Patricia R. Houck

The MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study

OBJECTIVES To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261). METHOD Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. RESULTS In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested. CONCLUSIONS Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0-9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.

Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly

OBJECTIVE To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. DESIGN Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). SETTING University medical center. PARTICIPANTS From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. MAIN OUTCOME MEASURES Regional PiB retention and cognitive test performance. RESULTS Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. CONCLUSIONS Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Healthy older adults' sleep predicts all-cause mortality at 4 to 19 years of follow-up.

Objective Evidence concerning whether sleep disturbances in older adults predict mortality is mixed. However, data are limited to self-reported sleep problems and may be confounded with other comorbidities. We examined whether electroencephalographic (EEG) sleep parameters predicted survival time independently of known predictors of all-cause mortality. Methods A total of 185 healthy older adults, primarily in their 60s through 80s, with no history of mental illness, sleep complaints, or current cognitive impairment, were enrolled in one of eight research protocols between October 1981 and February 1997 that included EEG sleep assessments. At follow-up (mean [SD] = 12.8 [3.7] years after baseline, range = 4.1–19.5), 66 individuals were positively ascertained as deceased and 118 remained alive (total N = 184). Results Controlling for age, gender, and baseline medical burden, individuals with baseline sleep latencies greater than 30 minutes were at 2.14 times greater risk of death (p = .005, 95% CI = 1.25–3.66). Those with sleep efficiency less than 80% were at 1.93 times greater risk (p = .014, CI = 1.14–3.25). Individuals with rapid eye movement (REM) sleep percentages in the lowest 15% or highest 15% of the total sample’s distribution (percentage of REM <16.1 or >25.7) were at 1.71 times greater risk (p = .045, CI = 1.01–2.91). Percentage of slow-wave sleep was associated with time to death at the bivariate level, but not after controlling for potential confounders. Conclusions Older adults with specific EEG sleep characteristics have an excess risk of dying beyond that associated with age, gender, or medical burden. The findings suggest that interventions to optimize and protect older adults’ sleep initiation, continuity, and quality may be warranted.

Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults

BACKGROUND Chronic insomnia is a common health problem with substantial consequences in older adults. Cognitive behavioral treatments are efficacious but not widely available. The aim of this study was to test the efficacy of brief behavioral treatment for insomnia (BBTI) vs an information control (IC) condition. METHODS A total of 79 older adults (mean age, 71.7 years; 54 women [70%]) with chronic insomnia and common comorbidities were recruited from the community and 1 primary care clinic. Participants were randomly assigned to either BBTI, consisting of individualized behavioral instructions delivered in 2 intervention sessions and 2 telephone calls, or IC, consisting of printed educational material. Both interventions were delivered by a nurse clinician. The primary outcome was categorically defined treatment response at 4 weeks, based on sleep questionnaires and diaries. Secondary outcomes included self-report symptom and health measures, sleep diaries, actigraphy, and polysomnography. RESULTS Categorically defined response (67% [n = 26] vs 25% [n = 10]; χ(2) = 13.8) (P < .001) and the proportion of participants without insomnia (55% [n = 21] vs 13% [n = 5]; χ(2) = 15.5) (P < .001) were significantly higher for BBTI than for IC. The number needed to treat was 2.4 for each outcome. No differential effects were found for subgroups according to hypnotic or antidepressant use, sleep apnea, or recruitment source. The BBTI produced significantly better outcomes in self-reported sleep and health (group × time interaction, F(5,73) = 5.99, P < .001), sleep diary (F(8,70) = 4.32, P < .001), and actigraphy (F(4,74) = 17.72, P < .001), but not polysomnography. Improvements were maintained at 6 months. CONCLUSION We found that BBTI is a simple, efficacious, and durable intervention for chronic insomnia in older adults that has potential for dissemination across medical settings. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00177203.

Symptoms of stress and depression as correlates of sleep in primary insomnia.

Objective: Previous studies have not evaluated the clinical correlates of the electroencephalographic spectral profile in patients with insomnia. In the preliminary study described here, we evaluated the extent to which symptoms of stress and depression are associated with subjective sleep complaints and quantitative measures of sleep in individuals with chronic insomnia. Methods: Subjects were 14 healthy adults who met criteria for primary insomnia as specified in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Measures of stress, depression, and subjective sleep quality were collected before subjects participated in a two-night laboratory sleep series. We hypothesized that elevated symptoms of stress and depression would be associated with subjective sleep complaints and electroencephalographic evidence of hyperarousal during sleep. Hyperarousal during sleep was defined as decreases in delta power and elevations in alpha and beta power throughout non–rapid eye movement sleep, and symptoms of stress were defined as the tendency to experience stress-related intrusive thoughts and the interaction between intrusion tendency and the number of recent stressful events (subjective stress burden). Results: A stronger tendency to experience stress-related intrusive thoughts was associated with greater sleep complaints and a trend toward higher beta power, whereas increases in subjective stress burden were associated with decreases in delta power. In addition, elevations in subclinical symptoms of depression were associated with greater sleep complaints and elevations in alpha power. Conclusions: Observed relationships among symptoms of stress, depression, subjective sleep complaints, and electroencephalographic power may be relevant to the discrepancy between subjective and objective measures of sleep in patients with insomnia and may be more broadly applicable to sleep complaints in association with stressful life events and major depression.

