The design and implementation of a multi-center, pragmatic, individual-level randomized controlled trial to evaluate Baby2Home, an mHealth intervention to support new parents.

BACKGROUND: Becoming a parent is a transformative experience requiring multiple transitions, including the need to navigate several components of health care, manage any mental health issues, and develop and sustain an approach to infant feeding. Baby2Home (B2H) is a digital intervention built on the collaborative care model (CCM) designed to support families during these transitions to parenthood. OBJECTIVES: We aim to investigate the effects of B2H on preventive healthcare utilization for the family unit and patient-reported outcomes (PROs) trajectories with a focus on mental health. We also aim to evaluate heterogeneity in treatment effects across social determinants of health including self-reported race and ethnicity and household income. We hypothesize that B2H will lead to optimized healthcare utilization, improved PROs trajectories, and reduced racial, ethnic, and income-based disparities in these outcomes as compared to usual care. METHODS: B2H is a multi-center, pragmatic, individual-level randomized controlled trial. We will enroll 640 families who will be randomized to: [1] B2H + usual care, or [2] usual care alone. Preventive healthcare utilization is self-reported and confirmed from medical records and includes attendance at the postpartum visit, contraception use, depression screening, vaccine uptake, well-baby visit attendance, and breastfeeding at 6 months. PROs trajectories will be analyzed after collection at 1 month, 2 months, 4 months, 6 months and 12 months. PROs include assessments of stress, depression, anxiety, self-efficacy and relationship health. IMPLICATIONS: If B2H proves effective, it would provide a scalable digital intervention to improve care for families throughout the transition to new parenthood.

Fetal behavior and gestational serotonin reuptake inhibitor exposure: relationships between behavior, drug dosage, plasma drug level, and a measure of drug bioeffect.

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior.

Effect of early medication adherence on behavioral treatment utilization and smoking cessation among individuals with current or past major depressive disorder.

SIGNIFICANCE: Little is known about the mechanisms by which medication adherence promotes smoking cessation among adults with MDD. We tested the hypothesis that early adherence promotes abstinence by increasing behavioral treatment (BT) utilization. METHODS: Data for this post-hoc analysis were from a randomized trial of 149 adults with current or past MDD treated with BT and either varenicline (n = 81) or placebo (n = 68). Arms were matched on medication regimen. Early medication adherence was measured by the number of days in which medication was taken at the prescribed dose during the first six of 12 weeks of pharmacological treatment (weeks 2-7). BT consisted of eight 45-minute sessions (weeks 1-12). Bioverified abstinence was assessed at end-of-treatment (week 14). A regression-based approach was used to test whether the effect of early medication adherence on abstinence was mediated by BT utilization. RESULTS: Among 141 participants who initiated the medication regimen, BT utilization mediated the effect of early medication adherence on abstinencea) an interquartile increase in early medication days from 20 to 42 predicted a 4.2 times increase in abstinence (Total Risk Ratio (RR) = 4.24, 95% CI = 2.32-13.37; p <.001); b) increases in BT sessions predicted by such an increase in early medication days were associated with a 2.7 times increase in abstinence (Indirect RR = 2.73, 95% CI = 1.54-7.58; p <.001); and c) early medication adherence effects on abstinence were attenuated, controlling for BT (Direct RR = 1.55, 95% CI = 0.83-4.23, p =.17). CONCLUSIONS: The effect of early medication adherence on abstinence in individuals with current or past MDD is mediated by intensive BT utilization.

Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic.

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

Components of Behavioral Activation Therapy for Depression Engage Specific Reinforcement Learning Mechanisms in a Pilot Study.

Background: Behavioral activation is an evidence-based treatment for depression. Theoretical considerations suggest that treatment response depends on reinforcement learning mechanisms. However, which reinforcement learning mechanisms are engaged by and mediate the therapeutic effect of behavioral activation remains only partially understood, and there are no procedures to measure such mechanisms. Objective: To perform a pilot study to examine whether reinforcement learning processes measured through tasks or self-report are related to treatment response to behavioral activation. Method: The pilot study enrolled 13 outpatients (12 completers) with major depressive disorder, from July of 2018 through February of 2019, into a nine-week trial with BA. Psychiatric evaluations, decision-making tests and self-reported reward experience and anticipations were acquired before, during and after the treatment. Task and self-report data were analysed by using reinforcement-learning models. Inferred parameters were related to measures of depression severity through linear mixed effects models. Results: Treatment effects during different phases of the therapy were captured by specific decision-making processes in the task. During the weeks focusing on the active pursuit of reward, treatment effects were more pronounced amongst those individuals who showed an increase in Pavlovian appetitive influence. During the weeks focusing on the avoidance of punishments, treatment responses were more pronounced in those individuals who showed an increase in Pavlovian avoidance. Self-reported anticipation of reinforcement changed according to formal RL rules. Individual differences in the extent to which learning followed RL rules related to changes in anhedonia. Conclusions: In this pilot study both task- and self-report-derived measures of reinforcement learning captured individual differences in treatment response to behavioral activation. Appetitive and aversive Pavlovian reflexive processes appeared to be modulated by separate psychotherapeutic interventions, and the modulation strength covaried with response to specific interventions. Self-reported changes in reinforcement expectations are also related to treatment response. Trial Registry Name: Set Your Goal: Engaging in GO/No-Go Active Learning, #NCT03538535, http://www.clinicaltrials.gov.