Childhood trauma and insulin resistance in patients suffering from depressive disorders.

Objective: Insulin resistance (IR) is a metabolic dysfunction often co-morbid with major depressive disorder (MDD). The paths to development of MDD remain largely unspecified, highlighting a need for identification of risk factors. Here, we tested whether specific subscales of childhood trauma as well as family history of type-2 diabetes (Fam-Hx-Dm2) are risk factors for development of metabolic dysfunction and severity of depressive symptoms.

Early life adversity blunts responses to pioglitazone in depressed, overweight adults.

Purpose: Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression.

Neural correlates of liraglutide effects in persons at risk for Alzheimer's disease.

Unlabelled: Insulin resistance (IR) is a metabolic state preceding development of type 2 diabetes (DM2), cardiovascular disease, and neurodegenerative disorders, including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP) agonist, is an insulin-sensitizing agent with neuroprotective properties, as shown in animal studies. The purpose of this double-blinded, placebo-controlled study was to examine the neural effects of administration of liraglutide in cognitively normal late middle-aged individuals with subjective cognitive complaints (half of subjects had family history of AD).

Determinants of cognitive function in individuals with type 2 diabetes mellitus: A meta-analysis.

Background: Type 2 diabetes mellitus (T2DM) is associated with deficits across multiple cognitive domains; however, the determinants of cognitive impairment in T2DM are not well characterized. We aimed to evaluate body mass index (BMI), glycemic control, and T2DM duration as moderators of cognitive dysfunction in T2DM.

Methods: We conducted a meta-analytic review of the literature reporting data on BMI, hemoglobin A1c (HbA1c), T2DM duration, and validated measures of processing speed (ie, Digit Symbol Substitution Test, Trail Making Test [TMT]-A), verbal learning and memory (ie, Rey Auditory Verbal Learning Test), and working memory/executive function (ie, TMT-B) among individuals with vs without T2DM.

Adjuvant pioglitazone for unremitted depression: Clinical correlates of treatment response.

Previous studies suggest that insulin-sensitizing agents could play a significant role in the treatment of major depression, particularly depression in patients with documented insulin resistance or those who are resistant to standard psychopharmacological approaches. This study aimed to assess the effects on depressive symptoms with adjuvant treatment with the PPARγ-agonist pioglitazone. Patients (N=37) with non-psychotic, non-remitting depression receiving standard psychiatric regimens for depression were randomized across an insulin sensitivity spectrum in a 12-week double blind, randomized controlled trial of pioglitazone or placebo.

Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease.

Objective: Use of estrogen-based hormone therapy (HT) as a protection from cognitive decline and Alzheimer disease (AD) is controversial, although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT.

Methods: Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT.

Association between insulin resistance and cognition in patients with depressive disorders: exploratory analyses into age-specific effects.

Unlabelled: The current preliminary cross sectional study sought to examine the effects of insulin resistance (IR) and body mass index (BMI) on cognitive performance in adult patients with a history depression, currently not in an acute Major Depressive Episode (MDD). As an exploratory post hoc investigation, special consideration was given to adults <45 years and ≥45 years old. Subjects included men and women ages 19-71 (N = 39) with a history of a non-psychotic, non-melancholic MDD.

Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.

Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up.

Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia.

Unlabelled: The objective of this study was to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT-) therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET).

Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity.

This paper reviews the clinical implications of topiramate (TPM)-induced cognitive deficits in patients with epilepsy, migraine headache, obesity, and in normal populations, followed by reviews of the literature describing the reversal of such deficits upon medication discontinuation. It also discusses animal investigations of TPM's role of neuroprotection in brain injury. TPM's most intolerable adverse effects (AEs) are on verbal fluency and reaction time, resulting in high discontinuation rates in patients taking it for epilepsy and migraine headache.

Differences in verbal memory performance in postmenopausal women receiving hormone therapy: 17β-estradiol versus conjugated equine estrogens.

Objective: Much controversy exists and many questions remain unanswered about the effects of hormone therapy (HT) on cognition in postmenopausal women. There is growing evidence suggesting that HT compounds containing conjugated equine estrogen (CEE) have negative effects on cognition whereas 17β-estradiol (17β-E) either has positive or neutral effects. The present study sought to further examine this issue in a sample of postmenopausal women with risk factors for Alzheimer's disease (AD).

Insulin resistance and hippocampal volume in women at risk for Alzheimer's disease.

Insulin resistance (IR) is the main pathological condition underlying vascular disorders, such as diabetes and cardiovascular disease, which are well established risk factors for cognitive decline and Alzheimer disease (AD). Hippocampal atrophy has been associated with cognitive decline, but little is known about the influence of IR on hippocampus integrity in non-diabetic, cognitively intact individuals. Herein, 50 women ages 50-65, current users of hormone therapy, underwent magnetic resonance imaging, cognitive testing, and homeostatic assessment of insulin resistance (HOMA-IR), as part of a longitudinal study examining brain structure and function in postmenopausal women at risk for AD.

Mood and neuropsychological changes in women with midlife depression treated with escitalopram.

Objective: This study assessed mood and neuropsychological function in a population of middle-aged women with major depressive disorder treated with escitalopram.

Methods: Psychometric data measuring severity of depression were collected from 19 women and neuropsychological data were collected from 17 women aged between 45 and 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depression in a study in the Behavioral Neuroendocrinology Program at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. All women were treated with escitalopram in an open-label design.

Estrogen and response to sertraline in postmenopausal women with major depressive disorder: a pilot study.

Objective: Pilot study examining the effects of estrogen therapy (ET) on antidepressant response in postmenopausal women with major depressive disorder (MDD).

Methods: Twenty-two subjects received sertraline at 50mg/day for one week, with an increase to 100mg/day at week 2 for a 10-week trial. Transdermal estrogen or placebo patches 0.