2013 NARSAD Young Investigator Grantees

Basic Research

To understand what happens in the brain to cause mental illness

ANXIETY (See also Anxiety and Depression)

Martin Levesque, Ph.D., Laval University, will examine the role of a transcription factor, Lmx1a/b, in obsessive-compulsive disorder. Transcription factors regulate gene activity and Lmx1a/b regulates the expression of a gene family involved in the dopamine neurotransmitter system and in OCD-like disorders, including Tourette’s syndrome. Studies will be conducted with mice to better understand the function of Lmx1a/b.

Natalina Salmaso, Ph.D., Yale University, is intrigued by the theory that fibroblast growth factor 2 (fgf2), a potent cellular growth factor involved in brain development and the birth of new brain cells (neurogenesis), may be involved in the manifestation of anxiety behavior both in rodents and in humans. Using rodent models, she will try to determine the role of fgf2 in the development of anxiety behavior and explore its therapeutic potential for anxiety symptoms.

Demetrio Sierra, Ph.D., Massachusetts General Hospital, Harvard University, will use non-human primates to find whether there is an anatomical segregation of prefrontal cortex subregions in aversive and rewarded behaviors. He will assess the contribution of neuronal activity in the primate dorsal anterior cingulate cortex to help understand the balance between avoidance and reward. The results will shed light on causes underlying addiction and obsessive-compulsive disorder.

Xiaojing Ye, Ph.D., New York University, will study two brain regions in rats important for emotional memory formation: the dorsal hippocampus and the basolateral amygdala. He will examine whether insulin-like growth factor-II (IGF-II), a memory enhancer, is engaged in this process by regulating synaptic connections within and between these regions. Findings will advance knowledge of memory reconsolidation and strengthening, and may suggest novel strategies for cognitive improvement and means of disrupting maladaptive memory strengthening in PTSD and addiction.

ANXIETY AND DEPRESSION (See also Anxiety; See also Depression)

Kate D. Fitzgerald, M.D., University of Michigan, will conduct a study of children aged five to seven in an effort to elucidate biological and behavioral processes that mark susceptibility to anxiety and depressive symptoms before the onset of full blown illness. This should help identify those at risk and support interventions to promote resilience.

Katharina Kircanski, Ph.D., Stanford University, will compare the functioning of pre- and post-pubertal youths with a history of early life stress to a low-risk group to examine neuroendocrine, autonomic and affective responses to a laboratory stress-induction task. This work will assess brain reactivity and recovery and examine the relation of these measures to diagnoses and symptoms of depression and anxiety disorders.

Heide Klumpp, Ph.D., University of Illinois at Chicago, plans to identify neural predictors of response to cognitive behavioral therapy (CBT) in people with depression and anxiety. Though CBT can be effective for these disorders, many patients remain symptomatic. The evaluation of neural markers linked to effectiveness of CBT is a critical step towards developing a reliable predictor of CBT success.

Jodi Lukkes, Ph.D., McLean Hospital, Harvard University, will study gender-dependent increased vulnerability in adolescent girls to depressive and anxiety-like disorders. New evidence shows that social stress during childhood delays the onset of menstruation. Delayed exposure to estrogen may alter development of emotional brain regions. The project will investigate a link between estrogen, social stress and alterations in stress-related brain regions during adolescent development.

Katie A. McLaughlin, Ph.D., Children’s Hospital, Boston, aims to examine how exposure to maltreatment in childhood influences the architecture of the developing brain in ways that increase risk for anxiety and depression. The work will focus on neural networks involved in emotion regulation, particularly on areas of the brain involved in emotional reactivity and the ability to modulate emotional experiences.

Alina Patke, Ph.D., The Rockefeller University, will explore the genetic basis of the association between a strong preference for evening hours and sleeping late in the day. She has identified a genetic origin for this so-called late chronotype in a patient with a history of clinical depression and plans to investigate the mechanism by which this mutation affects circadian-clock behavior and its connection to mood.

YoneJung Yoon, Ph.D., Weill Cornell Medical College, Cornell University, studies a novel mechanism regulating expression of the serotonin transporter, the molecular target of selective serotonin reuptake inhibitor (SSRI)-class antidepressants. Dr. Yoon seeks to understand the pharmacology and signaling pathways that activate or repress the mechanism, in hope of enhancing early detection of individuals at risk for mood and anxiety disorders and likelihood of response to SSRI treatment.


Nicola M. Grissom, Ph.D., University of Pennsylvania, will explore the interaction of pre- and post-natal diet in a mouse model of ADHD. ADHD prevalence is elevated in children born too large for gestational age (LGA) or too small (SGA). The study will examine how attention is affected by feeding a high-fat diet to mice born SGA, LGA or typical development.

Julie S. Haas, Ph.D., Lehigh University, is interested in how the brain focuses attention. Attention deficits occur in ADHD and schizophrenia. The brain center of attention is found within the thalamic reticular nucleus (TRN), a subsection of the thalamus. This study will explore the plasticity of synapses in the TRN in the context of normal and abnormal brain activity.

Maria Kharitonova, Ph.D., Children’s Hospital, Boston, will investigate the cognitive and neural dysfunction in early childhood that constitute the central deficits in ADHD. The proposed functional magnetic resonance imaging (MRI) study will examine the role of working memory maintenance and interference control, two cognitive constructs that have been inconsistently postulated to be critically impaired in ADHD.

Hagai Maoz, M.D., Tel Aviv University, will explore the hypotheses that children with ADHD have deficits in empathy and “theory of mind,” which is the ability to ascribe mental states, beliefs and intentions to oneself and others. Dr. Maoz will also investigate whether low levels of oxytocin, which enhances social bonds, are associated with theory of mind and empathy deficits in ADHD.


Jyothi Arikkath, Ph.D., University of Nebraska Medical Center, will investigate how mutation in the gene CDKL5 leads to Rett syndrome, a neurodevelopmental disorder associated with ASD, epilepsy and intellectual disabilities. Alterations in synapses, the communication juncture between neurons, have been linked to the syndromes; the CDKL5 gene in cells called astrocytes is important for controlling the structure and function of synapses.

Guy Horev, Ph.D., Cold Spring Harbor Laboratory, will assess brain development in mouse embryos with a genetic deletion on the chromosomal 16p11.2 region, a deletion that occurs in people with ASD. This study aims to pinpoint the genes that lead to autism-like impairment and establish a cellular assay for impairment and, ultimately, to see if reversing the developmental impairment will correct the behavioral impairments.

Christelle Golzio, Ph.D., Duke University, will use zebrafish as a model for developing tools to identify genes from copy number variations (CNVs) associated with ASD. CNVs are genetic alterations resulting in abnormal numbers of copies of sections of the DNA. The data generated should identify a number of genes responsible for ASD and provide a platform for the systematic study of CNVs discovered in patients.

Alaine C. Keebaugh, Ph.D., Emory University, will explore the protective effect of oxytocin signaling and early-life immune activation on the development of social cognition. Dr. Keebaugh will develop an animal model to test the hypothesis that decreased expression of the oxytocin receptor gene will interact with early-life immune activation, resulting in the development of impaired social cognition such as that seen in ASD.

Ji-Ann Lee, Ph.D., University of California, Los Angeles, hopes to elucidate mechanisms that underlie neural circuit dysfunction in ASD and identify targets for treatment. Abnormalities in RNA processing in neurons contribute to ASD and Lee has identified the RNA-binding protein Rbfox1/A2BP1 as a candidate gene. Dr. Lee will explore the hypothesis that loss of Rbfox1 activity contributes to RNA dysregulation and development of the illness. .

Lucas Matt, Ph.D., University of California, Davis, is studying a major ASD gene, PSD-95, the central structural element of postsynaptic excitatory synapses. His focus is a factor called a-actinin, that he thinks is responsible for PSD-95 localization. Defining how PSD-95 is anchored will fill a crucial gap in information about synaptic structure and could aid in the development of new ASD therapies.

Tabrez J. Siddiqui, Ph.D., University of British Columbia, studies synapses, and specifically, alterations in proteins that organize and maintain them, which have been implicated in ASD, schizophrenia, ADHD and intellectual disability. This project, using mice, will test the theory that disruption of a protein complex called LRRTM4-HSPG impairs cognitive function and underlies certain forms of ASD by altering brain connections.

Courtney L. Thaxton, Ph.D., University of North Carolina, Chapel Hill, studies Pitt-Hopkins Syndrome (PTHS), on the spectrum of autism disorder, that is caused by de novo mutation(s) or partial deletion(s) in a single copy of a gene called TCF4. She seeks to develop a new mouse model of TCF4 that better mimics human PTHS so she can study symptom onset function of TCF4 in the nervous system.


June Gruber, Ph.D., Yale University, will examine the behavioral and neural mechanisms that underlie the regulation of reward in BP. This work is based on her theory that reward dysregulation is a core marker of dysfunction in BP and is characterized by increased reward reactivity on the one hand, and decreased regulation for such responses on the other.

Shizhong Han, Ph.D., University of Iowa, hopes to speed gene discovery for BP, for which few genes have been found, by identifying rare or low-frequency gene variants that may contribute to susceptibility for developing the illness. The research will utilize newly available genetic and genomic data and will follow up with sequencing of candidate genes.

