Quantifying the behavioural relevance of hippocampal neurogenesis

Few studies that examine the neurogenesis--behaviour relationship formally establish covariation between neurogenesis and behaviour or rule out competing explanations. The behavioural relevance of neurogenesis might therefore be overestimated if other mechanisms account for some, or even all, of the experimental effects. A systematic review of the literature was conducted and the data reanalysed using causal mediation analysis, which can estimate the behavioural contribution of new hippocampal neurons separately from other mechanisms that might be operating. Results from eleven eligible individual studies were then combined in a meta-analysis to increase precision (representing data from 215 animals) and showed that neurogenesis made a negligible contribution to behaviour (standarised effect = 0.15; 95% CI = -0.04 to 0.34; p = 0.128); other mechanisms accounted for the majority of experimental effects (standardised effect = 1.06; 95% CI = 0.74 to 1.38; p = 1.7 $\times 10^{-11}$).Comment: To be published in PLoS ON

Markup and price dynamics: linking micro to macro. National Bank of Belgium, Working Paper No. 357

We analyze the aggregate markup of a small-open economy, Belgium, using a firm-level dataset that includes all non-financial, private firms. The dataset covers the period 1980-2016 and merges the annual firm accounts over three periods when firms faced different reporting thresholds for the key variables we use. After harmonizing the data, we find that for the median firm the revenue share of service intermediates doubles, to some extent at the expense of in-house employment. As this general patterns holds true for the vast majority of firms and all sectors of the economy, we need to control for it in the calculation of our firm-level markup estimates. We document increasing markups in the overall economy throughout the first fifteen years of our sample, 1980-1995, and a continued rise in manufacturing until the early 2000s. In the remaining years, the aggregate markup, although cyclical, remained relatively stable. These patterns are driven by the dynamics in the sales-to-expenditure ratio, with only a small role for changes in the technology parameters. Two decompositions illustrate that the aggregate pattern masks systematic dynamics at the sector and firm level. We find that in periods where the aggregate markup rises—for the full economy or for one of the major sectors—it is almost entirely due to the within component, i.e. firm-level markup growth. In periods where the aggregate markup is stable, the average hides a strong process of reallocation. Firms or sectors with high markups increase their market share, which raises the aggregate markup, but this is dominated by a negative correlation between changes in market share and markups, which depresses the aggregate

Serum brain-derived neurotrophic factor (BDNF) is not regulated by testosterone in transmen

Brain morphology significantly differs between the sexes. It has been shown before that some of these differences are attributable to the sex-specific hormonal milieu. Brain-derived neurotrophic factor (BDNF) is involved in myriads of neuroplastic processes and shows a sexual dimorphism. Transsexual persons may serve as a model to study sex steroid-mediated effects on brain plasticity. We have recently demonstrated that serum levels of BDNF are reduced in transwomen following 12 months of cross-sex hormone treatment. We now wanted to look at the effects of testosterone treatment on BDNF in transmen. In contrast to our initial hypothesis, BDNF levels did not significantly change, despite dramatic changes in the sex-hormonal milieu. Our data indicate that testosterone does not seem to play a major role in the regulation of BDNF in females

Effects of sex hormone treatment on the metabolic syndrome in transgender individuals : focus on metabolic cytokines

Context: Hormonal treatment in transgender persons affects many components of the metabolic syndrome (MS). Objective: To determine the role of direct hormonal effects, changes in metabolic cytokines, and body composition on metabolic outcomes. Design, Setting, and Participants: 24 transwomen and 45 transmen from the European Network for the Investigation of Gender Incongruence were investigated at baseline and after 12 months of hormonal therapy. Outcome Measures: Best predictors for changes in components of MS, applying least absolute shrinkage and selection operator regression. Results: In transwomen, a decrease in triglyceride levels was best explained by a decrease in fat mass and an increase in fibroblast growth factor 21 (FGF-21); the decrease in total and low-density lipoprotein cholesterol levels was principally due to a decrease in resistin. A decrease in high-density lipoprotein cholesterol depended on an inverse association with fat mass. In contrast, in transmen, an increase in low-density lipoprotein cholesterol was predicted by a decrease in FGF-21 and an increase in the waist/hip ratio; a decrease in the high-density lipoprotein/total cholesterol ratio depended on a decline in adiponectin levels. In transwomen, worsened insulin resistance and increased early insulin response seemed to be due to a direct treatment effect; however, improvements in hepatic insulin sensitivity in transmen were best predicted by a positive association with chemerin, resistin, and FGF-21 and were inversely related to changes in the waist/hip ratio and leptin and adipocyte fatty acid-binding protein levels. Conclusions: The effects of hormonal therapy on different components of the MS are sex-specific and involve a complex interplay of direct hormonal effects, changes in body composition, and metabolic cytokine secretion

