NEW ARTICLES
Blocking Pro-inflammatory Tumor Necrosis Factor with Remicade for Treatment-Resistant Depression
Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants. A drug that targets inflammation may assist in the treatment of depression in individuals with high levels of inflammation. Results of a proof-of-concept study by him, Charles Raison, M.D., an associate professor of psychiatry at the University of Arizona, and colleagues showed that a biologic medication was able to reduce depressive symptoms in some subjects who had suffered from major depression for an average of 15 years.
Screening For Depression In Patients With Diabetes
The prevalence of depression is increased in people with diabetes and there are both national and international recommendations for screening of depression in people with diabetes. Most screening is currently sporadic and there are no formal screening programs. Further research is needed to evaluate the most clinically effective and cost effective way of doing so in structured screening programs.
Citalopram, QTc Interval Prolongation, and Torsade de Pointes
Recently, both the manufacturer of citalopram and the US Food and Drug Administration have warned health care providers and patients about new information implicating drug-induced QTc interval prolongation and torsade de pointes when using citalopram in doses >40 mg/day. This warning is not placed in the context of either benefits or risks in real-world clinical practice, leaving clinicians with an untenable choice between depriving patients of high-dose citalopram or malpractice litigation. We reviewed the literature and found no cases of citalopram-induced sudden cardiac death among patients taking up to 60 mg/day of citalopram and free of risk factors for QTc interval prolongation and torsade de pointes. Because psychotropic drug-induced sudden cardiac death is an outlier in the absence of identified risk factors for QTc interval prolongation and torsade de pointes, we do not believe current Phase 3 and Phase 4 studies provide sufficient information to limit current prescribing practices for citalopram (20 mg to 60 mg/day).
Sympathetic Overactivation Increases Inflammatory Immune Markers.
Several stress-related states and conditions that are considered to involve sympathetic overactivation are accompanied by increased circulating levels of inflammatory immune markers. β-AR sensitivity was lower in people with higher C-reactive protein concentration receiving Isoproterenol. This study demonstrates a link between in vivo β-adrenergic receptor function and selected circulating inflammatory markers (CRP) in humans.
Low-Dose Aripiprazole in the Treatment of SSRI-Induced Bruxism.
Bruxism is characterized by involuntary, repetitive movements of jaw-clenching and teeth-grinding. Several reports in the literature suggest that selective serotonin reuptake inhibitors (SSRIs) might induce bruxism. In that event, clinicians face difficult treatment decisions, especially in cases whereby SSRIs cannot be discontinued or decreased, as in obsessive-compulsive disorder (OCD). In the following, we report the case of a patient with severe OCD and SSRI-induced bruxism successfully treated with low-dose aripiprazole.
Metformin Prevents and Reverses Inflammation in a Non-Diabetic Nonalcoholic Fatty Liver Disease
Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance. Administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis.
Unpredictable Chronic Mild Stress Promotes Atherosclerosis
Chronic psychological stress may contribute to the development of atherosclerosis by enhancing vascular inflammation and decreasing endothelial nitric oxide bioavailability. Unpredictable chronic mild stress (UCMS) exposure significantly increased the plaque size (p = .003) and decreased the plaque stability (decreased the contents of collagen and smooth muscle and increased the amount of macrophage and matrix metalloproteinases). The proatherogenic effects of UCMS were unrelated to changes in serum cholesterol level but accompanied by increased blood pressure (p < .001) and vascular inflammation (up-regulation of tumor necrosis factor α, C-reactive protein, and monocyte chemoattractant protein 1, all p values < .01). Serum concentrations of nitrate/nitrite were lower in UCMS-treated animals (p = .01). Vessels from UCMS-treated animals exhibited augmented phosphorylation of p38 and c-Jun N-terminal kinase and activation of nuclear factor κB.
Abdominal Migraine
Abdominal migraine is a diagnostically challenging disorder, characterized by recurrent episodes of abdominal pain. Our findings demonstrate that abdominal migraine occurs and should be considered in the differential diagnosis of recurrent abdominal pain in adults, especially if there is a family history of migraine headaches.
