IMPORTANCEIt is critical to evaluate the risk of comorbid psychiatric diagnoses to meet the needs of individuals with autism spectrum disorder (ASD).OBJECTIVE To examine whether individuals with ASD are at greater risk for comorbid diagnoses of depression, anxiety, or bipolar disorder. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from a population-based birth cohort of 31 220 individuals born in Olmsted County, Minnesota, from January 1, 1976, to December 31, 2000. Patients with research-identified ASD were previously identified using a multistep process that evaluated signs and symptoms abstracted from medical and educational records. For each of the 1014 patients with ASD, 2 age-and sex-matched referents who did not meet criteria for ASD were randomly selected from the birth cohort (n = 2028). Diagnosis codes for anxiety, depression, and bipolar disorders were electronically obtained using the Rochester Epidemiological Project records-linkage system. Data analysis was performed from July 1, 2018, to April 1, 2019. MAIN OUTCOMES AND MEASURESCumulative incidence of clinically diagnosed depression, anxiety, and bipolar disorder through early adulthood in individuals with ASD compared with referents. RESULTS A total of 1014 patients with ASD (median age at last follow-up, 22.8 years [interquartile range, 18.4-28.0 years]; 747 [73.7%] male; 902 [89.0%] white) and 2028 referents (median age at last follow-up, 22.4 years [interquartile range, 18.8-26.2 years]; 1494 [73.7%] male; 1780 [87.8%] white) participated in the study. Patients with ASD were significantly more likely to have clinically diagnosed bipolar disorder (hazard ratio [HR], 9.34; 95% CI, 4.57-19.06), depression (HR, 2.81; 95% CI,, and anxiety (HR, 3.45; 95% CI, 2.96-4.01) compared with referents. Among individuals with ASD, the estimates of cumulative incidence by 30 years of age were 7.3% (95% CI, 4.8%-9.7%) for bipolar disorder, 54.1% (95% CI, 49.8%-58.0%) for depression, and 50.0% (95% CI, 46.0%-53.7%) for anxiety. Among referents, cumulative incidence estimates by 30 years of age were 0.9% (95% CI, 0.1%-1.7%) for bipolar disorder, 28.9% (95% CI, 25.7%-32.0%) for depression, and 22.2% (95% CI, 19.3%-25.0%) for anxiety. CONCLUSIONS AND RELEVANCEThe findings suggest that individuals with ASD may be at increased risk for clinically diagnosed depression, anxiety, and bipolar disorder compared with age-and sex-matched referents. This study supports the importance of early, ongoing surveillance and targeted treatments to address the psychiatric needs of individuals with ASD.

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2–4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 mcg/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 mcg/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/mL) versus that of controls (1.11 ± 0.17 mcg/mL) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

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Background Mental health problems are common after pediatric traumatic brain injury (TBI). Many patients in need of mental health services do not receive them, but studies have not consistently used prospective and objective methods or followed samples for more than 1 year. Objective To examine adolescents’ use of mental health services after TBI. Design Secondary analysis from multicenter prospective randomized controlled trial. Setting Five level 1 US trauma centers. Participants Adolescents aged 12 to 17 years with moderate-to-severe TBI were recruited for a randomized clinical trial (n=132 at baseline, 124 at 6 months, 113 at 12 months, and 101 at 18 months). Methods Participants were randomly assigned to counselor-assisted problem-solving or Internet resource comparison. Follow-up assessments were completed at 6, 12, and 18 months after baseline. Generalized estimating equations with a logit link were used to examine use of mental health services. Treatment group and participant impairment were examined as predictors of use. Main Outcome Measurements Mental health care use was measured with the Service Assessment for Children and Adolescents; daily functioning and clinical outcome with the Child and Adolescent Functional Assessment Scale; behavioral and emotional functioning with the Child Behavior Checklist; and executive dysfunction with the Behavior Rating Inventory of Executive Function. Results Use of mental health services ranged from 22% to 31% in the 2 years post-TBI. Participants with impairments were about 3 times more likely than those without impairments to receive services (odds ratio, 4.61; 95% CI, 2.61–8.14; P<.001). However, 50% to 68% of patients identified as impaired had unmet mental health care needs. Conclusions Less than half of adolescents with behavioral health needs after TBI received mental health services. Future studies are needed to examine barriers associated with seeking services after TBI and psychoeducation as preventive care for this population.

Background: Type 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin treated T1D individual alters brain function. Methods: We therefore, performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ±0.6 hours of insulin deprivation in 14 T1D and compared to 14 age-, sex-, and body mass index-matched, nondiabetic (ND) participants with no interventions. Results: Insulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. T1D participants showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between T1D and ND at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in T1D participants. Insulin deprivation also reduced brain adenosine triphosphate levels and altered phosphocreatine/ adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between T1D and ND were noted and on insulin deprivation further alterations in functional connectivity between regions especially cortical and hippocampus-caudate regions were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition. Conclusions: Transient insulin deprivation thus, caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications as many patients with T1D inadvertently have periods of transient insulin deprivation.

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Introduction: Diabetes is associated with impaired cognition but the effect of the transient insulin deprivation on cognition and its underlying mechanisms remain unclear. Objective: We determined whether transient insulin deprivation in type 1 diabetic adults (T1D) and adolescents alters brain structure, functions and blood flow compared to nondiabetics (ND). Methods: We performed structural MRI, phosphorous31 NMR spectroscopy, and neuropsychiatric testing at baseline and following 6 hours of insulin deprivation in 14 adolescent (14-17 years) and adult (18-44 years) T1D and age- sex- and BMI-matched ND controls. Results: There were no significant changes on baseline structural MRI between the groups. After insulin deprivation, T1D had a significantly greater blood glucose (272 vs. 85 mg/dL), greater beta hydroxybutyrate (1.45 vs. 0.3 mmol/L), and decreased bicarbonate level (25.5 vs. 21.5 mmol/L) at six hours compared to ND. Following insulin deprivation, there was a significant difference in T1D left cortical volume compared to ND. On diffusion tensor imaging at baseline and after insulin deprivation, T1D had a higher fractional anisotropy compared to ND. T1D also had a significant decline in phosphocreatine/ATP after insulin deprivation compared to ND. Lastly after insulin deprivation, T1D failed to have learned improvement on repeat neuropsychiatric testing, with ND having significantly greater improvements in executive function, attention and working memory compared to T1D. Conclusion: Transient hyperglycemia and insulin deprivation caused a significant decline in some important aspects of cognition and brain energy metabolism, indicating that even transient insulin deprivation affects brain function and morphology. This may have important clinical implications as many diabetic patients inadvertently have occasional periods of transient insulin deprivation. Disclosure A. Creo: Consultant; Self; Ultragenyx. T.M. Cortes: None. A.R. Huebner: None. A. Lteif: None. J. Port: None. K. Nair: None.