Glyphosate Exposure Associated with Human Neurodegenerative Disorders: A Scoping Review

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

Smoking in schizophrenic patients:A critique of the selfmedication hypothesis

A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980 s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers.

Integrating insulin-like growth factor 1 and sex hormones into neuroprotection:Implications for diabetes

Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1(IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sexhormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinasesignaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones.

Neuropsychological Assessment of Learning and Memory in Rats Following Ketamine Exposure during Late Adolescence

With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.

Absence of Ketamine Effects on Learning &Memory Following Exposure during Early Adolescence: A Preliminary Report

Traditionally, ketamine was considered useful as a dissociative anesthetic. More recently, ketamine has been examined for its effects as a fast-acting antidepressant, for treatment-resistant depression, and as a non-opiate treatment of chronic pain. Unfortunately, ketamine has enjoyed popularity as a recreational drug among both adolescents and young adults. While some research suggests the use of this drug during neurodevelopment is not without consequence, relatively little work has been conducted to examine the chronic effects of ketamine on the adolescent brain at different stages of neural development. Using a rodent model of development, we probed the effects of early adolescent exposure to ketamine. Between postnatal days 22 to 40, a period comprising early to mid-adolescence, rats were exposed to one of two doses of ketamine or saline. Beginning at 90 days of age and drug free for 50 days, a series of neuropsychological assessments were employed to examine general activity, spatial navigation, as well as nonspatial response learning. Contrary to prediction, except for differences in general activity levels, no spatial or nonspatial impairments were found among the drug- and saline-treated animals. The present results are considered in light of ketamine-associated effects found in a related study with older adolescent rats and the role of drug exposure during different points in adolescent brain development.

5-HTR2A Polymorphisms rs6311 and rs6313 and Major Depressive Disorder: A Meta-Analysis

rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I2. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in type 2 diabetes mellitus patients presenting to a functional medicine clinic

This study explores the relationship of 25-hydroxylvitamin D blood levels in 106 randomly selected patient files with diagnosed type 2 Diabetes Mellitus (t2DM) who enrolled in a functional medicine diabetes reversal program from a chiropractic clinic located in Annapolis, Maryland, USA. Using a conservative recommendation for normal serum 25-hydroxyvitamin D concentration of 32 ng/ml, insufficiency level of 20 - 30 ng/ml, and deficiency level < 20 ng/ml, 21% (22/106) of our population were normal, 39% (41/106) were insufficient, and alarmingly, 35% (37/106) were outright deficient. Clinically, 74% (78/ 106) of our entire sample had significantly low vitamin D levels. Ou et al. (2011) determined the optimal concentration of serum 25OHD to be 40 ng/ml in order to optimize insulin sensitivity. In our sample 100/ 106 (94%) had vitamin D levels at or below this optimal cut-off level. BMI was negatively correlated with vitamin D;that is, the greater the BMI of the patient the less their vitamin D level. Both obesity and hypovitaminosis D are each mutually exclusive predictors for t2DM. Obesity and vitamin D deficiency may work synergistically to propel an individual into the diseased state of t2DM. As this study demonstrates that the majority of people with t2DM suffer from inadequate amounts of vitamin D, vitamin D testing should be routine for all people at risk for t2DM, prediabetics and those currently suffering with t2DM in order to elevate levels sufficiently to improve insulin sensitivity and improve long-term outcomes.

Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study

The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.