in 92 of 103 participants. We used pattern-mixture models to account for dropout. Low-expression alleles (S and Lg) predicted greater early and overall side effects of citalopram and early treatment discontinuation. These results remained unchanged after excluding African–American participants and in covariate analyses. Unexpectedly, low-expression alleles seemed to predict greater early side effects of risperidone (but not early discontinuation) and poorer early response of psychosis symptoms to risperidone. In conclusion, 5-HTTLPR may be a useful biomarker of SSRI intolerance in dementia. Our findings of intolerance of a second-generation antipsychotics and persistence of psychosis in patients with low-expression alleles needs to be replicated.

Incidence and predictors of relapse during continuation treatment of major depression with SSRI, interpersonal psychotherapy, or their combination.

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6‐month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety, 2011.

An Integrated Risk Reduction Intervention can reduce body mass index in individuals being treated for bipolar I disorder: results from a randomized trial.

We conducted a randomized, controlled trial comparing the efficacy of an Integrated Risk Reduction Intervention (IRRI) to a control condition with the objective of improving mood stability and psychosocial functioning by reducing cardiometabolic risk factors in overweight/obese patients with bipolar I disorder.

Coping with health stresses and remission from late-life depression in primary care: a two-year prospective study

Identifying the predictors of late‐life depression that are amenable to change may lead to interventions that result in better and faster remission. Thus, the authors investigated the impact of two different strategies for coping with physical illness on depression in older, primary care patients. Health‐oriented goal engagement strategies involve the investment of cognitive and behavioral resources to achieve health goals. Conversely, disengagement strategies involve the withdrawal of these resources from obsolete or unattainable health goals, combined with goal restructuring.

Social rhythm disrupting events increase the risk of recurrence among individuals with bipolar disorder

As outlined in the social zeitgeber hypothesis, social rhythm disrupting (SRD) life events begin a cascade of social and biological rhythm disruption that may lead to the onset of affective episodes in those vulnerable to bipolar disorder. Thus, the study of SRD events is particularly important in individuals with this chronic condition. The purpose of the current study was to evaluate (i) the extent to which SRD life events increased the risk of recurrence of a bipolar mood episode, and (ii) whether the social rhythm disruption associated with the event conferred an increased risk of recurrence, after accounting for the level of threat associated with the life event.

The role of day-to-day emotions, sleep, and social interactions in pediatric anxiety treatment

Do day-to-day emotions, social interactions, and sleep play a role in determining which anxious youth respond to supportive child-centered therapy (CCT) versus cognitive behavioral therapy (CBT)? We explored whether measures of day-to-day functioning (captured through ecological momentary assessment, sleep diary, and actigraphy), along with clinical and demographic measures, were predictors or moderators of treatment outcome in 114 anxious youth randomized to CCT or CBT. We statistically combined individual moderators into a single, optimal composite moderator to characterize subgroups for which CCT or CBT may be preferable. The strongest predictors of better outcome included: (a) experiencing higher positive affect when with ones mother and (b) fewer self-reported problems with sleep duration. The composite moderator indicated that youth for whom CBT was indicated had: (a) more day-to-day sleep problems related to sleep quality, efficiency, and waking, (b) day-to-day negative events related to interpersonal concerns, (c) more DSM-IV anxiety diagnoses, and (d) college-educated parents. These findings illustrate the value of both day-to-day functioning characteristics and more traditional sociodemographic and clinical characteristics in identifying optimal anxiety treatment assignment. Future studies will need to enhance the practicality of real-time measures for use in clinical decision making and evaluate additional anxiety treatments.