Maria De Las Mercedes Perez Rodriguez, M.D., Ph.D., Icahn School of Medicine at Mount Sinai, will follow-up research showing that people with BP and their unaffected siblings show some specific cognitive impairments. She will conduct brain imaging studies to learn whether the abnormalities found in the patients’ brains also occur in the unaffected siblings, and whether the patients’ brain abnormalities are associated with specific cognitive symptoms.

Hyung W. Nam, Ph.D., Mayo Clinic, will investigate whether acamprosate, a medication used to counter alcohol abuse, is beneficial for people with co-existing alcohol dependency and BP. Both disorders are regulated by glutamate neurotransmission. Therefore, inhibition of glutamate signaling by acamprosate treatment may be effective not only for avoiding alcohol, but also for alleviating the manic symptoms of BP.

DEPRESSION (See also Anxiety and Depression)

Nicole L. Baganz, Ph.D., Vanderbilt University, will explore the possible relationship between depression and an inappropriate expression of immune response triggered by infectious agents. Patients with depression often display higher plasma levels of immune chemicals called cytokines. Peripheral administration of bacterial extracts or of pro-inflammatory cytokines has been shown to produce depressive-like effects in rodent and human studies.

Adrienne J. Betz, Ph.D., Quinnipiac University, will explore cells and structures of the hippocampus to identify potential mechanisms underlying the effects of chronic stress in stress-related psychiatric illnesses such as depression. The main objective is to determine the role of a specific transcription factor that controls genes involved in stress-induced immune and inflammatory responses, which can play a role in depression.

Paul R. Burghardt, Ph.D., University of Michigan, will investigate the link between mood disorders and abnormal insulin sensitivity, which is the largest contributor to mortality among people with depression. To shed light on how these diseases can lead to and worsen one another, the research will utilize biomarker screening, psychobehavioral testing and neuroimaging to investigate common biological systems underlying depression and metabolic dysfunction.

Erin C. Dunn, Sc.D., M.P.H., Massachusetts General Hospital, Harvard University, will examine the interplay of genes and environment in depression, using data from the Avon Longitudinal Study of Parents and Children to examine the relationship between genes, exposure to adversity and functioning. The results may help identify when exposure to adversity is most harmful.

Jian Feng, Ph.D., Icahn School of Medicine at Mount Sinai, will use a mouse model of depression to explore the hypothesis that a gene called TET1 and a novel “epigenetic” regulation of DNA play a crucial role in mediating major mood disorders such as depression. (Epigenetic changes are changes in gene expression that do not alter DNA sequence.) This research may provide new targets for depression treatment.

Ellen K. Grishman, M.D., University of Texas Southwestern Medical Center at Dallas, will correlate severity of symptoms in depressed obese adolescents at risk for diabetes with levels of ceramides (fat molecules involved in insulin resistance) and adiponectin (a fat-tissue secretion that decreases risk of diabetes and inflammation by decreasing ceramide levels). Adiponectin levels are lower and ceramide levels higher in people with insulin resistance.

Tamar Lea Gur, M.D., Ph.D., University of Pennsylvania, will study the effect of stress and antidepressants on “epigenetic” regulation in reproduction. Epigenetics refers to environmental impacts that alter gene expression without altering DNA sequence. This research will examine epigenetic changes in eggs and sperm of mice exposed to stress and to antidepressants to determine whether epigenetic changes are passed on to offspring.

Avram Holmes, Ph.D., Harvard University Medical School, plans to establish common and unique patterns of dysfunction in people with unipolar and bipolar depression. This work is based on his recent identification of a biological “marker” of preferential disruption of the frontoparietal control network in individuals with bipolar disorder relative to the general population. Patients with major depressive disorder will be recruited and the data will be coupled with an ongoing study of bipolar disorder.

Jianxiong Jiang, Ph.D., Emory University School of Medicine, will study inflammation in epilepsy-related depression (ERD). Current antidepressants are helpful for patients with this disorder, but can exacerbate seizures, especially when high doses are required. Dr. Jiang will test a hypothesis on the role of prostaglandin receptor signaling in inflammation and ERD, which could lead to novel treatment developments for the disorder.

Ilia N. Karatsoreos, Ph.D., Washington State University, Vancouver, will explore the question of whether disrupting the circadian clock can lead to changes in affect regulation. The research will use a combination of environmental disruptions with mice to probe how the circadian clock and environmental disruption of the clock can modulate behavior and may be not only a symptom of depression but perhaps also a contributing cause.

Stephanie H. Parade, Ph.D., Brown University, will conduct a clinical trial with 150 mothers and their infants to explore whether and how the infant hypothalamic-pituitary-adrenal (HPA) axis, the body’s stress response system, is involved in the intergenerational transmission of major depressive disorder. The aim is to determine whether interparental violence and maternal depression in pregnancy are associated with infant HPA-axis functioning and emotion regulation.

Christophe Proulx, Ph.D., University of California, San Diego, studies the lateral habenula (LHb) area of the brain, implicated in depression pathology. He will manipulate activity of LHb neurons projecting to a dopamine center, and measure impact on depressive behaviors in rats. His hypothesis is that increased activity of neurons projecting to the dopaminergic center will promote––and inhibition will alleviate––depressive behaviors in rats.

Crystal E. Schiller, Ph.D., University of North Carolina, Chapel Hill, will manipulate reproductive hormones in non-pregnant, healthy women to mimic the changes that occur during pregnancy and the postpartum period. This endocrine manipulation paradigm will be used to probe brain activity associated with the regulation of mood and reward processing under different conditions. Using MRI scans, she will examine whether those with a past episode of postpartum depression show differences in emotional arousal and reward processing relative to healthy controls.

Anne L. S. Teissier, Ph.D., Research Foundation for Mental Hygiene, Inc., Columbia University, studies the role of serotonin in the development of mood disorders. This study will focus on a sensitive period of postnatal development during which increased serotonin signaling leads to permanent alterations in adult mood and cognitive behaviors. She will test if a causal relationship exists between serotonin receptor-driven neuronal activity and emotional as well as cognitive behaviors, under normal and pathological conditions.

Brent J. Thompson, Ph.D., University of Texas Health Science Center, San Antonio, will study rodents given early-life exposure to selective serotonin reuptake inhibitor (SSRI) antidepressant medications, at a time corresponding to the 3rd trimester of human development. He will examine biological causes of the anxiety-like symptoms observed in such animals. The results will indicate potential risks of prenatal SSRI exposure to developing fetuses.

Anne Venner, Ph.D., Beth Israel Deaconess Medical Center, Harvard University, seeks to provide insight into the role of serotonin in the regulation of rapid eye movement (REM) sleep and establish a clear link between selective REM sleep manipulation and the development and improvement of major depression. In order to do so she will create and work with a mouse model of depression in which she will identify downstream brain regions involved in REM sleep.


Jonathan D. Morrow, M.D., Ph.D., University of Michigan, will conduct studies in animal models of the neurocircuitry of conditioned fear and reward-seeking behavior to gain deeper understanding of the neurobiology underlying individual differences in vulnerability to co-existing PTSD and addiction. The research will pave the way for future studies aimed at prevention and treatment.


Sandra Ahrens, Ph.D., Cold Spring Harbor Laboratory, will study the role of a brain circuit called the thalamic reticular nucleus circuit and its dysfunction in a genetically-engineered mouse model of schizophrenia. The thalamic reticular nucleus is thought to play a critical role in sensory processing and in cognitive functions such as attention. Attention deficit is a core feature of schizophrenia.

Hannah E. Brown, M.D., Massachusetts General Hospital, Harvard University, will focus on a gene variant associated with schizophrenia’s “negative” symptoms (decrease in motivation, lack of attention and affect, memory loss, social withdrawal), cognitive impairment and brain dysfunction. This gene, MTHFR, is important in how the body processes folate, and influences DNA expression. The study will compare the way genes are expressed in people with schizophrenia who have different variants of the gene.

Solange P. Brown, M.D., Ph.D., Johns Hopkins University, will investigate the poorly understood role of particular neurons located below the cerebral cortex, known to be abnormally distributed in patients with schizophrenia. Using mouse models, Dr. Brown’s goal is to determine the impact of these neurons in generating the cognitive and behavioral symptoms of the illness.

Sarah E. Canetta, Ph.D., Columbia University, will use mouse models of maternal immune activation, a prenatal risk factor for development of schizophrenia in offspring. She will study effects on neuronal circuits related to cognition and working (short-term) memory, seeking to identify a relationship between maternal immune activation and development of prefrontal cortex neurons in the offspring.

Ioana Carcea, M.D., Ph.D., New York University School of Medicine, will examine the hypothesis that the rate of release of the neurotransmitter dopamine in the prefrontal cortex dictates adaptive behaviors. Dysfunction in the regulation of dopamine release could account for the incapacity to adapt to sudden changes in external conditions, which severely affects the quality of life in people with schizophrenia.

Anne L. Collins, Ph.D., University of North Carolina at Chapel Hill, will seek to learn whether and how the genetic pathways and processes regulated by microRNA-137 (miR-137) are involved in schizophrenia. (MicroRNAs are molecules that play a role in gene expression.) MiR-137 is also implicated in Alzheimer’s disease and may have broad relevance to neuronal development and neurological disease.

