Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebocontrolled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

Pediatric anxiety disorders characterized as Generalized, Separation, and Social Anxiety Disorders, are chronic debilitating conditions that leave children feeling tense and isolated, both physically and emotionally. Selective serotonin reuptake inhibitors (SSRIs) are a classification of antidepressants that can be prescribed to children diagnosed with these disorders. SSRIs have been shown to be effective in treating anxiety disorders in children. The purpose of this literature review was to examine and determine if there are more risks or benefits associated with SSRIs, as well as evaluate teaching and education regarding anxiety disorder medication compliance in both children and parents. A secondary purpose of this research was to provide recommendations in nursing practice to allow children to feel more involved in their medical regimen. The following databases were used for the search: CINAHL, Academic Search Premier, and Web of Science. Key terms used in the search include but are not limited to: child* and anxiety, not autism, and selective serotonin reuptake inhibitors, OR SSRI*, OR adolsecen*, not med*, pediatric*, OR side effects. The results suggest that the benefits of SSRI therapy in children with anxiety disorder, when taken on a regularly scheduled basis, outweigh the risks, however more research aimed at compliance with SSRI therapy in children and parents is necessary. Further research analyzing children with anxiety disorders is needed to assess SSRI usage based specifically on their developmental age, and the inclusion of appropriate teaching and explanation related to their diagnoses to identifying stressors that can include behavioral therapy as well.

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No description available.

Obsessive-compulsive disorder (OCD) is heterogeneous. Clinical presentation of OCD differs by sex and age-of-onset and evidence supports classification based on these subtypes. The prevalence of OCD in the general population is 2%. However, it has been established that women tend to experience onset and exacerbation of OCD during reproductive milestones. In particular, the prevalence of postpartum OCD is between 4 to 9%. This study seeks to examine the effects of past childhood maltreatment and S/Lg-allele status of the 5-HTTLPR polymorphism on perinatal obsessive-compulsive symptoms and aberrant resting state functional connectivity in the postpartum period. Forty women participated in the first visit and sixteen women have been followed up with in the postpartum period. 5-HTTLPR genotype was determined from whole blood samples via polymerase chain reaction and a restriction fragment length digest. We used the Yale-Brown Obsessive-Compulsive Scale and Perinatal Obsessive-Compulsive scale to measure symptom severity. Resting state functional connectivity was determined from functional magnetic resonance imaging data. Obsessive-compulsive symptoms during late pregnancy are significantly predicted by 5-HTTLPR genotype, past history of total childhood maltreatment or childhood emotional neglect and trait anxiety symptoms. Whereas obsessive-compulsive symptoms during the postpartum period are predicted by poor sleep quality and childhood emotional maltreatment or 5-HTTLPR genotype, childhood emotional maltreatment and trait anxiety symptoms. Seed to region-of-interest analysis was employed to evaluate resting state functional connectivity differences between OCD patients and healthy controls in the postpartum period. Compared to healthy controls, OCD patients show greater connectivity between the caudate nucleus with the orbitofrontal cortex, the pars triangularis and the cingulate area. The insular cortex shows decreased connectivity between the right and left, the dorsal anterior cingulate area and the pars opercularis. The amygdala has increased connectivity with the cingulate area, the calcarine fissure, the supramarginal gyrus and decreased connectivity with the gyrus rectus. The above clinical and neuroimaging findings are in line with past work. However, this is the first study to show both 5-HTTLPR genotype and history of childhood maltreatment predict obsessive-compulsive symptoms in a perinatal population. Further, the resting state data replicates findings in the OCD literature but the study is the first to show this in postpartum women. This study serves as a platform for future work to further investigate both gene-environment interactions and distinct neuroimaging correlates in perinatal OCD. / Thesis / Master of Science (MSc)

