Faculty Bibliography

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro-circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context. While allowing for adaptation, such sensitive periods are also windows of vulnerability during which external and internal factors can confer risk to brain disorders by derailing adaptive developmental programs. Our group has been particularly interested in developmental periods that are sensitive to serotonin (5-HT) signaling, and impact behavior and cognition relevant to psychiatry. Specifically, we review a 5-HT-sensitive period that impacts fronto-limbic system development, resulting in cognitive, anxiety, and depression-related behaviors. We discuss preclinical data to establish biological plausibility and mechanistic insights. We also summarize epidemiological findings that underscore the potential public health implications resulting from the current practice of prescribing 5-HT reuptake inhibiting antidepressants during pregnancy. These medications enter the fetal circulation, likely perturb 5-HT signaling in the brain, and may be affecting circuit maturation in ways that parallel our findings in the developing rodent brain. More research is needed to better disambiguate the dual effects of maternal symptoms on fetal and child development from the effects of 5-HT reuptake inhibitors on clinical outcomes in the offspring. Birth Defects Research 109:924-932, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND: The care of traumatized children would benefit significantly from accurate predictive models for Posttraumatic Stress Disorder (PTSD), using information available around the time of trauma. Machine Learning (ML) computational methods have yielded strong results in recent applications across many diseases and data types, yet they have not been previously applied to childhood PTSD. Since these methods have not been applied to this complex and debilitating disorder, there is a great deal that remains to be learned about their application. The first step is to prove the concept: Can ML methods - as applied in other fields - produce predictive classification models for childhood PTSD? Additionally, we seek to determine if specific variables can be identified - from the aforementioned predictive classification models - with putative causal relations to PTSD. METHODS: ML predictive classification methods - with causal discovery feature selection - were applied to a data set of 163 children hospitalized with an injury and PTSD was determined three months after hospital discharge. At the time of hospitalization, 105 risk factor variables were collected spanning a range of biopsychosocial domains. RESULTS: Seven percent of subjects had a high level of PTSD symptoms. A predictive classification model was discovered with significant predictive accuracy. A predictive model constructed based on subsets of potentially causally relevant features achieves similar predictivity compared to the best predictive model constructed with all variables. Causal Discovery feature selection methods identified 58 variables of which 10 were identified as most stable. CONCLUSIONS: In this first proof-of-concept application of ML methods to predict childhood Posttraumatic Stress we were able to determine both predictive classification models for childhood PTSD and identify several causal variables. This set of techniques has great potential for enhancing the methodological toolkit in the field and future studies should seek to replicate, refine, and extend the results produced in this study.

OBJECTIVE: To identify the predictive value of juvenile factors for adult suicidal behavior. METHODS: We reviewed clinical records to compare factors identified in childhood and adolescence between adult suicidal versus nonsuicidal major affective disorder subjects. RESULTS: Suicide attempts occurred in 23.1% of subjects. Age-at-1st-symptom was 14.2 vs 20.2 years among suicidal versus nonsuicidal subjects (p < 0.0001). More prevalent in suicidal versus non-suicidal subjects by multivariate analysis were: depressive symptoms, hyper-emotionality, younger-at-1st-affective-episode, family suicide history, childhood mood-swings, and adolescence low self-esteem. Presence of one factor yielded a Bayesian sensitivity of 64%, specificity of 50%, and negative predictive power of 86%. COMMENT: Several juvenile factors were associated with adult suicidal behavior; their absence was strongly associated with a lack of adult suicidal behavior.

The psychological mechanisms of action involved in psilocybin-assisted psychotherapy are not yet well understood. Despite a resurgence of quantitative research regarding psilocybin, the current study is the first qualitative study of participant experiences in psilocybin-assisted psychotherapy. Semistructured interviews were carried out with 13 adult participants aged 22 to 69 years (M = 50 years) with clinically elevated anxiety associated with a cancer diagnosis. Participants received a moderate dose of psilocybin and adjunctive psychotherapy with an emphasis on the process of meaning-making. Verbatim transcribed interviews were analyzed by a five-member research team using interpretative phenomenological analysis. General themes found in all or nearly all transcripts included relational embeddedness, emotional range, the role of music as conveyor of experience, meaningful visual phenomena, wisdom lessons, revised life priorities, and a desire to repeat the psilocybin experience. Typical themes found in the majority of transcripts included the following: exalted feelings of joy, bliss, and love; embodiment; ineffability; alterations to identity; a movement from feelings of separateness to interconnectedness; experiences of transient psychological distress; the appearance of loved ones as guiding spirits; and sharing the experience with loved ones posttreatment. Variant themes found in a minority of participant transcripts include lasting changes to sense of identity, synesthesia experiences, catharsis of powerful emotion, improved relationships after treatment, surrender or letting go, forgiveness, and a continued struggle to integrate experience. The findings support the conclusion that psilocybin-assisted psychotherapy may provide an effective treatment for psychological distress in cancer patients. Implications for theory and treatment are discussed.