Jennifer M. Coughlin, M.D., Johns Hopkins University, will examine the hypothesis that oxidative stress (excess of free radicals) and associated inflammatory response in the brain may play a role in schizophrenia in high-risk people. She will test cerebrospinal fluid and serum from a large number of patients with recent-onset schizophrenia for predictive markers of increased oxidative stress and neuroinflammation. Results may aid in early treatment intervention.

Juan A. Gallego, M.D., Feinstein Institute for Medical Research, will compare MicroRNA expression profiles in patients with first- episode schizophrenia and healthy volunteers. MicroRNAs are small molecules involved in gene regulation. Recent studies have linked alterations in MicroRNA expression to schizophrenia, and the hope is that they can be useful biological markers of brain abnormalities and/or responsiveness to antipsychotic treatment.

Kazue Hashimoto-Torii, Ph.D., Children’s National Medical Center, will investigate how genetic and prenatal environmental factors contribute to the pathogenesis of schizophrenia, a disorder in which the first episode is usually delayed until young adulthood. The study will explore the interaction of oxidative stress induced in neural progenitor cells by a variety of prenatal environmental factors.

Xiao-Hong Lu, Ph.D., University of California, Los Angeles, will take advantage of the recent discovery of a major risk factor for schizophrenia by generating a mouse model of over-expression of a gene called VIPR2 with a genetic switch that can be turned off in selective brain regions and at different periods of brain development. This research aims to identify how this particular mutation leads to schizophrenia.

Heline Mirzakhanian, Ph.D., University of California, San Diego, will investigate whether there is a relationship between the neurotransmitter glutamate and cortical thickness in people with first-episode psychosis. Abnormalities in the glutamatergic system may account for some abnormalities in schizophrenia; Dr. Mirzakhanian will study whether an increase in cortical glutamatergic activity leads to structural brain changes, including reduced cortical thickness, that in turn leads to neurocognitive impairments.

Amanda C. Mitchell, Ph.D., Icahn School of Medicine at Mount Sinai, will examine the association of epigenetic gene dysregulation with schizophrenia. Epigenetic activity, such as the addition of methyl chemicals to DNA, can alter a gene’s expression without changing the underlying DNA sequence. The cause of schizophrenia is unknown, and few susceptibility genes have been found, but numerous gene-regulation alterations have been reported.

Lauren V. Moran, M.D., Massachusetts General Hospital, Harvard University, is looking for biological “markers” to account for the increased craving for and higher rate of smoking among people with schizophrenia. The research will follow up findings that the connection between two regions of the brain is decreased in nicotine addiction, and that smokers with schizophrenia have even greater impairment in this connection.

Semanti Mukherjee, Ph.D., Feinstein Institute for Medical Research, will examine as a risk factor for schizophrenia what are called runs of homozygosity, which are extended genomic regions in which the genetic material is inherited identically from both parents. This will be studied in an Ashkenazi Jewish population in which the overall occurrence of this phenomenon is higher than average.

Jess Nithianantharajah, Ph.D., University of Edinburgh, will investigate how key scaffold genes that are integral for organizing synapses (connections between brain cells) control different complex behaviors and mental processes and are involved in cognitive dysfunction in psychiatric disorders such as schizophrenia. Assessing mice with mutations in two scaffold genes will initiate identification of clusters of complex cognitive behaviors according to their distinct genetic underpinnings.

Katie L. Nugent, Ph.D., Maryland Psychiatric Research Center, University of Maryland, will conduct tests to learn why female schizophrenia patients fare better after illness onset than males, a response that may occur because more females than males employ adaptive strategies for coping with social stress, leading to differing biological stress responses. Results of the study may suggest specific targeted interventions for coping with social stress.

Melissa L. Perreault, Ph.D., Centre for Addiction and Mental Health, University of Toronto, will focus on how a specific protein, brain-derived neurotrophic factor, may contribute to the cognitive deficiencies of schizophrenia by inducing increased activation of the protein GSK-3β and altered activity of neurons that regulate cognitive function. Reduced GSK-3β activation has been associated with marked in cognitive function in a number of other neurological disorders.

Todd F. Roberts, Ph.D., University of Texas Southwestern Medical Center at Dallas, is interested in disordered speech and thought patterns, as well as auditory hallucinations and delusions in psychosis. He will test the theory that these “positive” core symptoms of schizophrenia arise from a disruption in structures called corollary discharge pathways in the brain. He will test whether the genetic lesions of this pathway in rodents cause disordered sequencing of learned vocalizations that may be akin to disordered speech in schizophrenia.

Juan Song, Ph.D., Johns Hopkins University School of Medicine, seeks to discover the cause of disturbances in gamma-frequency oscillation––rhythms that emerge during performance of cognitive tasks––which are thought to be a source of brain dysfunction in schizophrenia. Focusing on a specific type of neuron called PV+, he hopes to get to the bottom of defects in neuronal synchrony to guide development of new schizophrenia medications.

Theodorus Tsetsenis, Ph.D., Stanford University, will create a mouse model of schizophrenia based on “truncating” mutations in the gene encoding the neurexin 1 protein. He will use this model to identify the specific circuits involved in disease pathophysiology to shed light on the molecular and cellular underpinnings of schizophrenia. He hopes to uncover new information about the dysfunction of specific brain circuits to guide therapeutic interventions.


Mulugeta S. Abebe, Ph.D., Columbia University, will use a monkey model of human neural processing to develop a more comprehensive understanding of memory formation, specifically with environmental memory––or memory of objects in a particular location—which may, if needed, be turned into working, or short-term memory. Memory impairment is a significant factor in psychiatric disorders such as schizophrenia and depression.

Frederic Ambroggi, Ph.D., University of California, San Francisco, wants to explain the dysfunction in motivation common to many mental illnesses, including drug addiction, depression and eating disorders, by determining how internal information in the brain is communicated to the nucleus accumbens, where information is translated into actions in pursuit of rewards.

Laura M. Fiori, Ph.D., University of Ottawa, will investigate the relationship between gene expression and specific DNA methylation marks (a field known as “epigenetics”) associated with early childhood adversity and the development of psychopathology later in life. Methylation is a process that adds methyl chemicals to DNA to change gene expression but not DNA sequence. Ultimately, these processes represent novel targets for early diagnosis and treatment of brain and behavior disorders.

Judy Liu, Ph.D., Children’s National Medical Center, hopes to improve understanding of the cell biology behind the development of axons, the projections on nerve cells that carry the cell’s signals. Disorders such as schizophrenia, autism spectrum disorder (ASD) and epilepsy may result from problems in axonal development. The study will explore the role of doublecortin, a gene crucial to axon guidance.


Beth E. Cohn, M.D., University of California, San Francisco, will examine the role of inflammation in PTSD and depression, using data from a large, ongoing study to determine whether patients with lower inflammation levels are more likely to recover and people with higher levels more likely to develop these disorders. The study will compare inflammation changes in patients whose symptoms improve, worsen or remain stable.

Christina Gross, Ph.D., Emory University, will examine an enzyme of the PI3K/mTOR pathway, a molecular complex that is often defective in both autism spectrum disorder (ASD) and schizophrenia. This pathway is essential for neurons to respond to external signals, and thus might serve as a therapeutic target. The study will analyze molecular mechanisms in cells from patients with ASD and schizophrenia that carry defects in the enzyme.

Benjamin Y. Hayden, Ph.D., University of Rochester, is interested in the brain changes that underlie the decreases in cognitive flexibility that characterize schizophrenia and addiction and are thought to derive from changes to the striatum brain region. Neural activity in the striatum of healthy rhesus monkeys performing a cognitive flexibility task will first be recorded to establish typical activity.

Jia Sheng Hu, Ph.D., University of California, San Francisco, will explore the disruption in the balance between excitation and inhibition in brain activity by dysfunctional inhibitory neurons, a condition tied to epilepsy, schizophrenia and ASD. Building on work on the Coup-TF2 gene, identified as important in maintaining a distribution of inhibitory neurons across the brain, this study will explore its pre-natal development.

Soo Young Kim, Ph.D., University of California, Berkeley, will examine mechanisms that underlie early-life stress-induced anxiety disorders and schizophrenia. Specifically, the study will look at the effects of stress on the development of the extracellular matrix (the space outside of cells in the brain) and on the maturation of GABAergic neurons, nerve cells involved in the activity of GABA, the brain’s major inhibitory neurotransmitter.

Torsten Klengel, M.D., Max Planck Institute for Psychiatry, seeks to identify the impact of early-life stress on epigenetic changes, which affect gene expression but do not alter DNA sequence, in a research model with primates. By assessing epigenetic, endocrine and behavioral changes over time, it may be possible to determine when the organism is most vulnerable to stress and when lasting epigenetic modifications are established.

Pan Li, Ph.D., Johns Hopkins University, will explore a possible regulatory mechanism affecting a protein called DISC (Disrupted-In-Schizophrenia) which is involved in development of the disease. This research will follow up on findings that led Li to hypothesize that DISC2 regulates DISC1, with implications for schizophrenia and bipolar disorder, and will advance the little explored area of RNA-mediated pathogenesis in psychiatric diseases.