Introduction: La fibromyalgie (FM) et la dépression majeure (MDD) sont des comorbidités fréquentes qui partagent des altérations communes dans la neurotransmission sérotoninergique. Cependant, on ignore encore si ces altérations sont persistantes ou transitoires. Objectifs : Le but principal de cette étude était (i) de mesurer les changements dans l’expression du transporteur de sérotonine (SERT) chez les patients FM, MDD et FM/MDD, par rapport aux volontaires sains (VS); et (ii) d’évaluer l’effet des traitements pharmacologiques (quétiapine et divers antidépresseurs) sur l’expression du SERT chez ces sujets. Des analyses exploratoires de l’expression du transporteur de dopamine (DAT) ont aussi été réalisées. Méthodologie: Les PBMC sont isolées chez les patients FM (n=55), MDD (n=50), et FM/MDD (n=120), et chez les VS (n=62). L’expression de SERT et de DAT a été analysée au niveau de l’ARNm par PCRq. La signification statistique est analysée par des analyses de variance et des modèles linéaires mixtes. Résultats: L’expression de l’ARNm du SERT est significativement diminuée chez les patients MDD, par rapport aux VS (p<0.001), mais pas elle est inchangée chez les patients FM et FM/MDD. Les traitements pharmacologiques entrainaient une amélioration des symptômes cliniques de la FM et de la MDD, mais ils n’avaient aucun effet sur l’expression de l’ARNm du SERT chez les patients. Comparativement au SERT, l’ARNm du DAT est indétectable chez plusieurs participants. Discussion/Conclusion : Ces résultats corroborent le rôle du SERT dans la physiopathologie de la MDD. De plus, ils démontrent que la diminution de l’expression du SERT est un phénomène persistant plutôt que transitoire. / Introduction: Fibromyalgia (FM) and major depression disorder (MDD) are frequent comorbidities. Both disorders may share common serotonergic alterations, but it is still unclear whether these alterations are persistent or transient. Objectives: The primary objective of this study was to (i) examine the changes in expression of serotonin transporter (SERT) in peripheral blood mononuclear cells (PBMC) in FM, MDD and FM/MDD subjects, compared to healthy controls; and to (ii) evaluate the effect of drug treatment (quetiapine and various antidepressants) on the expression of SERT in these subjects. Exploratory analyses on the expression of the dopamine transporter (DAT) were also performed. Methods PBMC were isolated from FM, MDD and FM/MDD subjects, and healthy controls. SERT and DAT expression were analysed at the mRNA level by qPCR. Statistical analyses were performed using analyses of variance and linear mixed-effects model. Results: The mRNA expression of SERT was significantly reduced in MDD subjects compared to healthy controls (p<0.001), but not in FM nor in FM/MDD subjects. Although drug treatments improved symptoms in FM, MDD and FM/MDD subjects, they had no significant effect on SERT mRNA expression. Comparatively to SERT, DAT mRNA expression was undetectable in several participants. Discussion/Conclusion: These results corroborate the role of SERT in the pathophysiology of MDD. They also show that the decreased expression of SERT mRNA is a persistent rather than a transient phenomenon in MDD.

Background The serotonin (5-HT) hypothesis of anorexia nervosa (AN) posits that individuals predisposed toward or recovered from AN (recAN) have a central nervous hyperserotonergic state and therefore restrict food intake as a means to reduce 5-HT availability (via diminished tryptophan-derived precursor supply) and alleviate associated negative mood states. Importantly, the 5-HT system has also been generally implicated in reward processing, which has also been shown to be altered in AN. Methods In this double-blind crossover study, 22 individuals recAN and 25 healthy control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing an established instrumental reward learning paradigm during acute tryptophan depletion (ATD; a dietary intervention that lowers central nervous 5-HT availability) as well as a sham depletion. Results On a behavioral level, the main effects of reward and ATD were evident, but no group differences were found. fMRI analyses revealed a group × ATD × reward level interaction in the ventral anterior insula during reward anticipation as well as in the medial orbitofrontal cortex during reward consumption. Discussion The precise pattern of results is suggestive of a ‘normalization’ of reward-related neural responses during ATD in recAN compared to HC. Our results lend further evidence to the 5-HT hypothesis of AN. Decreasing central nervous 5-HT synthesis and availability during ATD and possibly also by dieting may be a means to normalize 5-HT availability and associated brain processes.

