Words and Faces on Left and Right: Perceptual Asymmetries as a Marker for SSRI Responsiveness

<p>Vulnerability to depression has been associated with greater relative right hemisphere frontal activity, as measured by EEG recordings of alpha activity. However, there is much heterogeneity in the patterns of hemispheric asymmetries in people at risk for depression. These different patterns of hemispheric asymmetries may be related to whether an individual responds to Selective Serotonin Reuptake Inhibitor (SSRI) medication. Response to SSRIs is associated with a pattern of overall relative LH activity, whereas non-response to SSRIs is associated with a pattern of overall relative RH activity. Very little is known about how these asymmetries in neural activity relate to asymmetries in cognition. The current study investigated hemispheric differences in the processing of emotional faces and words, in individuals not vulnerable to depression (a Never Depressed group) and in individuals vulnerable to depression (a Previously Depressed group). In the chimeric faces task, the Previously Depressed group had a significantly larger left hemispatial bias compared to the Never Depressed group. This may reflect relatively greater posterior RH activity/arousal in the Previously Depressed group. No differences were found between SSRI Responders and Non-responders in the chimeric faces task. In the divided visual field task, hemispheric differences in the processing of emotional words were found between the SSRI Responders and SSRI Non-responders. In contrast to SSRI Responders and Never Depressed controls, SSRI Non-responders showed a relative advantage for negative over positive words when they were presented to their LVF/RH; and an advantage for negative words presented to their LVF/RH compared to their RVF/LH. Additionally, they were more sensitive to perceiving the valence of a word that was presented to their LVF/RH. This suggests that their RH semantic systems may differ from that of SSRI Responders and Never Depressed controls. Genetic, hormonal and cognitive factors are discussed in relation to these patterns of hemispheric asymmetries and responsiveness to SSRI medication.</p>

Words and Faces on Left and Right: Perceptual Asymmetries as a Marker for SSRI Responsiveness

<p>Vulnerability to depression has been associated with greater relative right hemisphere frontal activity, as measured by EEG recordings of alpha activity. However, there is much heterogeneity in the patterns of hemispheric asymmetries in people at risk for depression. These different patterns of hemispheric asymmetries may be related to whether an individual responds to Selective Serotonin Reuptake Inhibitor (SSRI) medication. Response to SSRIs is associated with a pattern of overall relative LH activity, whereas non-response to SSRIs is associated with a pattern of overall relative RH activity. Very little is known about how these asymmetries in neural activity relate to asymmetries in cognition. The current study investigated hemispheric differences in the processing of emotional faces and words, in individuals not vulnerable to depression (a Never Depressed group) and in individuals vulnerable to depression (a Previously Depressed group). In the chimeric faces task, the Previously Depressed group had a significantly larger left hemispatial bias compared to the Never Depressed group. This may reflect relatively greater posterior RH activity/arousal in the Previously Depressed group. No differences were found between SSRI Responders and Non-responders in the chimeric faces task. In the divided visual field task, hemispheric differences in the processing of emotional words were found between the SSRI Responders and SSRI Non-responders. In contrast to SSRI Responders and Never Depressed controls, SSRI Non-responders showed a relative advantage for negative over positive words when they were presented to their LVF/RH; and an advantage for negative words presented to their LVF/RH compared to their RVF/LH. Additionally, they were more sensitive to perceiving the valence of a word that was presented to their LVF/RH. This suggests that their RH semantic systems may differ from that of SSRI Responders and Never Depressed controls. Genetic, hormonal and cognitive factors are discussed in relation to these patterns of hemispheric asymmetries and responsiveness to SSRI medication.</p>

Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer’s disease

Background Both serotonergic signalling disruption and systemic inflammation have been associated with the pathogenesis of Alzheimer’s disease (AD). The common denominator linking the two is the catabolism of the essential amino acid, tryptophan. Metabolism via tryptophan hydroxylase results in serotonin synthesis, whilst metabolism via indoleamine 2,3-dioxygenase (IDO) results in kynurenine and its downstream derivatives. IDO is reported to be activated in times of host systemic inflammation and therefore is thought to influence both pathways. To investigate metabolic alterations in AD, a large-scale metabolic phenotyping study was conducted on both urine and serum samples collected from a multi-centre clinical cohort, consisting of individuals clinically diagnosed with AD, mild cognitive impairment (MCI) and age-matched controls. Methods Metabolic phenotyping was applied to both urine (n = 560) and serum (n = 354) from the European-wide AddNeuroMed/Dementia Case Register (DCR) biobank repositories. Metabolite data were subsequently interrogated for inter-group differences; influence of gender and age; comparisons between two subgroups of MCI - versus those who remained cognitively stable at follow-up visits (sMCI); and those who underwent further cognitive decline (cMCI); and the impact of selective serotonin reuptake inhibitor (SSRI) medication on metabolite concentrations. Results Results revealed significantly lower metabolite concentrations of tryptophan pathway metabolites in the AD group: serotonin (urine, serum), 5-hydroxyindoleacetic acid (urine), kynurenine (serum), kynurenic acid (urine), tryptophan (urine, serum), xanthurenic acid (urine, serum), and kynurenine/tryptophan ratio (urine). For each listed metabolite, a decreasing trend in concentrations was observed in-line with clinical diagnosis: control > MCI > AD. There were no significant differences in the two MCI subgroups whilst SSRI medication status influenced observations in serum, but not urine. Conclusions Urine and serum serotonin concentrations were found to be significantly lower in AD compared with controls, suggesting the bioavailability of the neurotransmitter may be altered in the disease. A significant increase in the kynurenine/tryptophan ratio suggests that this may be a result of a shift to the kynurenine metabolic route due to increased IDO activity, potentially as a result of systemic inflammation. Modulation of the pathways could help improve serotonin bioavailability and signalling in AD patients.

Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway

Background Evidence indicates that pro-inflammatory Th17 and Th1 cells are involved in major depressive disorder (MDD) pathogenesis. Development of Th17 and Th1 are regulated by IL-6 and IFN-γ, respectively. In this study, the levels of IL-6 and IFN-γ, and mRNA expression of related signaling components and, Th17/Th1 transcription factors were investigated in MDD patients with/without selective serotonin reuptake inhibitor (SSRI) medication. Materials and methods Forty-six patients and 38 healthy controls (HCs) were recruited. Twenty patients were received the SSRI (sertraline 50–200 mg/day) for at least 1 year, and 26 patients were not received medication. Expression of IL-6R, IFN-γR, JAK1, JAK2, TYK2, STAT1, STAT3, T-bet and RORγt were assessed with Real-Time-PCR. Serum and supernatant levels of IL-6 and IFN-γ were determined using ELISA. Results and discussion The serum and supernatant levels of IL-6 were increased in patients without (SSRI−) compared with HCs, while its levels was reduced in SSRI+. Elevated expressions of IL-6R, STAT3 and RORγt were observed in SSRI− compared with HCs. Expressions of IL-6R, STAT3, RORγt and IFN-γR, were decreased in SSRI+ compared to SSRI− patients. Conclusion Increased IL-6 involved in MDD, and SSRI regulates IL-6 pathway and IL-6 production. MDD patients may benefit from IL-6/IL-6R targeted therapeutic intervention.

Physical Exercise is Negatively Correlated with Premature Ejaculation Symptom Severity

Objective: To examine associations between symptoms of premature ejaculation and erectile dysfunction and the lifestyle factors alcohol use and physical exercise. Design and Method: An invitation to an online survey was sent out to a population-based sample of Finnish twins and siblings of twins in 2012. Of the 2559 individuals invited, 1054 responded, giving a response rate of 41%. Individuals who used SSRI-medication for any reason were excluded, leaving a final sample of 843. Premature ejaculation was measured by the validated Multiple Indicators of Premature Ejaculation questionnaire, erectile dysfunction by the International Index of Erectile Function – 5, alcohol use by the Alcohol Use Disorders Identification Test, and physical exercise by the Godin Leisure-Time Exercise Questionnaire. Bivariate correlations were used to test associations between variables. Results: There was a significant negative correlation between physical exercise and premature ejaculation symptoms. Premature ejaculation and erectile dysfunction were significantly positively correlated. Effect sizes were moderately small. No significant correlations were found between the other variables. Conclusions: Our results indicate that physical exercise may possibly prevent or counteract premature ejaculation. Future studies could incorporate physical exercise in treatment trials.

Searching for answers and validation: Australian women’s experiences of coping with the adverse sexual effects of antidepressants

Sexual difficulties relating to selective serotonin reuptake inhibitor (SSRI) medication have an impact on quality of life and are a common cause for non-adherence to medication. While most research has focussed on the prevalence and treatment of sexual difficulties, little is known about how patients cope with the adverse sexual effects of SSRIs. This qualitative study, using Interpretive Phenomenological Analysis (IPA), investigated the experiences of 10 Australian women currently coping with the adverse sexual effects of this antidepressant by conducting semi-structured interviews. This paper presents one major theme from the study and reports the findings related to women’s self-reported experiences of interacting with GPs in their search for answers and validation of their concerns. Findings from the study add to the current literature by providing an insight into how interactions with GPs impact on women’s abilities to cope with adverse sexual effects. Empathic discussions and shared decision-making between GPs and women can provide the opportunity to improve the management of the adverse sexual effects of SSRIs and may lead to improved outcomes for women.

Evidence Map of Prevention and Treatment Interventions for Depression in Young People

Introduction.Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care.Methods.“Evidence mapping” methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains.Results.Prevention research is dominated by cognitive-behavioral- (CBT-) based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking.Conclusions.This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies.