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Eryilmaz, Huseyin Hamdi

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Eryilmaz

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Huseyin Hamdi

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Eryilmaz, Huseyin Hamdi
Author's Publications: search.filters.isAuthorOfPublication.0548bbcb-f5d2-40d3-849f-d6337a22b4be

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    Biochemical, physiologic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial
    (2017) Roffman, Joshua; Petruzzi, Liana J.; Tanner, Alexandra S.; Brown, Hannah; Eryilmaz, Huseyin Hamdi; Ho, New Fei; Giegold, Madeline; Silverstein, Noah J.; Bottiglieri, Teodoro; Manoach, Dara; Smoller, Jordan; Henderson, David; Goff, Donald C.
    Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiologic and clinical effects of L-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received L-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (PANSS, SANS, CDSS), cognition (MATRICS composite) and three complementary MRI measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared to placebo, L-methylfolate increased plasma methylfolate levels (d=1.00, p=.0009) and improved PANSS Total (d=.61, p=.03) as well as PANSS Negative and General Psychopathology subscales. While PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving L-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity, and increased cortical thickness. In conclusion, L-methylfolate supplementation was associated with salutary physiologic changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials.
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    Dopamine D1 signaling organizes network dynamics underlying working memory
    (American Association for the Advancement of Science, 2016) Roffman, Joshua; Tanner, Alexandra S.; Eryilmaz, Huseyin Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas; Abi-Dargham, Anissa; Buckner, Randy; Manoach, Dara; Rosen, Bruce; Hooker, Jacob; Catana, Ciprian
    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.
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    A Cross-Sectional Study of Dietary and Genetic Predictors of Blood Folate Levels in Healthy Young Adults
    (MDPI, 2017) Cummings, Daniel; Dowling, Kevin F.; Silverstein, Noah J.; Tanner, Alexandra S.; Eryilmaz, Huseyin Hamdi; Smoller, Jordan; Roffman, Joshua
    Since 1998, the U.S. has mandated folic acid (FA) fortification of certain grain products to reduce the risk of neural tube defects. Folate intake and red blood cell (RBC) folate concentrations increased substantially post-intervention, although recent studies raise concerns about the level of ongoing benefit. This study investigated blood folate level determinants in healthy young adults, including intake of naturally occurring food folate, synthetic FA, and the interaction of naturally occurring food folate with a common missense variant in the FOLH1 gene thought to affect absorption. Participants (n = 265) completed the Diet History Questionnaire II, RBC folate testing, and were genotyped for the 484T>C FOLH1 variant. Men reported significantly greater intake of all folate sources except for supplemental FA, but RBC folate levels did not significantly differ by sex. Synthetic FA was a stronger predictor of RBC folate than naturally occurring food folate. In the largest racial group, synthetic FA and the interaction of FOLH1 genotype with naturally occurring food folate significantly predicted RBC folate, with the overall model accounting for 13.8% of the variance in RBC folate levels. Blood folate levels rely on a complex interaction of natural and synthetic folate intake as well as FOLH1 genotype.