Brexanolone Treatment in a Real-World Patient Population: A Case Series and Pilot Feasibility Study of Precision Neuroimaging.

PURPOSE/BACKGROUND: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown. METHODS/PROCEDURES: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone. FINDINGS/RESULTS: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores. IMPLICATIONS/CONCLUSIONS: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.

Nurse home visitation with vulnerable families in rural areas: A qualitative case file review.

OBJECTIVE: Nurse home visiting may address challenges and resource disparities that threaten maternal and infant well-being in rural areas, but little is known about United States' program implementation. This qualitative study explored how family and community characteristics affected rural nurse home visiting. SAMPLE: The sample for content analysis included families beginning services in 2010-2011 living in the rural counties with the highest caseloads (433 families). DESIGN: Electronic nurse home visiting case files from three rural counties were analyzed using a content analysis approach. The partner agency provided input on key constructs of interest but independent coding was also done to capture additional themes. Quantitative county level data and comments from member checking informed interpretation. Member checking included individual nurses serving the selected counties (n = 3) and input from an agency level supervisory meeting for validation. RESULTS: Concerns of families served (e.g., mental health) may not be unique to rural areas, but challenges to accessing resources and constellation of needs were. Nurses adapted engagement and service strategies to meet these needs. CONCLUSION: Agencies serving rural areas should allocate resources and adapt training to support nurses based on unique community profiles. More research on rural nurse home visiting practice and outcomes is needed.

Parental Warmth and Risks of Substance Use in Children with Attention-Deficit/Hyperactivity Disorder: Findings from a 10-12 Year Longitudinal Investigation.

OBJECTIVE: The study examined factors in the risk trajectory for Substance Use Disorder (SUD) over a 10-12 year period in children with ADHD. METHOD: N=145 children between the ages of 7 and 16 with ADHD and healthy controls were assessed every 2 years for 10-12 years as part of a larger, longitudinal investigation. Onset of substance use disorder was examined using Cox proportional hazards modeling, and included child and parent psychopathology, and parental warmth as well as other key factors. RESULTS: Low paternal warmth and maternal SUD were predictors of SUD in n=59 ADHD participants after adjusting for gender, child ODD, paternal SUD, maternal/paternal ADHD, maternal/paternal major depressive disorder (MDD), maternal/paternal anxiety, and low maternal warmth in the Cox model. CONCLUSIONS: Longitudinal study findings suggest that in addition to the established risk of ADHD and maternal SUD in development of child SUD, low paternal warmth is also associated with onset of SUD. This was evident after controlling for pertinent parent and child psychopathology. These findings suggest that paternal warmth warrants further investigation as a key target for novel interventions to prevent SUD in children with ADHD. More focused investigations examining paternal parenting factors in addition to parent and child psychopathology in the risk trajectory from ADHD to SUD are now warranted.

Reducing Abuse and Neglect Recurrence Among Young Foster Children Reunified With Their Families.

BACKGROUND AND OBJECTIVES: Child maltreatment (CM) is a recurrent adverse life event known to cause enduring psychiatric impairment throughout life. For young children in protective custody for a first episode of CM, specialized court-coordinated intervention to optimize reunification has shown promise for preventing CM recidivism, with case series documenting short-term successes. METHODS: We tracked 10-year (Nov 2011-March 2022) court re-entry outcomes in a cohort of 272 young children, birth to six years, reunited with their families following placement in protective custody and court referral to the SYNCHRONY Project, a voluntary clinical service providing Incredible YearsTM parenting education, parental psychiatric care, and serial dyadic clinical evaluation to inform medical recommendations on safety for visitation and reunification. Re-entry was operationalized as rereferral to any Missouri Court and proportions compared with contemporaneous State and national data. RESULTS: SYNCHRONY-enrolled/reunified children experienced frequencies of guardianship (22%) and reunification (46%), in keeping with Missouri averages. In these categories, 3.4% and 7.1% respectively were re-referred to the Court over the 10-year follow-up. In care as usual nationally for this age group, the re-referral proportions are 18% (OR 7.5, P < .0001) and 35% (OR 6.1, P < .0001) respectively. In care as usual in Missouri across all ages, the re-referral proportion is 16% (odds ratio [OR] 3.09, P < .0001). CONCLUSIONS: Judicious implementation of evidence-based parenting education, 2-generation psychiatric care, and clinical consultation were associated with marked reduction in court re-entry versus care-as-usual and warrant consideration in intervention standards for young children in foster care.

