Faculty Bibliography

Theories of posttraumatic stress disorder (PTSD) highlight the role of cognitive and behavioral factors in its development, maintenance, and treatment. This study investigated the relationship between changes in factors specified in Ehlers and Clark's (2000) model of PTSD and PTSD symptom change in 217 patients with PTSD who were treated with cognitive therapy for PTSD (CT-PTSD) in routine clinical care. Bivariate latent change score models (LCSM) of session-by-session changes in self-report measures showed that changes in PTSD symptoms were preceded by changes in negative appraisals, flashback characteristics of unwanted memories, safety behaviours, and unhelpful responses to intrusions, but not vice versa. For changes in trauma memory disorganization and PTSD symptoms we found a bidirectional association. This study provides evidence that cognitive and behavioral processes proposed in theoretical models of PTSD play a key role in driving symptom improvement during CT-PTSD.

Behavioral treatment, stimulants, and their combination are the recommended treatments for childhood attention-deficit/hyperactivity disorder (ADHD). The current study utilizes within-subjects manipulations of multiple doses of methylphenidate (placebo, 0.15, 0.30, and 0.60 mg/kg/dose t.i.d.) and intensities of behavioral modification (no, low, and high intensity) in the summer treatment program (STP) and home settings. Outcomes are evaluated in the home setting. Participants were 153 children (ages 5-12) diagnosed with ADHD. In alignment with experimental conditions implemented during the STP day, parents implemented behavioral modification levels in three-week intervals, child medication status varied daily, and the orders were randomized. Parents provided daily reports of child behavior, impairment, and symptoms and self-reported parenting stress and self-efficacy. At the end of the study, parents reported treatment preferences. Stimulant medication led to significant improvements across all outcome variables with higher doses resulting in greater improvement. Behavioral treatment significantly improved child individualized goal attainment, symptoms, and impairment in the home setting and parenting stress and self-efficacy. Effect sizes indicate that behavioral treatment combined with a low-medium dose (0.15 or 0.30 mg/kg/dose) of medication results in equivalent or superior outcomes compared to a higher dose (0.60 mg/kg/dose) of medication alone. This pattern was seen across outcomes. Parents overwhelmingly reported preferring treatment with a behavioral component as a first-choice treatment (99%). Results underscore the need to consider dosing as well as parent preference when utilizing combined treatment approaches. This study provides further evidence that combining behavioral treatment and stimulant medication may reduce the stimulant dose needed for beneficial effects.

BACKGROUND:Sleep difficulties are common in children with attention-deficit/hyperactivity disorder (ADHD). However, sleep problems are multifaceted and little is known about the variation in sleep difficulties across children with ADHD. We examined the profiles of sleep difficulties in children with ADHD and associated clinical factors (e.g. co-occurring mental health conditions, stimulant use and parent mental health). METHODS:Data from two harmonised studies of children with ADHD (total: N = 392, ages 5-13 years) were used. Parents completed measures of children's sleep, co-occurring mental health conditions and their own mental health. Both parents and teachers completed measures of child ADHD symptoms and emotional and conduct symptoms. Latent profile analysis was used to identify sleep profiles, and multinomial logistic regression assessed clinical correlates of the groups. RESULTS:Five sleep profiles were identified: (a) insomnia/delayed sleep phase (36%), (b) generalised sleep difficulties at sleep onset and overnight (25%), (c) high anxious/bedtime resistance difficulties (11%), (d) overnight sleep difficulties including obstructive sleep apnoea and parasomnias (5%) and (e) no sleep difficulties (22%). Compared with the group without sleep difficulties, the generalised, anxious/bedtime resistance and insomnia/delayed sleep phase sleep had greater parent-reported emotional and conduct symptoms, co-occurring anxiety and increased parent mental health difficulties. The generalised and anxious/bedtime resistance groups also had greater parent-reported ADHD symptoms, with the anxious/bedtime resistance sleep group also having more frequent co-occurring depression and teacher-reported emotional symptoms. CONCLUSIONS:The sleep difficulties experienced by children with ADHD are varied. Supports to help children with ADHD need to consider the particular profiles of sleep difficulties experienced and broader clinical characteristics. Tailored intervention approaches are likely needed (including a need to address parent mental health).

Treatment gaps in meeting the neuropsychological needs of young adult (YA) cancer survivors can be attributed to several clinical and systemic reasons. Access to neurocognitive care can be increased through the effective integration of neuropsychological monitoring and intervention in survivorship care. In this brief report, we aim to compare the efficacy of a brief neuropsychological screener (DIVERGT) in meeting the assessment and referral needs of pediatric and YA cancer survivors (n = 40) as part of a wellness and survivorship clinic. Participants (n = 40) were patients who presented to a pediatric oncology survivorship clinic over the span of 15 months.

OBJECTIVE:Childhood maltreatment (CM) is a potent risk factor for developing psychopathology later in life. Accumulating research suggests that the influence is not limited to the exposed individual but may also be transmitted across generations. In this study, we examine the effect of CM in pregnant women on fetal amygdala-cortical function, prior to postnatal influences. METHOD/METHODS:Healthy pregnant women (N = 89) completed fetal resting-state functional magnetic resonance imaging (rsfMRI) scans between the late second trimester and birth. Women were primarily from low socioeconomic status households with relatively high CM. Mothers completed questionnaires prospectively evaluating prenatal psychosocial health and retrospectively evaluating trauma from their own childhood. Voxelwise functional connectivity was calculated from bilateral amygdala masks. RESULTS:Connectivity of the amygdala network was relatively higher to left frontal areas (prefrontal cortex and premotor) and relatively lower to right premotor area and brainstem areas in fetuses of mothers exposed to higher CM. These associations persisted after controlling for maternal socioeconomic status, maternal prenatal distress, measures of fetal motion, and gestational age at the time of scan and at birth. CONCLUSION/CONCLUSIONS:Pregnant women's experiences of CM are associated with offspring brain development in utero. The strongest effects were found in the left hemisphere, potentially indicating lateralization of the effects of maternal CM on the fetal brain. This study suggests that the time frame of the Developmental Origins of Health and Disease research should be extended to exposures from mothers' childhood, and indicates that the intergenerational transmission of trauma may occur prior to birth.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I² statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.

Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.