Recent Publications | Department of Psychiatry

January 2021

Genome-Wide Association Analysis of Neonatal White Matter Microstructure

White matter, which provides the connection between different brain regions and allows fast and efficient processing of information, is often abnormal in psychiatric disease. We identified genes that influence white matter development in a large sample of newborns.

PI: John H Gilmore, Professor

Zhang J, Xia K, Ahn M, Jha SC, Blanchett R, Crowley JJ, Szatkiewicz JP, Zou F, Zhu H, Styner M, Gilmore JH, Knickmeyer RC. Cereb Cortex. 2021 Jan 5;31(2):933-948.

A simultaneous [11C] Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation of Striatal Dopamine Binding in Autism

Professor Gabriel Dichter, CIDD investigator and Associate Director of the UNC Intellectual and Developmental Disabilities Research Center (IDDRC), and his colleagues published UNC’s first simultaneous PET-MR psychiatry study in Translational Psychiatry. Using the tracer [11C]raclopride, Dr. Dichter’s lab found decreased striatal phasic dopamine release and decreased striatal activation during reward processing in individuals with autism spectrum disorder. Co-authors on this study included Erin Walsh, PhD, a UNC K awardee in Dr. Dichter’s lab who is receiving training in PET-MR methods, CIDD faculty member Jessica Kinard, PhD CCC-SLP, graduate students Rachel Phillips and Paul Cernasov in UNC’s clinical psychology program, BRIC faculty David Lalush, PhD, Eric Smith, PhD, and Zibo Li, PhD, and collaborators Jacob Hooker, PhD and Nicole Zürcher, PhD from the Athinoula A. Martinos Center for Biomedical Imaging at Harvard University.

PI: Gabriel S. Dichter, PhD, Professor of Psychiatry and Psychology & Neuroscience

Zürcher, N.R.*, Walsh, E.C.*, Phillips, R.D., Cernasov, P.M., Tseng, C.-E.J., Dharanikota, A., Smith, E., Li, Z., Kinard, J.L., Bizzell, J.C., Greene, R.K., Dillon, D., Pizzagalli, D., Izquierdo-Garcia, D., Lalush, D., Truong, K., Hooker, J.M., and Dichter, G.S. (2021). A Simultaneous [11C]Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation of Striatal Dopamine Binding in Autism; Translational Psychiatry ; 11(1), 33. *co-first authors.

Recurrent Network Dynamics Shape Direction Selectivity in Primary Auditory Cortex

In our daily verbal communication, our brain needs to recognize changes in sound frequencies (voice inflections) to extract meanings—for example, upward frequency changes indicate questions in English, and upward and downward changes give different meanings to words in Mandarin. In this work, we discovered an important role of cortical recurrent networks in the extraction and encoding of sound frequency changes, which could serve as a neural substrate for vocal communication in complex human brains.

PI: Hiroyuki Kato, Assistant Professor

Authors: Destinee A. Aponte, Gregory Handy, Amber M. Kline, Hiroaki Tsukano, Brent Doiron & Hiroyuki K. Kato.

Increased Alcohol Self-Administration Following Exposure to the Pedator Odor TMT in Active Coping Female Rats

In this paper we show that individual differences in coping strategies during stress can predict subsequent escalations in alcohol drinking.

PI: Joyce Besheer, PhD

Ornelas LC, Tyler RE, Irukulapati P, Paladugu S, Besheer J (in press) Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats. Behavioural Brain Research.

Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a Large Female Sample of Adults with and without Eating Disorders

This study gathered data on the Norwegian Patient Health Questionnaire-9, a questionnaire used to assess depressive symptoms, among women with and without

PI: Cynthia Bulik, Ph.D

Wisting, L., Johnson, S. U., Bulik, C. M., Andreassen, O. A., Rø, Ø., & Bang, L. (2021). Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a large female sample of adults with and without eating disorders. BMC psychiatry, 21(1), 6. https://doi.org/10.1186/s12888-020-03013-0

Genome-wide Association Study of Patients with a Severe Major Depressive Episode Treated with Electroconvulsive Therapy

This GWAS targeted the severe end of the MDD spectrum, looking specifically at patients who had a major depressive episode occurring in the context of major depressive disorder. Severe MDE cases had smaller genetic correlations with neuroticism and neurodevelopment disorders than moderate MDD cases but higher genetic risk scores for bipolar disorder. This suggests that there may be a different genetic architecture at the severe end of the MDD spectrum, and further study of these severe cases is supported.

PI: Dr. Patrick Sullivan

Clements, C. C., Karlsson, R., Lu, Y., Juréus, A., Rück, C., Andersson, E., Boberg, J., Pedersen, N. L., Bulik, C. M., Nordenskjöld, A., Pålsson, E., Sullivan, P. F., & Landén, M. (2021). Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy. Molecular psychiatry, 10.1038/s41380-020-00984-0. Advance online publication. https://doi.org/10.1038/s41380-020-00984-0

Shared Genetic Risk Between Eating Disorder- and Substance-use-related Phenotypes: Evidence from Genome-Wide Association Studies

This study used data from genome-wide association studies to calculate individual genetic correlations between four eating disorder- and eight substance use- phenotypes. They found significant positive associations between alcohol use disorder and AN, cannabis initiation and AN, and cannabis initiation and AN with binge eating. Additionally, there were negative correlations between smoking phenotypes and AN without binge eating, highlight the complex relationships among all of these behaviors.

