CSR&D Research Career Development Transition Award Application

有一种“孤独的流行病”，20%的平民和高达50%的退伍军人报告说感到孤独， 社会孤立。这在临床上很重要，因为孤独和社会孤立是 身体健康状况恶化和过早死亡。精神疾病与这种流行病密切相关，因为它 孤独和社会孤立会导致并恶化这两种情况。精神疾病的社会缺陷， 最强烈地导致孤独和社会孤立。这些社会缺陷包括难以理解 其他人的行为以及在社交场合表现得体的困难。尽管它们很重要， 这些社交缺陷在神经和行为层面上的了解很少，并且难以量化。 此外，对他们的现有治疗是不够的。我是这个世界的连结与调音的主任， 神经精神疾病（BAND）实验室，由一名初级教员组成，由CSR&D支持 职业发展奖，5名博士后，包括MD和PhD，4名研究生，6名带薪 研究助理，20多名志愿者。我们认为，心理健康和幸福的关键始于 牢固的关系。我们的使命是开发新的药理学和认知干预措施， 精神疾病使患者能够加强与他人和世界的联系。我们 工作主要集中在理解心理，行为，生理和神经的影响， 神经肽催产素在多种精神疾病中的应用。比如我们有 进行了许多研究，确定催产素给药对患有 精神分裂症这项工作的一个亮点是，我们发现， 精神分裂症患者在高级社会认知过程中的神经活动正常化， 正常化与行为表现的改善相关。这项工作导致了VA CSR&D优点 该奖项旨在进行最大的关于精神分裂症患者反复服用催产素的随机临床试验， 约会我们还进行了研究，调查催产素作为治疗患有 酒精，阿片类药物和兴奋剂使用障碍，以及共同发生的创伤后应激障碍（PTSD）， 酒精使用障碍（一种常见且难以治疗的合并症）。我们最近还完成了一个大型的 在健康个体中进行基于实验室研究，以确定急性催产素给药是否 加快团队凝聚力的发展。这项工作使我们假设， 影响社会过程的治疗可以与心理社会治疗相结合， 取得协同增效的积极成果。为了调查这种可能性，我们进行了研究配对 施用各种具有社会影响的药物，包括催产素、3，4-亚甲二氧基甲基苯丙胺 （MDMA）和裸盖菇素，与各种心理治疗干预，包括基于团体的心理治疗。在 在非药物竞技场，我们一直在研究通过一种 作为创伤后应激障碍的治疗方法我们的研究结合了多种分析方法，包括 社会行为的客观测量，如目光注视，面部表情，团队凝聚力和表现， 社会认知能力的量化，神经影像学方法，实验室渴求诱导 范式，心理生理变化和人际同步性的量化。总之，我有 开发了一个广泛的和高生产力的跨诊断研究计划，并组装了一个大的， 充满活力的多学科研究小组，专注于开发和测试新的治疗方法， 很难治疗大多数精神疾病的社会缺陷。通过改善社会赤字 疾病，退伍军人将有更好的社会功能和降低症状的严重程度，并将能够 更有效地动员他们的社会支持网络，并参与其他精神病治疗。这将导致 更好的健康结果和降低成本的VA卫生系统。

There is an “epidemic of loneliness” with 20% of civilians and up to 50% of veterans reporting feeling lonely or socially isolated. This is clinically important because loneliness and social isolation are strong predictors of worse physical health and early mortality. Mental illness is intimately entwined with this epidemic because it both causes and is worsened by loneliness and social isolation. It is the social deficits of mental illness that most strongly contribute to loneliness and social isolation. These social deficits include difficulty understanding other people’s behavior and difficulty behaving appropriately in social situations. Despite their importance, these social deficits are poorly understood at the neural and behavioral levels and are difficult to quantify. Moreover, available treatments for them are inadequate. I am the Director of the Bonding and Attunement in Neuropsychiatric Disorders (BAND) lab, which comprises one junior faculty member supported by a CSR&D Career Development Award, 5 postdoctoral fellows including MDs and PhDs, 4 graduate students, 6 paid research assistants, over 20 volunteers. We believe the key to mental health and well-being starts with strong relationships. Our mission is to develop novel pharmacological and cognitive interventions for mental illness that enable patients to strengthen their connections to other people and the world. Our work has primarily focused on understanding the psychological, behavioral, physiological, and neural effects of administration of the neuropeptide oxytocin across multiple psychiatric illnesses. For example, we have conducted numerous studies determining the acute effects of oxytocin administration in individuals with schizophrenia. One highlight of this work is that we found that a single administration of oxytocin to individuals with schizophrenia normalized neural activity during high-level social cognitive processing and that this normalization was associated with improved behavioral performance. This work led to a VA CSR&D Merit Award to conduct the largest randomized clinical trial of repeated administration of oxytocin in schizophrenia to date. We have also conducted studies investigating oxytocin as a potential treatment for individuals with alcohol, opioid, and stimulant use disorders, and co-occurring post-traumatic stress disorder (PTSD) and alcohol use disorder (a common and difficult-to-treat comorbidity). We also recently completed a large laboratory-based study in healthy individuals to determine whether acute oxytocin administration can accelerate the development of team cohesion. This work led us to hypothesize that pharmacological treatments that affect social processes could be paired with psychosocial treatments to possibly achieve synergistically positive outcomes. To investigate this possibility, we have conducted studies pairing administration of various drugs with social effects, including oxytocin, 3,4-methylenedioxy-methamphetamine (MDMA), and psilocybin, with various psychotherapy interventions including group-based psychotherapy. In the non-pharmacological arena, we have been investigating attention bias modification delivered through a smartphone app as a treatment for PTSD. Our studies incorporate multiple analytic approaches including objective measures of social behavior such as eye-gaze, facial expressivity, team cohesion and performance, quantification of social cognitive abilities, neuroimaging approaches, laboratory-based craving induction paradigms, and quantification of psychophysiological changes and interpersonal synchrony. In sum, I have developed a broad and highly productive trans-diagnostic program of research and assembled a large, energetic, and multidisciplinary research group focused on developing and testing novel treatments for the difficult to treat social deficits that cut across most psychiatric disorders. By improving social deficits across disorders, veterans will have better social functioning and decreased symptom severity and will be able to more effectively mobilize their social support networks and engage in other psychiatric treatment. This will lead to better health outcomes and decreased costs for the VA health system.