Breaking the Stigma: Major Depressive Disorder

Major Depressive Disorder (MDD) is a mood and mental disorder affecting the brain; it is caused by the reduction of three monoamine neurotransmitters: serotonin, norepinephrine, and dopamine (Rot, M. A., Mathew, S. J., & Charney, D. S. 2009). MDD is one of the world’s most common mental disorders, affecting a predicted 4% of the world’s population and roughly 16.1 million adults in United States alone (Major Depression. 2019; Ritchie, H., & Roser, M. 2018). The concentrations of these neurotransmitters are reduced in the brains of people with MDD due to their increased reabsorption from synapses in the brain back into presynaptic neurons (Ruhé, H. G., Mason, N. S., & Schene, A. H. 2007). In attempt to regulate the concentrations of these neurotransmitters in people with MDD, medications like SSRIs, SNRIs, TCAs, and MAOIs can be prescribed (Yeragani, V., Ramachandraih, C., Subramanyam, N., Bar, K., & Baker, G. 2011). In addition to neurochemical changes, neuroanatomical changes have also been reported in people with MDD (Treadway, M. T., & Pizzagalli, D. A. 2014). In recent years, depressive disorders have captured brief media attention due to celebrities sharing their experiences with MDD, as well as celebrities dying by suicide. Although depressive disorders are more frequently being acknowledged and discussed in a public spotlight, there remains a stigma surrounding mental illness including MDD. This partially stems from a lack of public understanding that mental disorders are, indeed, illnesses. Societal pressures may prevent people suffering from mental illnesses from accepting that they have a disorder, seeking help from medical professionals, and not being ashamed of their disorder (Corrigan, P. W., Druss, B. G., & Perlick, D. A. 2014). Furthermore, individuals that have sought help often talk to a physician or psychiatrist about their diagnosis, but they may struggle to understand the information presented to them. The purpose of this project was to create several illustrations and an animation that would strengthen public and patient education and understanding of MDD in attempt to help break some of the stigma that surrounds this mental illness

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Background: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from reinfection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157: H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. Results: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed. Conclusions: Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157: H7 (Stx(-)) due to an upregulation of immune suppressive effects (7/12 genes) or a downregulation of immunostimulatory effects (69/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function

Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders

Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown to be effective for tic control, but are also associated with poor tolerability because of their adverse effects. The newer antipsychotic medication aripiprazole is characterized by a unique mechanism of action (D2 partial agonism), and over the last decade has increasingly been used for the treatment of tics. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders (age range: 4–18 years). Our search identified two randomized controlled trials (involving 60 and 61 participants) and ten open-label studies (involving between six and 81 participants). The majority of these studies used two validated clinician-rated instruments (Yale Global Tic Severity Scale and Clinical Global Impression scale) as primary outcome measures. The combined results from randomized controlled trials and open-label studies showed that aripiprazole is an effective, safe, and well-tolerated medication for the treatment of tics. Aripiprazole-related adverse effects (nausea, sedation, and weight gain) were less frequent compared to other antidopaminergic medications used for tic management and, when present, were mostly transient and mild. The reviewed studies were conducted on small samples and had relatively short follow-up periods, thus highlighting a need for further trials to assess the long-term use of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders with measurement of its efficacy using both clinician-rated and self-report scales

Immunolocalization of a Drosha-Like Protein in Tetrahymena thermophila

Drosha is an enzyme used by animals to process pri-miRNA into pre-miRNA. This processing normally occurs in the nucleus. The partly processed RNA molecule is then exported to the cytosol, where it is fully processed and then used in gene regulation. While much is known about this process in animals, less is known about how unicellular organisms process miRNA. We wanted to compare miRNA processing in the unicellular eukaryote, Tetrahymena thermophila with miRNA processing in the animal kingdom. In our past studies, we have successfully purified miRNA from Tetrahymena thermophila. Our searches of the Tetrahymena Genome Database indicated the presence of multiple genes with very high levels of homology to the miRNA processing enzymes Drosha and Dicer. Because of these data, we postulated that an anti-Drosha antibody would bind to a number of proteins in Tetrahymena. We hypothesized that a Drosha-like protein would immunolocalize to the nucleus of Tetrahymena, as seen in animal systems

Histaminergic modulation in Tourette syndrome

Introduction: Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor tics and at least one vocal/phonic tic. Clinical phenotypes show a wide variability, often incorporating behavioral symptoms. The exact pathophysiology of Tourette syndrome is unknown, however genetic vulnerability and alterations in dopaminergic neurotransmission have consistently been reported. Other biochemical pathways, including histaminergic neurotransmission, are likely to be involved but have received relatively little attention until recently. Areas covered: We conducted a systematic literature review focusing on the role of histaminergic neurotransmission and its pharmacological modulation in Tourette syndrome. We identified a number of relevant original studies published over the last five years, mainly focusing on genetic aspects. Expert opinion: There is converging evidence from recent studies supporting the hypothesis that histaminergic neurotransmission may play a role in the pathophysiology of Tourette syndrome. Most studies focused on the role of the histidine decarboxylase gene and the potential usefulness of histidine decarboxylase knockout mice as an experimental model for studying neurochemical function in Tourette syndrome. There have been no large scale studies assessing the use of histaminergic medications in the management of Tourette syndrome. This would be an important area for future research, with direct implications for the clinical management of selected phenotypes

Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures

About one third of patients with epilepsy are refractory to medical treatment. For these patients, alternative treatment options include implantable neurostimulation devices such as vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation systems (RNS). We conducted a systematic literature review to assess the available evidence on the clinical efficacy of these devices in patients with refractory epilepsy across their lifespan. VNS has the largest evidence base, and numerous randomized controlled trials and open-label studies support its use in the treatment of refractory epilepsy. It was approved by the US Food and Drug Administration in 1997 for treatment of partial seizures, but has also shown significant benefit in the treatment of generalized seizures. Results in adult populations have been more encouraging than in pediatric populations, where more studies are required. VNS is considered a safe and well-tolerated treatment, and serious side effects are rare. DBS is a well-established treatment for several movement disorders, and has a small evidence base for treatment of refractory epilepsy. Stimulation of the anterior nucleus of the thalamus has shown the most encouraging results, where significant decreases in seizure frequency were reported. Other potential targets include the centromedian thalamic nucleus, hippocampus, cerebellum, and basal ganglia structures. Preliminary results on RNS, new-generation implantable neurostimulation devices which stimulate brain structures only when epileptic activity is detected, are encouraging. Overall, implantable neurostimulation devices appear to be a safe and beneficial treatment option for patients in whom medical treatment has failed to adequately control their epilepsy. Further large-scale randomized controlled trials are required to provide a sufficient evidence base for the inclusion of DBS and RNS in clinical guidelines

Sensory aspects of Tourette syndrome

Motor and vocal tics have long been recognised as the core features of Tourette syndrome (TS). However, patients’ first-person accounts have consistently reported that these involuntary motor manifestations have specific sensory correlates. These sensory symptoms are often described as feelings of mounting inner tension (“premonitory urges”) and are transiently relieved by tic expression. Multimodal hypersensitivity to external stimuli, perceived as triggers and/or exacerbating factors for specific tic symptoms, is also commonly reported by patients with TS. This article focuses on the rapidly expanding literature on the clinical and neurobiological aspects of the premonitory urge and multimodal hypersensitivity in patients with TS, with particular attention to pathophysiological mechanisms and possible treatment implications. These findings suggest that TS is a neurobehavioural condition characterised by intrinsic perceptual abnormalities involving the insula and sensorimotor areas, in addition to basal ganglia dysfunction. Further research will clarify the role of sensory symptoms in TS, as well as the effects of external sensory input on underlying motor abnormalities