PI: Dr. Melissa Munn-Chernoff

Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. L., Coleman, J., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hübel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppä, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodríguez, P., … Agrawal, A. (2021). Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies. Addiction biology, 26(1), e12880. https://doi.org/10.1111/adb.12880

Pinging the Brain with Transcranial Magnetic Stimulation Reveals Cortical Reactivity in Time and Space

Using several advanced methods, we tested how the effects of single-pulse transcranial magnetic stimulation (TMS) in the human motor cortex may be recorded in electroencephalography (EEG) as it impacts cortex excitability. Combining TMS with EEG can be used to investigate the mechanisms underlying brain network engagement.

PI: Flavio Frohlich PhD MSc ETH Associate Professor Associate Vice Chair of Research Department of Psychiatry

Ahn, S., & Fröhlich, F. (2021). Pinging the Brain with Transcranial Magnetic Stimulation Reveals Cortical Reactivity in Time and Space. Brain Stimulation. https://doi.org/10.1016/j.brs.2021.01.018

A case study of the feasibility of weekly tACS for the treatment of auditory hallucinations in schizophrenia

We report on the successful completion of 20 weekly 40-min transcranial alternating current stimulation (tACS) sessions and an increase in the sense of controllability of the auditory hallucinations by the patient. Our study supports the feasibility and safety of prolonged, weekly tACS paradigms in patients with schizophrenia.

PI: Flavio Frohlich PhD MSc ETH Associate Professor Associate Vice Chair of Research Department of Psychiatry

Force, R. B., Riddle, J., Jarskog, L. F., & Fröhlich, F. (2021). A case study of the feasibility of weekly tACS for the treatment of auditory hallucinations in schizophrenia. Brain Stimulation. https://doi.org/10.1016/j.brs.2021.01.014

Use of Mobile Technology Paired with Heart Rate Monitor to Remotely Quantify Behavioral Health Markers among Military Reservists and First Responders

Psychological resilience, an individual’s ability to recover from an adverse event and return to physiological homeostasis and mental well-being, can be assessed through Heart rate variability (HRV), a biological marker that reflects an individual’s autonomic nervous system regulation, indicated by higher resting HRV. The Biofeedback Assisted Resilience Training (BART) study evaluates a Digital Health Platform (DHP) intervention model to build resilience, with or without HRV biofeedback. This article evaluates the feasibility of remote psychophysiological research by validating the HRV data collected and introduces a DHP to deliver a targeted Intervention.

PI: Maria I. Davila, Research Assistant Professor

Davila MI, Kizakevich PN, Eckhoff R, Morgan J, Meleth S, Ramirez D, Morgan T, Strange LB, Lane M, Weimer B, Lewis A, Lewis GF, Hourani LI. Use of Mobile Technology Paired with Heart Rate Monitor to Remotely Quantify Behavioral Health Markers among Military Reservists and First Responders. Mil Med. 2021 Jan 25;186(Suppl 1):17-24. doi: 10.1093/milmed/usaa395. PMID: 33499533.

December 2020

Screen-detected disordered eating and related traits in a large population sample of females in mainland China: China Health and Nutrition Survey

In China, the prevalence of disordered eating in females has increased from 2009 to 2015. The distribution varies by several sociodemographic factors, which suggests new directions for detection and intervention in China in the future.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Yao, S., Zhang, R., Thornton, L. M., Peat, C. M., Qi, B., Du, S., Wang, H., Zhang, B., & Bulik, C. M. (2020). Screen-detected disordered eating and related traits in a large population sample of females in mainland China: China Health and Nutrition Survey. The International journal of eating disorders, 10.1002/eat.23409. Advance online publication. https://doi.org/10.1002/eat.23409

Identifying mechanisms that predict weight trajectory after bariatric surgery: rationale and design of the biobehavioral trial

Bariatric surgery is the most successful and lasting intervention for severe obesity, but many patients experience extreme weight loss or regain during post-op. This paper describes a study that will identify post-op predictors of weight loss by measuring eating behaviors, diet, and physical activity.

PI: Christine Peat, PhD, Assistant Professor

Heinberg, L. J., Bond, D. S., Carroll, I., Crosby, R., Fodor, A., Fouladi, F., Gunstad, J., Mitchell, J., Peat, C., & Steffen, K. (2020). Identifying mechanisms that predict weight trajectory after bariatric surgery: rationale and design of the biobehavioral trial. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 16(11), 1816–1826. https://doi.org/10.1016/j.soard.2020.06.020

Emotion dysregulation and suicidality in eating disorders

This study found that emotion dysregulation may contribute to suicidality in individuals with EDs. The prevalence of suicidality differs between ED subtypes, but emotion dysregulation was found to be a risk trait for suicidality across all subtypes.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Rania, M., Monell, E., Sjölander, A., & Bulik, C. M. (2020). Emotion dysregulation and suicidality in eating disorders. The International journal of eating disorders, 10.1002/eat.23410. Advance online publication. https://doi.org/10.1002/eat.23410

Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ~1,000 individuals in the United States and the Netherlands

This survey revealed that participants of all eating disorder types reported increased symptoms and concerns due to COVID. On the other hand, they also reported some positive effects such as increased time for self-care and motivation to recover.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Termorshuizen, J. D., Watson, H. J., Thornton, L. M., Borg, S., Flatt, R. E., MacDermod, C. M., Harper, L. E., van Furth, E. F., Peat, C. M., & Bulik, C. M. (2020). Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ~1,000 individuals in the United States and the Netherlands. The International journal of eating disorders, 53(11), 1780–1790. https://doi.org/10.1002/eat.23353

Comparing eating disorder characteristics and treatment in self-identified competitive athletes and non-athletes from the National Eating Disorders Association online screening tool.

This study compared eating disorder characteristics between athletes and non-athletes. While the distribution of diagnoses was similar between the two groups, symptom profiles and frequency may differ with further research.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Flatt, R. E., Thornton, L. M., Fitzsimmons-Craft, E. E., Balantekin, K. N., Smolar, L., Mysko, C., Wilfley, D. E., Taylor, C. B., DeFreese, J. D., Bardone-Cone, A. M., & Bulik, C. M. (2020). Comparing eating disorder characteristics and treatment in self-identified competitive athletes and non-athletes from the National Eating Disorders Association online screening tool. The International journal of eating disorders, 10.1002/eat.23415. Advance online publication. https://doi.org/10.1002/eat.23415

Eating disorder symptoms in Asian American college students.

PI: Melissa Munn-Chernoff, PhD, MPE Assistant Professor

Uri, R. C., Wu, Y. K., Baker, J. H., & Munn-Chernoff, M. A. (2020). Eating disorder symptoms in Asian American college students. Eating behaviors, 40, 101458. Advance online publication. https://doi.org/10.1016/j.eatbeh.2020.101458

Association between food addiction and body dissatisfaction among college students: The mediating role of eating expectancies

There is an association between food addiction and body dissatisfaction in college students. This study discovered that this association is partially mediated by an eating expectancy that eating leads to feeling out of control. Addressing this eating expectancy in interventions can help better address the co-occurence of food addiction and body dissatisfaction.

PI: Jessica Baker, PhD Assistant Professor

Wu, Y. K., Zimmer, C., Munn-Chernoff, M. A., & Baker, J. H. (2020). Association between food addiction and body dissatisfaction among college students: The mediating role of eating expectancies. Eating behaviors, 39, 101441. https://doi.org/10.1016/j.eatbeh.2020.101441

Interventions to Empower Adults with Eating Disorders and Their Partners around the Transition to Parenthood

This paper discusses the importance of researching parental eating disorders and their effects on families. Couple-focused and family based treatments for eating disorders are developing, but not universally available. Therefore, it is extremely imperative to prepare individuals with eating disorder histories for the transition to parenthood.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Sadeh-Sharvit, S., Sacks, M. R., Runfola, C. D., Bulik, C. M., & Lock, J. D. (2020). Interventions to Empower Adults with Eating Disorders and Their Partners around the Transition to Parenthood. Family process, 59(4), 1407–1422. https://doi.org/10.1111/famp.12510

Interventions to Empower Adults with Eating Disorders and Their Partners around the Transition to Parenthood

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Alternative Frameworks for Advancing the Study of Eating Disorders

The basic underlying mechanisms of eating disorders are understudied, and this paper identifies new avenues of research that can help develop informed prevention and treatment interventions. One of these avenues is studying neuroimmune diseases with restrictive feeding components to provide insight into the biological component of eating disorders.

PI: Cynthia Bulik, PhD, FAED Distinguished Professor of Eating Disorders

Stern, S. A., & Bulik, C. M. (2020). Alternative Frameworks for Advancing the Study of Eating Disorders. Trends in neurosciences, 43(12), 951–959. https://doi.org/10.1016/j.tins.2020.10.001

Using digital imagery to quantify students’ added sugar intake at lunch in Title I schools with universal free meals

This study looked at the added sugar component of school meals. Students’ on average added sugar consumption fell within daily Dietary Guidelines for Americans, supporting the claim that school lunches are low in added sugar.

PI: Laura Thornton, PhD Assistant Professor

Adams, E. L., Raynor, H. A., Thornton, L. M., Mazzeo, S. E., & Bean, M. K. (2020). Using digital imagery to quantify students’ added sugar intake at lunch in Title I schools with universal free meals. Preventive medicine reports, 20, 101253. https://doi.org/10.1016/j.pmedr.2020.101253

November 2020

Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivational Salient Stimuli

Prenatal exposures to different substances impact fetal/infant brain development of functional connectivity (FC) in different patterns during neonatal functional MRI. Connections that showed significant drug effects also demonstrated significant correlations with 3-month behavioral outcomes, and mediation analyses supported a mediation role of the detected brain FCs between PDE status and cognitive/language outcomes

PI: Jose Rodriguez-Romaguera, PhD

Rodriguez-Romaguera J*, Ung RL*, Nomura H, Otis JM, Basiri ML, Namboodiri VMK, Zhu X, Robinson JE, van den Munkhof HE, McHenry JA, Eckman LEH, Kosyk O, Jhou TC, Kash TL, Bruchas MR and Stuber GD. (2020) “Prepronociceptin-expressing neurons in the extended amygdala encode and promote rapid arousal responses to motivational salient stimuli”. *co-first authors. Cell Reports, 33, 108362.