Machteld C. Marcelis, M.D., Ph.D., Maastricht University, plans to study the relationship between a novel intervention for early psychopathology and brain changes in young people at high risk for developing depression and/or psychosis. Patients will receive a self-management intervention training that targets stress in daily life and provides feedback of patterns of reactivity with the aim of helping participants identify and remedy dysfunctional emotional patterns.

Nadine M. Melhem, Ph.D., University of Pittsburgh, will conduct a study to look for biological “markers” (or predictors) of depression and PTSD in the stress-associated hypothalamic-pituitary-adrenal (HPA) axis. The goal is to create a biological model of stress response with pre- and post-stress measures of HPA-axis activity to identify biological markers that signal risk for depression and PTSD.

Frederick C. Nucifora, Ph.D., D.O., M.H.S., Johns Hopkins University School of Medicine, will focus on NPAS3, a protein associated with schizophrenia, bipolar disorder and antipsychotic treatment efficacy. NPAS3 belongs to a family of transcription factors involved in important neurobiological processes, including response to cell signaling and regulation of the birth of new nerve cells (neurogenesis). The proposed experiments will determine whether mutant NPAS3 leads to abnormal neuronal structure and function.

Fereshteh, S. Nugent, Ph.D., Uniformed Services University of the Health Sciences, will explore the role of dysfunction in the lateral habenula brain region in stress-related disorders, including depression, anxiety, psychosis and drug addiction. Specifically, the effect of a key mediator of stress response in the brain, corticotropin releasing factor (CRF), on neurons in the lateral habenula will be studied.

Edwin C. Oh, Ph.D., Duke University, will probe the role(s) of a single gene, Kctd13, located in a region of the genome called 16p11.2, which has most often been found to be deleted or multiplied abnormally in autism spectrum disorder (ASD) and schizophrenia. The aim is to resolve uncertainty about which gene in an abnormal genome region containing many genes is specifically responsible for pathology, a model that might be applicable in similar instances across the genome.

Angela R. Ozburn, Ph.D., University of Pittsburgh, will follow up strong evidence that circadian genes are important in the expression of mood-related symptoms in psychiatric disorders. Circadian gene expression is altered by stress, depression and drug abuse. The research will focus on the circadian transcription factor NPAS2.

Dirk J.A. Smit, Ph.D., Vrije Universiteit Amsterdam, is interested in how the brain can switch from a state of attentiveness to one of inattentiveness. While generally a normal brain activity, inattentiveness is excessive in some psychiatric disorders. This project will test whether “brain switching” also explains differences in attentiveness in pairs of twins and could help clarify attention deficits in various psychiatric disorders.

Joyce So, M.D., Ph.D., Centre for Addiction and Mental Health, University of Toronto, wants to determine the prevalence of common genetic conditions in psychiatric patients who have other medical or developmental issues. She is recruiting patients with birth defects, neurological conditions, unusual facial features, developmental delay, autism spectrum disorder (ASD), or a family history of these. The hope is to identify “red flags” that may aid in achieving a genetic diagnosis in the future for patients with similar histories.

Eli A. Stahl, Ph.D., Icahn School of Medicine at Mount Sinai, will use genomic data for schizophrenia and bipolar disorder that are part of ongoing genetic studies to build risk prediction models for 1) schizophrenia or bipolar disorder (BP), and 2) schizophrenia versus BP. Resulting models will be used to predict conversion to psychosis in clinically high-risk patients, in a longitudinally followed sample of early-onset (or “prodromal”) patients.

Bin Xu, Ph.D., Columbia University, will clarify the functional impact of three genes involved in epigenetic regulation that are mutated in both schizophrenia and autism spectrum disorder (ASD). “Epigenetics” refers to environmental factors that affect gene expression without altering the underlying DNA sequence. Using mouse models, Dr. Xu will study their temporal and spatial expression pattern, , identify target genes and evaluate the functional impact of altered activity of these genes on brain development.



Jia-Hua Hu, Ph.D., Johns Hopkins University, seeks to identify how the mechanisms of a protein he identified as regulating D1 dopamine receptor signaling are linked to cocaine addiction. Using knock-out and transgenic mouse models that he generated, he will examine dysfunctions of dopaminergic systems also known to be associated with schizophrenia, Parkinson’s disease, bipolar disorder and ADHD.

Shahrdad Lotfipour, Ph.D., University of California, Los Angeles, will use data from a study of 1,024 adolescents, half of whom have been exposed to maternal cigarette smoking. This research aims to determine the relationship between a particular genetic variation in a nicotinic receptor subunit, maternal smoking during pregnancy and susceptibility for increased substance use in offspring. He will look specifically at structural changes in reward-related brain regions.

Eating Disorders

Patricia Bonnavion, Ph.D., Stanford University, seeks to establish a model of chronic stress disturbances in anorexia to provide better understanding of its pathogenesis and to guide new treatment strategies. Dr. Bonnavian will explore what triggers the self-induced starvation and anxiety in anorexia nervosa by investigating the role of leptin, a hormone that modulates stress response.

Ida A.K. Nilsson, Ph.D., Karolinska Institutet, will study the neurobiology of anorexia to understand how the normal drive to eat becomes suppressed. The project will focus on the hypothalamus, the brain area where hunger and food intake is regulated, following up studies with animal models that show a breakdown of neuronal functioning in the hypothalamus and dysfunction in the mitochondria, the cellular energy factory.


Hanan D. Trotman, Ph.D., Emory University, will do a first-time study of longitudinal changes in gonadal hormones and subsequent effects on symptom progression and risk for psychosis in high-risk individuals. Using samples from patients with psychosis collected in the North American Longitudinal Study, Dr. Trotman will delineate the relation of gonadal hormones with symptom progression and with cortisol.


Molly Adrian, Ph.D., University of Washington, will explore four types of genetic variations called single nucleotide polymorphisms (SNPs). These SNPs are associated with dysregulation of the HPA axis, the body’s stress system, and an increased risk for suicidal behaviors during adolescence. The project is based on the hypothesis that SNPs affect emotion regulation, causing hopelessness and impulsive-aggression traits, leading to suicide attempts.

Rashelle J. Musci, Ph.D., Johns Hopkins University School of Medicine, will explore the relationship between aggressive and impulsive suicidal behavior and genes associated with serotonin neurotransmission, using a dataset from the Center for Prevention Research begun in 1993 with African American first-graders in Baltimore, and continued yearly since. This research could facilitate prevention programs by individualizing identification of people at risk of suicide.


New Technologies

to advance or create new ways of studying and understanding the brain

ANXIETY (See also Anxiety and Depression)

Mark Aizenberg, Ph.D., University of Pennsylvania, will examine how abnormalities in fear responses can lead to anxiety disorders and PTSD. A central feature of anxiety disorders is inability to distinguish between dangerous and safe situations. Using newly developed optogenetic tools, the research will test a neuronal circuit in the auditory cortex as a candidate for regulation of generalized fear responses in mouse models.

Anthony N. Burgos-Robles, Ph.D., Massachusetts Institute of Technology, will combine the use of animal models, optogenetics and neuronal recording to examine the mechanisms that regulate competing fear and reward memories in anxiety disorders and as related to the symptom of anhedonia (the inability to experience pleasure). The research will focus on two brain regions––the basolateral amygdala and the medial prefrontal cortex––to learn how they interact and coordinate these conflicting behaviors.

Gerard Clarke, Ph.D., University College Cork, will investigate the role of bacteria in the gut in anxiety disorders. MicroRNAs are molecules involved in controlling gene expression (activation) and in the development of anxiety disorders. Gene expression in the brain also can be controlled by gut bacteria. This research will seek to determine whether MicroRNAs important for anxiety can be influenced by gut bacteria.

Eli R. Lebowitz, Ph.D., Yale University, will study avoidance behavior in anxiety disorders. Youths aged eight to 16 diagnosed with clinical anxiety will take part in a clinical trial using an innovative motion-tracking technology, the Yale Interactive Kinect Environment Software, to quantifiably measure avoidance, to relate it to self-report of anxiety and explore other questions such as to what extent anxiety is specific to a given trigger.

Sue-Hyun Lee, Ph.D., National Institute of Mental Health, aims to develop an effective strategy to disrupt fear memory in PTSD. To test the hypothesis that different components of the recalled memory are maintained in distinct cortical areas, Dr. Lee will use functional magnetic resonance imaging (fMRI) to identify target areas and transcranial magnetic stimulation (TMS) as a treatment immediately after memory recall to see if the memory is disrupted.

Kay M. Tye, Ph.D., Massachusetts Institute of Technology, will use optogenetics technology to manipulate neurons in specific pathways implicated in anxiety disorders. She will observe the effect on neural activity as well as corresponding behaviors. She ultimately seeks to “crack the neural code of anxiety” and achieve new insight towards effectively treating these disorders.

ANXIETY AND DEPRESSION (See also Anxiety; See also Depression)

Philip Trovote, Ph.D., Friedrich Miescher Institute, is interested in defensive avoidance and related coping strategies which are maladapted in human anxiety and mood disorders. Through careful dissection and analysis of defensive circuits in the midbrain periaqueductal grey (PAG) area using optogenetics and other advanced techniques in freely moving animals, he hopes to find potential targets for future therapeutic interventions.


