Research

/Research
17 04, 2019

Cellular and Molecular Mechanisms Leading to Early Brain Overgrowth

Cellular and Molecular Mechanisms Leading to Early Brain Overgrowth Need/Problem: Autism spectrum disorder (ASD) is an etiologically heterogeneous disorder that affects 1 in 68 individuals, and confers a lifelong burden to most affected individuals and their families. ASD has been consistently characterized by early brain overgrowth in neuroimaging studies. Grant Summary: We will generate and study neural cells from individuals with ASD and matched controls who have been profiled with behavioral assessments and neuroimaging since infancy in order to identify cellular and molecular mechanisms leading to early brain overgrowth. Goals and Projected Outcomes: Insight into these mechanisms will further understanding of disease pathogenesis, delineate convergent biological pathways within a heterogeneous disorder, and will inform targeted early therapeutic intervention. Heather Hazlett Jason Stein Grant Details: Induced pluripotent stem cells (iPSCs) are an excellent model system to study [...]

16 04, 2019

The gut microbiome and Perinatal Mood and Anxiety Disorders (PMAD): A pilot study to examine the microbiome in relation to perinatal changes in stress and immune systems | Kimmel

The gut microbiome and Perinatal Mood and Anxiety Disorders (PMAD): A pilot study to examine the microbiome in relation to perinatal changes in stress and immune systems Need/Problem: PMAD are common and can have grave consequences for mother including a risk of suicide and negative effects on the child’s development. However, the biologic mechanisms underlying PMAD are unclear. There is evidence that certain gut microbiota are associated with depression and anxious behaviors. Grant Summary: This grant is a novel approach to studying PMAD by studying the microbiota of women across the perinatal period (pregnancy and the postpartum time period) in relation to the development of depression and anxiety. Goals and Projected Outcomes: The goal of the study is to collect and analyze the gut microbiota samples in each trimester and 8 weeks postpartum from women with histories of mood and [...]

16 04, 2019

Genomics of Postpartum Depression–Action towards Causes and Treatment (gPACT); PACT for the Cure | Meltzer-Brody & Sullivan

Genomics of Postpartum Depression–Action towards Causes and Treatment (gPACT); PACT for the Cure Need/Problem: Postpartum depression (PPD) and postpartum psychosis (PPP) affect millions of women worldwide and are the leading cause of maternal morbidity and mortality. Research on the causes of PPD and PPP are greatly underfunded leaving researchers and clinicians with an incomplete understanding of who is at risk. Grant Summary: This project is an innovative and novel approach to rapidly elucidate the genetic basis of PPD and PPP by conducting an extremely rapid and large genome-wide association study. This will improve detection, prevention and treatment of these conditions. Goals and Projected Outcomes: Our goal is to learn more about the biological basis of PPD and PPP by conducting a large genome-wide association study using Apple’s newly created open-source Research Kit software. We anticipate enrolling 100,000 women in the [...]

16 04, 2019

Single cell transcriptional profiling to identify novel neurocircuit targets for reproductive mood disorders | Stuber

Single cell transcriptional profiling to identify novel neurocircuit targets for reproductive mood disorders Need/Problem: Rationale strategies for therapeutic targeting of neuronal cell types in the brain for the treatment of neuropsychiatric disease are largely absent. We propose to utilize state of the art high throughput sequencing technology establish an experimental and computational pipeline to quantitatively assess the number of cell types on the mammalian hypothalamus and how these are regulated by various reproductive hormonal manipulations. Grant Summary: This grant proposes experiments to classify the number of phenotype of neurons in the mammalian brain. Goals and Projected Outcomes: The goal of the study is to develop a high throughput experimental and computational pipeline for accurately classifying and describing changes neuronal cell gene expression in response to environmental or hormonal manipulations. This approach will identify many novel therapeutic targets for the [...]

16 04, 2019

Characterizing the Hormone Sensitive Phenotype of Postpartum Depression: An Experimental Investigation of Mood and Behavior | Schiller

Characterizing the Hormone Sensitive Phenotype of Postpartum Depression: An Experimental Investigation of Mood and Behavior Need/Problem: Despite decades of research, little is known about the biological causes of postpartum depression. Our past research showed that changes in pregnancy hormone levels cause depression in some women, but at present, there is no simple way to identify these women. Grant Summary: This research provides a novel approach to testing risk for postpartum depression. Goals and Projected Outcomes: The purpose of this project is to test two simple, non-invasive approaches to identifying women at high-risk for postpartum depression. The projected outcome of this project is the ability to distinguish those at high and low risk for postpartum depression using minimally invasive, easy-to-implement protocols, thus potentially enabling the identification of women at risk for postpartum depression prior to its development. Crystal Edler Schiller, [...]

