Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study.

BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.

Gestational thyroid hormones and autism-related traits in the EARLI and HOME studies.

Thyroid hormones are essential for neurodevelopment. Few studies have considered associations with quantitatively measured autism spectrum disorder (ASD)-related traits, which may help elucidate associations for a broader population. Participants were drawn from two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI), enrolling pregnant women who already had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study, following pregnant women from the greater Cincinnati, OH area. Gestational thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured in mid-pregnancy 16 (±3) weeks gestation serum samples. ASD-related traits were measured using the Social Responsiveness Scale (SRS) at ages 3-8 years. The association was examined using quantile regression, adjusting for maternal and sociodemographic factors. 278 participants (132 from EARLI, 146 from HOME) were included. TSH distributions were similar across cohorts, while FT4 levels were higher in EARLI compared to HOME. In pooled analyses, particularly for those in the highest SRS quantile (95th percentile), higher FT4 levels were associated with increasing SRS scores (ß = 5.21, 95% CI = 0.93, 9.48), and higher TSH levels were associated with decreasing SRS scores (ß = -6.94, 95% CI = -11.04, -2.83). The association between TSH and SRS remained significant in HOME for the 95% percentile of SRS scores (ß = -6.48, 95% CI = -12.16, -0.80), but not EARLI. Results for FT4 were attenuated when examined in the individual cohorts. Our results add to evidence that gestational thyroid hormones may be associated with ASD-related outcomes by suggesting that relationships may differ across the distribution of ASD-related traits and by familial likelihood of ASD.

A Comparative Analysis of the Full and Short Versions of the Social Responsiveness Scale in Estimating an Established Autism Risk Factor Association in ECHO: Do we Get the Same Estimates?

PURPOSE: Prior work developed a shortened 16-item version of the Social Responsiveness Scale (SRS), a quantitative measure of social communication and autism spectrum disorder (ASD)-related traits. However, its properties for use in risk factor estimation have not been fully tested compared to the full SRS. We compared the associations between gestational age (previously established risk factor for ASD) and the 65-item "full" and 16-item "short" versions of the SRS to test the shortened version's ability to capture associations in epidemiologic analyses of ASD risk factors. METHODS: We used data from participants in the Environmental influences on Child Health Outcomes (ECHO) Program (n = 2,760). SRS scores were collected via maternal/caregiver report when children were aged 2.5-18 years. We compared estimates of associations between gestational age and preterm birth between the full and short SRS using multivariable linear regression, quantile regression, and prediction methods. RESULTS: Overall, associations based on full and short SRS scores were highly comparable. For example, we observed positive associations between preterm birth with both full ([Formula: see text]=2.8; 95% CI [1.7, 4.0]) and short ([Formula: see text]=2.9; 95% CI [1.6, 4.3]) SRS scores. Quantile regression analyses indicated similar direction and magnitude of associations across the distribution of SRS scores between gestational age with both short and full SRS scores. CONCLUSION: The comparability in estimates obtained for full and short SRS scores with an "established" ASD risk factor suggests ability of the shortened SRS in assessing associations with potential ASD-related risk factors and has implications for large-scale research studies seeking to reduce participant burden.

Prepregnancy BMI, gestational weight gain, and susceptibility to autism-related traits: the EARLI and HOME studies.

OBJECTIVE: Excessive gestational weight gain (GWG) has been associated with autism spectrum disorder (ASD). This study sought to examine whether familial susceptibility for autism, intensity of ASD-related behaviors, or prepregnancy BMI influences the association of GWG with ASD-related behaviors. METHODS: Using data from the Early Autism Risk Longitudinal Investigation (EARLI) study (n = 136), a familial enriched cohort of mothers who had a previous child with ASD, and the Health Outcomes and Measures of the Environment (HOME) study (n = 253), a general population cohort, gestational age and prepregnancy BMI category-specific GWG z scores were calculated. Caregivers completed the Social Responsiveness Scale (SRS) to assess the presence and severity of ASD-related traits in children aged 3 to 8 years. Using quantile regression, the association between GWG z scores and ASD-related behaviors in children was estimated. RESULTS: In HOME, among mothers who had overweight or obesity prepregnancy BMI values, GWG z scores and SRS scores were positively associated in children with more ASD-related traits (higher SRS scores), but not in children with fewer ASD-related traits. Similar patterns were observed in EARLI among mothers with prepregnancy obesity. CONCLUSIONS: GWG may be associated with autism-related behaviors among children who have a greater predisposition to these behaviors and who have mothers with prepregnancy overweight or obesity.

