Alterations in resting-state functional activity and connectivity for major depressive disorder appetite and weight disturbance phenotypes.

BACKGROUND: Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing. METHODS: Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement. RESULTS: Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD. CONCLUSIONS: Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.

Paraprofessional delivery of online narrative exposure therapy for firefighters.

Firefighters are at increased risk for developing posttraumatic stress disorder (PTSD) and face numerous barriers to accessing mental health care. Innovative ways to increase access to evidence-based interventions are needed. This study was a case series testing the acceptability, feasibility, and preliminary effectiveness of a paraprofessional-delivered, virtual narrative exposure therapy (eNET) intervention for PTSD. Participants were 21 firefighters who met the criteria for clinical or subclinical probable PTSD and completed 10-12 sessions of eNET via videoconference. Participants completed self-report measures pre- and postintervention and at 2- and 6-month follow-ups as well as a postintervention qualitative interview. Paired samples t tests evidenced statistically significant decreases in PTSD, anxiety, and depressive symptom severity and functional impairment from pre- to postintervention, ds = 1.08-1.33, and in PTSD and anxiety symptom severity and functional impairment from preintervention to 6-month follow-up, ds = 0.69-1.10. The average PTSD symptom severity score fell from above to below the clinical cutoff for probable PTSD at postintervention and follow-ups. Qualitative interviews indicated that paraprofessionals were considered central to participants' success and experience with the intervention. No adverse events or safety concerns were raised. This study is an important step in demonstrating that appropriately trained and supervised paraprofessionals can effectively deliver eNET to firefighters with PTSD.

Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

BACKGROUND: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. METHODS: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. RESULTS: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. CONCLUSION: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Parenting-related trauma exposure among parents of children with intellectual and developmental disorders: Development and validation of the Parenting Trauma Checklist.

Parents of children with intellectual and developmental disorders (IDDs) often encounter parenting-related traumatic events. Trauma exposure is a risk factor for mental health problems, including posttraumatic stress disorder (PTSD). Little is known regarding the types of traumatic events that parents commonly experience and how to best assess parenting-related trauma exposure. To address this gap, we developed the Parenting Trauma Checklist (PTC) and tested its psychometric properties. The PTC was created based on an extensive literature review and consultation with stakeholders, which led to the creation of a 17-item instrument. Participants (N = 424) were Canadian parents of children with IDDs who completed an online test battery that included the PTC and several questionnaires to assess PTSD symptoms, global mental and physical health, lifetime trauma exposure, and functional impairment, which were included to test the validity of the new instrument. The PTC demonstrated good construct validity. Ninety four percent of the sample reported parenting-related trauma exposure. Parents reported having experienced an average of 5.79 parenting-related traumatic events, with seeing their child undergo a medical procedure the most frequently endorsed event (68.6%). Experiencing more parenting-related traumatic events was positively associated with higher PTSD symptom levels, r = .35, p < .001. The PTC is a promising instrument that can be used to examine parenting-related trauma exposure. The measure can be used as a screening tool to detect parents' risk of traumatic stress disorders, evaluate traumatic experiences, and assess whether trauma-focused treatment is warranted.

How to measure barriers in accessing mental healthcare? Psychometric evaluation of a screening tool in parents of children with intellectual and developmental disabilities.

Caring for children with intellectual and developmental disabilities (IDD) can cause an enormous physical and emotional burden, and therefore these parents have an elevated risk to experience mental health problems. The characteristics of current healthcare systems and parents' responsibilities to care for their children seem to impede their access to mental healthcare. There is so far a lack of instruments to screen for such obstacles. The aim of this study was to develop and validate a scale for measuring barriers to accessing mental healthcare. The Parental Healthcare Barriers Scale (PHBS) was developed on the basis of an extensive literature research, input and discussion from experts and parents with lived experience. A cross-sectional survey was used to collect data from 456 parents of children with IDD. Physical health, mental health, social support, and parenting were measured for concurrent and discriminant validity of the PHBS. The PHBS scale revealed acceptable to good reliability and validity. It consists of four subscales (i.e., support accessibility, personal belief, emotional readiness, and resource availability). The PHBS found parents prioritized their children's treatments over their own mental health challenges (93.4%), did not have enough time (90.4%), and had financial concerns (85.8%). Parents in rural and remote areas had more limited resources. Findings from our study suggest increasing financial support for the parents seeking mental health services, introducing evidence-based treatments, increasing the availability of healthcare services for parents, and adjusting current services to their needs.

Effectiveness of an Internet-Based and Telephone-Assisted Training for Parents of 4-Year-Old Children With Disruptive Behavior: Implementation Research.

