DEPRESSION AND BRAIN STRUCTURE IN TYPE 1 DIABETES

描述(申请人提供)：越来越多的证据表明，1型糖尿病导致抑郁障碍患病率增加，初步数据表明，与糖尿病相关的代谢障碍，包括严重低血糖和持续性高血糖，都会导致大脑结构和认知的变化。这些发现，加上对没有糖尿病的抑郁症患者大脑结构变化的研究，表明糖尿病可能会导致大脑结构变化，从而导致抑郁症。目前还没有研究评估1型糖尿病患者抑郁的发病机制。使用横断面研究设计，我们建议研究六组受试者：所有受试者(N=180)年龄为30-40岁，右利手，并根据年龄、性别和社会经济地位匹配。糖尿病患者将有15-25年的糖尿病类型病史。将有三组无精神病史的糖尿病受试者：1.控制良好(0-1次严重低血糖；平均糖化血红蛋白等于或等于8.0%)。2.反复低血糖(等于或等于3次严重低血糖；平均糖化血红蛋白等于或等于8.0%)。3.持续性高血糖(平均糖化血红蛋白等于或&gt；9.0%；0-1次低血糖发作)。第四组有单相抑郁症病史的糖尿病受试者也将被研究，他们同样代表了其他三组糖尿病患者的血糖控制特征。此外，两个非糖尿病对照组(有抑郁史；没有精神病史)也将被研究。我们将使用磁共振成像(MRI)评估这些患者的大脑结构；使用DMS IV结构化临床访谈(SCID)评估抑郁症；使用韦氏成人智力量表III(WAIS III)和其他神经心理学测试记忆、精神运动速度和精神效率来评估认知。我们还将评估医学因素(例如，血糖控制-HbA1c；以及严重低血糖病史)。我们将检验是否：1)结构异常在糖尿病受试者中比匹配的社区对照组更常见；2)糖尿病特有的医学变量，如长期血糖控制与脑结构异常之间存在关系；3)结构异常在有单相抑郁症病史的糖尿病患者中比无抑郁症病史的糖尿病患者更常见；以及4)有单相抑郁病史的糖尿病患者大脑结构异常的频率与抑郁症对照组不同。这项拟议的研究将首次提供关于大脑结构变化与糖尿病抑郁障碍之间联系的证据，以及关于I型糖尿病及其伴随的新陈代谢障碍与大脑结构变化关系的证据。

DESCRIPTION (provided by applicant): There is growing evidence that type 1 diabetes leads to an increased prevalence of depressive disorders and preliminary data suggesting that the metabolic disturbances associated with diabetes, both severe hypoglycemia and persistent hyperglycemia, lead to changes in brain structure and cognition. These findings, together with research on structural changes in the brain among depressed patients without diabetes, suggest that diabetes could cause structural changes in the brain that lead to depression. No studies have evaluated mechanisms underlying the etiology of depression among patients with type 1 diabetes. Using a cross sectional research design, we propose to study six groups of subjects: All subjects (N = 180) will be ages 30-40, right-handed and matched according to age, gender and SES. Diabetic patients will have between a 15-25 year history of types of diabetes. There will be three groups of diabetic subjects without psychiatric history: 1. Well controlled (0-1 episodes of severe hypoglycemia; mean HbA1c over history of diabetes equal to or < 8.0%). 2. Recurrent hypoglycemia ( equal to or >3 episodes of severe hypoglycemia; mean HbA1c over time equal to or <8.0%). 3. Persistent hyperglycemia (mean HbA1c over time equal to or >9.0%; 0-1 hypoglycemic episodes). A fourth group of diabetic subjects with a history of unipolar major depression and who equally represent the glycemic control characteristics of the other three diabetic groups will also be studied. In addition, two non-diabetic control groups (history of depression; no psychiatric history) will also be studied. We will assess these patients as to brain structure, using Magnetic Resonance Imaging (MRI); depression, using the Structured Clinical Interview for DMS IV (SCID); and cognition using the Wechsler Adult Intelligence Scale III (WAIS III) and other neuropsychological tests of memory, psychomotor speed and mental efficiency. We will also evaluate medical factors (e.g., glycemic control-HbA1c; and history of severe hypoglycemia). We will examine whether: 1) structural abnormalities are more common in diabetic subjects compared to the matched community controls; 2) there is a relationship between diabetes specific medical variables, such as long-term glycemic control, and brain structure abnormalities; 3) structural abnormalities are more common in diabetic patients with a history of unipolar major depression than diabetic patients without a history of depression; and 4) the frequency of structural abnormalities in the brain among diabetic patients with a lifetime history of unipolar depression differs from the depression control group. The proposed research will, for the first time, provide evidence regarding the linkage between structural changes in the brain and depressive disorder in diabetes, and evidence about the relationship of type I diabetes and its attendant metabolic disturbances to structural changes in the brain.