Functional Dissection of Prenatal Drug Effects on Baby Brain and Behavioral Development

MPI’s: Karen Grewen, Professor of Psychiatry, UNC Chapel Hill; Wei Gao, Ph.D., Associate Professor Radiology, Cedars Sinai Medical Center

Salzwedel A, Chen G, Chen Y, Grewen K, Gao W.
Hum Brain Mapp. 2020 Dec;41(17):4789-4803. doi: 10.1002/hbm.25158. Epub 2020 Aug 11.
PMID: 32779835

HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women

Highlights
• Blunted regulation of the stress response is associated with lower peripheral blood TNF and FKBP5 methylation
• Caregiving stress burden is associated with lower peripheral blood IL6 methylation
• Lower TNF methylation is associated with higher TNF expression after immune cell stimulation

PI: Anthony Zannas, Assistant Professor of Psychiatry and Genetics

Palma-Gudiel H, Prather AA, Lin J, Oxendine JD, Guintivano J, Xia K, Rubinow DR, Wolkowitz O, Epel ES, Zannas AS. Brain Behav Immun. 2020 Nov 19

Reconsidering Scarce Drug Rationing: Implications for Clinical Research

We present a case of a national drug shortage of intravenous thiamine in the context of a phase II trial of intravenous thiamine for delirium prevention in patients undergoing hematopoietic stem cell transplantation to emphasize several shortcomings in the overarching ethical prioritization of clinical over research uses of scarce drugs.

PI: Zev Nakamura, MD, Assistant Professor

Nakamura ZM, MacKay DP, Davis AM, Brassfield ER, Joyner BL Jr, Rosenstein DL.
Reconsidering scarce drug rationing: implications for clinical research.
J Med Ethics. 2020 Nov 27:medethics-2020-106739. doi: 10.1136/medethics-2020-106739.
Online ahead of print.
PMID: 33246996

Self-Compassion and Current Close Interpersonal Relationships: A Scoping Literature Review

This is a scoping review on literature that links self-compassion with outcomes in close personal relationships.

PI: Karen Bluth, PhD

Lathren, C., Rao, S., Park, J., Bluth, K. (in press). Self-Compassion and Current Close Interpersonal Relationships: A Scoping Literature Review. Mindfulness.

October 2020

Individual Variation of Human Cortical Structure is Established in the First Years of Life.

Most psychiatric illnesses are associated with abnormalities of brain structure, though it is not known when these abnormalities arise in development. We found that individual differences in cortical structure are present very early in life, indicating that abnormalities associated with psychiatric disease may be present early in childhood, and that interventions to normalize brain development and decrease risk may need to be targeted to early childhood.

PI: John Gilmore, MD

Gilmore JH, Langworthy BW, Girault JB, Fine J, Jha SC, Kim SH, Cornea E, Styner M. Individual variation of human cortical structure is established in the first years of life. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2020 Jun 9:S2451-9022(20)30137-3. doi: 10.1016/j.bpsc.2020.05.012. Online ahead of print. PMID: 32741702.

Low-dose Alcohol: Interoceptive and Molecular Effects and the Role of Dentate Gyrus in Rats

Most research on alcohol use focuses on the consequences of moderate to high levels of alcohol. However, even at low concentrations, alcohol is capable of producing effects in the brain that can ultimately affect behavior. Here we show that a low alcohol dose modulates expression of immediate early genes in brain regions in a variety of brain regions and that the dentate gyrus (a subregion of the hippocampus) is involved in modulating the interoceptive/subjective effects of a low dose of alcohol.

PI: Joyce Besheer, MD

Patrick A Randall, Dennis F Lovelock, Kalynn VanVoorhies, Verda E Agan, Thomas L Kash, Joyce Besheer (in press). Low-dose alcohol: Interoceptive and molecular effects and the role of dentate gyrus in rats. Addiction Biology.

Subdural Hemorrhage in Asymptomatic Neonates: Neurodevelopemntal Outcomes and MRI Findings at 2 years

We previously found that a significant number of newborns have asymptomatic subdural hemorrhages after vaginal birth. It is not known if these bleeds impact cognitive development. We found that children with these neonatal bleeds are developing normally at age 2 years, a reassuring finding.

PI: John Gilmore, MD

Zamora C, Sams C, Cornea EA, Yuan Z, Smith JK, Gilmore JH. Subdural hemorrhage in asymptomatic neonates: Neurodevelopemntal outcomes and MRI findings at 2 years. Radiology 2020 doi.org/10.1148/radiol.2020201857 Online ahead of print. PMID: 33107801

Association Between Depression and HIV Care Engagement Outcomes Among Patients Newly Initiating ART in Lilongwe, Malawi

The prevalence of depression among this population of adults newly initiating ART was 27%. Depression at ART initiation was not associated with either retention or viral suppression. Further investigation of the relationship between depression and HIV is needed to understand the ways depression impacts the different aspects of HIV care engagement.

