All Publications


  • Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults. Translational psychiatry Ayub, R. n., Sun, K. L., Flores, R. E., Lam, V. T., Jo, B. n., Saggar, M. n., Fung, L. K. 2021; 11 (1): 93

    Abstract

    Alterations in sensorimotor functions are common in individuals with autism spectrum disorder (ASD). Such aberrations suggest the involvement of the thalamus due to its key role in modulating sensorimotor signaling in the cortex. Although previous research has linked atypical thalamocortical connectivity with ASD, investigations of this association in high-functioning adults with autism spectrum disorder (HFASD) are lacking. Here, for the first time, we investigated the resting-state functional connectivity of the thalamus, medial prefrontal, posterior cingulate, and left dorsolateral prefrontal cortices and its association with symptom severity in two matched cohorts of HFASD. The principal cohort consisted of 23 HFASD (mean[SD] 27.1[8.9] years, 39.1% female) and 20 age- and sex-matched typically developing controls (25.1[7.2] years, 30.0% female). The secondary cohort was a subset of the ABIDE database consisting of 58 HFASD (25.4[7.8] years, 37.9% female) and 51 typically developing controls (24.4[6.7] years, 39.2% female). Using seed-based connectivity analysis, between-group differences were revealed as hyperconnectivity in HFASD in the principal cohort between the right thalamus and bilateral precentral/postcentral gyri and between the right thalamus and the right superior parietal lobule. The former was associated with autism-spectrum quotient in a sex-specific manner, and was further validated in the secondary ABIDE cohort. Altogether, we present converging evidence for thalamocortical hyperconnectivity in HFASD that is associated with symptom severity. Our results fill an important knowledge gap regarding atypical thalamocortical connectivity in HFASD, previously only reported in younger cohorts.

    View details for DOI 10.1038/s41398-021-01221-0

    View details for PubMedID 33536431

  • Anxiety Disorders Transition-Age Youth Mental Health Care Sun, K. L., Shivakumar, V., Kishore, A. R. edited by Chan, V., Derenne, J. Springer. 2021: 123-151
  • Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism. Psychoneuroendocrinology Chew, L., Sun, K. L., Sun, W., Wang, Z., Rajadas, J., Flores, R. E., Arnold, E., Jo, B., Fung, L. K. 2020; 123: 105039

    Abstract

    Autism spectrum disorder (ASD) has been associated with imbalance between excitatory and inhibitory (E/I) neurotransmission systems, as well as with neuroinflammation. Sitting at the crossroads between E/I imbalance and neuroinflammation is a class of endogenous hormones known as neurosteroids. Current literature points to dysregulated steroid metabolism and atypical neurosteroid levels in ASD as early as in utero. However, due to the complexity of neurosteroid metabolomics, including possible sex differences, the impact of neurosteroids on ASD symptomatology remains unclear. In this study, we assessed neurosteroid levels and ASD symptom severity of 21 males with ASD and 20 full-scale-IQ-matched typically developing (TD) males, all aged 18-39. Using liquid chromatography-tandem mass spectrometry, concentrations of allopregnanolone, cortisol, dehydroepiandrosterone, progesterone, and testosterone were measured in saliva and serum. With the exception of cortisol's, all neurosteroids' concentrations were found to have ASD vs. TD group differences in distribution, where one group was normally distributed and the other non-normally distributed. Serum allopregnanolone levels in males with ASD were found to negatively correlate with clinician-rated measures of restricted and repetitive behavior measures (ADOS-2 RRB and ADI-R RRSB domain scores). Additionally, lower serum allopregnanolone levels were found to predict more negative camouflaging scores, which represent greater differences in self- and clinician-rated symptom severity, of both ASD symptomatology overall and repetitive behaviors in particular. Taken together, our findings demonstrate that in adult males with ASD, decreased serum allopregnanolone levels are associated with more severe restricted and repetitive behaviors and with less insight into the severity of these behaviors.

    View details for DOI 10.1016/j.psyneuen.2020.105039

    View details for PubMedID 33161257

  • Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder. Molecular psychiatry Fung, L. K., Flores, R. E., Gu, M. n., Sun, K. L., James, D. n., Schuck, R. K., Jo, B. n., Park, J. H., Lee, B. C., Jung, J. H., Kim, S. E., Saggar, M. n., Sacchet, M. D., Warnock, G. n., Khalighi, M. M., Spielman, D. n., Chin, F. T., Hardan, A. Y. 2020

    Abstract

    The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger's Diagnostic Scale-Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water's relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.

    View details for DOI 10.1038/s41380-020-0756-y

    View details for PubMedID 32376999

  • Child and Adolescent Psychiatry Perceptions and Career Preference: Participation in a National Medical Student Conference Improves Outcomes. Journal of the American Academy of Child and Adolescent Psychiatry Kishore, A., Sun, K., Guth, S., Kolevzon, A., Martin, A. 2019

    Abstract

    OBJECTIVE: Since 2002, the Klingenstein Third Generation Foundation (KTGF) has supported a network of medical schools across the country with the explicit aim of enhancing interest in, and eventual recruitment into the field of child and adolescent psychiatry (CAP). An active component of the KTGF network has been its annual National Medical Student Conference (NMSC).METHOD: The Thirteenth Annual NMSC, supported by the KTGF, was held at Stanford University on February 8 and 9, 2019. We designed a 17-item survey with five underlying themes (balance, finances, patients, systems, and stigma), intended to quantify students' perceptions of the field of CAP. We also rated students' prospective career choices. Surveys were electronically collected at baseline, after the NMSC, and 90 days later.RESULTS: Our baseline sample consisted of 79 students (57% women) from 14 medical schools. We found improvements over time in overall perceptions of child psychiatry (F2,206=7.5, p<0.000), and in four out of five domain scores (F2,206 ≥3.6, p≤0.03). Prospective career preferences increased over time for CAP (F2,206=3.9, p=0.02), although the effect was time-limited and did not persist after 90 days. We found no change in preference for psychiatry or pediatrics over time.CONCLUSION: An intensive, 2-day conference entirely dedicated to CAP content had salutary effects among medical students in improving their perceptions about the field, and in their reported likelihood of pursuing CAP after graduation.

    View details for DOI 10.1016/j.jaac.2019.07.949

    View details for PubMedID 31585159

  • Neural and Endocrine Correlates of Early Life Abuse in Youth With Depression and Obesity FRONTIERS IN PSYCHIATRY Sun, K. L., Watson, K. T., Angal, S., Bakkila, B. F., Gorelik, A. J., Leslie, S. M., Rasgon, N. L., Singh, M. K. 2018; 9