Research Spotlight

Vogel, K. R., E. Arning, T. Bottiglieri and K. M. Gibson (2017). “Multicompartment analysis of protein-restricted phenylketonuric mice reveals amino acid imbalances in brain.” J Inherit Metab Dis 40(2): 227-235.

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BACKGROUND: The mainstay of therapy for phenylketonuria (PKU) remains dietary protein restriction. Developmental and neurocognitive outcomes for patients, however, remain suboptimal. We tested the hypothesis that mice with PKU receiving protein-restricted diets would reveal disruptions of brain amino acids that shed light on these neurocognitive deficits. METHOD: Phenylalanine hydroxylase-deficient (PKU) mice and parallel controls (both wild-type and heterozygous) were fed custom diets containing 18, 6, and 4 % protein for 3 weeks, after which tissues (brain, liver, sera) were collected for amino acid analysis profiling. RESULTS: Phenylalanine (phe) was increased in all tissues (p < 0.0001) of PKU mice and improved with protein restriction. In sera, decreased tyrosine (p < 0.01) was corrected (defined as not significantly different from the level in control mice receiving 18 % chow) with protein restriction, whereas protein restriction significantly increased many other amino acids. A similar trend for increased amino acid levels with protein restriction was also observed in liver. In brain, the effects of protein restriction on large neutral amino acids (LNAAs) were variable, with some deficit correction (threonine, methionine, glutamine) and no correction of tyrosine under any dietary paradigm. Protein restriction (4 % diet) in PKU mice significantly decreased lysine, arginine, taurine, glutamate, asparagine, and serine which had been comparable to control mice under 18 % protein intake. CONCLUSION: Depletion of taurine, glutamate, and serine in the brain of PKU mice with dietary protein restriction may provide new insight into neurocognitive deficits of PKU.

Scherrer, J. F., J. Salas, F. D. Schneider, K. K. Bucholz, M. D. Sullivan, L. A. Copeland, B. K. Ahmedani, T. Burroughs and P. J. Lustman (2017). “Characteristics of new depression diagnoses in patients with and without prior chronic opioid use.” J Affect Disord 210: 125-129.

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Chronic use (>90 Days) of opioid analgesics significantly increases the risk of development of new depression episodes (NDE). It is unclear whether depression that develops in this manner is similar to or different from NDE in persons not exposed to opioid analgesic use (OAU). METHODS: VA patients were classified into two groups, those who did not receive an opioid and developed depression (non-OAU+NDE, n=4314) and those that had >90 days OAU and developed NDE (OAU+NDE, n=444). OAU+NDE patients were compared to non-OAU+NDE in terms of depression severity (PHQ-9 scores), incidence of PTSD, other anxiety disorders and substance use disorders after NDE, receipt of acute phase antidepressant treatment, dual antidepressant treatment, mood stabilizers and atypical antipsychotics. Prior to computing bivariate analysis, the prevalence of pain conditions and average maximum pain scores were equalized between the two groups using propensity scores and inverse probability of treatment weighting. RESULTS: Controlling for pain, OAU+NDE patients had more depression symptoms (p=.012), more incident PTSD (p=.04) and opioid abuse/dependence and were more likely to receive 12 weeks of antidepressant treatment (p<.0001). Last, non-OAU+NDE were more likely to have incident diagnoses for any other anxiety disorder (p=.014). CONCLUSIONS: Within the limitations of electronic medical record data, results indicate OAU+NDE patients have more depression symptoms, greater treatment adherence and different comorbid psychiatric conditions compared to non-OAU+NDE, independent of pain. Overall OAU related depression is as severe as non-OAU related depression and repeated depression screening in chronic opioid therapy may be warranted for pain patients, regardless of pain severity.

Wilson, D. K., A. M. Sweeney, H. Kitzman-Ulrich, H. Gause and S. M. St George (2017). “Promoting social nurturance and positive social environments to reduce obesity in high-risk youth.” Clin Child Fam Psychol Rev: 2017 Feb [Epub ahead of print].

