Faculty Bibliography

Background: Volumetric analyses of MRI data have been employed to predict conversion to Alzheimer's disease (AD), and individuals with preclinical AD tend to show atrophy in the right medial temporal lobe, which includes the hippocampus. In this study, we set out to compare a volumetric measurement of the hippocampus to a newly developed measure of hippocampal integrity in their respective potential for prediction of generalized cognitive performance (MMSE) over time. Methods: Ninety participants, who were cognitively intact at baseline and aged 60 or older, were recruited for a study on major depressive disorder (MDD) and tested twice, over three years. Linear regression models were applied to the data with the change in MMSE score as outcome, and hippocampal integrity (HI), hippocampal volume (HV), age and MDD status among the predictors. HI was measured for the left and right hippocampi as the ratio of the parenchymal voxels to the total number of voxels in an automatically determined hippocampus ROI. The ROI was determined by local affine registration of 65 previously delineated hippocampus atlases to the test subject. HVs were extracted from MRI images using an automated volumetric approach. Results: Change in MMSE performance was significantly predicted by both integrity and volume: greater HI and HV values were associated with less decline. However, when comparing predictors' contributions to the models, HI was slightly better than HV for the right side, and explained more of the variance in MMSE performance; HI and HV contributions were largely comparable for the left side. Conclusions: More research is needed to evaluate whether hippocampal integrity or hippocampal volume is a more accurate predictor of cognitive decline, but tentative results from this study appear to suggest that right side HI measures have the potential to be sensitive to future changes in general cognitive ability

Background: GWAS studies in schizophrenia have not yielded targets for person-specific interventions. Alternatively, studies can focus on genes that were initially identified as harboring disruptive de novo mutations in sporadic cases. We examined the impact of four such genes on illness phenotypes. Methods: Structured interviews (DIGS), cognition (WAIS III), symptoms (PANSS) were examined in 48 genotyped cases finding that over 30% of the sample carried a rare/ missense mutations in any of 4 genes. Gene carrier groups were compared to cases without any of these mutations and healthy controls. Results: Carriers of disrupted genes showed significant differences, as follows: SLC39A13 (zinc transporter) (n=4) had the greatest psychopathology and severe cognitive deficits; TGM5 (n=4) had fewer symptoms but slower processing speed; PTPRG (n=5) had prematurity, childhood psychosis and good cognition except poor working memory; ARMS/KIDINS220 (n=5) had comparable severe pathology in all symptom factors and cognitive scores, though degeneration is suggested in light of their early accomplishments. Individual case vignettes highlighted familial psychosis, learning disorders, substance abuse, traumatic brain injuries and medical comorbidity in all 4 subgroups. Conclusions: The results suggest that genes prone to de novo mutations in sporadic cases may provide missing leverage to resolve the complexity of schizophrenia. A differential focus on working memory, processing speed, neuroprotection and zinc treatment should be pursued for these newly identified conditions. Other findings are that ethnicity may not limit genetic research when the focus is on gene function rather than particular sequence variations, and that premorbid exposures may sometimes reflect pleiotrophic effects of psychosis vulnerability genes rather than exposures producing nongenetic phenocopies. This novel approach may be applicable to other complex disorders

Introduction: EUS-guided transmural drainage (TM) of pancreatic pseudocysts is well established. It . remains unclear if TM alone is sufficient treatment in pseudocysts containing solid debris. Aim: To compare clinical outcomes in patients who undergo TM of pancreatic pseudocysts that are debris-free (PDF) vs those that contain solid debris (PSD). Methods: Multi-center retrospective cohort study across 15 centers of patients who underwent TM of pancreatic pseudocysts during a 6-year period (2008-2014). Outcome measures included technical success, symptom resolution, radiologic resolution, endoscopic re-intervention and adverse events (AE). PSD was defined as a pseudocyst containing solid material at time of index EUS TM drainage. Patients with obvious walled-offnecrosis on index imaging were excluded. Technical success was defined as drainage with successful placement of > of 1 transmural stent. Short-term (ST) followup was designated as > 2 weeks following TM, but before stent removal. Long-term (LT) follow-up was defined as > 2 weeks following stent removal. Symptom resolution was defined as the complete absence of symptoms at follow-up. Radiologic resolution was defined as the absence of the pseudocyst on repeat imaging. Re-intervention was defined as the need to repeat endoscopic drainage within a 4-week period. Results: A total of 142 patients underwent TM: 90 PDF and 52 PSD. There were no differences in patient characteristics, indication for drainage, size and location of pseudocyst between the two groups (Table 1). Technical success: PDF 87/90 (97%) vs PSD 51/52 (98%, p=1.00). Endoscopic re-intervention rate was similar between the two groups: PDF 5/90 (6%) vs PSD 6/52 (12%, p=0.21). One patient with PSD underwent endoscopic necrosectomy following initial TM. Median ST and LT follow-up were similar between the two cohorts (Table 2). There was no statistically significant difference in ST symptom resolution rate and LT outcomes in the two groups. ST radiologic resolution was higher in PDF 45/68(66%) compared to PSD 21/41(51%; p=0.009). Overall, procedure-related AE occurred in 13 (14%) in the PDF and 9 (17%) in the PSD group (P=0.64). Conclusion: There is no difference in technical success, ST or LT clinical outcomes in performing TM of PSD, when compared to patients with PDF. Thus, TM alone can be considered a suitable initial intervention in patients with PSD, without increased risk of infectious complications or need for endoscopic debridement. (Table Presented)

Background: Numerous studies have suggested that the APOE e4 allele, an established risk factor for AD, may act synergistically with depression to increase the risk for progressive cognitive decline and conversion to MCI/AD. However, these findings remain controversial and have been reported inconsistently. A possible reason for these conflicting results is differences in methodologies across studies, including differences in the definition of depression, failure to properly diagnose depression or AD, short duration of follow up, differences in age, and possible inclusion of individuals with preexisting cognitive decline or MCI. These considerations prompted us to conduct a 3-year longitudinal prospective study in cognitively intact elderly individuals, who either had a diagnosis of MDD or were healthy controls, to determine if e4 and depression interacted with respect to progressive cognitive decline. We focused primarily on neurobehavioral tests sensitive to early AD and also examined the CSF total tau/Ab42 ratio, which has been linked to incident MCI/AD-related decline. Methods: 91 participants were included in this study, 60 older and with an MMSE score of at least 28 at the beginning of the 3-year longitudinal investigation. 45 participants had a diagnosis of MDD. APOE status and CSF AD biomarkers were determined at baseline and participants underwent a comprehensive neuropsychological test battery that included the Buschke Selective Reminding Test and the Boston Naming Task. Regression models examining change scores from baseline to follow-up were employed to test our hypotheses. Results: Adjusting for age and MMSE score, elderly participants with depression and carrying APOE e4 showed greater decline on average in the Boston Naming Task (p < 0.01) and a trend with high imagery performance (p = 0.05). A higher CSF total tau/Ab42 ratio was associated with decline in memory performance among depressed subjects (r =-0.45, p = 0.03, n = 23), regardless of APOE status, but not in controls. Conclusions: Our results indicate that cognitively intact depressive e4 carriers have greater decline in selective cognitive tests especially in a confrontation naming task even during a relatively short three year longitudinal period compared to controls. Additionally, increased brain AD pathology as reflected by the CSF tau/Ab42 ratio appeared to be associated with greater decline in memory performance in all depressives, regardless of APOE e4 status

The purpose of this study was to determine the benefits of a multiple family group (MFG) service delivery model compared with services as usual (SAU) in improving the functioning of youth with oppositional defiant/conduct disorder in families residing in socioeconomically disadvantaged communities. Participants included 320 youth aged 7 to 11 and their families who were referred to participating outpatient clinics. Participants were assigned to the MFG or the SAU condition, with parent report of child oppositional behavior, social competence, and level of youth impairment as primary outcomes at post-treatment. Family engagement to MFG was measured by attendance to each group session. Caregivers of youth in the MFG service delivery model condition reported significant improvement in youth oppositional behavior and social competence compared with youth in the SAU condition. Impairment improved over time for both groups with no difference between treatment conditions. The MFG led to greater percentage of youth with clinically significant improvements in oppositional behavior. Attendance to the MFG was high, given the high-risk nature of the study population. The MFG service delivery model offers an efficient and engaging format to implement evidence-based approaches to improving functioning of youth with oppositional defiant and/or conduct disorder in families from socioeconomically disadvantaged communities.

Homelessness affects a large and increasing number of families in the United States, and exposure to violence and other potentially traumatic events is common among homeless families. It is important to understand more about this population and, more specifically, about the relationship between youth mental health and caregiver mental health and trauma exposure among homeless families, in order to better serve the needs of this vulnerable population. The objective of this study is to explore the relationships between caregiver exposure to violence, caregiver depression, and youth depression and behavioral problems among homeless families. Preliminary findings indicate that among this sample of homeless families, caregiver violence exposure has statistically significant relationships with both youth behavioral problems and youth depression symptoms, as mediated by caregiver depression. These findings indicate that youth behavioral health is associated with caregiver mental health, which, in turn, is associated with caregiver trauma exposure. This highlights the importance of taking into account adult mental health while treating youth externalizing and internalizing behaviors and ensuring that caregivers, too, have access to adequate treatment and supports. Furthermore, this treatment should be trauma informed, given the link between trauma and mental health.