BACKGROUND: There is a lack of effectiveness studies when digital parent training programs are implemented in real-world practice. The efficacy of the internet-based and telephone-assisted Finnish Strongest Families Smart Website (SFSW) parent training intervention on the disruptive behavior of 4-year-old children was studied in a randomized controlled trial setting in Southwest Finland between 2011 and 2013. After that, the intervention was implemented nationwide in child health clinics from 2015 onwards. OBJECTIVE: The main aim of this study was to compare the treatment characteristics and effectiveness of the SFSW parent training intervention between the families who received the intervention when it was implemented as a normal practice in child health clinics and the families who received the same intervention during the randomized controlled trial. METHODS: The implementation group comprised 600 families who were recruited in the SFSW intervention between January 2015 and May 2017 in real-world implementation. The RCT intervention group comprised 232 families who were recruited between October 2011 and November 2013. The same demographic and child and parent measures were collected from both study groups and were compared using linear mixed-effect models for repeated measurements. The child psychopathology and functioning level were measured using the Child Behavior Checklist (CBCL) version 1.5-5 for preschool children, the Inventory of Callous-Unemotional Traits (ICU), and a modified version of the Barkley Home Situations Questionnaire. Parenting skills were measured using the 31-item Parenting Scale and the shorter 21-item Depression, Anxiety and Stress Scale (DASS-21). The estimated child and parent outcomes were adjusted for CBCL externalizing scores at baseline, maternal education, duration of the behavior problems, and paternal age. The baseline measurements of each outcome were used as covariates. RESULTS: The implementation group was more likely to complete the intervention than the RCT intervention group (514/600, 85.7% vs 176/232, 75.9%, respectively; P<.001). There were no significant differences between the implementation and RCT intervention groups with regard to child measures, including CBCL externalizing score (-0.2, 95% CI -1.3 to 1.6; P=.83), total score (-0.7, 95% CI -3.0 to 4.5; P=.70), internalizing score (-0.3, 95% CI -1.0 to 1.6; P=.64), and ICU total score (-0.4, 95% Cl -1.9 to 1.2; P=.64). No significant difference was detected in the Parenting Scale total score (0.0, 95% Cl -0.1 to 0.1; P=.50), while DASS-21 total score differed nearly significantly (2.5, 95% Cl 0.0-5.1; P=.05), indicating better improvement in the implementation group. CONCLUSIONS: The internet-based and telephone-assisted SFSW parent training intervention was effectively implemented in real-world settings. These findings have implications for addressing the unmet needs of children with disruptive behavior problems. Our initiative could also provide a quick socially distanced solution for the considerable mental health impact of the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT01750996; https://clinicaltrials.gov/ct2/show/NCT01750996. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-2458-13-985.

Discovery and replication of cerebral blood flow differences in major depressive disorder.

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.

Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals.

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. A total of 222 unmedicated adults with MDD randomized to receive sertraline (n = 110) or placebo (n = 112) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study completed demographic and clinical assessments, and pretreatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression (HSRD) over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on week-8 depression levels (Fs ≥ 9.67, ps ≤ 0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pretreatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pretreatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment.

Baseline reward processing and ventrostriatal dopamine function are associated with pramipexole response in depression.

The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen's d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.

Deficits of white matter axial diffusivity in bipolar disorder relative to major depressive disorder: No relationship to cerebral perfusion or body mass index.

OBJECTIVE: To compare white matter integrity (WMI) in bipolar disorder (BD) relative to healthy volunteers (HVs) and major depressive disorder (MDD). To determine the relationship of bipolar-specific differences in WMI to cerebral perfusion, body mass index (BMI), and blood pressure as indices of cardiovascular function. METHODS: Thirty-two participants with BD, 44 with MDD, and 41 HV were recruited. All BD and MDD participants were in a major depressive episode, and all but 12 BD participants were medication-free. 64-direction diffusion tensor imaging (DTI) and arterial spin labeling (ASL) sequences were obtained. Tract-based spatial statistics (TBSS) on four DTI indices were employed to distinguish patterns of DTI in BD relative to HV and MDD groups. BMI, blood pressure, and medical histories were also obtained for the BD participants. RESULTS: A cluster of lower axial diffusivity (AD) was found in BD participants in comparison to the HVs in the left posterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and internal capsule. Mean AD in the significant cluster was not associated with cerebral blood flow (CBF) in the region as measured by ASL, and was not associated with BMI or blood pressure. A cluster of lower AD was also found in the BD group when compared to MDD that had spatial overlap with the HV comparison. CONCLUSIONS: The results indicate a deficit of AD in BD when compared to MDD and HV groups. No association between AD values and either cerebral perfusion, BMI, or blood pressure was found in BD.

Understanding the needs of caregivers of persons with dementia: a scoping review.