Growth Hormone-Releasing Hormone improves Cognition in Older Adults and Adults with Mild Cognitive Impairment
Growth hormone-releasing hormone (GHRH), growth hormone, and insulinlike growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI). The intent-to-treat analysis indicated a favorable effect of GHRH on cognition which was comparable in adults with MCI and healthy older adults. Subsequent analyses indicated a positive GHRH effect on executive function and a trend showing a similar treatment-related benefit in verbal memory. Treatment with GHRH increased insulinlike growth factor 1 levels by 117%, which remained within the physiological range, and reduced percent body fat by 7.4%. Treatment with GHRH increased fasting insulin levels within the normal range by 35% in adults with MCI but not in healthy adults. Adverse events were mild and were reported by 68% of GHRH-treated adults and 36% of those who received placebo.
Thioridazine Inhibits Peroxisomal β-oxidation, Leading to Increased Very Long Chain Fatty Acids and Beta-Amyloid Peptide and an Increased Risk of Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by the accumulation of the β-amyloid peptide (Aβ), which is generated from sequential cleavages of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Increased very long chain fatty acid (VLCFA) levels in AD brains imply that peroxisomal β-oxidation dysfunction may be associated with AD pathogenesis. Thioridazine is a selective peroxisomal β-oxidation inhibitor. Thioridazine caused VLCFA accumulation and increases in Aβ(40) content, APP immunoreactivity and APP(751+770) mRNA expressions in the rat cerebral cortex. Impaired peroxisomal function may play an important role in the progression of AD pathology.
Graves Disease Review
Autoimmune thyrotoxicosis or Graves’ disease (GD) is the most common cause of hyperthyroidism in the United States. GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders.
SSRI-Use vs. Non-Use for Depression During Pregnancy
Untreated maternal depression was associated with slower rates of fetal body and head growth. Pregnant mothers treated with SSRIs had fewer depressive symptoms and their fetuses had no delay in body growth but had delayed head growth and were at increased risk for preterm birth.
Higher Levels of Adipocytokines Increase the Risk for Stroke
Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10-year risk of ischemic stroke among healthy middle-aged men. Resistin, adipsin, and total adiponectin, but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin.
Inflammatory prostaglandin E(2) Signaling on EP3 Receptors Lead to Pro-inflammatory Changes Contributing to Alzheimer’s Disease
There is significant evidence for a central role of inflammation in the development of Alzheimer disease (AD). Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. Stimulation of the the PGE(2) EP3 receptor activates proinflammatory, proamyloidogenic, and synaptotoxic signaling pathways. Deletion of the PGE(2) EP3 receptor in a model of Aβ(42) peptide-induced neuroinflammation reduced proinflammatory gene expression, cytokine production, and oxidative stress. Deletion of the EP3 receptor blocked induction of proinflammatory gene and protein expression and lipid peroxidation, and levels of Aβ peptides were significantly decreased, as were β-secretase and β C-terminal fragment levels.
Psychoneuroimmunology of Psoriasis
Bi-directional communication between the Central Nervous System and the Endocrine System has been known for many years. Some of the hormones, themselves, are secreted by the Brain. The CNS and Endocrine System are also involved in a bi-directional communication with the Immune System. This has been a target of intense research in recent decades. Psychological states are related to changes in immune meidators. These influence the development of diseases. This review looks at the role of psychoneuroimmunology in psoriasis.
Stress Activates Immune System Pro-inflammatory Changes Contributing to Coronary Artery Disease
The evidence for the effects of acute and chronic psychological stress on the onset and progression of CAD is consistent and convincing. Psychological stressors change endothelial function and lead to chemotaxis. Acute psychological stressors lead to leukocytosis, increased natural killer cell cytotoxicity and reduced proliferative response to mitogens. Psychological stressors will increase haemostatic factors and acute phase proteins, possibly leading to thrombus formation and myocardial infarction.
Obesity results in chronic low-grade pro-inflammatory signaling that contributes to anxiety and depressive behaviors
Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression.
Insomnia Increases Pro-Inflammatory Signaling Contributing To Cardiovascular Disease
Bidirectional communication between the brain and the immune system is carried out through a complex network of autonomic nerves, endocrine hormones, and cytokines. Insomnia perturbs the functioning of this network and therefore contribute to elevations in inflammatory mediators which lead to cardiovascular disease.