Associations of individual and cumulative urinary phthalate and replacement biomarkers with gestational weight gain through late pregnancy.

BACKGROUND/AIMS: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) - a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. METHODS: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. RESULTS: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (Æ©DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (Æ©DiNCH), and di(2-ethylhexyl) terephthalate (Æ©DEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified Æ©DEHP, Æ©DEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (Æ©DiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (ß: -0.29; 95% CI: -0.70, 0.12). In women carrying females, Æ©DEHP contributed to the marginal inverse joint association (ß: -0.54; 95% CI: -1.09, 0.03). However, there was no overall association in women carrying males (ß: 0.00; 95% CI: -0.60, 0.59), which was explained by approximately equal negative (driven by Æ©DEHTP) and positive (driven by Æ©DiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. CONCLUSIONS: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because Æ©DEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.

Associations between folic acid supplement use and folate status biomarkers in the first and third trimesters of pregnancy in the Maternal-Infant Research on Environmental Chemicals (MIREC) Pregnancy Cohort Study.

BACKGROUND: Achieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit. OBJECTIVE: Here, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy. METHODS: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors. RESULTS: Almost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 µg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 µg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI. CONCLUSIONS: In the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses.

Maternal Folate Status and the Relation between Gestational Arsenic Exposure and Child Health Outcomes.

Gestational arsenic exposure adversely impacts child health. Folate-mediated 1-carbon metabolism facilitates urinary excretion of arsenic and may prevent arsenic-related adverse health outcomes. We investigated the potential for maternal folate status to modify associations between gestational arsenic exposure and child health. We used data from 364 mother-child pairs in the MIREC study, a prospective pan-Canadian cohort. During pregnancy, we measured first trimester urinary arsenic concentrations, plasma folate biomarkers, and folic acid supplementation intake. At age 3 years, we evaluated twelve neurodevelopmental and anthropometric features. Using latent profile analysis and multinomial regression, we developed phenotypic profiles of child health, estimated covariate-adjusted associations between arsenic and these phenotypic profiles, and evaluated whether folate status modified these associations. We identified three phenotypic profiles of neurodevelopment and three of anthropometry, ranging from less to more optimal child health. Gestational arsenic was associated with decreased odds of optimal neurodevelopment. Maternal folate status did not modify associations of arsenic with neurodevelopmental phenotypic profiles, but gestational arsenic was associated with increased odds of excess adiposity among those who exceed recommendations for folic acid (>1000 µg/day). However, arsenic exposure was low and folate status was high. Gestational arsenic exposure may adversely impact child neurodevelopment and anthropometry, and maternal folate status may not modify these associations; however, future work should examine these associations in more arsenic-exposed or lower folate-status populations.

Variability and concordance of sulcal patterns in the orbitofrontal cortex: A twin study.

Sulcogyral patterns have been identified in the orbitofrontal cortex (OFC) based on the continuity of the medial and lateral orbital sulci. Pattern types are named according to their frequency in the population, with Type I present in ∼60%, Type II in ∼25%, Type III in ∼10%, and Type IV in ∼5%. Previous work has demonstrated that psychiatric conditions with high estimated heritability (e.g. schizophrenia, bipolar disorder) are associated with reduced frequency of Type I patterns, but the general heritability of the OFC sulcogyral patterns is unknown. We examined concordance of OFC patterns in 304 monozygotic (MZ) twins relative to 172 dizygotic (DZ) twins using structural magnetic resonance imaging data. We find that the frequency of pattern types within MZ and DZ twins are similar and bilateral concordance rates across all pattern types in DZ twins were 14% and 21% for MZ twins. Results from follow-up analyses confirm that continuity in the rostral-caudal direction is an important source of variability within the OFC, and subtype analyses indicate that variability is present in other sulci that are not represented by overall OFC pattern type. Overall, these results suggest that OFC sulcogyral patterns may reflect important variance that is not genetic in origin.

Does early life phthalate exposure mediate racial disparities in children's cognitive abilities?

