Faculty Bibliography

Objective: To examine the impact of reinforcement on reaction time (RT) and RT variability (RT standard deviation [RTSD]) in preschoolers with ADHD with and without oppositional defiant disorder (ODD), and a typically developing (TD) comparison group. Method: Participants were administered a computerized task consisting of two conditions: simple RT (SRT) and reinforced SRT (SRTr). Data were analyzed using two-way (Group x Condition) mixed ANOVAs and followed-up using pairwise comparisons. Results: RTs were significantly shorter and less variable during the SRTr than the SRT condition. A significant Group x Condition interaction was observed for RTSD (F= 3.38, p < .05); post hoc analyses indicated that the RTSD of the ADHD + ODD group was significantly more variable than that of the TD group during the SRT condition (F = 4.81, p < .05). However, their RTSD was statistically indistinguishable from the other groups during the SRTr condition. Conclusion: Preschoolers who are oppositional/defiant and hyperactive are the most responsive to feedback/reward. (J. of Att. Dis. 2011; XX(X) 1-XX).

Adolescent depression is a prevalent and disabling condition resulting in emotional suffering and social and educational dysfunction. Care for adolescent depression is suboptimal and could be improved through the development and use of quality indicators (QIs). This article reports on the development of a care pathway and QIs for the primary and specialty care management of adolescent depression from case identification through symptom remission. It presents evidence from a review of adolescent clinical practice guidelines and research literature to support QIs at critical nodes in the pathway, and describes implications for practice based on existing evidence. Barriers to measure development are identified, including gaps in empirical evidence, and a research agenda is suggested.

OBJECTIVE: Pregnant adolescents have high rates of poor birth outcomes, but the causes are unclear. We present a prospective, longitudinal study of pregnant adolescents assessing associations between maternal psychobiological stress indices and offspring gestational age at birth and birthweight. METHOD: Healthy nulliparous pregnant adolescents were recruited (n=205) and followed during pregnancy. Ambulatory assessments over 24h of perceived psychological stress (collected every 30 min) and salivary cortisol (6 samples) and a summary questionnaire, the Perceived Stress Scale, were collected at three time points (13-16, 24-27, and 34-37 gestational weeks). Corticotropin-releasing hormone, C-reactive protein, and interleukin 6 were assayed from blood taken at the latter 2 sessions. A final sample of 119 participants was selected for analyses. RESULTS: The ambulatory assessment of perceived psychological stress was positively correlated with the Perceived Stress Scale (r=.20, p=.03) but neither was associated with any of the biological assays (all ps>.20). Based on backward selection regression models that included all stress variables and relevant covariates, the ambulatory assessments of perceived psychological stress and cortisol - though not the Perceived Stress Scale - were negatively associated with gestational age at birth (F(4, 107)=3.38, p=.01) while cortisol was negatively related to birthweight (F(5, 107)=14.83, p<.0001). CONCLUSIONS: Targeted interventions to reduce psychological and biological indicators of heightened stress during pregnancy may have positive public health benefits for the offspring given the associations of shortened gestation and lower birthweight with risk for poor mental and physical health outcomes.

Despite advances in the treatment of schizophrenia over the past half-century, the illness is frequently associated with a poor outcome. This is principally related to the late identification and intervention in the course of the illness by which time patients have experienced a substantial amount of socio-occupational decline that can be difficult to reverse. The emphasis has therefore shifted to defining psychosis-risk syndromes and evaluating treatments that can prevent transition to psychosis in these ultra-high risk groups. To consider the appropriateness of adding psychosis risk syndrome to our diagnostic nomenclature, the psychotic disorders work group extensively reviewed all available data, consulted a range of experts, and carefully considered the variety of expert and public comments on the topic. It was clear that reliable methods were available to define a syndrome characterized by sub-threshold psychotic symptoms (in severity or duration) and which was associated with a very significant increase in the risk of development of a full-fledged psychotic disorder (schizophrenia spectrum, psychotic mood disorder, and other psychotic disorders) within the next year. At the same time, the majority of individuals with "attenuated psychotic symptoms" had one or more other current psychiatric comorbid conditions (usually mood or anxiety disorders, substance use disorder; Fusar-Poli 2012) and exhibited a range of psychiatric outcomes other than conversion to psychosis (significant proportions either fully recover or develop some other psychiatric disorder, with a minority developing a psychotic disorder). Although the reliability of the diagnosis is well established in academic and research settings, it was found to be less so in community and other clinical settings. Furthermore, the nosological relationship of attenuated psychosis syndrome (APS) to schizotypal personality disorder and other psychiatric conditions was unclear. Further study will hopefully resolve these questions. The work group decided to recommend the inclusion of attenuated psychosis syndrome as a category in the appendix (Section 3) of DSM-5 as a condition for further study.