PI: Bradley Gaines, MD

Stockton MA, Gaynes BN, Hosseinipour MC, Pettifor AE, Maselko J, Mphonda SM, Kulisewa K, Udedi M, Pence BW. AIDS Behav. 2020 Sep 24. doi: 10.1007/s10461-020-03041-7. Epub ahead of print. PMID: 32970274.

Prepronociceptin expressing neurons in the extended amygdala encode and promote rapid arousal responses to motivational salient stimuli

Rodriguez-Romaguera et al. find an ensemble of neurons within the extended amygdala (BNST) that expresses the prepronociceptin gene and functions to encode the rapid arousal responses that are triggered by motivational stimuli.

PI: Jose Rodriguez-Romaguera, PhD and Garret Stuber, PhD

Rodriguez-Romaguera J*, Ung RL*, Nomura H, Otis JM, Basiri ML, Namboodiri VMK, Zhu X, Robinson JE, van den Munkhof HE, McHenry JA, Eckman LEH, Kosyk O, Jhou TC, Kash TL, Bruchas MR and Stuber GD. “Prepronociceptin expressing neurons in the extended amygdala encode and promote rapid arousal responses to motivational salient stimuli”. *co-first authors. Cell Reports. 33(6):108362. *Equal contribution

Phenotyping CCL2 Containing Central Amygdala Neurons Controlling Alcohol Withdrawal-Induced Anxiety

Neuroimmune proteins, such as chemokine (C-C motif) ligand 2 (CCL2), are altered by environmental factors, such as drugs of abuse and stress, and are thought to play a role in many important associated behaviors. This paper shows that in the case of an alcohol related behavior, CCL2 from neurons alters behavior indicating that non-immune cells of the nervous system are an important source of CCL2 related to behavior.

PI: Kathryn Harper, PhD and George Breese, PhD

Harper Kathryn M., Knapp Darin J., Todd Caroline A., Balan Irina, Aurelian Laure, Criswell Hugh E., Breese George R., Phenotyping CCL2 Containing Central Amygdala Neurons Controlling Alcohol Withdrawal-Induced Anxiety. Frontiers in Cellular Neuroscience. 14. 2020. 296. DOI=10.3389/fncel.2020.580583

September 2020

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer

This study evaluated patient and provider reported depression and anxiety symptoms during chemotherapy for breast cancer. The prevalence of these symptoms doubled during treatment with 26% reporting at least moderately severe depression and 41% reporting at least moderately severe anxiety during chemotherapy.

PI: Zev Nakamura, MD

Zev M Nakamura, Allison M Deal, Kirsten A Nyrop, Yi Tang Chen, Laura J Quillen, Tucker Brenizer, Hyman B Muss Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer Oncologist. 2020 Sep 18. doi: 10.1002/onco.13528.

Deficits in auditory predictive coding in individuals with the psychosis risk syndrome: Prediction of conversion to psychosis

Brain electrophysiological responses to expected pattern of auditory information and deviations form these expected patterns are key aspects of pattern recognition and prediction of environmental expectations. This research demonstrates that the ability to generate predictive coding to identify repetition of auditory patterns and detection of information deviation is impaired in psychosis, deficits precede psychosis onset and predict future psychosis risk in Psychosis Risk Syndrome (PRS) individuals.

PI: Aysenil Belger, Professor, Department of Psychiatry and Director Frank Porter Graham Child Development Institute

Authors: Fryer SL, Roach BJ, Hamilton HK, Bachman P, Belger A, Carrión RE, Duncan E, Johannesen J, Light GA, Niznikiewicz M, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, McGlashan TH, Perkins DO, Seidman L, Tsuang M, Walker EF, Woods SW, Mathalon DH.
Publication: J Abnorm Psychol.
Date: 2020 Aug;129(6):599-611.
doi: 10.1037/abn0000513.
PMID: 32757603

Neonatal brain connectivity outliers identify over forty percent of IQ outliers at 4 years of age

This paper continues to explore approaches to improve our understanding of how early brain functional connectivity can be used to predict later IQ.

PI: John Gilmore, Eure Professor and Vice Chair for Research

Neonatal brain connectivity outliers identify over forty percent of IQ outliers at 4 years of age.
Gao W, Chen Y, Cornea E, Goldman BD, Gilmore JH. Brain Behav. 2020 Sep 17:e01846. doi: 10.1002/brb3.1846. Online ahead of print. PMID: 32945129

The Subgrouping Structure of Newborns with Heterogenous Brain-Behavior Relationships

This study explores a novel approach to understanding how heterogeneous functional brain connections in newborns can be used to precinct IQ at 4 years of age. This paper is part of an ongoing effort to identify early childhood imaging biomarkers of behavioral outcomes a risk for psychiatric disease.