BACKGROUND: The number of people living with dementia (PWD) is increasing worldwide, corresponding with an increasing number of caregivers for PWD. This study aims to identify and describe the literature surrounding the needs of caregivers of PWD and the solutions identified to meet these needs. METHOD: A literature search was performed in: PsycInfo, Medline, CINAHL, SCIELO and LILACS, January 2007-January 2018. Two independent reviewers evaluated 1,661 abstracts, and full-text screening was subsequently performed for 55 articles. The scoping review consisted of 31 studies, which were evaluated according to sociodemographic characteristics, methodological approach, and caregiver's experiences, realities, and needs. To help extract and organize reported caregiver needs, we used the C.A.R.E. Tool as a guiding framework. RESULTS: Thirty-one studies were identified. The most common needs were related to personal health (58% emotional health; 32% physical health) and receiving help from others (55%). Solutions from the articles reviewed primarily concerned information gaps (55%) and the education/learning needs of caregivers (52%). CONCLUSION: This review identified the needs of caregivers of PWD. Caregivers' personal health emerged as a key area of need, while provision of information was identified as a key area of support. Future studies should explore the changes that occur in needs over the caregiving trajectory and consider comparing caregivers' needs across different countries.

Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits. METHODS: Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics. RESULTS: Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58). CONCLUSIONS: A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.

Harmonization of cortical thickness measurements across scanners and sites.

With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as "scanner effects", can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.

Development and evaluation of a multimodal marker of major depressive disorder.

This study aimed to identify biomarkers of major depressive disorder (MDD), by relating neuroimage-derived measures to binary (MDD/control), ordinal (severe MDD/mild MDD/control), or continuous (depression severity) outcomes. To address MDD heterogeneity, factors (severity of psychic depression, motivation, anxiety, psychosis, and sleep disturbance) were also used as outcomes. A multisite, multimodal imaging (diffusion MRI [dMRI] and structural MRI [sMRI]) cohort (52 controls and 147 MDD patients) and several modeling techniques-penalized logistic regression, random forest, and support vector machine (SVM)-were used. An additional cohort (25 controls and 83 MDD patients) was used for validation. The optimally performing classifier (SVM) had a 26.0% misclassification rate (binary), 52.2 ± 1.69% accuracy (ordinal) and r = .36 correlation coefficient (p < .001, continuous). Using SVM, R2 values for prediction of any MDD factors were <10%. Binary classification in the external data set resulted in 87.95% sensitivity and 32.00% specificity. Though observed classification rates are too low for clinical utility, four image-based features contributed to accuracy across all models and analyses-two dMRI-based measures (average fractional anisotropy in the right cuneus and left insula) and two sMRI-based measures (asymmetry in the volume of the pars triangularis and the cerebellum) and may serve as a priori regions for future analyses. The poor accuracy of classification and predictive results found here reflects current equivocal findings and sheds light on challenges of using these modalities for MDD biomarker identification. Further, this study suggests a paradigm (e.g., multiple classifier evaluation with external validation) for future studies to avoid nongeneralizable results.

A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial.

BACKGROUND: One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials. METHODS: Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probabilities of response and remission. RESULTS: Lower baseline depression severity, younger age, absence of melancholic features or history of physical abuse, less anxious arousal, less anhedonia, less neuroticism, and higher average theta current density in the rostral anterior cingulate predicted a higher likelihood of improvement with placebo. The Bayesian model predicted remission and response with an actionable degree of accuracy (both AUC > 0.73). An interactive calculator was developed predicting the likelihood of placebo response at the individual level. CONCLUSION: Easy-to-measure clinical, behavioral, and electrophysiological assessments can be used to identify placebo responders with a high degree of accuracy. Development of this calculator based on these findings can be used to identify potential placebo responders.

Pioneer Paper: An Accidental Scientist: Chance, Failure, Risk-Taking, and Mentoring.

I never intended to become a scientist. My career developed on the basis of chance happenings, repeated failure, the willingness to take risks and the acceptance and provision of mentoring. My career has included periods of difficulty and shifted back and forth between academic health centers and universities in Canada. Although I have been amply recognized for my successes, my greatest learning has come from my failures. My greatest satisfaction has been in the development, evaluation and dissemination of interventions. The combination of intellectual stimulation and emotional gratification has meant a rewarding career.

Does parental mental health moderate the effect of a telephone and internet-assisted remote parent training for disruptive 4-year-old children?

This study explores the moderators affecting the success of an Internet-based and telephone assisted remote parent training intervention and compares them to an educational control group. We prospectively identified 464 parents who reported at a health check that their 4-year-old children showed elevated levels of externalizing behavior. The moderators explored included parental attention deficit and hyperactivity disorder (ADHD) and parental distress. The dependent variables were child externalization scores and self-reported parenting skills. The measures were completed at baseline, six and 12-months follow-up. The 232 families randomized to active treatment received 11 Internet-based training sessions with weekly phone calls from a coach. The other 232 families had access to a website that provided general positive parenting advice and one 45-minute phone-call from a coach. Using hierarchical linear models, we explored if the parental ADHD or parental distress modified the treatment effects on child externalizing behavior or parenting skills. The results showed that none of the independent variables moderated intervention effects on child externalizing behavior or parenting skills. The lack of significant moderator effects could have been due to the treatment's personalization, the format's flexibility and adaptability to when and how the parents wanted to complete the sessions or the relatively low levels of ADHD and parental distress among the participants.

