DEPRESSION AND BRAIN STRUCTURE IN TYPE 1 DIABETES

描述（由申请人提供）：越来越多的证据表明，1型糖尿病导致抑郁症患病率增加，初步数据表明，与糖尿病相关的代谢紊乱，包括严重低血糖和持续高血糖，会导致大脑结构和认知的改变。这些发现，再加上对非糖尿病抑郁症患者大脑结构变化的研究，表明糖尿病可能导致大脑结构变化，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病因机制。采用横断面研究设计，我们拟研究六组受试者：所有受试者（N = 180）年龄为30-40岁，右撇子，根据年龄、性别和社会经济地位进行匹配。糖尿病患者通常有15-25年的糖尿病史。将有三组无精神病史的糖尿病受试者：1。控制良好（0-1次严重低血糖发作；糖尿病史平均HbA1c等于或< 8.0%）。2. 反复低血糖（≥3次严重低血糖，平均HbA1c≥8.0%）。3. 持续性高血糖（平均HbA1c≥9.0%，0-1次低血糖发作）。第四组糖尿病受试者具有单极重性抑郁症病史，他们的血糖控制特征与其他三组糖尿病患者相同，也将被研究。此外，两组非糖尿病对照组（有抑郁症病史，无精神病史）也将被研究。我们将使用磁共振成像（MRI）来评估这些患者的大脑结构；抑郁症，使用DMS IV （SCID）的结构化临床访谈；和认知使用韦氏成人智力量表III （WAIS III）和其他神经心理学测试的记忆，精神运动速度和精神效率。我们还将评估医学因素（如血糖控制- hba1c和严重低血糖史）。我们将研究是否：1)与匹配的社区对照相比，结构异常在糖尿病受试者中更常见；2)糖尿病特定医学变量（如长期血糖控制）与脑结构异常之间存在关系；3)结构异常在有单极重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；4)有单极抑郁史的糖尿病患者脑结构异常频率与抑郁对照组不同。这项研究将首次为大脑结构变化与糖尿病抑郁症之间的联系提供证据，并为I型糖尿病及其伴随的代谢紊乱与大脑结构变化之间的关系提供证据。

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.