Feasibility and Acceptability of Mindfulness-based Stress Reduction and Prenatal Sleep Classes for Poor Prenatal Sleep Quality: Pilot Randomized Controlled Trial.

OBJECTIVES: The main objectives of the current paper were to examine the feasibility, acceptability, and adherence of a remotely delivered intervention consisting of mindfulness-based stress reduction plus prenatal sleep classes (MBSR+PS) compared with treatment as usual (TAU). METHOD: In this pilot randomized controlled trial, 52 pregnant women with poor sleep quality were randomized to MBSR+PS or TAU. MBSR was delivered through eight weekly 2.5-hour sessions, and PS was delivered through eight weekly 30-minute sessions. PS content drew material from cognitive behavioral therapy for insomnia tailored for the perinatal period and from a mindfulness- and acceptance-based lens. Participants completed endpoint measures 10-12 weeks after randomization. RESULTS: We surpassed all acceptability targets, including the percentage of eligible participants willing to be randomized (96%), percentage of participants who initiated treatment (88%), and satisfaction scores (Client Satisfaction Questionnaire-8 score M = 28.04, SD = 3.6). We surpassed all feasibility targets, including our enrollment target, retention rate (92%), and measure completion (96%). Finally, we surpassed adherence targets, including MBSR and PS session attendance (≥80%). Though sleep outcomes were exploratory, increases in sleep efficiency were greater in the MBSR+PS group relative to TAU (SMD=.68). CONCLUSIONS: Patient-reported poor sleep quality during pregnancy has high public health significance because it is common, consequential, and under-treated. The current feasibility and acceptability data for using remotely delivered MBSR and PS to improve prenatal sleep quality are encouraging and warranting future research that is sufficiently powered and designed to provide efficacy data. In addition, exploratory sleep outcomes offer preliminary evidence that this sleep program may improve sleep efficiency during pregnancy.

ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan.

BACKGROUND: Alzheimer's disease is a large and growing unmet medical need. Clinical trial designs need to assess disease-related outcomes earlier to accelerate the development of better treatments for Alzheimer's disease. ACU193 is a monoclonal antibody that selectively targets amyloid ß oligomers, thought to be the most toxic species of Aß that accumulates early in AD and contributes to downstream pathological effects. Nonclinical data indicate that ACU193 can reduce the toxic effects of amyloid ß oligomers. ACU193 is currently being investigated in a phase 1 clinical trial designed with the properties described in this report. This phase 1 trial is designed to provide data to enable a go/no-go decision regarding the initiation of a subsequent phase 2/3 study. OBJECTIVES: To design a phase 1 study that assesses target engagement and incorporates novel measures to support more rapid development of a potential disease-modifying treatment for Alzheimer's disease. DESIGN: The INTERCEPT-AD trial for ACU193 is an ongoing randomized, placebo-controlled phase 1a/b study that assesses safety, tolerability, pharmacokinetics, target engagement, clinical measures, and several Alzheimer's disease biomarkers, including novel digital and imaging biomarkers. SETTING: For INTERCEPT-AD, brief inpatient stays for patients in the single ascending dose portion of the study, with the remainder of the evaluations being performed as outpatients at multiple clinical trial sites in the U.S. PARTICIPANTS: Patients with early Alzheimer's disease (mild cognitive impairment or mild dementia with a positive florbetapir positron emission tomography scan). INTERVENTION: ACU193 administered intravenously at doses of 2- 60 mg/kg. MEASUREMENTS: Safety assessments including magnetic resonance imaging for the presence of amyloid-related imaging abnormalities, clinical assessments for Alzheimer's disease including the Alzheimer's Disease Rating Scale-cognition and Clinical Dementia Rating scale, pharmacokinetics, a measure of target engagement, and digital and imaging biomarkers, including a computerized cognitive test battery and a measure of cerebral blood flow using arterial spin labelling magnetic resonance imaging. RESULTS: A phase 1 study design was developed for ACU193 that allows collection of data that will enable a go/no-go decision for initiation of a subsequent adaptive phase 2/3 study. CONCLUSIONS: A phase 1a/b trial and an overall clinical development plan for an Alzheimer's disease treatment can be designed that maintains patient safety, allows informed decision-making, and achieves an accelerated timeline by using novel biomarkers and adaptive study designs.

Depression symptoms during pregnancy.

Pregnancy impacts common symptoms of major depressive disorder (MDD), such as energy, appetite, weight change, and sleep and somatic complaints. However, it is not known whether the presentation of depression during pregnancy is different from that at other times in women's lives. This study compares the severity of symptoms of depression in 61 pregnant women with MDD (PD), 50 nonpregnant women with MDD (D), and 41 pregnant women without MDD (P). Despite equivalent overall depression severity, PD women had lower scores on suicidality, guilt, and early insomnia and higher scores on psychomotor retardation than D women. The severity of other depressive symptoms was similar in the two depressed groups. As expected on the basis of the selection criteria, overall depression severity and the severity of individual symptoms were significantly higher in the PD group than in the P group but effect sizes for somatic symptoms were smaller than for psychological symptoms. The results suggest that the profile of depression symptoms of women with MDD who are pregnant does not differ much from that of depressed nonpregnant women. Depressive symptoms, particularly psychological symptoms of depression, during pregnancy should be taken seriously and not be dismissed as a normal part of the pregnancy experience.

Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication.

BACKGROUND: We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition. METHOD: Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.

Six-month depression relapse rates among women treated with acupuncture.

Conventional treatments for Major Depression, although reasonably effective, leave many without lasting relief. Alternative approaches would therefore be welcome for both short- and long-term treatment of depression. Thirty-eight women were randomized to one of three treatment conditions in a double-blind randomized controlled trial of acupuncture in depression. All participants eventually received eight weeks of acupuncture treatment specifically for depression. From among the 33 women who completed treatment, 26 (79%) were intertiewed at six-month follow-up. Relapse rates were comparable to those of established treatments, with four of the 17 women (24%) who achieved full remission at the conclusion of treatment experiencing a relapse six months later. Compared to other empirically validated treatments, acupuncture designed specifically to treat major depression produces results that are comparable in terms of rates of response and of relapse or recurrence. These results suggest a larger trial of acupuncture in the acute- and maintenance-phase treatment of depression is warranted.

Valence-dependent modulation of psychophysiological measures: is there consistency across repeated testing?

The present study used the picture perception paradigm to examine the extent to which three well-documented psychophysiological measures demonstrate consistency across time in response to emotional stimuli. The three measures were the eye-blink startle response and the activation in two facial muscle regions (zygomatic and corrugator). Twenty-seven young women were assessed on two occasions, 2 weeks apart. Whereas activation in the corrugator and zygomatic muscle regions demonstrated the predicted patterns at both assessments (with some attenuation in the zygomatic muscle regions), the startle response had limited consistency across the two assessments. The startle response revealed the predicted linear pattern of valence modulation during the first assessment. During the second assessment, startle magnitude response was a quadratic function of valence ratings and a linear function of arousal ratings. The unexpected pattern of startle response during the second session appeared to be related to the content of the pleasant slides, with action slides generating quadratic valence modulation and erotic slides continuing to exhibit the expected linear valence modulation.

The Arizona Sexual Experience Scale (ASEX): reliability and validity.

Although sexual dysfunction is common in psychiatric patients, quantification of sexual dysfunction is limited by the paucity of validated, user-friendly scales. In order to address this problem, the authors have developed the Arizona Sexual Experiences Scale (ASEX), a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. This study assesses the internal consistency, test-retest reliability, and convergent and discriminant validity of the ASEX.

Sex, steroids, and sleep: a review.

The present article reviews direct and indirect evidence of the effects of sex steroids on different aspects of sleep. It begins with a review of what is known about the effects of steroid hormones on sleep and on central nervous system processes related to sleep, such as the GABA-ergic system, in animals. It continues with a review of the effects of exogenous hormones on human sleep and a review of studies comparing sleep during hypogonadal states secondary to surgical or natural menopause. The article proceeds to review the data on the effects of the menstrual cycle on both subjective and objective aspects of sleep and circadian temperature and melatonin rhythms in samples of healthy women, women with premenstrual dysphoric disorder, and women with primary insomnia. Then, the article reviews gender differences in sleep during depression and raises the possibility that sex steroids moderate these differences. Finally, the article concludes with a discussion of the implications of the data reviewed for basic clinical, and methodological aspects of sleep research.

Sleep and the menstrual cycle.

To evaluate changes in sleep across the phases of the menstrual cycle, sleep-wake diaries were completed by 32 healthy women twice daily for 2 menstrual cycles. There was a significant increase in sleep onset latency and a significant decrease in sleep efficiency and sleep quality during the luteal phase. This increase in sleep disturbance was observed in the entire sample and was not related to the severity of other premenstrual symptoms. However, women having increased severity of other premenstrual symptoms reported greater luteal increase in daytime sleepiness. Thus, although menstruating women are likely to show increased sleep disturbance during the luteal phase, those with other, more severe premenstrual symptoms are more likely to experience a luteal increase in daytime sleepiness.

The effects of regularizing sleep-wake schedules on daytime sleepiness.

The present study evaluated the differential effects of two manipulations of sleep-wake schedules on daily subjective ratings of daytime sleepiness of college undergraduate students. Two experimental conditions were compared: a sleep only group and a regularity group. Subjects in both conditions were given a lower limit for total sleep time (7.5 hours). Subjects in the regularity group received an additional instruction to keep a regular sleep schedule. The study was longitudinal and prospective. Following a baseline period (12 days), the experimental conditions were introduced. The experimental phase lasted 4 weeks and overall compliance was good. A follow-up phase (1 week) began 5 weeks past termination of the experimental phase. The findings indicated that when nocturnal sleep is not deprived, regularization of sleep-wake schedules is associated with reduced reported sleepiness. Subjects in the regular schedule condition reported greater and longer lasting improvements in alertness compared with subjects in the sleep only condition and reported improved sleep efficiency.