Do mothers enjoy playing sensitively with their infants?

BACKGROUND: Early sensitive caregiver-infant interactions form an important foundation for infant development. Although mutual enjoyment is thought to motivate proximity and continued interactions, there is no empirical evidence that mothers enjoy interacting and behaving sensitively. Research to date has focused on the influence of stable/pathological maternal negative emotions on parenting, with parenting often assessed on one occasion only. Therefore, little is known about what accounts for the variability in sensitivity across interactions. OBJECTIVES: The objective of the present study was to evaluate what makes sensitivity reinforcing to typical mothers and thus more likely to be repeated. We hypothesised that 15- to 28-week-old infants' positive and active engagement would mediate the relationship between their mothers' sensitivity and change in emotion state from pre- to post-interaction. METHOD: Using a naturalistic, repeated-measures design, 390 unique interactions from 49 mothers (mean age: M = 29.90 years, SD = 5.41) and their infants (25 female; mean age: M = 22.53 weeks, SD = 3.77) were rated using the Global Rating Scales of Mother-Infant Interaction. Mothers completed measures of their own mood (Profile of Mood States - 15) before and after each interaction. RESULTS: Mothers reported feeling slightly less negative and more vigorous after interacting with their infants. The more sensitively they behaved, the more engaged their infants were and the more vigorous the mothers felt thereafter. Infant engagement did not mediate the relationship between sensitivity and change in negative emotion or in vigour. CONCLUSIONS: Results suggest that upon behaving sensitively, mothers feel more vigorous regardless of their infants' engagement.

Parental and child factors associated with participation in a randomised control trial of an Internet-assisted parent training programme.

BACKGROUND: Parental training is an effective way to treat and prevent children's conduct problems, but knowledge of who participates in such initiatives is limited. METHOD: This study examined child and family factors associated with participation in an Internet-assisted parent training programme. The parents of 4-year-old children with high levels of disruptive behaviour in a region of Finland were offered the opportunity to participate in a randomised controlled trial of the Strongest Families Smart Website intervention (SFSW). The participants and nonparticipants were compared using the Strengths and Difficulties Questionnaire (SDQ), duration of child problems and information about family demographics, which were routinely collected prior to randomisation to the SFSW and control group. RESULTS: We found that 464 (64.5%) of the 709 parents of children fulfilling the screening criteria, participated. In the multivariable analysis, nonparticipation was most strongly associated with a child only having minor difficulties [odds ratio (OR): 2.1; 95% confidence interval (CI): 1.5-3.0] and a shorter duration of problems, for less than 12 months (OR: 1.7, 95% CI: 1.2-2.5), after controlling for other child factors. Nonparticipation was significantly associated with mothers spending a shorter time in the education system (OR: 1.6, 95% CI: 1.2-2.3) after controlling for other parental factors. CONCLUSIONS: A larger percentage of parents of children with longer lasting and more severe problems seemed to be motivated to participate in this remote parent training programme. Future studies on how to encourage parents with shorter duration of education to participate in early intervention programmes are warranted.

White matter tract integrity is associated with antidepressant response to lurasidone in bipolar depression.

OBJECTIVES: Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter disruptions may be associated with resistance to antidepressant medication, but this has never been investigated in a prospective study using a Food and Drug Administration (FDA)-approved medication. METHODS: Eighteen subjects with bipolar disorder who were in a major depressive episode and off all medications were recruited. Magnetic resonance imaging was acquired using a 64-direction diffusion tensor imaging sequence on a 3T scanner. Subjects were treated with 8 weeks of open-label lurasidone. The Montgomrey-Asberg Depression Rating Scale (MADRS) was completed weekly. Tract-Based Spatial Statistics were utilized to perform a regression analysis of fractional anisotropy (FA) data with treatment outcome as assessed by percent change in MADRS as a regressor while controlling for age and sex, using a threshold of P (threshold-free cluster enhancement-corrected) <.05. RESULTS: FA was positively correlated with antidepressant treatment response in multiple regions of the mean FA skeleton bilaterally, including tracts in the frontal and parietal lobes. CONCLUSIONS: Greater disruptions in the white matter tracts in bipolar disorder were associated with poorer antidepressant response to lurasidone. The disruptions may potentially indicate treatment with a different antidepressant medication class. These results are limited by the open-label study design, sample size and lack of a healthy control group.