Author name: Romeo Mariano, M.D.

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).

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.

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 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.

Astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits. Astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction. Heterosynaptic long-term depression (hLTD) at synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation. Heterosynaptic long-term depression in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from synaptic terminals via activation of P2Y receptors. Selective stimulation of astrocytes resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors. Blocking P2Y receptors or buffering astrocyte intracellular Ca(2+) at a low level prevented hLTD without affecting LTP

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.

Vitamin D deficiency is a potential risk factor for cardiometabolic disease. Vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia. Vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (β: -0.029 [-0.049, -0.0091], P=.004) and triglyceride (β: -0.094 [-0.15, -0.039] P=.001) levels. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P=.014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P <.001) in adjusted models.

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 (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.

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.