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy

Background: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. Methods: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase) and immediately after intravenous application of the chemotherapy (T1). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. Results: Healthy subjects showed significantly (P <.001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase. An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. Conclusion: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication. © 2020 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd

Compulsive sexual behavior disorder in obsessive–compulsive disorder: Prevalence and associated comorbidity

Background and aims: Compulsive sexual behavior disorder (CSBD) will be included in ICD-11 as an impulse-control disorder. CSBD also shares clinical features with obsessive–compulsive spectrum disorders (OCSDs) and behavioral addictions. There has been relatively little systematic investigation of CSBD in obsessive–compulsive disorder (OCD), the paradigmatic compulsive disorder. We aimed to determine prevalence of CSBD in OCD, and its associated sociodemographic and clinical features, including associated comorbidity, to learn more about the nature of CSBD. Methods: Adult outpatients with current OCD (N = 539) participated in this study. The Structured Clinical Interview for OCSDs was used to diagnose OCSDs (Tourette’s syndrome, compulsive shopping, pathological gambling, kleptomania, pyromania, intermittent explosive disorder, self-injurious behavior, and CSBD). Prevalence rates of OCSDs in male versus female patients as well as comorbid disorders in OCD patients with and without CSBD were compared. Results: Lifetime prevalence of CSBD was 5.6% in patients with current OCD and significantly higher in men than women. OCD patients with and without CSBD were similar in terms of age, age of onset of OCD, present OCD illness severity, as well as educational background. Lifetime prevalence rates of several mood, obsessive-compulsive, and impulse-control disorders were considerably elevated in patients with lifetime CSBD. Discussion and conclusions: A substantive number of OCD patients suffered from CSBD. CSBD in OCD was more likely comorbid with other mood, obsessive–compulsive, and impulse-control disorders, but not with disorders due to substance use or addictive behaviors. This finding supports conceptualization of CSBD as a compulsive-impulsive disorder

Psychopathological Profiles in Transsexuals and the Challenge of Their Special Status among the Sexes

OBJECTIVE:Investigating psychopathological profiles of transsexuals raises a very basic methodological question: are control groups, which represent the biological or the phenotypic sex, most suited for an optimal evaluation of psychopathology of transsexuals? METHOD:Male-to-female (MtF) (n=52) and female-to-male transsexuals (FtM) (n=32), receiving cross-sex hormone treatment, were compared with age matched healthy subjects of the same genetic sex (n=178) and with the same phenotypic sex (n=178) by means of the Symptom Check List-90-Revisited instrument (SCL-90-R). We performed analyses of covariance (ANCOVA) to test for group and sex effects. Furthermore, we used a profile analysis to determine if psychopathological symptom profiles of transsexuals more closely resemble genotypic sex or phenotypic sex controls. RESULTS:Transsexual patients reported more symptoms of psychopathological distress than did healthy control subjects in all subscales of the SCL-90-R (all p<0.001), regardless of whether they were compared with phenotype or genotype matched controls. Depressive symptoms were more pronounced in MtF than in FtM (SCL-90-R score 0.85 vs. 0.45, p = 0.001). We could demonstrate that FtM primarily reflect the psychopathological profile of biological males rather than that of biological females (r = 0.945), while MtF showed a slightly higher profile similarity with biological females than with biological males (r = 0.698 vs. r = 0.685). CONCLUSION:Our findings suggest that phenotypic sex matched controls are potentially more appropriate for comparison with the psychopathology of transsexual patients than are genetic sex matched controls

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy

Background: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. Methods: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase) and immediately after intravenous application of the chemotherapy (T1). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength‐tunable diode laser‐based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. Results: Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase. An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. Conclusion: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co‐medication

Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety