Faculty Bibliography

This paper describes the application of mixed method designs in implementation research in 22 mental health services research studies published in peer-reviewed journals over the last 5 years. Our analyses revealed 7 different structural arrangements of qualitative and quantitative methods, 5 different functions of mixed methods, and 3 different ways of linking quantitative and qualitative data together. Complexity of design was associated with number of aims or objectives, study context, and phase of implementation examined. The findings provide suggestions for the use of mixed method designs in implementation research.

Implementation science is an emerging field of research with considerable penetration in physical medicine and less in the fields of mental health and social services. There remains a lack of consensus on methodological approaches to the study of implementation processes and tests of implementation strategies. This paper addresses the need for methods development through a structured review that describes design elements in nine studies testing implementation strategies for evidence-based interventions addressing mental health problems of children in child welfare and child mental health settings. Randomized trial designs were dominant with considerable use of mixed method designs in the nine studies published since 2005. The findings are discussed in reference to the limitations of randomized designs in implementation science and the potential for use of alternative designs.

Maltreatment from the caregiver induces vulnerability to later life psychopathologies, yet attraction and comfort is sometimes provided by cues associated with early life maltreatment. We used a rat model of early life maltreatment with odor-0.5mA shock conditioning to produce depressive-like behaviors and questioned whether stimuli associated with maltreatment would restore emotional neurobehavioral function to control levels. Pups received daily novel odor-0.5mA shock conditioning from postnatal day 8 to 12. This procedure produces a new maternal odor that controls pups' attachment behaviors. In adulthood, either with or without the infant odor, animals received a Forced Swim Test, Sucrose Preference Test or assessment of amygdala and olfactory system functioning using field potential signal evoked by olfactory bulb paired-pulse electrical stimulation. Following neonatal odor-shock pairings, but not unpaired controls, adults without the odor present showed increased depression-like behavior in the Forced Swim Test and Sucrose Preference Test and a deficit in paired-pulse inhibition in amygdala and piriform (olfactory) cortex. All effects were brought to control levels when the infant conditioned odor was presented during behavioral and neural tests. The ability of cues associated with early life maltreatment to normalize behavior and amygdala activity suggests these cues provide adaptive value in adulthood

Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood. Here, we identified and characterized marked intraneuronal amyloid-beta peptide/amyloid and lysosomal system pathology in the Alzheimer's disease mouse model TgCRND8 similar to that previously described in Alzheimer's disease brains. We further establish that the basis for these pathologies involves defective proteolytic clearance of neuronal autophagic substrates including amyloid-beta peptide. To establish the pathogenic significance of these abnormalities, we enhanced lysosomal cathepsin activities and rates of autophagic protein turnover in TgCRND8 mice by genetically deleting cystatin B, an endogenous inhibitor of lysosomal cysteine proteases. Cystatin B deletion rescued autophagic-lysosomal pathology, reduced abnormal accumulations of amyloid-beta peptide, ubiquitinated proteins and other autophagic substrates within autolysosomes/lysosomes and reduced intraneuronal amyloid-beta peptide. The amelioration of lysosomal function in TgCRND8 markedly decreased extracellular amyloid deposition and total brain amyloid-beta peptide 40 and 42 levels, and prevented the development of deficits of learning and memory in fear conditioning and olfactory habituation tests. Our findings support the pathogenic significance of autophagic-lysosomal dysfunction in Alzheimer's disease and indicate the potential value of restoring normal autophagy as an innovative therapeutic strategy for Alzheimer's disease

This study examines the efficacy of ParentCorps among 4-year-old children (N = 171) enrolled in prekindergarten in schools in a large urban school district. ParentCorps includes a series of 13 group sessions for parents and children held at the school during early evening hours and facilitated by teachers and mental health professionals. ParentCorps resulted in significant benefits on effective parenting practices and teacher ratings of child behavior problems in school. Intervention effects were of similar magnitude for families at different levels of risk and for Black and Latino families. The number of sessions attended was related to improvements in parenting. Study findings support investment in and further study of school-based family interventions for children from underserved, urban communities

Attentional biases for negative stimuli have been observed in school-age and adolescent children of depressed mothers and may reflect a vulnerability to depression. The direction of these biases and whether they can be identified in early childhood remains unclear. The current study examined attentional biases in 5-7-year-old children of depressed and non-depressed mothers. Following a mood induction, children participated in a dot-probe task assessing biases for sad and happy faces. There was a significant interaction of group and sex: daughters of depressed mothers attended selectively to sad faces, while children of controls and sons of depressed mothers did not exhibit biases. No effects were found for happy stimuli. These findings suggest that attentional biases are discernible in early childhood and may be vulnerability markers for depression. The results also raise the possibility that sex differences in cognitive biases are evident before the emergence of sex differences in the prevalence of depression.

Adolescence reflects a period of increased rates of anxiety, depression, and suicide. Yet most teens emerge from this period with a healthy, positive outcome. In this article, we identify biological factors that may increase risk for some individuals during this developmental period by: (1) examining changes in neural circuitry underlying core phenotypic features of anxiety as healthy individuals transition into and out of adolescence; (2) examining genetic factors that may enhance the risk for psychopathology in one individual over another using translation from mouse models to human neuroimaging and behavior; and (3) examining the effects of early experiences on core phenotypic features of anxiety using human neuroimaging and behavioral approaches. Each of these approaches alone provides only limited information on genetic and environmental influences on complex human behavior across development. Together, they reflect an emerging field of translational developmental neuroscience in forming important bridges between animal models of neurodevelopmental and neuropsychiatric disorders.

OBJECTIVE: Schizophrenia affects men more than women, but this may not be true at all ages. This study examines the incidence of first hospitalization for treatment of schizophrenia in each sex over different ages. METHODS: We compared the incidence of first admission for treatment in a cohort of 46,388 males and 43,680 females followed from birth until ages 29-41, using life tables and proportional hazards methods. RESULTS: Life table estimates of cumulative incidence by age 40 were 1.44% in males and 0.86% in females. For over all ages the relative risk (RR) in males was 1.6 (95% confidence limits=1.4-1.8) compared with females. Before age 17 there was no significant difference between the sexes (RR=0.86, 0.56-1.3). Excess risk in males was observed only from age 17 (RR=1.7, 1.4-1.9). There was no evidence of the incidence in females catching up with that in males, during the 30s. CONCLUSION: In this population, there was a significant change, over age, in the relative incidence of first hospitalization for schizophrenia between the sexes; the excess incidence in males first developed at age 17