PI: John Gilmore, Eure Professor and Vice Chair for Research

The Subgrouping Structure of Newborns with Heterogenous Brain-Behavior Relationships.
Chen Y, Liu S, Salzwedel A, Stephens R, Cornea E, Goldman BD, Gilmore JH, Gao W. Cereb Cortex. 2020 Sep 18:bhaa226. doi: 10.1093/cercor/bhaa226. Online ahead of print. PMID: 32946557

The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats

In this paper we show that a single exposure to a stressor induced a lasting increase in alcohol drinking and blunted neuronal activation in the amygdala in response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the emergence of escalated alcohol consumption following stress exposure

PI: Joyce Besheer, PhD

Makhijani VH, Franklin JP, Van Voorhies K, Fortino B, Besheer J (in press) The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats. Psychopharmacology.

August 2020

Cognitive Function in Patients Prior to Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

This study evaluated cognitive function in patients presenting to the hospital for bone marrow transplantation. Investigators identified that patients with greater number of medical problems and history of alcohol or substance use were at increased risk for worse cognitive function.

PI: Zev Nakamura, MD

Zev M Nakamura, Allison M Deal, Donald L Rosenstein, Laura J Quillen, Stephanie A Chien, William A Wood, Thomas C Shea, Eliza M Park. Support Care Cancer. 2020 Aug 23. doi: 10.1007/s00520-020-05697-2. PMID: 32829465.

Functional Dissection of Prenatal Drug Effects on Baby Brain and Behavioral Development

Prenatal drug exposure is known to affect fetal brain development with documented long-term consequences. In this study, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole-brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth/scan, sex, birth weight, and maternal depression).

PI: Karen Grewen, PhD

Salzwedel A, Chen G, Chen Y, Grewen K, Gao W. (2020 Aug 11 Online ahead of print).
Functional dissection of prenatal drug effects on baby brain and behavioral development, Hum Brain Mapp.

The NIMH Global Mental Health Research Community and COVID-19

The National Institute of Mental Health (NIMH) supports a network of global research Hubs designed to address questions that arise as low- and middle-income countries widely implement sustainable, evidence-based mental health services. These so-called “NIMH Scale-Up Hubs” are interdisciplinary, with interest and expertise of the people involved in increasing the reach, accessibility, adoption, quality, costs, and effectiveness of mental health services, enhancing collaborative learning and development, building local capacity for implementation research, and establishing relationships with governmental, non-governmental, and community-based stakeholders. We present examples of replicable programs that can support the United Nation’s call for addressing the mental health and well-being of whole societies have been severely impacted by this crisis and are a priority to be addressed urgently.

PI: Bradley N. Gaynes, MD,MPH

Rahman A, Naslund JA, Betancourt TS, Black CJ, Bhan A, Byansi W, Chen H, Gaynes BN, et al. The NIMH global mental health research community and COVID-19 [published online ahead of print, 2020 Aug 21]. Lancet Psychiatry. 2020;S2215-0366(20)30347-3. doi:10.1016/S2215-0366(20)30347-3

Exposure to the Predator Odor TMT Induces Early and Late Differential Gene Expression Related to Stress and Excitatory Synaptic Function throughout the Brain in Male Rats

In this paper we show that a single exposure to a stressor induces molecular adaptations in the brain related to stress and excitatory systems. These findings from this preclinical study could help us understand the persistent glutamatergic dysfunction observed in post-traumatic stress disorder (PTSD).

PI: Joyce Besheer, PhD

Ryan E Tyler, Benjamin Z S Weinberg, Dennis F Lovelock, Laura C Ornelas, Joyce Besheer (in press) Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats. Genes Brain, and Behavior.

Potential Roles of Redox Dysregulation in the Development of Schizophrenia

Most people have heard that “antioxidants” are “good” for our health, implying that “oxidants” are “bad”. When uncontrolled oxidants damage our bodies, but oxidants are not “all bad”, as oxidants are also needed, in controlled doses, to regulate normal cellular functions. We propose that impaired regulation of oxidant levels contributes to risk of schizophrenia and that molecules controlling oxidant levels are attractive drug targets for individualized drug therapy trials for the contexts of prevention and treatment of schizophrenia.

PI: Diana Perkins, MD, MPH

Perkins DO, Jeffries CD, Do KQ. Potential Roles of Redox Dysregulation in the Development of Schizophrenia. Biological Psychiatry. 2020 Aug 15;88(4):326-336. doi: 10.1016/j.biopsych.2020.03.016

Deficits in Auditory Predictive Coding in Individuals with the Psychosis Risk Syndrome: Prediction of Conversion to Psychosis

We found that a measure of brain electrical activity, as recorded by EEG, predicted later development of psychosis.

PI: Diana Perkins, MD, MPH

Fryer SL, Roach BJ, Hamilton HK, et al. Deficits in auditory predictive coding in individuals with the psychosis risk syndrome: Prediction of conversion to psychosis. J Abnorm Psychol. 2020;129(6):599-611. doi:10.1037/abn0000513

Associations Between Childhood Adversity, Cognitive Schemas and Attenuated Psychotic Symptoms

An indication of when childhood trauma make increase psychosis vulnerability may be when the child then intends to generally interpret other people as threatening.