Seung-Hee Lee, Ph.D., University of California, Berkeley, will combine molecular, physiological, anatomical and behavioral techniques to probe the neuromodulatory circuit in the basal forebrain, a brain structure important in attention. The focus will be on unraveling specific circuit mechanisms by which the basal forebrain adjusts the level of attention. Insights gained should be applicable to the treatment of Alzheimer’s disease and attention deficit disorder.


Ronald M. Carter, Ph.D., Duke University, will use game play to probe the neural basis of social and motivational differences in ASD. Failures in social function thought to be due to deficits in social processing could be linked to deficits in motivation toward social stimuli. Analysis will focus on the temporal parietal junction, which the lab has shown to be uniquely involved in this differentiation.

Gianafilippo Coppola, Ph.D., Yale University, will develop an integrative and comprehensive analysis of the gene regulatory networks underlying the pathophysiology of ASD using the resources of a unique database. Reducing the problem from thousands of genes to a few modules could shed light on the cause and genetic architecture of the illness and identify network hubs as potential targets for medications and/or diagnostic tests.

Holly N. Cukier, Ph.D., University of Miami, will study the role played by the gene RBFOX1 in neuronal development and identify potential pathogenic mechanism(s) that could underlie the development of ASD. The research will utilize advanced stem cell technology and RNA sequencing to identify key pathways, functions and regulatory networks associated with either RBFOX1 silencing or over-expression.

Yongsoo Kim, Ph.D., Cold Spring Harbor Laboratory, will explore aspects of a finding that intranasal oxytocin can improve social behavior in ASD. The study seeks to determine the associated physiological mechanisms in an animal model and to identify what brain regions respond to the treatment and how brain activity is altered to lead to improvement in social behavior.

Keerthi Krishnan, Ph.D., Cold Spring Harbor Laboratory, will seek to unravel the pathogenesis of Rett syndrome, which falls on the spectrum of autism disorder. Rett syndrome is hypothesized to result from inappropriate neuronal maturation, function and plasticity. The study will advance methods of genomic analysis to characterize the altered gene expression of MeCP2 in relevant brain regions and examine the functionally relevant cells.

Hyungbae Kwon, Ph.D., Max Planck Florida Institute for Neuroscience, will examine proteins called neuroligins, mutations found in familial forms of ASD. The study will explore how they contribute to synapse formation to help answer open questions about neural circuit development and structural plasticity relating to the pathogenesis of ASD.

Setsuko Sahara, Ph.D., Institute of Psychiatry, King’s College London, studies autistic macrocephaly, an enlargement of the brain seen in 20 percent of ASD patients. This project seeks to identify candidate genes and investigate their role in cortical development, in both mouse brains and induced-pluripotent stem cell-derived (iPSC) cortical progenitor cells gathered from patients with mutations of the candidate genes. The goal is to aid development of treatments tailored to specific subtypes of the disorder.

Jason W. Triplett, Ph.D., Children’s National Medical Center, studies deficits in sensory processing and integration that can occur in neurodevelopmental disorders including ASD. He seeks to determine molecular mechanisms by which converging sensory inputs are organized during development, using genetic techniques to silence activity in specific neurons. He hopes to lay a foundation for future studies of the functional and behavioral consequences of misalignment of spatial “maps” generated by the brain.

Lasani S. Wijetunge, Ph.D., University of Edinburgh, will use a powerful new kind of microscopy and an animal model of Fragile X syndrome to examine the state of synapses in the brain. The extremely high resolution microscope allows visualization of synapses and suggests their ability to transmit information in living brain tissue. It is hoped that this work will improve understanding of how the brain develops differently in people with ASD.

Akira Yoshii, M.D., Ph.D., Massachusetts Institute of Technology, will study a genetic syndrome called Tuberous Sclerosis Complex (TSC) that sometimes accompanies ASD. Using 2-photon microscopy and molecular imaging, he will seek to determine if serotonin synapses are dysregulated in TSC, providing information on the causal relationship between dysregulated serotonin function during early brain development and ASD.


Liping Hou, Ph.D, National Institute of Mental Health, will identify gene(s) on the X-chromosome that may affect the risk for developing BP by conducting a comprehensive study of X-chromosome markers derived from all of the genome-wide association studies of BP that have been published in five different trials.

Casey P. Johnson, Ph.D., University of Iowa, aims to identify new “biomarkers” (biological predictors) of BP and provide insight into the disease mechanisms. He will use advanced fast, high resolution quantitative methods of magnetic resonance imaging (MRI) that can produce exceptionally detailed and diverse images and will generate three-dimensional “maps” of a number of measures related to specific biophysical properties of the brain.

Nathan Kolla, M.D., Centre for Addiction and Mental Health, University of Toronto, will compare levels of a brain chemical called monoamine oxidase A (MAO-A) in people with BP depression and healthy volunteers. Patients with BP may have too much oxidative stress in their body causing damage to brain cells, and this could be caused in part by MAO-A.

Minjie Wu, Ph.D., University of Illinois at Chicago, will use innovative neuroimaging methods to delineate mood-specific biomarkers in pediatric BP in spontaneous activity at a resting state; in affect regulation and emotional memory domains during a task; and in interactions of rest and task. Dr. Wu aims to enhance understanding of functional differences between multiple mood states and permit detailed delineation of mood-specific treatment targets.

DEPRESSION (See also Anxiety and Depression)

Jerome Brunelin, Ph.D., Lyon University, will use a new, noninvasive brain stimulation technique called transcranial direct current stimulation to investigate the relationship between frontal cortex activity, decision-making abilities and activity during acute stress. This relationship will be investigated first in healthy controls to determine the specific role of right and left frontal activity and then in people with major depression.

Xiaofu He, Ph.D., Columbia University, will use magnetic resonance imaging (MRI) data from a three-generational study of familial patterns of psychiatric and behavioral issues―from childhood through adulthood―in offspring at high and low risk for depression. Functional and structural interrelationships among the brain regions will be analyzed in search of a common cortical architecture in children and adolescents with depression.

Elaine Setiawan, Ph.D., Centre for Addiction and Mental Health, University of Toronto, will conduct a first-of-its-kind study to explore whether unrecognized and untreated inflammation in the brain is one reason for the high rate of non-response to depression treatments. She will scan people with clinical depression using a new kind of brain imaging method that can detect inflammation to determine if treatment-resistant clinical depression is associated with brain inflammation.

Michael Treadway, Ph.D., McLean Hospital, Harvard University, will use simultaneously acquired positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scan measures of inflammation in the brain to test the theory that this is an underlying cause of major depressive disorder. The results could help establish the role of corticostriatal neuroinflammation as a biological “marker” for impaired motivation, a common symptom of depression.


Michael V. Baratta, Ph.D., University of Colorado, Boulder, aims to elucidate the neural mechanisms that promote resilience to stress, information that could lead to the development of better therapies for PTSD. Previous work identified the medial prefrontal cortex (mPFC) as being involved in this process. The research will employ optogenetic strategies for determining the critical features of mPFCfunction that produce the enduring effects of resilience.

Meeryo C. Choe, M.D., University of California, Los Angeles, will study sports-related concussions in middle school athletes to identify possible resulting psychiatric diagnoses. Animal models of mild traumatic brain injury point to specific brain regions that may correlate with the development of PTSD. Advanced imaging shows promise of correlating brain structural abnormalities with symptoms and may help determine treatment and prognosis.

Clarissa C. Parker, Ph.D., University of Chicago, will use mouse models to study conditioned fear as a way of identifying genes important in human PTSD. She proposes to map sites on the chromosome affecting naturally occurring variability in conditioned fear, hypothesizing that some of the genes identified in the mice will also be involved in human PTSD, and therefore candidates for further study.

Erel Shvil, Ph.D., New York State Psychiatric Institute, Columbia University, is studying irregularities in the hippocampus, a brain area central to memory and learning, as they correlate with PTSD. The volume of the hippocampus declines in people with the illness. This will be the first MRI-based study that will determine shrinkage (if any) in various sub-regions of the hippocampal formation, comparing brains of affected people with “controls.”


Mera S. Barr, Ph.D., University of Toronto, will examine cannabis use as a risk factor for developing schizophrenia. Chronic cannabis use results in the down regulation of GABA, a neurotransmitter that inhibits activity in the cortex of the brain. Patients with schizophrenia show deficits in cortical inhibition; cannabis abuse may further exacerbate it.

Chad Bousman, Ph.D., University of Melbourne, plans to identify a panel of genetic variants, such as single nucleotide polymorphisms (or SNPs), associated with schizophrenia. The research will be based on data from thousands of schizophrenia patients and healthy controls, so as to create a method that could be used to expedite and standardize schizophrenia diagnosis.

Kathleen Cho, Ph.D., University of California, San Francisco, will study parvalbumin interneurons, an inhibitory type of nerve cell in the prefrontal cortex of the brain. She seeks to determine how the properties of excitatory and inhibitory neurons or their interactions might be altered in ways that produce neural imbalance and give rise to abnormal brain-wave oscillations such as those observed in people with schizophrenia.

Inbal Goshen, Ph.D., Hebrew University, will investigate how astrocytes in the prefrontal cortex modulate behavior and neuronal activity in a mouse model of schizophrenia. Astrocytes are cells of the type called glia, which surround and support neurons. The ability to study astrocytic activity in real time is now possible with optogenetics, which combines optics and genetics to control cell activity in living animals.