16 04, 2019

Depression Susceptibility in Adolescent Females: Estrogen Variability, Stress Exposure, and Fronto-Limbic Brain Dynamics | Andersen

Depression Susceptibility in Adolescent Females: Estrogen Variability, Stress Exposure, and Fronto-Limbic Brain Dynamics Need/Problem: Dramatic fluctuations in reproductive hormones (e.g., estrogen), refinement of brain circuitry involved in cognitive and emotional processing, and elevated psychosocial stress during the pubertal transition (peripuberty) accompany a substantially increased risk for depression, particularly for adolescent girls. Although normal changes in estrogen provoke affective symptoms in vulnerable women during reproductive events, the role of changing estrogen levels in depression risk has not been studied in peripubertal girls. Furthermore, the neurophysiologic mechanisms underlying the vulnerability to estrogen fluctuations have yet to be identified. Grant Summary: : Estrogen exerts significant modulatory effects on the cortisol stress response and brain circuitry involved in regulating affective (mood) state. With the Foundation of Hope’s support, this research will use a novel multimodal approach involving precise ovarian hormone measurements, neurophysiological assessments of [...]

16 04, 2019

Next Generation Non-Invasive Brain Stimulation: A Novel Solution Enabled by Mobile Technology and Big Data | Frohlich | $200,000

Next Generation Non-Invasive Brain Stimulation: A Novel Solution Enabled by Mobile Technology and Big Data Award: $200,000 Need/Problem: Psychiatry urgently needs new treatment paradigms that are effective, safe, and affordable. Non-invasive brain stimulation such as transcranial current stimulation has the potential to take such a role of a disruptive technology that will fundamental improve the landscape of treatment options for psychiatric disorders. Grant Summary: Today, the field of transcranial current stimulation (TCS) is dominated by small, underpowered studies performed by individual, relatively isolated research groups. We argue that the solution to this problem is new device technology that allows the centralized execution and large-scale analysis of multiple TCS clinical studies. Goals and Projected Outcomes: To implement and evaluate a networked and portable TCS device and server-side cloud-based infrastructure for remote control and collection of data on TCS and its [...]

16 04, 2019

Achieving Synergy with Multimodal Brain Stimulation: Electricity meets Magnetism | Frohlich | $156,613

Achieving Synergy with Multimodal Brain Stimulation: Electricity meets Magnetism Award: $156,613 Need/Problem: One effective treatment strategies for mental illnesses is to combine medications to achieve maximal therapeutic benefit. In contrast, despite the emergence of multiple, different forms of non-invasive brain stimulation for the treatment of mental illnesses, very little is known about the potential therapeutic synergy of different forms of non-invasive brain stimulation. Grant Summary: This is the first study of its kind to investigate the targeted combination of transcranial magnetic stimulation and transcranial alternating current stimulation (tACS) for modulating brain rhythms. Goals and Projected Outcomes: The goal of this study is to introduce a novel therapeutic approach which is based on leveraging network neuroscience to develop individualized treatment strategies. Dr. Flavio Frohlich Grant Details: By combining tACS and TMS, we will accelerate [...]

16 04, 2019

Mechanism of Action of Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder | Frohlich | $100,000

Mechanism of Action of Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder Award: $100,000 Need/Problem: Depression is a serious illness and many patients do not find relief with the current treatment options. Our Carolina Center for Neurostimulation has pioneered a novel form of non-invasive brain stimulation that applies a very weak but smart current to modulate brain rhythms. This potential new treatment is very safe (most patients cannot even feel the electricity) and potentially efficacious for the treatment of depression. Based on promising pilot data, we are excited to move ahead with this new study to better understand how the stimulation modulates brain rhythms such that we can further optimize the stimulation to develop personalized treatment protocols. Grant Summary: In collaboration with Dr. David Rubinow, Chair of the Department of Psychiatry at UNC – Chapel Hill, [...]

16 04, 2019

The genomics of severe major depressive disorder (MDD) and response to electroconvulsive therapy (ECT) | Soda | $39.990

The genomics of severe major depressive disorder (MDD) and response to electroconvulsive therapy (ECT) Award: $39,990 Depression is the leading cause of disability worldwide. It can lead to suicide which is the second leading cause of death in 15-29 year olds. We need to identify patients with the most severe forms of depression, characterize them well, and include these patients in genomic studies. We know that such an approach will lead to new discoveries faster than studying patients with more mild forms of these disorders. We think that we have a way to do this. We want to identify people that have been treated with electroconvulsive therapy (ECT) for depression and include them in genetic studies. We think that findings from this study can lead to predictive algorithms. We want to learn whether we can, very early on in [...]