Reliability and validity of the Panic Disorder Severity scale: replication and extension

UNLABELLED The Panic Disorder Severity Scale (PDSS) is a recently developed seven-item instrument to rate overall severity of Panic Disorder. The scale has previously shown good psychometric properties in a sample of Panic Disorder patients with no more than mild agoraphobia. The purpose of this paper is to confirm reliability and validity, to provide an estimate of a cut-score discriminating the presence or absence of current DSM-IV Panic Disorder, and to determine the factor structure of the instrument. PROCEDURES 104 psychiatric outpatients, including 54 with current Panic Disorder, underwent structured diagnostic assessment and the PDSS interview. The PDSS was repeated within 3-17 days. RESULTS we confirmed reliability and validity of the instrument and found a one-factor solution fit the data. A cut-off score of eight identifies patients with current panic with a sensitivity of 83.3%, and a specificity of 64%. CONCLUSION the PDSS is a simple, reliable instrument for use in Panic Disorder studies. A cut-score of eight may be useful as a tool to screen patients in settings such as primary care, for diagnosis-level symptoms.

Family-Based Treatment of Severe Pediatric Obesity: Randomized, Controlled Trial

OBJECTIVE: We evaluated the efficacy of family-based, behavioral weight control in the management of severe pediatric obesity. METHODS: Participants were 192 children 8.0 to 12.0 years of age (mean ± SD: 10.2 ± 1.2 years). The average BMI percentile for age and gender was 99.18 (SD: 0.72). Families were assigned randomly to the intervention or usual care. Assessments were conducted at baseline, 6 months, 12 months, and 18 months. The primary outcome was percent overweight (percent over the median BMI for age and gender). Changes in blood pressure, body composition, waist circumference, and health-related quality of life also were evaluated. Finally, we examined factors associated with changes in child percent overweight, particularly session attendance. RESULTS: Intervention was associated with significant decreases in child percent overweight, relative to usual care, at 6 months. Intent-to-treat analyses documented that intervention was associated with a 7.58% decrease in child percent overweight at 6 months, compared with a 0.66% decrease with usual care, but differences were not significant at 12 or 18 months. Small significant improvements in medical outcomes were observed at 6 and 12 months. Children who attended ≥75% of intervention sessions maintained decreases in percent overweight through 18 months. Lower baseline percent overweight, better attendance, higher income, and greater parent BMI reduction were associated with significantly greater reductions in child percent overweight at 6 months among intervention participants. CONCLUSIONS: Intervention was associated with significant short-term reductions in obesity and improvements in medical parameters and conferred longer-term weight change benefits for children who attended ≥75% of sessions.

Inducing lifestyle regularity in recovering bipolar disorder patients : Results from the maintenance therapies in bipolar disorder protocol

On the basis of theories we articulated in earlier papers (Ehlers et al 1988: Arch Gen Psychiatry 45:948-952, 1993: Depression 1:285-293), we have developed an adjunctive psychosocial intervention for patients with bipolar 1 disorder. Central to this intervention is the establishment of regularity in daily routines. In this report, we present data from a controlled investigation comparing this new treatment, interpersonal and social rhythm therapy (IPSRT), with a conventional medication clinic approach. Despite comparable changes in symptomatology over a treatment period lasting up to 52 weeks, subjects assigned to IPSRT (n = 18) show significantly greater stability (p = .047) of daily routines with increasing time in treatment, while subjects assigned to the medication clinic condition (n = 20) show essentially no change in their social routines as measured by Social Rhythm Metric (SRM-Monk et al 1990: J Nerv Ment Dis 178(2):120-126) score. We conclude that IPSRT is capable of influencing lifestyle regularity in patients with bipolar 1 disorder, with the possible benefit of protection against future affective episodes.

Serotonin 1A receptor binding and treatment response in late-life depression.

Depression in late life carries an increased risk of dementia and brittle response to treatment. There is growing evidence to support a key role of the serotonin type 1A (5-HT1A) receptor as a regulator of treatment response, particularly the 5-HT1A autoreceptor in the dorsal raphe nucleus (DRN). We used [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis that 5-HT1A receptor binding in the DRN and prefrontal cortex is altered in elderly depressives and that these measures relate to treatment responsivity. We studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major depression (four men, 13 women; mean age: 71.4±5.9) and 17 healthy control subjects (eight men, nine women; mean age: 70.0±6.7). Patients were subsequently treated with paroxetine as part of a clinical trial of maintenance therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and binding potential (BP) values derived using compartmental modeling. We observed significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP=2.31±0.90) relative to control (BP=3.69±1.56) subjects (p=0.0016). Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating Scores (r=0.60, p=0.014) in the depressed cohort. A trend level correlation between DRN binding and time to remission (r=0.52, p=0.067) was observed in the 14 depressed patients for whom these data were available. Our finding of decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly depressed patients supports evidence of altered 5-HT1A autoreceptor function in depression. Further, this work indicates that dysfunction in autoreceptor activity may play a central role in the mechanisms underlying treatment response to selective serotonin reuptake inhibitors in late-life depression.