Christopher Harvey, Ph.D., Harvard University Medical School, will apply advanced microscopy methods to measure the flow of information between two brain areas––the prefrontal cortex and the posterior parietal cortex––thought to be central to cognitive processing which is impaired in schizophrenia. The study will use mice trained to perform navigation tasks that require decision making, memory and planning.

Chiara Magri, Ph.D., Brescia University, will conduct genetic sequencing studies of people with schizophrenia who have high levels of autozygosity, a situation that occurs from inbreeding, when two chromosomal segments that are identical, coming from a common ancestor, are inherited from each parent. The identification of the mutations responsible should be useful in helping to clarify the biological mechanisms at the basis of schizophrenia.

David J, Margolis, Ph.D., Rutgers University, will investigate cortical neurons called parvalbumin positive (PV) cells, which have been implicated in the cognitive deficits in schizophrenia. The study will aim to define the impact of PV cells on local neural signaling and long-range propagation of neural activity to enhance understanding of the neural circuit plasticity mechanisms underlying the onset and progression of schizophrenia.

Gemma Modinos, Ph.D., Institute of Psychiatry, King’s College London, will use brain imaging technology to study people at high risk for schizophrenia, who are experiencing psychotic symptoms but do not meet the criteria for a clinical diagnosis. She will investigate whether they show abnormal brain activation while processing emotional information and whether the neurotransmitter glutamate modulates this activation, identifying how it may affect emotional and social functioning.

Krishnan Padmanabhan, Ph.D., Salk Institute for Biological Studies, hopes to develop insights into the still largely elusive biological basis of schizophrenia, using reprogrammed human stem cells in an animal system. Neurons derived from patients with schizophrenia will be studied by engrafting neuronal precursor cells into mice to observe the anatomical and physiological changes that occur.

Krystal L. Parker, Ph.D., University of Iowa, will investigate the relationship between the cerebellum and prefrontal cortex, brain areas essential for accurate timing control, which is impaired in schizophrenia. She will record neural activity in both areas in mice, analyze their interaction during a timing task and use optogenetics to stimulate the cerebellum in an attempt to normalize prefrontal activity and restore timing ability.

Panagiotis Roussos, M.D., Ph.D., Icahn School of Medicine at Mount Sinai, will identify and map non-protein coding sequences in the genome that are often irregular in people with schizophrenia. Many such regions are thought to have functions, but these are as yet unknown. Dr. Roussos will use postmortem human brain specimens, focusing study on cells in parts of the cortex and hippocampus that have consistently shown abnormalities in schizophrenia.

Karun K. Singh, Ph.D., McMaster University, will examine the impact on brain development of a gene copy-number variation on chromosome 15. The region has been associated with schizophrenia, but it’s not known which of the seven genes in the region are specifically involved. Dr. Singh will use an innovative cost-effective method to determine this and his work could identify genes that might be targets for novel therapies.

Joshua Woolley, M.D., Ph.D., University of California, San Francisco, will investigate the neurophysiological mechanisms of the drug oxytocin and its prosocial effects in people with schizophrenia and controls using magnetoencepholagraphy (MEG). This is the first study to investigate the neurophysiological effects induced by oxytocin in schizophrenia using any imaging modality, and the first study to use MEG to examine the effects of oxytocin on neural processing.


Chi-Hua Chen, Ph.D., University of California, San Diego, aims to develop new approaches to gene discovery relevant to schizophrenia, bipolar disorder (BP) and Alzheimer’s disease. The research will apply novel brain phenotypes (outward, observable characteristics) and statistical approaches in a large sample with brain imaging and data on genotype (genetic makeup of a cell). The goal is to establish a database that has information about the contribution of specific genetic types to variation of characteristics in specific parts of the brain.

Kristen Foster, Ph.D., Duke University, will apply a novel approach that simultaneously monitors activity in large populations of neurons to provide identification of each cell type and its spatial relationship to other cells. This approach will be applied to the striatum, a brain region thought to have a critical role in obsessive-compulsive disorder (OCD), Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, eating disorders, ADHD and addiction.

Yongjun Gao, Ph.D., Johns Hopkins University, aims to develop more effective radioligands––radioactive molecules that bind to receptor molecules––for use in PET imaging to examine the distribution of the α7 nicotinic acetylcholine receptors. These receptors are implicated in neuropsychiatric disorders including schizophrenia, Alzheimer’s disease, anxiety, depression and drug addiction. They may be useful for diagnosis and assessing treatment response.

Aryn H. Gittis, Ph.D., Carnegie Mellon University, will study neural circuits in the basal ganglia region of the brain involved in motor suppression and compulsive behavior. Compulsive behavior is a symptom of disorders such as OCD, ADHD, Tourette’s syndrome, Huntington’s disease and Parkinson’s disease. The inability to control or suppress unwanted movements can arise from dysfunction of motor-suppressing circuits.

Conor Liston, M.D., Ph.D., Stanford University, will investigate how chronic stress during adolescence affects the development of neural circuits and assess whether it has a lasting impact on circuit function in adulthood. Using imaging and optogenetic tools for interrogating neural circuits, the research will focus on stress-sensitive brain regions of the medial prefrontal cortex and striatum, known to be central to the regulation of attention and other cognitive processes.

Gyorgy Lur, Ph.D., Yale University, will explore the association between alterations of the brain chemical norepinephrine with depression and PTSD. He seeks to determine how norepinephrine levels control function in the prefrontal region of the brain both at the network and cellular level, and how its dysregulation leads to the emotional and behavioral impairments seen in these disorders.

João Peca, Ph.D., University of Coimbra, aims to discern the biological mechanisms that disrupt social behavior in schizophrenia and autism spectrum disorder (ASD). The research will identify synaptic proteins that vary with changing social environments and map the neuronal pathways in the brain that regulate social behaviors, applying optogenetics in animal models to directly manipulate the predisposition to seek or avoid social interactions.



Uma Vaidyanathan, Ph.D., University of Minnesota, seeks to determine whether brain structure and function anomalies (e.g., loss of frontal cortex neurons and disruptions in hippocampal plasticity) that are associated with alcohol misuse are a cause or consequence of the misuse. She will use functional and structural magnetic resonance imaging (MRI) to longitudinally compare the brains of identical twins who differ on alcohol use and/or abuse.

Eating Disorders

Zachary A. Knight, Ph.D., University of California, San Francisco, is seeking to better understand binge eating, the most common eating disorder in the U.S., using a technology he developed to map neurons that are activated when mice engage in voracious eating. These neurons express dynorphin; Dr. Knight will test the function of dynorphin neurons in regulating feeding behavior.

Sunila Nair, Ph.D., University of Washington, will conduct obesity studies to examine the role of the lateral habenula region of the brain in cue-induced relapse to seeking high-fat food. The research will utilize state-of-the-art genetic and chemical technology to selectively manipulate lateral habenula neurons in mouse models of obesity to elucidate the neuronal circuits that underlie cue-induced relapse.


Ramin Pashaie, Ph.D, University of Wisconsin-Milwaukee, will study electrical activity in the cerebral cortex area of the brain, known to be associated with epilepsy. He will apply a combination of advanced technologies to record from large areas of neural networks in the cortex and will also use optogenetics to stimulate cortical activity.


Next Generation Therapies

to reduce symptoms of mental illness and retrain the brain


Paul Siegel, Ph.D., New York State Psychiatric Institute, Columbia University, studies the impact of non-conscious behaviors on anxiety disorders. Here he seeks to connect brain and behavior in the “very brief exposure (VBE) effect:” the reduction of phobic fear by presentation of a continuous series of non-conscious phobic images. Can phobic avoidance be reduced without conscious cognition? An MRI imaging experiment will test the hypothesis that VBE will reduce fear responses of phobic individuals.

Lisa E. Williams, Ph.D., University of Wisconsin-Madison, wants to know how cognitive behavioral therapy (CBT) for childhood anxiety changes brain function. She will test the theory that stronger amygdala-frontal connectivity predicts better response to CBT by taking a brain scan before and after treatment in children with anxiety. She argues a deeper understanding of the relationship between functional brain networks, anxiety symptoms and treatment outcome is needed to inform and improve treatment for childhood anxiety.


Michael L. Gonzales, Ph.D., University of California, Davis Medical Center, will explore the modes of action of Methyl CpG Binding Protein 2 (MeCP2), an important regulator of neuronal development, to help inform selection of therapeutic targets for MeCP2-derived disorders, including a number of neurodevelopmental disorders, including Rett Syndrome, Fragile X-linked intellectual disability and ASD.

Hye Young Lee, Ph.D. , University of California, San Francisco, is seeking new targets for treating Fragile X Syndrome, a disease associated with a high risk for developing ASD. Dr. Lee will test a potential target of Fragile X, Kv4.2 potassium channels, in mouse models. This work is based on evidence that a 50-percent reduction of Kv4.2 improved some autistic-like behaviors in mice.

Yoshitake Sano, Ph.D., University of California, Los Angeles has discovered that decreasing levels of the DISC1 protein in the dentate gyrus––a part of the hippocampus region of the brain linked to the ongoing birth of new neurons (neurogenesis)––causes cognitive and affective disorders in rodents. This project will investigate whether an FDA-approved drug (rapamycin) can reverse such behavioral abnormalities in a mouse model of ASD, which could open a new path for treatment of millions of adults with ASD.