PI: Diana Perkins, MD, MPH

LoPilato AM, Zhang Y, Pike M, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman L, Perkins DO, Tsuang MT, Woods SW, Walker EF. Associations between childhood adversity, cognitive schemas and attenuated psychotic symptoms. Early Interv Psychiatry. 2020 Aug 7. doi: 10.1111/eip.13017.

June 2020

A Nexus Model of Restricted Interests in Autism Spectrum Disorder

This paper proposes a new way to understand restricted interests in autism. This model suggests that brain networks that typically process social information may instead to process restricted interests instead.

PI: Gabriel Dichter, PhD

Carter, R.M.; Jung, H., Reaven, J., Blakeley-Smith, A., Dichter, G.S.; (2020); Frontiers in Human Neuroscience: Cognitive Neuroscience. Manuscript ID: 527958

A Systematic Review of Validated Screening Tools for Anxiety Disorders and PTSD in Low to Middle Income Countries

We conducted a systematic review of validated screening tools for detecting anxiety and PTSD in LMICs. While the use of brief screening instruments can bring much needed attention and research opportunities to various at-risk LMIC populations, many have been validated in inadequately designed studies, precluding any general recommendation for specific tools in LMICs. Locally validated screening tools for anxiety and PTSD need further evaluation in well-designed studies to assess whether they can improve the detection and management of these common disorders.

PI: Bradley Gaynes, MD, MPH

Mughal AY, Devadas J, Ardman E, Levis B, Go VF, Gaynes BN. BMC Psychiatry. 2020 Jun 30;20(1):338. doi: 10.1186/s12888-020-02753-3.PMID: 32605551

The Role of Patient-Provider Communication: a qualitative study of patient attitudes regarding co-occurring depression and chronic diseases in Malawi

Depression interventions alone are not effective at improving general medical outcomes, resulting in wide-reaching calls for integrated services. Integrated services are in a nascent phase in low- and middle-incomes in general and in Malawi in particular. This manuscript serves to clarify Malawian patients’ attitudes and perceptions towards depression integration into routine general medical services. We found that training and interventions that facilitate providers’ abilities to transfer their medical knowledge, use strategies to channel their power, and engage patients in a meaningful and collaborative relationship will be key to successfully integrating depression treatment into Malawian general medical clinics.

PI: Bradley Gaynes, MD, MPH

Akiba CF, Zimba CC, Thom A, Matewere M, Go V, Pence B, Gaynes BN, Masiye J. BMC Psychiatry. 2020 May 19;20(1):243. doi: 10.1186/s12888-020-02657-2.PMID: 32429877

Harmonized Outcome Measures for Use in Depression Patient Registries and Clinical Practice

This project aimed to develop a minimum set of standardized outcome measures relevant to both patients and clinicians that can be collected in depression registries and clinical practice. A multistakeholder panel representing clinicians; payers; government agencies; industry; and medical specialty, health care quality, and patient advocacy organizations categorized the 27 identified measures using the Agency for Healthcare Research and Quality’s supported Outcome Measures Framework. The panel identified 10 broadly relevant measures and harmonized definitions for these measures through in-person and virtual meetings, representing a minimum set of outcomes that are relevant to clinicians and patients and appropriate for use in depression research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions, improve patient management and outcomes, and facilitate care coordination.

PI: Bradley Gaynes, MD, MPH

Gliklich RE, Leavy MB, Cosgrove L, Simon GE, Gaynes BN, Peterson LE, Olin B, Cole C, DePaulo JR Jr, Wang P, Crowe CM, Cusin C, Nix M, Berliner E, Trivedi MH. Ann Intern Med. 2020 Jun 16;172(12):803-809. doi: 10.7326/M19-3818. Epub 2020 May 12.PMID: 32422056

Eating Disorders in a Community-based Sample of Women with Alcohol Use Disorder and Nicotine Dependence

Women with lifetime diagnoses of alcohol use disorder and nicotine dependence are at high risk for eating disorder symptoms and diagnoses, underscoring the importance of assessing eating disorder symptoms among women with these disorders.

PI: Melissa Munn-Chernoff, PhD, MPE

Munn-Chernoff MA, Few LR, Matherne CE, Baker JH, Men VY, McCutcheon VV, Agrawal A, Bucholz KK, Madden PAF, Heath AC, Duncan AE. Drug Alcohol Depend. 2020 Jul 1;212:107981. doi: 10.1016/j.drugalcdep.2020.107981. Epub 2020 Apr 25. PMID: 32442752

Genome-Wide Gene-Environment Analyses of Major Depressive Disorder and Reported Lifetime Traumatic Experiences in UK Biobank

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry.

PI: Patrick Sullivan, MD, FRANZCP

Coleman JRI, Peyrot WJ, Purves KL, et al., Mol Psychiatry. 2020 May 18;:]. Mol Psychiatry. 2020;25(7):1430-1446. doi:10.1038/s41380-019-0546-6

The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction.