Abstract Background: The perinatal period provides unique opportunities to identify and intervene with the co-occurrence of perinatal depression, intimate partner violence (IPV), and substance use problems. Psychosocial screening recommended for women seen in maternal child health settings tends to target single rather than multiple risk factors; there is limited research examining the co-occurrence of these issues especially in racially and ethnically diverse women across the perinatal period. These analyses explore the relationships of sociodemographic, psychosocial, and behavioral characteristics in a large, diverse sample of women. Method: Women receiving perinatal services at routinely scheduled visits, including the 6-week postpartum visit, were recruited from 10 community obstetric/gynecologic clinics. Data were collected on perinatal depression, IPV, maternal substance use, and sociodemographic characteristics by bilingual, bicultural research assistants. Results: A total of 1868 women were screened, 1526 (82%) Latina, 1099 (58.8%) interviewed in Spanish; 20.4% (n=382) screened positive for depressive symptoms based on an Edinburgh Postnatal Depression Scale score of 10 or above, 20.9% reported harmful drinking, 4.3% reported drug use, 23% reported substance use problems, and 3.5% reported current or recent IPV. Women who were Black, Asian, Pacific Islander, or other race/ethnicity had greater odds for depressive symptoms relative to women who were Hispanic or Latino (odds ratio [OR]=1.81, p=0.005). Women reporting substance use problems (OR=2.37, p<0.0001) and IPV (OR=3.98, p<0.0001) had higher odds for depressive symptoms. Conclusion: In a predominately Latina sample, 1 in 5 mothers (20.4%) screened positive for depressive symptoms and over one third (36.7%) reported one or more psychosocial issues during the perinatal period. Screening for multiple risk factors rather than just one can help clinicians tailor interventions for the successful management of psychosocial issues.

OBJECTIVE: The current study evaluates a treatment intervention developed with the goal of reducing symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants. METHODS: A total of 105 mothers of preterm infants (25-34 weeks' gestational age; >600 g) were randomized to receive a 6-session intervention developed to target parental trauma as well as facilitate infant redefinition (n = 62) or to an active comparison group (n = 43). Mothers in the intervention group received a combination of trauma-focused treatments, including psychoeducation, cognitive restructuring, progressive muscle relaxation, and development of their trauma narrative. The intervention also incorporated material targeting infant redefinition, defined as the process of changing the mother's negative perceptions of her infant and the parenting experience. RESULTS: Mothers in the intervention group reported a greater reduction in both trauma symptoms (Cohen's d = 0.41, P = .023) and depression (Cohen's d = 0.59, P < .001) compared with the comparison group. Patients under both conditions improved significantly in terms of anxiety, with no differences between groups. Results of the moderator analysis showed that mothers with higher ratings of baseline NICU stress benefited more from the intervention compared with mothers who had lower ratings (P = .036). CONCLUSIONS: This short, highly manualized intervention for mothers of preterm infants statistically significantly reduced symptoms of trauma and depression. The intervention is feasible, can be delivered with fidelity, and has high ratings of maternal satisfaction. Given that improvements in mothers' distress may lead to improved infant outcomes, this intervention has the potential for a high public health impact.

OBJECTIVE This study evaluated demographic and clinical correlates and predictors of polypharmacy at baseline assessment in the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a cohort of children age six to 12 years at their first outpatient mental health visit at university-affiliated clinics. METHODS Use of medications in four classes (mood stabilizers, antidepressants, antipsychotics, and stimulants) was assessed, and the Service Assessment for Children and Adolescents classified lifetime and current use of various services. Analyses examined correlates of the number of medications prescribed and odds of polypharmacy, defined as use of two or more concurrent medications. RESULTS In the total sample, 201 of 698 participants (29%) were prescribed two or more medications. These participants had lower Children's Global Assessment Scale scores, more comorbid disorders, and higher baseline parent-reported mood symptoms than those prescribed no or one medication. White youths were three times as likely as nonwhite youths to be receiving two or more psychotropics, even after adjustment for other demographic and clinical characteristics. Of 262 participants (38% of sample) not being treated with medications, 252 (96%) had a diagnosis of at least one psychiatric disorder (74% had two or more). CONCLUSIONS Findings suggest that patients with greater severity and comorbidity were more likely to receive two or more medications. However, 38% of these children with serious disorders were not receiving psychotropic medication at the time of this assessment. Results counter findings suggesting overtreatment with medications of children with psychiatric disorders in the community.