Andre R. Brunoni, M.D., Ph.D., University of Sao Paolo, will conduct a clinical trial to determine whether transcranial direct current stimulation, which has been shown to be effective in treating unipolar depression, can also be effective for treating BP depression. This technique uses a weak, direct electric current to modify brain activity in the area where the current is applied.

Paul E. Croarkin, D.O., M.S.C.S., Mayo Clinic, wants to optimize treatment for adolescent mood disorders. The neurotransmitter glutamate is believed to play a key role in BP. He will measure glutamate levels and functioning in depressed adolescents who are at risk for later developing BP. Half will receive escitalopram, half lamotrigine, to examine if and how depressive symptoms and glutamate measures change.

Ryan W. Logan, Ph.D., University of Pittsburgh, will investigate the role of “epigenetics” (environmental factors affecting gene expression without altering the DNA sequence) on circadian rhythms, known to be disrupted in BP. The specific focus will be on histone deacetylases (HDACs), based on indications that they could be developed as novel mood stabilizing agents. HDACs are epigenetic enzymes that repress gene transcription and are involved in regulating circadian rhythms.


Roee Admon, Ph.D., McLean Hospital, Harvard University, will investigate neural networks linked to depressive mood symptoms in patients with depression. Stabilizing positive mood is an important end point of antidepressant treatments, and the hope is that insights derived from this study can help guide the selection of treatments that will prolong positive mood and help identify individuals at risk for depressive disorders.

Eléonore Beurel, Ph.D., University of Miami, hopes to clarify mechanisms underlying the rapid antidepressant effect of the drug ketamine as well as its usefulness in treating otherwise treatment-resistant patients. To provide a means for countering the transient antidepressant response to ketamine, the research will test to find out whether its effect can be sustained by prolonging inhibition of GSK3, an enzyme involved in mood disorders.

Ashley M. Blouin, Ph.D., Johns Hopkins University, will explore whether a gene called Narp (neuronal activity-regulated pentraxin) is acting in the brain to mediate the antidepressant effect of electroconvulsive therapy (ECT), and which signaling pathway plays a critical role. This information will aid in developing new treatment approaches for resistant depression with fewer side effects than ECT.

Anett Gyurak, Ph.D., Stanford University, will conduct a nationwide clinical trial of a cognitive-effective remediation training intervention for depression with 150 people. The trial consists of Internet-based computer exercises that translate emerging knowledge about the disorder into a novel biologically-based intervention. Wide-scale use of the protocol has the potential to advance current understanding of treatment response and to dramatically change the delivery of care to patients.

Mei-Hua Hall, Ph.D., Harvard University Medical School, will evaluate the effects of a cognitive remediation training intervention for people with depression. The study will examine the underlying neurobiological mechanisms mediating the changes observed after the training and the relationship between cognitive changes with changes in the cortex. The information acquired could guide further improvement of cognitive remediation intervention.

Shihoko Kojima, Ph.D., University of Texas Southwestern Medical Center at Dallas, aims to identify genes that play crucial roles in the fast antidepressant action of the drug ketamine. Better understanding of the mechanisms underlying ketamine’s activity could guide the design of new antidepressants that are as rapid, long-lasting and reliable, with fewer of the adverse side effects that limit ketamine’s use.

Li Li, M.D., Ph.D., University of Alabama at Birmingham, will study glucose metabolism and insulin sensitivity in 60 depressed patients with a history of early-life stress to determine how stress affects glucose levels, and whether a specific age range will put depressed patients at a greater risk for insulin resistance. Resolving this question will help clinicians identify people with depression at risk for developing diabetes.

Adriana Lori, Ph.D., Emory University, will explore evidence that variations in the ADRA1A gene influence response to antidepressant treatment. The variations, called single nucleotide polymorphisms (SNPs), showed a relationship to brain activity associated with remission. In the proposed study ADRA1A will be sequenced in samples from patients with depression to identify unique SNPs that affect the function of the gene.

Keri Martinowich, Ph.D., Johns Hopkins University, will explore the role of brain-derived neurotrophic factor (BDNF), a nerve growth factor protein, in mediating the behavioral response to electroconvulsive therapy (ECT) in the treatment of depression. The gene encoding BDNF is highly complex, producing multiple variants. The study will investigate the consequence of the most highly expressed variants on the response to ECT.

Eric F. Schmidt, Ph.D., The Rockefeller University, will tease apart and target neural circuits in the cerebral cortex that control mood and malfunction in mood disorders such as major depression. Two strains of genetically-engineered mice will be used to expose different populations of cells in the medial prefrontal cortex. The goal is to identify distinct cell populations within these circuits that may serve as novel candidates for better antidepressant therapies with fewer side effects.

Yong-Seok Oh, Ph.D., The Rockefeller University, will investigate ways to improve antidepressant therapy. Selective serotonin reuptake inhibitors (SSRIs), the most widely used antidepressants, take weeks to work, signifying complicated downstream molecular mechanisms. A novel chromatin remodeling factor involved in genetic regulation may be a possible mediator of antidepressant effects and this research aims to identify target genes in various neuronal subtypes.

Mariana Pereira, Ph.D., Rutgers University, will investigate recent evidence that postpartum depression (PPD) differs clinically from non-postpartum depression. Using rat models, she will examine whether alterations in dopamine function underlie the cognitive and motivational impairments in PPD that lead to deficits in parenting. Dr. Pereira will also evaluate use of the neuromodulator adenosine as a treatment for PPD.

Abigail M. Poulter, Ph.D., Brown University, studies the relation of stress to depression. Focusing on dopamine neurons of the ventral tegmental area (VTA), a crucial part of the brain’s reward processing system and affected by acute and chronic stress, she will examine inhibitory synapses in animals susceptible and resilient to depression. She will then test whether enhancing inhibitory signaling in the VTA can protect susceptible animals from the negative effects of chronic stress.

Alan R. Prossin, M.D., University of Michigan, will study activation of pathways in the central immune system as they pertain to major depressive disorder. It is hoped that more robust measures of immune functioning will facilitate development of novel immune-derived personalized treatment strategies, particularly for those whose depression resists treatment. In this study 10 patients and 10 controls will receive PET scans; central immune activation will be compared, and in the patient group, correlated with history of treatment resistance.

Denise M. Ramirez, Ph.D., University of Texas Southwestern Medical Center at Dallas, is studying the action of the drug ketamine on symptoms of refractory depression. She recently determined that ketamine blocks spontaneous transmission of the neurotransmitter glutamate; this project seeks to characterize the mechanism(s) behind this effect. A protein called presynaptic vesicle protein 7 that is involved in spontaneous neurotransmission is among the targets of this work.

Paraskevi V. Rekkas, Ph.D., Centre for Addiction and Mental Health, University of Toronto, believes early detection is a promising strategy for preventing major depression in perimenopause. This project will examine a protein in the brain and in the blood called monoamine oxidase A (MAO-A). New brain imaging and blood analysis technologies to measure MAO-A levels hold promise for the development of MAO-A biomarkers in perimenopause, the ultimate objective of this work.

Dorothy K.Y. Sit, M.D., University of Pittsburgh School of Medicine, investigates the effects of bright light therapy to treat bipolar depression. Improvement in symptoms with exposure to light is evidence of involvement of the circadian system in mood disorders. Some patients experience improved mood, sleep and energy by using morning light therapy but midday light therapy also can restore stable mood in people with rapid cycling bipolar illness. The study goal is to understand how light therapy works to improve bipolar symptoms.

Charles T. Taylor, Ph.D., University of California, San Diego, will use functional brain imaging and applied cognitive neuroscience to develop new ways of understanding and modifying the brain to improve treatment outcomes in depression. He will determine the ability of a computerized “cognitive bias modification” approach/avoidance training procedure to enhance activity in brain regions that regulate responses to rewards and thereby reduce vulnerability to depression. He asks: “Can we train the depressed brain to obtain rewards?”

Stuart Watson, MBBS, M.D., MRCPsych, University of Newcastle, will test the theory that treatment response to antidepressants can be predicted by the regulation of the stress response system. He is conducting a trial involving more than 200 individuals taking metyrapone, which blocks the synthesis of the stress hormone cortisol, in treatment-resistant depression. This will shed light on prognosis in depression and will show how metyrapone exerts its therapeutic response.


Michael H. Bloch, M.D., Yale University Child Study Center, will test N-Acetylcysteine (NAC), an over-the-counter supplement, as a treatment for OCD in children who do not respond to standard treatment with cognitive behavioral therapy or selective serotonin reuptake inhibitor (SSRI) antidepressants. People with OCD show elevated brain levels of the chemical glutamate and NAC has been shown to be a glutamate-modulating agent.


Chaya G. Bhuvaneswaran, M.D., M.P.H., University of Massachusetts Medical School, will conduct a trial of the blood pressure medication mecamylamine as a treatment for PTSD. Mecamylamine has been shown to have some affect in alleviating anxiety and depression. In animal models it disrupts long-term potentiation, a process involved in learning and memory and the hope is that mecamylamine can disrupt the recurring bad memories that characterize PTSD.