PI: Patrick Sullivan, MD, FRANZCP

Coleman JRI, Gaspar HA, Bryois J; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Biol Psychiatry. 2020;88(2):169-184. doi:10.1016/j.biopsych.2019.10.015

Chronicity and Sex Affect Genetic Risk Prediction in Schizophrenia

Schizophrenia (SCZ) is a severe mental disorder with immense personal and societal costs; identifying individuals at risk is therefore of utmost importance. Genomic risk profile scores (GRPS) have been shown to significantly predict cases-control status. Making use of a large-population based sample from Sweden, we replicate a previous finding demonstrating that the GRPS is strongly correlated with admission frequency and chronicity of SCZ. Furthermore, we were able to show a substantial gap in prediction accuracy between males and females. In sum, our results indicate that prediction accuracy by GRPS depends on clinical and demographic characteristics.

PI: Patrick Sullivan, MD, FRANZCP

Sandra M Meier, Anna K Kähler, Sarah E Bergen, Patrick F Sullivan, Christina M Hultman, Manuel Mattheisen, Front Psychiatry 2020 Jun 9;11:313. doi: 10.3389/fpsyt.2020.00313. eCollection 2020

Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. Studies of neuropsychiatric disorders and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios have reported multiple putatively causal genes. However, a joint analysis method designed to integrate DNMs from multiple studies has yet to be implemented. We here introduce multiple-trait TADA (mTADA) which jointly analyzes two traits using DNMs from non-overlapping family samples.

PI: Patrick Sullivan, MD, FRANZCP

Tan-Hoang Nguyen, Amanda Dobbyn, Ruth C Brown, Brien P Riley, Joseph D Buxbaum, Dalila Pinto, Shaun M Purcell, Patrick F Sullivan, Xin He, Eli A Stahl’ Nat Commun. 2020 Jun 10;11(1):2929. doi: 10.1038/s41467-020-16487-z

Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder

This study shows that an eye tracking measure may indicate whether a treatment is effective for adolescents and adults with autism.

PI: Gabriel Dichter, PhD

Greene, R.K., Parish-Morris, J., Sullivan, M., Kinard, J.L., Mosner, M.G., Turner-Brown, L.M., Penn, D.L., Wiesen, C.A., Pallathra, A.A., Brodkin, E.S., Schultz, R.T., and Dichter, G.S. (in press).

Design of a Randomized Placebo Controlled Trial of High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation

Dr. Nakamura and colleagues have designed a highly novel and innovative study investigating the use of high dose vitamin B1 to prevent delirium – a common and consequential neuropsychiatric condition in hospital settings – in patients receiving bone marrow transplantation.

PI: Zev Nakamura, MD

Nakamura ZM, Deal AM, Rosenstein DL, Quillen LJ, Chien SA, Wood WA, Shea TC, Park EM. Contemp Clin Trials. 2020 June 30:106076. Epub ahead of print. PMID: 32619524.

Extra-axial Cerebrospinal Fluid Relationships to Infant Brain Structure, Cognitive Development, and Risk for Schizophrenia

Excess cerebrospinal fluid (CSF) around the brain is a potential imaging biomarker of risk for autism in young children. This study characterized extra-axial CSF in a large sample of typically developing children and children at risk for schizophrenia and found that neither group has the amount seen in autism, suggesting it may be a good biomarker of risk for autism and related disorders.

PI: John Gilmore, MD

Murphy VA, Shen MA, Kim SH, Cornea E, Styner M, Gilmore JH. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2020 5:651-659.

White Matter Development from Birth to 6 years of age: a longitudinal study

White matter provides the connections between different parts of the brain and is altered in psychiatric disorders. We studied how white matter develops in early childhood to provide a basis of comparison for future studies of children at risk for psychiatric disorders.

PI: John Gilmore, MD

Stephens RL, Langworthy BW, Short SJ, Girault JB, Styner MA, Gilmore JH. Cerebral Cortex 2020: doi 10.1093/cercor/bhaa170 [Epub ahead of print].

Exploring the relationship between geomagnetic activity and human heart rate variability.

Does space weather (sun spots, solar flares) modulate human physiology as previously claimed? With the correct statistical methods, the answer seems to be “no.”

PI: Flavio Frohlich, PhD

Mattoni M, Ahn S, Fröhlich C, Fröhlich F. Eur J Appl Physiol. 2020 Jun;120(6):1371-1381.

Brain-derived Neurotrophic Factor (BDNF) Polymorphism may Influence the Efficacy of tACS to Modulate Neural Oscillations.

One small mutation in a gene appears to modulate the response of the brain to a novel form non-invasive brain stimulation that we study for the treatment of depression and schizophrenia.

PI: Flavio Frohlich, PhD

Riddle J, McPherson T, Atkins AK, Walker CP, Ahn S, Frohlich F.

Neuromodulation of Sleep Rhythms in Schizophrenia: Towards the rational design of non-invasive brain stimulation.

We propose that brain stimulation during sleep has promise as a potential new treatment for symptoms of schizophrenia.

PI: Flavio Frohlich, PhD

Fröhlich F, Lustenberger C. Schizophr Res. 2020 Jul;221:71-80.