Early life exposure to phthalates may be associated with reduced cognition. However, it is unknown if disproportionate exposure to phthalates contributes to racial disparities in children's intellectual abilities. Methods: We used data from 253 mother-child pairs in Cincinnati, OH (the Health Outcomes and Measures of the Environment study, 2003-2006). We measured urinary concentrations of 11 phthalate metabolites twice during pregnancy and up to six times in childhood. We evaluated children's cognitive abilities at ages 5 and 8 years. Using mediation models, we quantified covariate-adjusted direct and indirect effects of race on children's Full-Scale Intelligence Quotient (IQ) scores for individual phthalate metabolite concentrations during gestation and childhood. Results: Average IQ scores among Black children (n = 90) were 7.0 points lower (95% confidence interval [CI] = -12, -1.8) than among White children (n = 145) after adjustment for socioeconomic factors. Urinary monobenzyl phthalate and monoethyl phthalate (MEP) concentrations during gestation and childhood were higher among Black than White children. We did not observe evidence that phthalate concentrations mediated the race-IQ association, with the exception of MEP. Childhood MEP concentrations partially mediated the race-IQ association. For instance, each 10-fold increase in MEP concentrations at age 2 years contributed to a 1.9-point disparity in IQ scores between Black and White children (95% CI = -4.7, 0.7). Other phthalate metabolite concentrations during pregnancy or childhood did not mediate the race-IQ association. Conclusions: Despite observing racial disparities in exposure to some phthalates and IQ, we found little evidence that phthalates contribute to IQ disparities.

Gestational triclosan exposure and infant birth weight: A systematic review and meta-analysis.

BACKGROUND: Exposure to triclosan, an antimicrobial chemical used in some personal care and cleaning products, has been associated with reduced birth weight in some, but not all epidemiological studies. OBJECTIVES: We conducted a systematic review and meta-analysis to characterize the relation of gestational triclosan exposure with infant birth weight and identify sources of heterogeneity between studies. METHODS: We identified original studies measuring urinary triclosan concentrations during pregnancy and reporting their association with infant birth weight, gestational age (GA) adjusted birth weight (g), or GA-standardized birth weight z-scores. Using a random effects model, we estimated differences in these outcomes per 10-fold increase in triclosan concentrations and considered triclosan levels and infant sex as sources of heterogeneity. Using Navigation Guide Methods, we evaluated risk of bias within individual studies and across the body of evidence. RESULTS: Among thirteen studies, median triclosan concentrations varied by almost 2-orders of magnitude (0.6-29 ng/mL), with higher concentrations in North American and some European studies compared to Asian ones. Associations between triclosan and birth weight (ß:-20 g; 95% CI:-65, 26; n = 6) were stronger than those for GA-adjusted birth weight (ß:-12 g; 95% CI:-29, 5; n = 9). Triclosan was not associated with GA-standardized birth weight z-scores (ß:-0.04; 95% CI:-0.16, 0.07; n = 5). The association between triclosan and GA-adjusted birth weight was stronger in studies with median triclosan values ≥10 ng/mL compared to studies with median values < 10 ng/mL (ß:-27 g; 95% CI:-61, 7; n = 4 vs. ß:6g; 95% CI:-20, 31; n = 5). With a limited number of studies, we observed suggestive evidence that inverse associations were more apparent in studies with ≥ 2 prospective triclosan measures compared to those with one measure. DISCUSSION: Available evidence, with "low" risk of bias, provides limited evidence that triclosan exposure and reduces infant birth weight. We observed stronger inverse associations between triclosan concentrations and birth weight in populations with higher triclosan exposure.

Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies.

Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the 'tails' of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children's ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3-8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.

Association between self-reported caffeine intake during pregnancy and social responsiveness scores in childhood: The EARLI and HOME studies.

Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children's behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (ß: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (ß: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.

Complementary and Alternative Medicine Use in Children with a Developmental Disability and Co-occurring Medical Conditions.

OBJECTIVE: The primary aim of this study was to evaluate differences in the prevalence of complementary and alternative medicine (CAM) usage among children with and without developmental disabilities (DD). Secondarily, the association between CAM usage and comorbid chronic medical conditions was explored among children with DD. DESIGN: Data come from the 2012 Child Complementary and Alternative Medicine Supplement of the National Health Interview Survey, a nationally representative sample of children in the United States between the ages of 4 and 17 (n = 10,218).Main outcome measures Multiple logistical regression models provided insight into the relationships between parent-report CAM usage, DD, and chronic medical conditions. RESULTS: Children with developmental disabilities were more likely to use CAMs compared to their typically developing peers (21% vs 16%). Children with DDs and comorbid chronic medical conditions used CAMs at even higher rates (23% vs 18%). CONCLUSIONS: Results indicated that children with DD, especially those with a co-occurring chronic medical condition, use CAMs more often that typically developing children. Given scarcity of information on safety and effectiveness, clinical providers need to be alert to which children may be more likely to be exposed to CAMs. Communication between parents and providers needs to include discussion of CAM treatments.