Documenting Opportunity for Systematic Identification and Mitigation of Risk for Child Maltreatment.

This is a communication of preliminary data as a matter of priority in relation to Clinical Trials protocol ID 2018110118; NCT04438161. This protocol represents, to our knowledge, a first-ever attempt to convert an epidemiologic discovery on risk for child maltreatment (CM) into a readily deployable modification of obstetrical practice designed to offset risk for CM and its psychiatric sequelae. Before1 and during the coronavirus disease 2019 (COVID-19 pandemic),2,3 CM has incurred a burden of epidemic proportions to U.S. children, with confirmed incidents occurring on the order of 12% of the population. Wu et al.4 and Putnam-Hornstein and Needell5 previously established that profiles of risk ascertained exclusively from birth records identified specific groups of newborns at highly elevated risk for official-report CM. For example, infants with the joint characteristics of low birth weight, more than 2 siblings, and maternal characteristics of being unmarried, on Medicaid, and smoking during pregnancy (ascertained separately) were found to have a 7-fold risk for maltreatment compared with the population average.4 Putnam-Hornstein and Needell showed that newborns with 3 or more risk factors ascertained from birth records (including any of the above, delayed prenatal care, less than high school maternal education, and maternal age less than 24 years) comprised 15% of an epidemiologic birth cohort but accounted for more than half of all the children in the cohort who experienced substantiated official-report maltreatment by the age of 5 years. This study explored whether prospective implementation of birth records screening in an urban obstetrical service recapitulated the association with CM observed in an epidemiologic context and whether families in higher echelons of risk (ascertained in this manner through birth records) could be prospectively engaged in supportive interventions of demonstrated effect in reducing the occurrence of CM. This work follows on promising efforts elsewhere to use birth records information to prioritize support services for young families,6 though such innovations have yet to be systematically incorporated into obstetrical or newborn medical services of U.S. health systems.

An overview of the use of antidepressants in children and adolescents.

OBJECTIVE: To provide a relevant, evidence-based review of antidepressant use in children for primary care providers. METHOD: Selected published studies, reviews, and guidelines are synthesized. RESULTS: Best evidence supports combination treatment (Selective Serotonin Reuptake Inhibitor plus Cognitive Behavioral Therapy) for Major Depressive Disorder (MDD) and Anxiety disorders. Data for efficacious uses of antidepressants in Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism are scant but emerging. CONCLUSIONS: Despite recent FDA warnings, antidepressants are beneficial for a variety of childhood disorders (including MDD, Anxiety Disorders, ADHD, and Autism).

A Randomized Trial of Home Visitation for CPS-Involved Families: The Moderating Impact of Maternal Depression and CPS History.

Home visitation (HV) interventions may hold promise to improve parenting and prevent child maltreatment recidivism in families reported to child protective services (CPS) with young children, but this has rarely been studied. Findings are presented from an 18-month randomized controlled trial in which intact families ( N = 122) with at least one CPS report were provided with a facilitated connection to a paraprofessional evidence-based HV program or usual care services from child protection. Results are reported for changes in maternal stress, depression, and social support outcomes and repeat reports to CPS. No significant changes were found in maternal outcomes by group. Among nondepressed mothers or families without multiple CPS reports prior to study enrollment, HV was associated with a significantly lower likelihood of CPS report recidivism. These results indicate potential for HV to prevent maltreatment recidivism but suggest that higher intensity intervention is warranted for mothers exhibiting significant depressive symptoms or families with extensive CPS histories.