OBJECTIVE: This study compared health care access, utilization, and functional indicators among adults with and without serious psychological distress (SPD) in the years surrounding implementation of the Patient Portable and Affordable Care Act (ACA). METHODS: Adults ages 18 to 64 from the 2006-2014 National Health Interview Survey (N=207, 853) were examined on 11 access, utilization, and functional indicators: health insurance coverage (health coverage), insufficient money for medications, delay in health care (delay in care), insufficient money for health care, visiting a doctor ten or more times in the past 12 months, change in place of health care, change in place of health care due to insurance, limitations in ability to work, limitations in activities of daily living (ADLs), insufficient money for mental health care, and having seen a mental health care provider. RESULTS: Multivariate models that were adjusted for health coverage and sociodemographic characteristics indicated that compared with adults without SPD, adults with SPD had greater odds of lacking money for medications (AOR=10.0) and health care (AOR=3.1), experiencing delays in care (AOR=2.7), visiting a doctor ten or more times in the past 12 months (AOR=3.2), changing usual place of health care (AOR=1.5), changing usual place of health care because of insurance (AOR=1.5), and experiencing limitations in ADLs (AOR=3.6) and ability to work (AOR=1.8). The proportions of adults with SPD who lacked health coverage and money to buy prescriptions increased during the study period. Although this trend reversed in 2014, the proportion with SPD experiencing barriers remained above 2006 levels. CONCLUSIONS: Health care patterns among adults with SPD require greater attention.

Body odors are potent triggers of disgust and regulate social behaviors in many species. The role of olfaction in disgust-associated behaviors has received scant attention in the research literature, in part because olfactory disgust assessments have required laboratory testing with odors. We have devised the "Body Odor Disgust Scale" (BODS) to facilitate research on olfactory disgust. In this study, we evaluated whether individual differences in BODS scores would be associated with the perception of disgust for sweat samples in a laboratory setting. Results show that BODS was a strong predictor of disgust ratings of sweat samples even when controlling for general disgust sensitivity. In contrast, odor intensity ratings were unrelated to BODS scores. Our findings suggest that the BODS scores reflect body odor disgust perception. The BODS scale might facilitate research on olfactory disgust responses and associated behaviors.

Disgust plays a crucial role in the avoidance of pathogen threats. In many species, body odors provide important information related to health and disease, and body odors are potent elicitors of disgust in humans. With this background, valid assessments of body odor disgust sensitivity are warranted. In the present article, we report the development and psychometric validation of the Body Odor Disgust Scale (BODS), a measure suited to assess individual differences in disgust reaction to a variety of body odors. Collected data from 3 studies (total n = 528) show that the scale can be used either as a unidimensional scale or as a scale that reflects two hypothesized factors: sensitivity to one's own body odors versus those of others. Guided by our results, we reduced the scale to 12 items that capture the essence of these 2 factors. The final version of the BODS shows an excellent internal consistency (Cronbach's αs > 0.9). The BODS subscales show convergent validity with other general disgust scales, as well as with other olfactory functions measures and with aspects of personality that are related to pathogen avoidance. A fourth study confirmed the construct validity of the BODS and its measurement invariance to gender. Moreover, we found that, compared with other general disgust scales, the BODS is more strongly related to perceived vulnerability to disease. The BODS is a brief and valid assessment of trait body odor disgust sensitivity.

Many problems in medicine are inherently dynamic processes which include the aspect of change over time, such as childhood development, aging, and disease progression. From medical images, numerous geometric structures can be extracted with various representations, such as landmarks, point clouds, curves, and surfaces. Different sources of geometry may characterize different aspects of the anatomy, such as fiber tracts from DTI and subcortical shapes from structural MRI, and therefore require a modeling scheme which can include various shape representations in any combination. In this paper, we present a geodesic regression model in the large deformation (LDDMM) framework applicable to multi-object complexes in a variety of shape representations. Our model decouples the deformation parameters from the specific shape representations, allowing the complexity of the model to reflect the nature of the shape changes, rather than the sampling of the data. As a consequence, the sparse representation of diffeomorphic flow allows for the straightforward embedding of a variety of geometry in different combinations, which all contribute towards the estimation of a single deformation of the ambient space. Additionally, the sparse representation along with the geodesic constraint results in a compact statistical model of shape change by a small number of parameters defined by the user. Experimental validation on multi-object complexes demonstrate robust model estimation across a variety of parameter settings. We further demonstrate the utility of our method to support the analysis of derived shape features, such as volume, and explore shape model extrapolation. Our method is freely available in the software package deformetrica which can be downloaded at www.deformetrica.org.

BACKGROUND:F]FPEB and positron emission tomography (PET). Furthermore, we sought to determine the role glutamate plays on mGluR5 availability in MDD. METHODS:H MRS) to estimate anterior cingulate (ACC) glutamate, glutamine, and Glx (glutamate + glutamine) levels relative to creatine (Cr). RESULTS:negatively correlated with glutamate/Cr and Glx/Cr levels. CONCLUSIONS:examination, we show an inverse relationship between mGluR5 availability and glutamate levels. These data highlight the need to further investigate the role of glutamatergic system in depression.