| 1. |
- Cheong, Rachel Y., et al.
(författare)
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Imbalance of the oxytocin-vasopressin system contributes to the neuropsychiatric phenotype in the BACHD mouse model of Huntington disease
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- Neuropsychiatric disturbances with altered social cognition, depression and anxiety are among the most debilitating early features in the fatal neurodegenerative disorder Huntington disease (HD) which is caused by an expanded CAG repeat in the huntingtin gene. The underlying neurobiological mechanisms are not known. Neuropathological analyses of postmortem human HD hypothalamic tissue have demonstrated loss of the neuropeptides oxytocin and vasopressin. The dynamic interplay between these neuropeptides is crucial for modulating emotional and social behavior but its role in HD is unclear. In the present study, we have investigated the effect of expressing the mutant huntingtin gene on the development of behavioral changes using the transgenic BACHD mouse model at different ages. We show for the first time that BACHD mice exhibit deficits in social behavior with parallel aberrations in the balance of the oxytocin-vasopressin system. Importantly, our data also show that restoration of the interplay within the system with an acute dose of intranasal oxytocin immediately prior to behavioral testing can rescue the depressive-like phenotype but not anxiety-like behavior in this transgenic model. These findings demonstrate that imbalances in the oxytocin-vasopressin interplay contribute to the neuropsychiatric component of HD and suggest that interventions aimed at restoring the blunted levels of oxytocin may confer therapeutic benefits for this disease.
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| 4. |
- Jonsjö, Martin A., et al.
(författare)
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The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) : associations with symptoms
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations. Methods: 53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (beta-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-alpha, TGF-beta-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-alpha). Participants rated the average severity of symptoms (0-10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions. Results and conclusions: Only beta-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-alpha and TGF-beta-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-beta-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development.
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| 5. |
- Karalexi, Maria A., et al.
(författare)
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Gender-affirming hormone treatment and cognitive function in transgender young adults : a systematic review and meta-analysis
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 119
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Forskningsöversikt (refereegranskat)abstract
- Background: Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals.Methods: A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges' g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale.Outcomes: Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses.Interpretation: Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.
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| 6. |
- Lopez-Ferreras, Lorena, et al.
(författare)
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The supramammillary nucleus controls anxiety-like behavior; key role of GLP-1R
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 119:September
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Tidskriftsartikel (refereegranskat)abstract
- Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis, along with gastrointestinally-derived neuropeptides, like glucagon-like peptide-1 (GLP-1), are emerging as potential key regulators of emotionality, including anxiety behavior. However, the neuroanatomical substrates from which GLP-1 exerts its anxiogenic effect remain poorly characterized. Here we focus on a relatively new candidate nucleus, the supramammillary nucleus (SuM), located just caudal to the lateral hypothalamus and ventral to the ventral tegmental area. Our focus on the SuM is supported by previous data showing expression of GLP-1R mRNA throughout the SuM and activation of the SuM during anxiety-inducing behaviors in rodents. Data show that chemogenetic activation of neurons in the SuM results in an anxiolytic response in male and female rats. In contrast, selective activation of SuM GLP-1R, by microinjection of a GLP-1R agonist exendin-4 into the SuM resulted in potent anxiety-like behavior, measured in both open field and elevated plus maze tests in male and female rats. This anxiogenic effect of GLP-1R activation persisted after high-fat diet exposure. Importantly, reduction of GLP-1R expression in the SuM, by AAV-shRNA GLP-1R knockdown, resulted in a clear anxiolytic response; an effect only observed in female rats. Our data identify a new neural substrate for GLP-1 control of anxiety-like behavior and indicate that the SuM GLP-1R are sufficient for anxiogenesis in both sexes, but necessary only in females.
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| 7. |
- Magnusson Hanson, Linda L., et al.
(författare)
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Job insecurity and risk of coronary heart disease : Mediation analyses of health behaviors, sleep problems, physiological and psychological factors
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Job insecurity has been linked to increased risk of coronary heart disease (CHD), but underlying mechanisms remain uncertain. Our aim was to assess the extent to which this association is mediated through life style, physiological, or psychological factors. A total of 3917 men and women free from CHD provided data on job insecurity in the Whitehall II cohort study in 1997-1999. The association between job insecurity and CHD was decomposed into a direct and indirect effect mediated through unhealthy behaviors (smoking, high alcohol consumption, physical inactivity), sleep disturbances, 'allostatic load', or psychological distress. The counterfactual analyses on psychological distress indicated a marginally significant association between job insecurity and incident CHD (hazard ratio (HR) 1.32; 95 % confidence interval (CI) 1.00-1.75). This association was decomposed into a direct (HR 1.22, 95 %CI 0.92-1.63) and indirect association (1.08, 95 %CI 1.01-1.15), suggesting that about 30 % of the total relationship was mediated by psychological distress. No mediation was indicated via health behaviors, sleep disturbances, or allostatic load, although job insecurity was related to disturbed sleep and C-reactive protein, which, in turn were associated with CHD. In conclusion, our results suggest that psychological distress may play a role in the relation between job insecurity and CHD.