Three clinical cases of DSM-IV mania symptoms in preschoolers.

Despite a growing body of empirical data describing the discriminant and longitudinal validity of mania in older children, little research has been conducted investigating the presence of mania symptoms in preschool-aged children. This report describes three cases of preschool children (ages 3.6 to 5.2) who presented to a subspecialty mental health clinic manifesting age-adjusted mania-like symptoms. Developmental manifestations of DSM-IV mania symptoms described include grandiosity, hypersexuality, elation, racing thoughts, and decreased need for sleep. These symptoms have been shown to be highly specific to distinguish bipolar disorder from attention deficit hyperactivity disorder (ADHD) in older children. Possible manifestations of mood cycling are also described. Clinical observations, parental reports, and related family mental health history are reviewed.

Disruptive Behavior Disorders in Children 0 to 6 Years Old.

Disruptive behavior disorders (DBDs), specifically oppositional defiant disorder and conduct disorder, are common, serious, and treatable conditions among preschoolers. DBDs are marked by frequent aggression, deceitfulness, and defiance, and often persist through the lifespan. Exposure to harsh or inconsistent parenting, as frequently seen with parental depression and stress, increases DBD risk. Candidate genes that may increase DBD risk in the presence of childhood adversity have also been identified, but more research is needed. Neurophysiologic and structural correlates with DBD also exist. Parent management training programs, focusing on increasing parenting competence and confidence, are the gold standard treatment of preschool DBDs.

Attention Deficit Hyperactivity Disorder in Preschool-Age Children.

Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition.

Trajectories of ADHD severity over 10 years from childhood into adulthood.

The study examined unique trajectories of ADHD severity from childhood (7-16 yo at baseline) through adulthood in a sample of ADHD, bipolar and healthy subjects. Comorbid disorders and temperament were examined as correlates of course of ADHD. N = 81 participants with an ADHD diagnosis, ascertained as a comparison group in a study of bipolar disorder (BP-I), were followed over a 10-year period. Growth mixture modeling (GMM) of ADHD severity was used to investigate trajectories of ADHD severity over 10 years. GMM revealed four trajectories in the N = 251 participants included in these analyses. A persisting high ADHD trajectory had the highest rates of comorbid major depressive disorder and oppositional defiant disorder. This persisting high ADHD group also had higher fantasy and lower persistence and self-directedness compared with those who displayed a pattern of decreasing ADHD symptoms over time. Psychopathologic features that characterize divergent trajectories of ADHD into adulthood are elucidated, and additional, larger studies are warranted.

Nonverbal Reasoning in Preschool Children: Investigating the Putative Risk of Secondhand Smoke Exposure and Attention-Deficit/Hyperactivity Disorder as a Mediator.

BACKGROUND: Exposure to secondhand smoke (SHS) has been found to be associated with cognitive deficits in children. However, relatively little is known about the relationship between SHS exposure, cognitive deficits, and smoking-related psychopathology, specifically attention-deficit/hyperactivity disorder (ADHD) and externalizing disorders such as conduct disorder (CD) and oppositional defiant disorder (ODD) in preschool children. METHODS: Children (n = 54) between the ages of 4 and 6 years from a comprehensive, longitudinal study of preschool emotional development were included in this study. Each child's primary caregiver completed questionnaires and interviews related to childhood psychopathology. SHS exposure was estimated with the use of saliva cotinine values. RESULTS: After adjustment for sociodemographic factors (e.g., age, gender, an income-to-needs ratio) and for ADHD, CD, and ODD symptoms, exposure to SHS was found to be negatively associated with preschool children's nonverbal reasoning skills. Exposure to SHS continued to be negatively associated with nonverbal reasoning skills after adjustment for maternal education, maternal smoking during pregnancy, and maternal reports of exposure to SHS during pregnancy in separate models. CONCLUSIONS: Children who grow up in an environment with adults who smoke are vulnerable to several social and environmental risk factors. The findings of this study suggest that exposure to SHS during early childhood should also be considered as a potential variable in the risk trajectory and as a marker of other associated risks when formulating public health intervention and prevention strategies.