Orbitofrontal sulcogyral morphology in patients with cocaine use disorder.

Orbitofrontal cortex (OFC) is thought to be involved in appropriate processing of rewarding stimuli, and abnormal OFC structure and function has been found in patients with substance use disorders. Atypical patterns of the H-sulcus in the OFC have been primarily identified with schizophrenia, but also with bipolar disorder, both of which are associated with comorbid substance use. Given the high rates of substance use within Axis I psychiatric disorders, it is reasonable to consider how frequencies of OFC patterns in populations with only substance use compare to controls. This information is crucial to disentangle whether atypical frequencies of H-sulcus sulcogyral patterns within psychopathology are associated with the psychiatric or substance use phenotype. Here, we present the first analysis of H-sulcus sulcogyral patterns in a population of adult black men with (n = 84) and without (n = 24) cocaine use disorder (CUD). We find that OFC sulcogyral patterns are not significantly different from the control group, indicating that OFC sulcogyral patterns are not disrupted in patients with CUD. As exploratory analyses, we describe OFC sulcogyral pattern subtypes in this cohort as well as an additional control group (n = 52), in order to add to the growing body of literature on OFC sulcogyral pattern characterization.

The use of the orbitofrontal H-sulcus as a reference frame for value signals.

Understanding the factors that drive organization and function of the brain is an enduring question in neuroscience. Using functional magnetic resonance imaging (fMRI), structure and function have been mapped in primary sensory cortices based on knowledge of the organizational principles that likely drive a given region (e.g., aspects of visual form in primary visual cortex and sound frequency in primary auditory cortex) and knowledge of underlying cytoarchitecture. The organizing principles of higher-order brain areas that encode more complex signals, such as the orbitofrontal cortex (OFC), are less well understood. One fundamental component that underlies the many functions of the OFC is the ability to compute the reward or value of a given object. There is evidence of variability in the spatial location of responses to specific categories of objects (or value of said objects) within the OFC, and several reference frames have been proposed to explain this variability, including topographic spatial gradients that correspond to axes of primary versus secondary rewards and positive versus negative reinforcers. One potentially useful structural morphometric reference frame in the OFC is the "H-sulcus," a pattern formed by medial orbital, lateral orbital and transverse orbital sulci. In 48 human subjects, we use a structural morphometric tracing procedure to localize functional activation along the H-sulcus for face and food stimuli. We report the novel finding that food-selective responses are consistently found within the caudal portion of the medial orbital sulcus, but no consistency within the H-sulcus for response to face stimuli. These results suggest that sulcogyral anatomy of the H-sulcus may be an important morphological metric that contributes to the organizing principles of the OFC response to certain stimulus categories, including food.

Orbitofrontal sulcogyral morphology is a transdiagnostic indicator of brain dysfunction.

Atypical sulcogyral patterns in the orbitofrontal cortex (OFC) are associated with increased risk for schizophrenia, as well as with quantitative traits associated with schizophrenia, such as anhedonia. Here we conduct a cross-diagnostic comparison to assess whether atypical OFC sulcogyral patterns confer risk for multiple brain disorders. We examined structural images from 4 groups of adult participants (N = 189), including those diagnosed with schizophrenia (SZ; N = 49), bipolar disorder (BP; N = 46), attention deficit hyperactivity disorder (ADHD; N = 41), and controls (N = 53). OFC sulcogyral pattern types were determined based on the continuity of the medial and lateral orbitofrontal sulcus. Chi-square analysis was performed to compare the sulcogyral pattern frequency distributions between patient groups and controls. We find that both SZ and BP groups had atypical pattern distributions, with increased atypical pattern frequencies relative to controls in the left hemisphere, consistent with the overlapping clinical features and genetic etiology of these disorders (SZ: χ2 = 17.6; p < 0.001; BP: χ2 = 19.2, p < 0.001). The ADHD group distribution did not significantly differ from controls (χ2 = 5.5; p = 0.06, NS.). Similar sulcogyral pattern frequencies across BP and SZ suggest that the sulcogyral phenotype may map more directly to a trait that is transdiagnostic. These results suggest that sulcogyral patterns present a novel morphological indicator for increased susceptibility to multiple psychiatric diagnoses.