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| 8. |
- Peragine, Diana, et al.
(författare)
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KF Sex difference or hormonal difference in mental rotation? The influence of ovarian milieu
- 2020
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Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences in visuospatial cognition have long been reported, with men being advantaged on the Mental Rotations Test (MRT). The data, however, are variable, and sensitive to design parameters. When men and women are compared directly, with women in different hormonal milieus combined, there seem to be sex differences. When women alone are studied, taking into account different ovarian steroid concentrations and treatments, MRT performance varies with these changes. Indeed, several reports describe better performance among women with reduced estrogens. To better understand whether the sex difference in MRT persists once hormonal status is considered, we recruited reproductive age adults designated male and female at birth (MAB, FAB), and administered the Vandenberg-Kuse (V/K) MRT-comparing performance among MAB (n=169) and FAB (n=219). For FAB combined, we found a sex difference with MAB performing better than FAB. However, when FAB were analyzed by current menstrual cycle phase (Early Follicular (EF), Periovulatory (PO), Midluteal (ML)) or by hormone therapy (transmasculine testosterone administration (TM+), oral contraceptive (OC) ingestion prior to (OC+) or after cognitive testing (OC-)), low-estradiol groups (EF, OC-, TM+) performed as strongly as MAB, and had better MRT than cycling FAB in high-estradiol menstrual cycle phases (PO, ML). On a verbal memory control task, neither a sex difference nor a low estrogen advantage was detected, although performance varied with hormonal milieu. Our findings support a dynamic model of spatial performance and suggest that both MAB and FAB perform strongly on MRT, contingent on hormonal status.
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| 9. |
- Quinlan, Patrick, et al.
(författare)
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Altered thyroid hormone profile in patients with Alzheimer's disease
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have linked higher levels of thyroid hormones (THs) to increased risk of Alzheimer's disease (AD), whereas in advanced AD, THs have been unchanged or even decreased. In early AD dementia, little is known whether THs are related to AD neuropathology or brain morphology. Methods: This was a cross-sectional study of 36 euthyroid AD patients and 34 healthy controls recruited at a single memory clinic. Levels of THs were measured in serum and cerebrospinal fluid (CSF). In addition, we determined AD biomarkers (amyloid-beta(1-42), total tau and phosphorylated tau) in CSF and hippocampal and amygdalar volumes using magnetic resonance imaging.2 Results: Serum free thyroxine (FT4) levels were elevated, whereas serum free triiodothyronine (FT3)/FT4 and total T3 (TT3)/total T4 (TT4) ratios were decreased, in AD patients compared to controls. In addition, serum TT4 was marginally higher in AD (p = 0.05 vs. the controls). Other TH levels in serum as well as CSF concentrations of THs were similar in both groups, and there were no correlations between THs and CSF AD biomarkers. However, serum FT3 correlated positively with left amygdalar volume in AD patients and serum TT3 correlated positively with left and right hippocampal volume in controls. Conclusions: Thyroid hormones were moderately altered in mild AD dementia with increased serum FT4, and in addition, the reduced T3/T4 ratios may suggest decreased peripheral conversion of T4 to T3. Furthermore, serum T3 levels were related to brain structures involved in AD development.
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| 10. |
- Scheuringer, Andrea, et al.
(författare)
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Use of an estradiol-based combined oral contraceptives has no influence on attentional bias or depressive symptoms in healthy women
- 2020
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Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- Combined oral contraceptive (COC) use is associated with small, albeit significant, increases in mental symptom scores, predominantly irritability, depressed mood, and anxiety. Yet, randomized prospective trials are needed to better characterize the women at risk for COC-induced negative mood change. Thus, the primary aim of this sub-study to a placebo-controlled randomized trial was to determine wheher COC use influences emotional interference by negative and positive stimuli. Secondly, we wanted to evaluate what factors would predict depressive symptoms at the end of the trial, taking personality factors, history of mental disorders and other demographic factors into account. Sixty-nine women were included, randomized to three cycles of treatment with a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo. An emotional verbal Stroop task was used to measure interference of emotional stimuli, in which participants were asked to only name the color of a presented word, while ignoring the meaning of the word. Four different word categories were used; neutral, positive, depression, and anxiety. For the second aim of the study, rating on the Montgomery-Asberg Depression Rating Scale during the final days of the trial was used as outcome. We found no interaction between emotional verbal Stroop word category and treatment, indicating that COC treatment did not evoke any differences in emotional interference to the three word categories. Significant predictors for depressive symptoms at the end of the trial were trait anxiety at baseline and prior adverse mood effects by hormonal contraceptive use. Treatment (i.e. whether women had been treated with the COC or placebo) did not play a role in predicting depression scores at the end of the trial. In conclusion, we found no evidence that combined oral contraceptive use is associated with impaired cognitive-emotional processing. Instead, the main predictors of self-rated depression at the end of the trial were baseline trait anxiety and previous mental symptoms during hormonal contraceptive use.
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