Roger L. Clem, Ph.D., Icahn School of Medicine at Mount Sinai, will examine how emotional memory alters synaptic transmission in the amygdala in mice exposed to fear conditioning. The amygdala is a brain area critical for anxiety-related disorders such as PTSD. Dr. Clem will investigate the role of the molecule mGlu1 in regulating fear memory by reducing amygdala synaptic strength, and whether fear attenuation can be augmented with mGlu1-activating medications.

Jennifer S. Mascaro, Ph.D., Emory University, will look for hormonal and immunological biological “markers” (predictors) related to emotional numbing in 30 male military veterans diagnosed with PTSD, and test the effectiveness of an intervention called cognitively-based compassion training to increase empathy and social connectedness. The study will assess the patients’ levels of oxytocin, inflammation and self-reported emotional and social status before and after the training.

Gihyun Yoon, M.D., University of Minnesota, seeks to use intranasal insulin for PTSD. Emerging evidence indicates that it may reduce anxiety or stress-related behaviors. Dr. Yoon’s research will compare intranasal insulin and placebo in a randomized, double-blind, placebo­controlled crossover trial. Brain activity will be examined using functional magnetic resonance imaging (MRI).


Marco Armando, M.D., Ph.D., Bambino Gesu Children’s Hospital, will administer long chain omega-3 polyunsaturated fatty acids (PUFAs) to adolescents at high risk for schizophrenia due to a chromosomal abnormality associated with reduced PUFA. The goals are to identify the best neural targets for new treatments and to gain the ability to predict and prevent transition from the pre-psychotic to psychotic stage of illness.

Savita G. Bhakta, M.D., University of California, San Diego, aims to identify measures that counter the cognitive deficits common in schizophrenia. A variation in the gene for the enzyme catechol O methyl transferase (COMT) can affect cognition. The research will investigate the cognitive enhancing effects of tolcapone, a medication that blocks COMT activity.

Chi-Ming Chen, Ph.D, University of Connecticut, Hartford Hospital, will explore the hypothesis that the auditory verbal hallucinations that occur in schizophrenia are caused by abnormal connectivity between regions of the brain involved in language processing. Dr. Chen will test transcranial magnetic stimulation (TMS) to brain regions believed to be involved in verbal hallucinations as a potential treatment in patients who are not relieved by standard medications.

Derin J. Cobia, Ph.D., Northwestern University, will conduct a study on people with schizophrenia given amphetamines. The research will examine the relationship between different modes of brain activation and try to determine whether certain brain patterns can predict a positive response to amphetamine as a treatment for the negative symptoms of schizophrenia (social, emotional and motivational disturbances). Current treatments affect primarily the positive symptoms (hallucinations and delusions).

Vanessa L. Cropley, Ph.D., University of Melbourne, will use brain imaging in people with a first episode of psychosis to investigate whether increased dopamine function in the striatum, a region of the brain’s cortex, is related to abnormalities in psychosis seen in an associated brain circuitry called the frontostriatal network. Schizophrenia, and particularly symptoms of psychosis, are thought to involve dysregulation of dopamine.

Paul Gorczynski, Ph.D., Centre for Addiction and Mental Health, University of Toronto, aims to identify the key individuals and best approaches for delivering information on physical activity to people with schizophrenia, who tend to be less active than the general population. These patients experience high rates of obesity and diabetes, predisposing them to cardiovascular disease and a considerably shortened lifespan.

Laura M. Harrison, Ph.D., Louisiana State University, will use a mouse, deficient in a protein that regulates signaling by dopamine receptors, to learn which intracellular signaling pathways are affected by antipsychotic schizophrenia medications that act on the neurotransmitter dopamine. Targeting specific signaling, rather than all signaling, should help define which pathways are involved in therapeutic effect and which in unwanted side effects.

Charles Albert Hoeffer, Ph.D., New York University School of Medicine, will study a molecule called regulator of calcineurin1 (RCAN1) as a potential target for the development of more effective schizophrenia medications. Both RCAN1 and the enzyme calcineurin are important in cognition. The aim of the research is to identify RCAN1 signaling as a central pathway involved in the expression of calcineurin-mediated behavioral abnormalities of schizophrenia.

Margaret McNamara McClure, Ph.D., Icahn School of Medicine at Mount Sinai, will conduct a clinical trial of guanfacine, a blood pressure medication, to enhance working memory in people with schizophrenia. It will be administered in conjunction with a program of cognitive remediation. The project follows a pilot study in which participants who received guanfacine showed significant improvement in working memory, a process compromised in schizophrenia.

Eric B. Oleson, Ph.D., University of Maryland School of Medicine, will examine the interaction of the endocannbinoid and dopamine systems in the brain in an effort to improve the efficacy of antipsychotic treatment. Antipsychotic medications work by affecting dopamine release. The endocannbinoid system is altered in schizophrenia but necessary for regulation of dopamine release. Fine-tuning endocannabinoid control of dopamine release could offer more effective therapy for schizophrenia.

Bart Peters, M.D., Ph.D., Zucker Hillside Hospital, Feinstein Institute for Medical Research, notes deficiencies of omega-3 fatty acids have been found in people with schizophrenia. He will study whether omega-3 supplementation increases white matter integrity in patients with first-episode schizophrenia, as seen with diffusion tensor imaging, and whether changes in white matter integrity are associated with improvement in clinical status. This may provide a basis for future, larger clinical trials.

Jingchun Sun, Ph.D., Vanderbilt University, seeks to distinguish the method of action of “typical” vs. “atypical” antipsychotic medications. Using extensive database information regarding the action of these medications on genes and signaling pathway networks in the brain, he seeks to better understand their underlying mechanisms of action and identify genes involved in order to develop better diagnostic tests and more effective medication strategies for schizophrenia.

Pierre Trifilieff, Ph.D., Universite Bourdeaux II, studies the impact of n-3 PUFAs (polyunsaturated fats from the diet), which affect dopamine D2 receptors (D2Rs). D2R overexpression in development leads to dysfunction of the reward system, including behaviors that model the negative symptoms of schizophrenia. It may be that high-fat diets contribute to negative symptoms of schizophrenia. By identifying periods of vulnerability and reversibility of an imbalanced PUFA diet, this project could open new routes toward prevention and treatment.

Anne L. Wheeler, Ph.D., Centre for Addiction and Mental Health, University of Toronto, will use neuroimaging to determine the effects of transcranial magnetic stimulation (TMS) treatment on brain structure in people with schizophrenia who are given the treatment to address working memory deficits. This double-blind clinical trial will further understanding of how this treatment affects brain structures important for working memory performance.


Joshua W. Buckholtz, Ph.D., Harvard University, aims to aid development of new treatments for the impulsive behavior that is a hallmark of bipolar disorder, addiction, ADHD and personality disorders. The research will first explore the little understood biology of impulsivity and then test the therapeutic effects of direct current stimulation, a brain stimulation technique that can enhance the function of the frontal cortex.

Andrew C. Emery, Ph.D., National Institutes of Health, will look for specific molecules to act as potential therapeutic agents for stress-related psychiatric disorders such as depression and PTSD. The blockers would act by inhibiting the effects of a chemical, PACAP, which mediates the physiological response to stress and release of stress hormones, including cortisol.

Greg Perlman, Ph.D., Stony Brook University School of Medicine, will study people with schizophrenia and people with psychotic mood disorders and their unaffected siblings to find neural markers that distinguish between the two disorders. Establishing this distinction will facilitate use of event-related potential (ERP) technology to guide treatment decisions and identify risk. ERP is noninvasive and more cost-effective than other strategies to measure brain function.



Swapnil Gupta, M.D., Yale University, will test a treatment for cannabis-induced cognitive deficits, which are related to widespread release of and increase in the brain chemical glutamate. N-acetylcysteine reduces glutamate and should, in theory, attenuate the spatial working memory and verbal memory deficit effects of tetrahydrocannabinol, the main psychoactive compound in cannabis.

Borderline Personality Disorder (BPD)

Kate E. A. Saunders, BM, University of Oxford, uses a standard psychiatric test of “reciprocal altruism” called the Prisoner’s Dilemma to gauge how well treatment works for people with BPD. She theorizes that successful completion of treatment for the disorder will be associated with an improvement in the acquisition and maintenance of cooperative behavior in a repeat test. She will compare 20 individuals with BPD who have completed long-term psychotherapy, 20 untreated individuals and 20 controls.


Michael M. Francis, M.D., Indiana State University, aims to demonstrate the efficacy of high frequency repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in psychotic disorders and to detect increased cortical activation. It is expected that rTMS will result in greater increases in cerebral blood flow during performance of cognitive tasks. The study will help define optimal rTMS treatment parameters for cognitive dysfunction.

Jenifer L. Vohs, Ph.D., Indiana School of Medicine, notes that no current treatment adequately addresses poor insight––that is, a realistic sense of one’s situation––during the first few years of psychotic illness. She seeks to develop and test a stage I novel Integrated Metacognitive Therapy manual to improve insight in early psychosis. It will allow for close examination and determination of specific manual session tasks and content while also providing preliminary evidence to support efficacy of the intervention.


James M. Bolton, M.D., University of Manitoba, hopes to improve suicide prediction. Using a state-of-the-art database, he will follow a large group of people who attended emergency departments so as to clarify which characteristics increase suicidality (suicidal thinking or behavior). The study will test the effectiveness of a scale designed to predict suicide risk, which is widely used but has never been evaluated.