Secondhand Smoke Exposure and Severity of Attention-Deficit/Hyperactivity Disorder in Preschoolers: A Pilot Investigation.

BACKGROUND: Less is known about the effects of secondhand smoke (SHS) on mental health as compared with other medical disorders. OBJECTIVE: The aims of this study were to examine the following: 1) the association of SHS exposure with childhood attention-deficit/hyperactivity (ADHD) and disruptive disorders; and 2) the association of maternal recall of a child's SHS exposure and that child's exposure as measured by bioassay. METHOD: Sixty children had their saliva collected and assayed for cotinine when they were 4 years old and again when they were 6 years old. Phone interview data were collected to assess maternal recall of the children's exposure to SHS at these ages. The children were assessed annually for ADHD and disruptive disorders. Repeated measures analysis of exposure level by child characteristics was performed. RESULTS: Greater ADHD and conduct disorder severity scores were associated with greater child smoke exposure (ADHD severity, P = .043; conduct disorder severity, P = .035). A large proportion of mothers reported that their children had no exposure to SHS, despite high levels of measured cotinine in the children's saliva. CONCLUSIONS: An association between SHS exposure and ADHD and conduct disorder symptoms was found. Children and parents may benefit from parent education regarding the deleterious effects of SHS.

Parenting practices in pregnancy smokers compared to non smokers.

BACKGROUND: The present investigation compared parenting practices in a sample of preschoolers whose mothers reported smoking during pregnancy versus those who did not. METHODS: A sample of n = 216, 3.0- to 5.11-year-old children, participants in an ongoing longitudinal study, was separated into those reportedly exposed to smoking in utero and those who were not. Parenting practices were compared between the two groups, using T-tests and exact logistic regressions. Multiple linear regressions and multivariate logistic regressions were used to examine the association between smoking status and parenting, controlling for variables also known to be associated with parenting practices. RESULTS: Current study findings suggest that smoking during pregnancy is associated with harsh parenting practices. CONCLUSIONS: Study results highlight the possible role of parenting in disruptive outcomes well-known in toddlers exposed to nicotine in utero and have implications for targeting early interventions in these populations.

Preschool onset attention-deficit/hyperactivity disorder: course and predictors of stability over 24 months.

OBJECTIVE: The present study examined the course of ADHD over 24 months in a preschool population. METHOD: n=48 preschoolers with ADHD, aged 3.0-5.11 years, subjects included in a larger sample of preschoolers with depression and other disorders (n=306) were comprehensively assessed at 3 annual time points over 24 months in a prospective longitudinal follow-up study. RESULTS: Baseline diagnoses of preschool MDD, ODD, and CD were risk factors for ADHD diagnosis over 24 months in this preschool population. Among older preschoolers and after controlling for key demographic variables, ADHD predicted later ADHD diagnosis, along with other significant risk factors - baseline diagnosis of ODD, and/or family history of disruptive disorders, and stressful life events. CONCLUSIONS: ADHD showed greater homotypic continuity at later rather than earlier preschool ages. Other disruptive comorbidities also emerged as key predictors of stable ADHD course. Study findings may help to inform which preschool ADHD populations to target for early intervention. Larger sample sizes are needed to confirm these findings and to further explore the stability, course, and predictors of outcome of preschool onset ADHD.

Internalizing disorders in early childhood: a review of depressive and anxiety disorders.

This article reviews the use of the broad category of internalizing disorders and data on young children using this definition. It also reviews the emerging support for more specific internalizing diagnoses in very young children. The current empiric database on nosology and treatment of mood and anxiety disorders in young children is examined, and a clinical case example is included. Identification of recent advances in the understanding and treatment of anxiety disorders in young children and areas in which future studies are needed also are explored.