BACKGROUND:In the pediatric bipolar disorder literature, mania has eclipsed depression as the mood state of most interest. Though depressive episodes tend to be more prevalent and persisting than manic episodes, research about the associated consequences is limited. The goal of the present study was to compare the influences of depressive and manic symptoms on domains of functioning in which youth with bipolar disorder often demonstrate deficits. METHOD/METHODS:Youth meeting DSM-IV-TR criteria for bipolar spectrum disorders (I, II, and NOS) between the ages of seven and 13 were recruited from a clinic in a large Midwestern city (N=54). Both parent and clinician report of manic and depressive symptoms were used in regression analyses to determine how each set of symptoms was related to child functioning. RESULTS:Parent-rated child depression symptoms were associated with problem behaviors (p<0.05), and lower quality of life (p<0.001). Clinician-rated child depression was associated with greater psychiatric illness (p<0.05), lower child self-concept (p<0.001), lower quality of life (p<0.05), hopelessness (p<0.05), and suicidal ideation (p<0.05). Parent-rated mania was associated with better self-esteem (p<0.05) and physical wellbeing (p<0.05). Clinician-rated mania was associated with greater psychiatric illness (p<0.05) and physical wellbeing (p<0.05). LIMITATIONS/CONCLUSIONS:The specific outcomes predicted by parent and clinician-rated symptoms vary. Though the overall story told--that bipolar depression is associated with significant impairment in youth--is consistent, further research is necessary to more fully understand the impact of each mood state. CONCLUSION/CONCLUSIONS:Mania is undoubtedly destructive, but this study provides evidence to suggest that depression may be more deleterious to youths' psychosocial functioning and quality of life; more attention to understanding and ameliorating the effects of bipolar depression on youth is warranted.

BACKGROUND:A patent foramen ovale (PFO) may permit arterial embolization of thrombi that accumulate on the leads of cardiac implantable electronic devices in the right-sided cardiac chambers. We sought to determine whether a PFO increases the risk of stroke/transient ischemic attack (TIA) in patients with endocardial leads. METHODS AND RESULTS/RESULTS:We retrospectively evaluated all patients who had endocardial leads implanted between January 1, 2000, and October 25, 2010, at Mayo Clinic Rochester. Echocardiography was used to establish definite PFO and non-PFO cohorts. The primary end point of stroke/TIA consistent with a cardioembolic etiology and the secondary end point of mortality during postimplantation follow-up were compared in PFO versus non-PFO patients with the use of Cox proportional hazards models. We analyzed 6075 patients (364 with PFO) followed for a mean 4.7 ± 3.1 years. The primary end point of stroke/TIA was met in 30/364 (8.2%) PFO versus 117/5711 (2.0%) non-PFO patients (hazard ratio, 3.49; 95% confidence interval, 2.33-5.25; P<0.0001). The association of PFO with stroke/TIA remained significant after multivariable adjustment for age, sex, history of stroke/TIA, atrial fibrillation, and baseline aspirin/warfarin use (hazard ratio, 3.30; 95% confidence interval, 2.19-4.96; P<0.0001). There was no significant difference in all-cause mortality between PFO and non-PFO patients (hazard ratio, 0.91; 95% confidence interval, 0.77-1.07; P=0.25). CONCLUSIONS:In patients with endocardial leads, the presence of a PFO on routine echocardiography is associated with a substantially increased risk of embolic stroke/TIA. This finding suggests a role of screening for PFOs in patients who require cardiac implantable electronic devices; if a PFO is detected, PFO closure, anticoagulation, or nonvascular lead placement may be considered.

Bone morphogenetic protein (BMP) signaling has emerged as an important regulator of sensory neuron development. Using a three-generation forward genetic screen in mice we have identified Megf8 as a novel modifier of BMP4 signaling in trigeminal ganglion (TG) neurons. Loss of Megf8 disrupts axon guidance in the peripheral nervous system and leads to defects in development of the limb, heart, and left-right patterning, defects that resemble those observed in Bmp4 loss-of-function mice. Bmp4 is expressed in a pattern that defines the permissive field for the peripheral projections of TG axons and mice lacking BMP signaling in sensory neurons exhibit TG axon defects that resemble those observed in Megf8 (-/-) embryos. Furthermore, TG axon growth is robustly inhibited by BMP4 and this inhibition is dependent on Megf8. Thus, our data suggest that Megf8 is involved in mediating BMP4 signaling and guidance of developing TG axons. DOI:http://dx.doi.org/10.7554/eLife.01160.001.