Gene/Protein Disease Symptom Drug Enzyme Compound
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Depression during hospitalization for myocardial infarction (MI) is associated with subsequent mortality, but whether this risk persisted long term is not well studied. This study was performed to determine whether depression during hospitalization for MI, which predicted mortality at 4 months, predicted mortality 8 years later. This was a prospective observational study of 284 hospitalized patients with MI. Major depression and dysthymia were assessed using structured interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, and depressive symptoms, using the Beck Depression Inventory. Mortality was determined using the Social Security Death Index. Mean age during MI hospitalization was 64.8 years, 43.0% of patients were women, 66.7% had hypertension, and 35.7% had diabetes mellitus. Any depression (major depression, dysthymia, and/or Beck Depression Inventory score > or =10) was present in 76 patients (26.8%). The 8-year mortality rate was 47.9% (136 deaths). Any depression at the time of MI was not associated with mortality at 8 years in unadjusted (hazard ratio 1.25, 95% confidence interval 0.87 to 1.81, p = 0.22) or multivariate models (hazard ratio 0.76, 95% confidence interval 0.47 to 1.24, p = 0.27). In conclusion, depression after MI was associated with increased short-term mortality, but its relation with mortality over time appeared to wane, at least in a group of older patients who had multiple co-morbidities.
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PMID:Effect of depression on late (8 years) mortality after myocardial infarction. 1830 6

Depression and suicide tendencies are common in chronic diseases, especially in epilepsy and diabetes. Suicide is one of the most important causes of death, and is usually underestimated. We have analyzed several studies that compare mortality as a result of suicide in epileptic patients and in the general population. All the studies show that epileptic patients have a stronger tendency toward suicide than healthy controls. Moreover it seems that some kinds of epilepsy have a higher risk for suicide (temporal-lobe epilepsy). Among the risk factors are surgery therapy (suicide tendency five times higher than patients in pharmacological therapy), absence of seizures for a long time, especially after being very frequent, and psychiatric comorbidity (major depression, anxiety-depression disorders, personality disorders, substance abuse, psychoses). The aim of the review was to analyze the relationship between suicide and epilepsy, to identify the major risk factors, and to analyze effective treatment options.
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PMID:Epilepsy and suicide: pathogenesis, risk factors, and prevention. 1872 42

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95% Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.
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PMID:Heart disease, other circulatory diseases, and onset of major depression among community residents in Japan: results of the World Mental Health Survey Japan 2002-2004. 1876 7

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p <0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index > or =30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome.
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PMID:[Pharmacological therapy of obesity]. 1877 55

Stigma of mental illness is a major obstacle to its diagnosis and treatment and may be worse among Asians than Caucasians. This study compared the stigma of depression in 50 Chinese Americans (CA) and 50 Caucasian Americans (WA). Subjects were asked to read 5 case vignettes in the following order: diabetes mellitus (DB), major depressive disorder (MDD), somatoform depression (SD), psychotic depression (PD), and fever of unknown origin (HA). Diagnosis of each case was not revealed. Subjects then rated their response to each case, on a Likert scale from "strongly disagree" to "strongly agree," to 25 statements that contained 6 stigma factors: fear, shame, cognitive distortion, social consensus, discrimination, and sanction. Composite scores constructed from ratings of each factor were used to calculate the severity of stigma. Stigma of all 5 cases was worse in CA than WA. Both groups ranked DB and HA to be least and PD to be most stigmatizing. CA rated SD to be less stigmatizing than MDD but not WA. We concluded that stigma formation and severity were determined by fear, shame, cognitive distortion, social communication, consensus, and sanction. Mental symptoms, particularly psychotic symptoms, were more stigmatizing than physical symptoms, especially for CA. Belief that depression was like a physical illness did not diminish its stigma.
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PMID:Stigma of depression is more severe in Chinese Americans than Caucasian Americans. 1883 72

Depression is often comorbid with type 2 diabetes. Depression may increase vulnerability to and/or exacerbate existing cognitive deficits. Little is known about the brain pathophysiology underlying depression and cognitive abnormalities in diabetes. The aim of this study was to examine the relationship of orbitofrontal and anterior cingulate volumes with executive functioning and attention/processing speed in type 2 diabetic participants with and without major depression. A total of 21 diabetic participants with major depression, 23 diabetic participants with no depression, and 22 healthy controls were compared. Using brain magnetic resonance imaging, volumetric measures of the prefrontal cortex were examined in relation to executive functioning and attention/processing speed. Partial correlations suggested a significant positive relationship between right orbitofrontal regions and executive functioning in the group with diabetes and depression only, indicating that neurobiological changes in the orbitofrontal region may contribute to observed cognitive dysfunction.
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PMID:Neuroanatomical correlates of executive functioning in depressed adults with type 2 diabetes. 1893 77

Hypothalamus-pituitary-thyroid (HPT) axis dysfunction has been associated with pathophysiology of major depression. The aim of the study was to determine serum levels of total 3,5,3'-triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating-hormone (TSH) in patients with major depression and healthy controls. The study included 53 medication-free patients with depression and 49 healthy controls. Exclusion criteria for patients was: other axis-I and axis-II diagnoses, intensive psychotherapy or electroconvulsive therapy, prior clinical and/or laboratory evidence of hypo- or hyperthyroidism, alcohol or nicotine dependence, pregnancy, hormone supplement therapy, somatic illnesses (diabetes, renal or hepatic disorders), infections or autoimmune diseases, recent surgical treatment or significantly changed body weight. For controls: the presence of psychiatric disorders and/or thyroid dysfunctions. The diagnosis of major depression was made using structured clinical interview based on DSM-IV criteria. The results showed significantly lower T3 and TSH levels in patients compared to controls. There was no significant difference in T4 values between patients with depression and control subjects. The results showing altered levels of thyroid hormones in depression indicate that further research on thyroid hormone activity can contribute to the better understanding of the biological basis of depression. Based on the high frequency of the subtle neuroendocrine disorders coexisting with depression, the association of thyroid abnormalities and depression should not be underestimated. Future research should identify different behavioral endophenotypes characteristic for depression, which would greatly facilitate delineating the biological phenomena associated with this psychiatric illness.
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PMID:Thyroid activity in patients with major depression. 1898 76