Attention-deficit/hyperactivity disorder in preschool children: an investigation of validation based on visual attention performance.

OBJECTIVES: The present study compared the performance of preschoolers who met Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) criteria for attention-deficit/hyperactivity disorder (ADHD) to those who did not meet these criteria on a test of visual attention. The aim was to investigate whether attentional impairments in preschoolers with DSM-IV ADHD could be detected, informing the nosology of preschool ADHD. METHODS: A demographically diverse sample of n = 304 preschoolers, aged 3.0-5.11 years, was separated into two diagnostic groups: Those who met DSM-IV ADHD criteria and those who did not. Subtypes of ADHD were also examined. Parametric and nonparametric analyses were used to examine performance scores on accuracy, including errors of omission and commission. The sample was stratified into 3, 4-, and 5-year-old age groups. RESULTS: Overall ADHD but not subtype-specific ADHD was associated with poor performance accuracy in the 4-year-old age group after controlling for gender and age. CONCLUSIONS: Attentional impairments detected only in the 4-year-old age group suggest that DSM-IV ADHD criteria are useful and valid at this age. Study findings suggest modification to the DSM criteria may be needed for children younger than 4 and that further investigation of this issue using performance-based measures is now warranted.

Preschool bipolar disorder.

Although some empirical work has now been added to the larger body of case material, preschool bipolar disorder (BPD) remains a highly ambiguous diagnostic area. This is notable in the context of the significant progress that has been made in many other areas of psychopathology in the preschool period. While there is a need for well controlled empirical investigations in this area, a small but growing body of empirical literature suggests that some form of the disorder may arise as early as age 3. The need for large scale and focused studies of this issue is underscored by the high and increasing rates of prescriptions of atypical antipsychotics and other mood stabilizing agents for preschool children with presumptive clinical diagnosis of BPD or a related variant. Clarifying the nosology of preschool BPD may also be important to better understand of the developmental psychopathology of the disorder during childhood. Data elucidating this developmental trajectory could then inform the design of earlier potentially preventive interventions that may have implications for the disorder across the lifespan.

Preschool depression: homotypic continuity and course over 24 months.

CONTEXT: Childhood depression is a serious and relapsing psychiatric disorder. However, to date studies have focused mostly on children aged 6 years and older. Validation for depression in preschool children has been provided by 2 independent study samples. While several studies have demonstrated stability and poor outcomes of internalizing symptoms in preschoolers, there has not yet been longitudinal data available to inform the course of preschool depression and whether it shows homotypic continuity into early childhood. OBJECTIVE: To examine the 24-month course of preschool depression and whether it showed homotypic vs heterotypic continuity or was a developmentally transient phenomenon. DESIGN: Blindly rated, prospective, 24-month, longitudinal follow-up study. SETTING: Community sites. Patients Three hundred six preschoolers aged 3 to 6 years recruited from community sites and oversampled for symptoms of depression. Main Outcome Measure Recurrence/stability of depression and predictors of course. RESULTS: Preschoolers with depression at baseline had the highest likelihood of subsequent depression 12 and/or 24 months later compared with preschoolers with no baseline disorder and with those who had other psychiatric disorders. Preschoolers with depression at baseline were more likely to have later depression rather than other psychiatric disorders. Findings from a logistic regression analysis indicated that when controlling for demographic variables, risk factors, and comorbid disorders, depression during the preschool period and family history of affective disorders were the most robust and significant predictors of later depression. CONCLUSIONS: Preschool depression, similar to childhood depression, is not a developmentally transient syndrome but rather shows chronicity and/or recurrence. Homotypic continuity of preschool MDD during a 24-month period was found. These results underscore the clinical and public health importance of identification of depression as early as preschool. Further follow-up of preschoolers with depression is warranted to inform the longitudinal course throughout childhood.