Prospective association between obesity and depression: evidence from the Alameda County Study.
ABSTRACT To examine the temporal relation between obesity and depression to determine if each constitutes a risk factor for the other.
A two-wave, 5-y-observational study with all measures at both times.
A total of 2123 subjects, 50 y of age and older, who participated in the 1994 and 1999 waves of the Alameda County Study.
Obesity defined as body mass index (BMI)> or =30. Depression assessed using DSM-IV symptom criteria for major depressive episodes. Covariates include indicators of age, gender, education, marital status, social support, life events, physical health problems, and functional limitations.
Obesity at baseline was associated with increased risk of depression 5 y later, even after controlling for depression at baseline and an array of covariates. The reverse was not true; depression did not increase the risk of future obesity.
These results, the first ever on reciprocal effects between obesity and depression, add to a growing body of evidence concerning the adverse effects of obesity on mental health. More studies are needed on the relation between obesity and mental health and implications for prevention and treatment.
Full-textDOI: · Available from: George A Kaplan, May 05, 2015
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ABSTRACT: Obesity is often accompanied by hyperactivity of the neuroendocrine stress axis and has been linked to an increased risk of psychiatric disorders. Insulin is reciprocally regulated with the stress hormone corticosterone (CORT), raising the possibility that insulin normally provides inhibitory tone to the hypothalamus-adrenal-pituitary (HPA) axis. Here we examined whether disrupting signaling via the insulin receptor (InsR) in hypothalamic subpopulations impacts the neuroendocrine response to acute psychological stress. We used Nkx2.1-Cre, Sim1-Cre and Agrp-Cre transgenic driver lines to generate conditional knockouts of InsR signaling throughout the hypothalamus, paraventricular nucleus of the hypothalamus (PVH) and in neurons expressing Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARH), respectively. We used a combination of molecular, behavioral and neuroendocrine criteria to evaluate the consequences on HPA axis responsiveness. Endpoints related to body weight and glucose homeostasis were not altered in any of the conditional mutant lines. Consistent with observations in the neuronal Insr knockout mice (NIRKO), baseline levels of serum CORT were similar to controls in all three lines. In male mice with broad disruptions of InsR signals in Nkx2.1-expressing regions of the hypothalamus (IR(Nkx2.1) KO), we observed elevated arginine vasopressin (AVP) levels at baseline and heightened neuroendocrine responses to restraint stress. IR(Nkx2.1) KO males also exhibited increased anxiety-like behaviors in open field, marble burying, and stress-induced hyperthermia testing paradigms. HPA axis responsivity was not altered in IR(Sim1) KO males, in which InsR was disrupted in the PVH. In contrast to observations in the IR(Nkx2.1) KO males, disrupting InsR signals in ARH neurons expressing Agrp (IR(Agrp) KO) led to reduced AVP release in the median eminence (ME). We find that central InsR signals modulate HPA responsivity to restraint stress. InsR signaling in AgRP/NPY neurons appears to promote AVP release, while signaling in other hypothalamic neuron(s) likely acts in an opposing fashion. Alterations in InsR signals in neurons that integrate metabolic and psychiatric information could contribute to the high co-morbidity of obesity and mental disorders.
Article: Mood, food, and obesity[Show abstract] [Hide abstract]
ABSTRACT: Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.Frontiers in Psychology 09/2014; 5:925. DOI:10.3389/fpsyg.2014.00925 · 2.80 Impact Factor
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ABSTRACT: Background and purposeNeurodegenerative diseases are now recognized to be multifunctional, whereby heterogeneous set of reactions act independently or cooperatively, leading eventually to the demise of neurons. This has led our group to design and synthesize the multifunctional, nontoxic, brain permeable, iron chelator compound M30 with pluri-pharmacological properties. Considering the diverse beneficial neuroprotective properties of M30, this study provides a characterization of the brain molecular targets of the drug in type 2 diabetes mellitus (T2DM) animal models.Experimental ApproachHere, we examined the effect of M30 on neuroprotective-associated molecular mechanisms in the high fat diet (HFD) and ob/ob transgenic mouse models of T2DM.Key ResultsOur results demonstrate that M30 increased cerebral levels of insulin/insulin receptor and p-GSK-3β in HFD mice, as compared to vehicle-treated HFD mice. In both T2DM mice models, M30 treatment produced a significant up-regulation of cerebral hypoxia-inducible factor (HIF)-1α protein levels and induced the expression of several HIF-1-target genes involved in neuroprotection, glycolysis, neurogenesis, oxidative stress and anti-inflammation. Additionally, we found that M30 caused a significant inhibition of MAO-A and -B activities in the cerebellum. In accordance, M30 administration significantly reduced brain levels of the metabolites of dopamine and increased the levels of serotonin and noradrenaline.Conclusions and ImplicationsThe data presented here demonstrate that in the brain of HFD and ob/ob transgenic mice, M30 exerts various beneficial neuroprotective regulatory effects that may act synergistically and delay/prevent neurodegenerative processes associated with T2DM.British Journal of Pharmacology 07/2014; 171(24). DOI:10.1111/bph.12862 · 4.99 Impact Factor