Anxiety is a prevalent and impairing psychiatric condition among children and adolescents with inflammatory bowel disease (IBD). Despite the need for effective treatment, no studies have examined the benefit of cognitive-behavioral therapy (CBT) for anxiety disorders among children or adults with IBD. The aim of this paper is twofold: (a) to briefly describe a newly adapted CBT protocol, treatment of anxiety and physical symptoms related to IBD (TAPS + IBD), that concurrently addresses anxiety (including IBD-specific anxiety) and disease management among children and adolescents with IBD in pediatric medical offices; and (b) to present initial pilot data examining the feasibility and potential efficacy of TAPS + IBD compared to nondirective supportive therapy (NDST) among youth with comorbid IBD and anxiety. Twenty-two youth (59% female; mean age 13.2 +/- 2.1) with comorbid IBD and anxiety disorder were randomly assigned to a 13-session TAPS + IBD or NDST program. Following treatment, participants in TAPS + IBD demonstrated higher treatment response rates relative to the NDST control treatment. Compared with NDST, TAPS + IBD was associated with significantly greater reductions in IBD-specific anxiety immediately following treatment and 3 months later. TAPS + IBD shows initial promise for the treatment of anxiety in youth with IBD. The direct integration of behavioral health strategies into medical settings and use of a flexible CBT approach sensitive to acute disease fluctuations appears to be beneficial among youth with comorbid IBD and anxiety.

Background: Increased attention has been paid to identifying and responding to the mental health and social emotional needs of young children in low income countries. There is lack of brief screening scales and assessment tools to characterize child mental health burden or to evaluate impact of early intervention in Sub-Saharan African (SSA) countries. This study sought to determine reliability and validity of three different parent/caregiver brief screening tools in a SSA country - Uganda. The Pediatric Symptom Checklist (14 item Pictorial Scale) (Gardner et al., 2007), assesses child behavioral problems using a pictorial format that takes into account the low literacy rates in SSA countries. The Social Competence Scale (12 items) (Gouley, et al., 2007) utilizes a strength-based evaluation approach to assess children's emotional regulation and prosocial/communication competence. The Strength and Difficult Questionnaire (SDQ; 25 items) (Goodman, et al., 1997, 2009), is available in 80 languages, focuses on psychiatric symptoms and assesses hyperactivity, emotional symptoms, peer problems and conduct problems. Methods: Parents of 303 Ugandan 4-9 year-old children from the community were recruited and interviewed, and 103 of these who were also part of an ongoing school-based mental health intervention trial were interviewed a 2nd time (about 5 months after 1st assessment). Data from both time points were utilized to establish reliability and validity. Data from the control sample (n=42) were used for evaluating test-retest reliability. The mean age of participating parents was 35.92 years (SD = 9.80 years). About one third of parents (32%) were single, and 48% had primary or less education. Study children were an average 6.51 years old (SD = 1.08 years) and all were enrolled in Nursery to Primary 3 in Kampala, Uganda. For the purpose of validation measurement, we also included Patient Health Questionnaire (assessing parental depression; Kroenke et al., 2001; alpha=.83) and Parenting Stress Scale (PSI, Abidin, 1995; 5 items, alpha= .63). Findings: Consistent with developers' conceptual frameworks, two factors emerged from the Pictorial Scale (Internalizing and Externalizing problems) and Social Competence Scales (Emotion regulation and Prosocial/Communication skills). However, for the SDQ scale, only one-factor emerged, with estimated 21-27% of children having abnormal level of problem behaviors. All three brief screening tools applied in this study had adequate reliability and validity. Reliability (assessed by Chronbach's alpha) ranged from .61-.68 for Pictorial scale, .61-.63 for SDQ, and .71-.87 for Social Competence Scale. All social emotional and mental health scales included were related in expected ways. The strength-based Social Competence scale is also sensitive to intervention evaluation. Interpretation: Our findings suggest that selection of instruments needs to include parent literacy levels and cultural contexts. A strength-based measure may be more relevant than pathology-based measures in SSA context

This article provides an overview of the two books presented in the issue Journal of the American Academy of Child & Adolescent Psychiatry. The first book, Being a Teen: Everything Teen Girls and Boys Should Know About Relationships, Sex, Love, Health, Identity, and More By Jane Fonda is the culmination of the author's experience with teens and what the author believes teens need to know. The second book, Healing After Parent Loss in Childhood and Adolescence: Therapeutic Interventions and Theoretical Considerations edited by Phyllis Cohen, K. Mark Sossin, and Richard Ruth is a new volume dedicated to clinical work with children and adolescents who have lost a parent to death. Sickles reviews a book of advice for teens, and Weis reviews a new text describing therapeutic interventions for children after the loss of a parent.

In this month's Book Forum, the question is raised again: Where does love come from? Francesco Ferrari reviews an academic text on romantic love, full of theories and intellectual curiosity about this most important of topics, and Matthew J. Baker reviews a book that comes at the question from another angle, in a therapeutic guide book for daughters of mothers "who cannot love."