Major depression and the metabolic syndrome (MetS) are interacting clinical conditions influenced by genetic susceptibility. For both disorders, impaired serotonergic neurotransmission in specific brain areas has been suggested. This led us to investigate whether variants in the gene coding for tryptophan hydroxylase 2 (TPH2), the brain-specific and rate-limiting enzyme for serotonin biosynthesis, might be predictive for an increased liability for the development of MetS in depressed patients. In a case-control study consisting of 988 patients with recurrent unipolar depression (RUD) and 1023 psychiatric healthy controls, MetS components were ascertained according to the International Diabetes Foundation criteria. A total of 41 single nucleotide polymorphisms fully covering the TPH2 gene region were genotyped in stage 1 (300 patients/300 controls), resulting in significant genetic associations of polymorphisms located in exon 7 and intron 8 of TPH2 and the occurrence of MetS in depressed patients after correction for age, gender and multiple testing (51 RUD-MetS/179 RUD-non-MetS). We were able to confirm the significant association of rs17110690 in stage 2 (688 patients/723 controls; 110 RUD-MetS/549 RUD-non-MetS) and to link risk-genotypes and risk-haplotypes for MetS to lower TPH2 mRNA expression and to lower 5-hydroxyindoleacetic acid levels in cerebrospinal fluid previously reported in functional studies. Our findings suggest that TPH2 polymorphisms characterize a subgroup of depressed patients who are especially prone to develop metabolic disorders induced by a genotype-dependent impairment of serotonergic neurotransmission. Identifying depressed patients at high risk for MetS using genetic variants could have direct clinical impact on individualized disease management and prevention strategies.
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PMID:Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression. 1912 59

The repertoire of biochemicals (or small molecules) present in cells, tissue, and body fluids is known as the metabolome. Today, clinicians utilize only a very small part of the information contained in the metabolome, as revealed by the quantification of a limited set of analytes to gain information on human health. Examples include measuring glucose or cholesterol to monitor diabetes and cardiovascular health, respectively. With a focus on comprehensively studying the metabolome, the rapidly growing field of metabolomics captures the metabolic state of organisms at the global or "-omics" level. Given that the overall health status of an individual is captured by his or her metabolic state, which is a reflection of what has been encoded by the genome and modified by environmental factors, metabolomics has the potential to have a great impact upon medical practice by providing a wealth of relevant biochemical data. Metabolomics promises to improve current, single metabolites-based clinical assessments by identifying metabolic signatures (biomarkers) that embody global biochemical changes in disease, predict responses to treatment or medication side effects (pharmachometabolomics). State of the art metabolomic analytical platforms and informatics tools are being used to map potential biomarkers for a multitude of disorders including those of the central nervous system (CNS). Indeed, CNS disorders are linked to disturbances in metabolic pathways related to neurotransmitter systems (dopamine, serotonin, GABA and glutamate); fatty acids such as arachidonic acid-cascade; oxidative stress and mitochondrial function. Metabolomics tools are enabling us to map in greater detail perturbations in many biochemical pathways and links among these pathways this information is key for development of biomarkers that are disease-specific. In this review, we elaborate on some of the concepts and technologies used in metabolomics and its promise for biomarker discovery. We also highlight early findings from metabolomic studies in CNS disorders such as schizophrenia, Major Depressive Disorder (MDD), Bipolar Disorder (BD), Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD).
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PMID:Metabolomics tools for identifying biomarkers for neuropsychiatric diseases. 1930 40

BMI has been inversely associated with risk of completed suicide in several cohort studies, but putative mechanisms for this association and its generalizability throughout the United States are uncertain. We ascertained recent population-based, state-level data on rates of obesity, completed suicide (by method), firearm ownership, smoking, major depression, income, education, white race, and nonmetropolitan residence, compiled from federal agencies and surveys, and determined the adjusted population-weighted correlations of statewide obesity rates with measures of completed and attempted suicide. Statewide prevalence of obesity was strongly inversely correlated with age adjusted suicide rate (multivariable-adjusted r=-0.66; P<0.001). The correlation was somewhat stronger for rates of nonfirearm-related (r=-0.75; P<0.001) than firearm-related suicides (r=-0.53; P<0.001), and was of similar magnitude as the positive correlations of firearm prevalence with suicide rate (r=0.75; P<0.001) or of obesity with prevalence of diabetes (r=0.41; P=0.006). In analyses of fatal and nonfatal suicidal acts, obesity rates were inversely correlated with rates of suicidal acts using firearms (r=-0.53; P=0.02) and suffocation (r=-0.76; P<0.001) but not other methods. Obesity rates were also inversely correlated with the case-fatality ratios of acts using poisoning (r=-0.51; P=0.01). Thus, statewide rates of obesity are strongly inversely correlated with rates of completed suicide in multivariable analyses, a finding that appears to relate to fewer attempts by suffocation and a lower case-fatality ratio for poisonings, although the mechanism for the inverse correlation with firearm-related suicides requires further elucidation.
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PMID:BMI and rates of suicide in the United States: an ecological analysis. 1939 May 24


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