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Nurturing environments within the context of families, schools, and communities all play an important role in enhancing youth’s behavioral choices and health outcomes. The increasing prevalence rates of obesity among youth, especially among low income and ethnic minorities, highlight the need to develop effective and innovative intervention approaches that promote positive supportive environments across different contexts for at-risk youth. We propose that the integration of Social Cognitive Theory, Family Systems Theory, and Self-Determination Theory offers a useful framework for understanding how individual, family, and social-environmental-level factors contribute to the development of nurturing environments. In this paper, we summarize evidence-based randomized controlled trials that integrate positive parenting, motivational, and behavioral skills strategies in different contexts, including primary care, home, community, and school-based settings. Taken together, these studies suggest that youth and parents are most likely to benefit when youth receive individual-level behavioral skills, family-level support and communication, and autonomous motivational support from the broader social environment. Future investigators and healthcare providers should consider integrating these evidence-based approaches that support the effects of positive social climate-based interventions on promoting healthy eating, physical activity, and weight management in youth.

Wilson, C. S., M. Forchheimer, A. W. Heinemann, A. M. Warren and C. McCullumsmith (2017). “Assessment of the relationship of spiritual well-being to depression and quality of life for persons with spinal cord injury.” Disabil Rehabil 39(5): 491-496.

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OBJECTIVE: This study sought to describe the association between spiritual well-being, demographic characteristics, quality of life (QOL) and depressive symptoms following spinal cord injury (SCI). We hypothesized QOL and depressed mood would both be explained by extent of spiritual well-being, and meaning-focused (M&P) spirituality would have a stronger impact than faith-focused spirituality. METHODS: 210 individuals with SCI were screened as part of a randomized control trial of venlafaxine XR for major depressive disorder (MDD). 204 completed all measures: Patient Health Questionniare-9 (PHQ-9) assessed depression, the FACIT-Sp assessed spiritual well-being, the Neuro-QOL PAWB scale assessed QOL, and the PANAS assessed affect. RESULTS: Approximately 26% had major depression. Bivariate correlations of scores on PAWB and PANAS and FACIT-Sp showed that all four scales had strong associations with those on PAWB (p < 0.0005). As hypothesized, both the M&P and Faith scales of the FACIT-Sp were significant predictors of QOL (beta = 0.544; p < 0.0005 and beta = 0.151; p = 0.004), though only the M&P scale was an independently significant predictor of likely MDD. CONCLUSION: The findings support that spirituality, as measured by the FACIT-Sp, is strongly associated with QOL and likelihood of MDD. Assessment of spirituality should be included along with more traditional psychological measurements to better inform treatment. Implications for Rehabilitation Spiritual beliefs can contribute to quality of life and may help moderate depressive symptoms that accompany chronic illness and disability, suggesting that rehabilitation professionals should address spirituality in working with their patients with spinal cord injury (SCI). While spiritual issues are often deferred to pastoral counselors during hospitalization, it is clear that addressing these is not the domain of one discipline and does not end upon inpatient discharge. In addressing spirituality, clinicians should tap the spiritual strengths present in their clients, whether meaning/peace-focused or religious, understanding that spirituality involves more than religiosity and also that having a sense of meaning and peace appears to be of great importance.

Askar, M. (2017). “The killer immunoglobulin-like receptor dilemma: How do we harness the power of killer immunoglobulin-like receptors?” Biol Blood Marrow Transplant: 2017 Feb [Epub ahead of print].

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Alloreactive natural killer (NK) cells have been reported to significantly impact allogeneic hematopoietic cell transplantation (HCT) outcomes. How the interactions between killer immunoglobulin-like receptors (KIR) and HLA influence human NK cell functions has been demonstrated by elegant in vitro experiments [1]. Since the early 2000s, the published literature has been populated with numerous studies investigating the association between KIR genotype/haplotype and clinical outcomes of HCT, both independently and in the context of interaction with corresponding HLA ligands. Meanwhile, additional models for KIR modulation of NK cell functions have been proposed [2]. The method of KIR typing adds another layer of complexity in studying the associations between KIR and HCT outcomes. Most published studies in this domain rely on logistically attractive genotyping methods that allow identification of all KIR genes from archived DNA samples collected routinely for HLA typing and typically tested in large batches.