Background: Alterations of hypothalamic–pituitary–adrenal (HPA) axis activity and serotonergic signaling are implicated in the pathogenesis of human obesity and may contribute to its metabolic and mental complications. The association of these systems has not been investigated in human obesity. Objective: To investigate the relation of HPA responsiveness and serotonin transporter (5-HTT) availability in otherwise healthy individuals with obesity class II or III (OB) compared to non-obesity controls (NO). Study participants: Twenty-eight OB (21 females; age 36.6 10.6 years; body mass index (BMI) 41.2 5.1 kg/m2) were compared to 12 healthy NO (8 females; age 35.8 7.4 years; BMI 22.4 2.3 kg/m2), matched for age and sex. Methods: HPA axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic hormone (ACTH). The 5-HTT selective tracer [11C]DASB was applied, and parametric images of the binding potentials (BPND) were calculated using the multilinear reference tissue model and evaluated by atlas-based volume of interest (VOI) analysis. The self-questionnaires of behavioral inhibition system/behavioral activation system (BIS/BAS) with subscales drive, fun-seeking and reward were assessed. Results: OB showed significant positive correlations of ACTH curve parameters with overall 5-HTT BPND (ACTHAUC: r = 0.39, p = 0.04) and 5-HTT BPND of the caudate nucleus (ACTHAUC: r = 0.54, p = 0.003). In NO, cortisol indicators correlated significantly with BPND in the hippocampus (cortisolAUC: r = 0.59, p = 0.04). In OB, BAS reward was inversely associated with the ACTHAUC (r = 0.49, p = 0.009). Conclusion: The present study supports a serotonergic-neuroendocrine association, which regionally differs between OB and NO. In OB, areas processing emotion and reward seem to be in-volved. The finding of a serotonergic HPA correlation may have implications for other diseases with dysregulated stress axis responsiveness, and for potential pharmacologic interven-tions.

No / In the present study, we investigated the effect of 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists and antagonists on motion sickness in Suncus murinus, and the possibility that the emetic stimulus of 5-HT can alter the sensitivity of the animals to the different emetic stimulus of motion sickness. 5-HT (1.0, 2.0, 4.0 and 8.0 mg/kg ip) induced emesis and that was antagonised by methysergide (1.0 mg/kg ip), the 5-HT4receptor antagonist sulphamate[1-[2-[(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate (GR125487D; 1.0 mg/kg ip) and granisetron (0.5 mg/kg ip). Pretreatment with 5-HT caused a dose-related attenuation of the emetic response induced by a subsequent motion stimulus, which was not significantly modified by methysergide, granisetron or GR125487D pretreatment. (+)-1-(2,5-Dimethoxy-4-iodophenyl)-2-amino-propane (DOI; 0.5 and 1.0 mg/kg ip), 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg ip) but not methysergide, GR125487D or granisetron, attenuated motion-induced emesis, and that was not affected by pretreatment with ketanserin (2.0 mg/kg, ip) or N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide trihydrocholoride (WAY-100635; 1.0 mg/kg ip), respectively. Indeed, ketanserin alone (0.1, 0.3, 1.0 and 2.0 mg/kg ip) attenuated motion sickness. These data indicate that 5-HT1/2, 5-HT3 and 5-HT4 receptors are involved in the induction of 5-HT-induced emesis. However, agonist action at the 5-HT1A/7 and 5-HT2 receptors, and antagonist action at the 5-HT2A receptors can attenuate motion sickness in S. murinus.

A chronic hyperglycemic state often results in neuropathological complications such as peripheral diabetic neuropathy (PDN). PDN is a debilitating medical condition that impacts over half of the US population with diabetes. In this study, we used the model organism Caenorhabditis elegans to determine that glucose-supplemented diet leads to an increased rate of intrauterine egg hatching (IUEH) and the reduction of dopamine and serotonin is sufficient to suppress the glucose-induced IUEH. Moreover, in this research demonstrates that a glucose-supplemented diet impacts serotonin and dopamine-associated behaviors. Additionally, we demonstrate that a diet rich in glucose impacts the structure of the serotonergic neurons HSN and NSM. These findings highlight the utility of the model organism C. elegans in elucidating the impact of a glucose-supplemented diet on the nervous system. Finally, these studies show that a glucose-supplemented diet impacts transgenerational and intergenerational phenotypes as well as changes in the transcriptional profile of subsequent generations.