| 1. |
- Zettergren, Anna, 1978, et al.
(författare)
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Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.
- 2016
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Ingår i: Psychoneuroendocrinology. - Stockholm : Elsevier BV. - 1873-3360 .- 0306-4530. ; 68, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out.
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| 2. |
- Adermark, Louise, 1974, et al.
(författare)
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Weight gain and neuroadaptations elicited by high fat diet depend on fatty acid composition.
- 2021
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Overconsumption of food is a major health concern in the western world. Palatable food has been shown to alter the activity of neural circuits, and obesity has been linked to alterations in the connectivity between the hypothalamus and cortical regions involved in decision-making and reward processing, putatively modulating the incentive value of food. Outlining neurophysiological adaptations induced by dietary intake of high fat diets (HFD) is thus valuable to establish how the diet by itself may promote overeating. To this end, C57BL/6 mice were fed HFD rich in either saturated fatty acids (HFD-S) or polyunsaturated fatty acids (HFD-P), or a low-fat control diet (LFD) for four weeks. Food and energy intake were monitored and ex vivo electrophysiology was employed to assess neuroadaptations in lateral hypothalamus (LH) and corticostriatal circuits, previously associated with food intake. In addition, the effects of dietary saturated and polyunsaturated fatty acids on the gene expression of NMDA, AMPA and GABAA receptor subunits in the hypothalamus were investigated. Our data shows that mice fed HFD-P had increased daily food and energy intake compared with mice fed HFD-S or LFD. However, this increase in energy intake had no obesogenic effects. Electrophysiological recordings demonstrated that HFD-P had a selective effect on glutamatergic neurotransmission in the LH, which was concomitant with a change in mRNA expression of AMPA receptor subtypes Gria1, Gria3 and Gria4, with no effect on the mRNA expression of NMDA receptor subtypes or GABAA receptor subtypes. Furthermore, while synaptic output from corticostriatal subregions was not significantly modulated by diet, synaptic plasticity in the form of long-term depression (LTD) was impaired in the dorsomedial striatum of mice fed HFD-S. In conclusion, this study suggests that the composition of fatty acids in the diet not only affects weight gain, but may also modulate neuronal function and plasticity in brain regions involved in food intake.
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| 3. |
- Anckarsäter, Rolf, 1956, et al.
(författare)
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Association between thyroid hormone levels and monoaminergic neurotransmission during surgery.
- 2007
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 32:8-10, s. 1138-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. METHODS: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. RESULTS: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T(3)/T(4) ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T(3)/T(4) ratio decreased (p<0.0001), while the CSF T(3)/T(4) ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T(3) and T(4) at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. CONCLUSIONS: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress.
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| 4. |
- Anderberg, Rozita H, 1976, et al.
(författare)
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GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality.
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 65, s. 54-66
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1), produced in the intestine and hindbrain, is known for its glucoregulatory and appetite suppressing effects. GLP-1 agonists are in clinical use for treatment of type 2 diabetes and obesity. GLP-1, however, may also affect brain areas associated with emotionality regulation. Here we aimed to characterize acute and chronic impact of GLP-1 on anxiety and depression-like behavior. Rats were subjected to anxiety and depression behavior tests following acute or chronic intracerebroventricular or intra-dorsal raphe (DR) application of GLP-1 receptor agonists. Serotonin or serotonin-related genes were also measured in the amygdala, DR and the hippocampus. We demonstrate that both GLP-1 and its long lasting analog, Exendin-4, induce anxiety-like behavior in three rodent tests of this behavior: black and white box, elevated plus maze and open field test when acutely administered intraperitoneally, into the lateral ventricle, or directly into the DR. Acute central GLP-1 receptor stimulation also altered serotonin signaling in the amygdala. In contrast, chronic central administration of Exendin-4 did not alter anxiety-like behavior but significantly reduced depression-like behavior in the forced swim test. Importantly, this positive effect of Exendin-4 was not due to significant body weight loss and reduced food intake, since rats pair-fed to Exendin-4 rats did not show altered mood. Collectively we show a striking impact of central GLP-1 on emotionality and the amygdala serotonin signaling that is divergent under acute versus chronic GLP-1 activation conditions. We also find a novel role for the DR GLP-1 receptors in regulation of behavior. These results may have direct relevance to the clinic, and indicate that Exendin-4 may be especially useful for obese patients manifesting with comorbid depression.
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| 5. |
- Börchers, Stina, et al.
(författare)
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Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences.
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Women are more likely to develop an anxiety disorder than men. Yet, preclinical models of anxiety were largely developed in male rodents, with poorly understood predictive validity for sex differences. Here, we investigate whether commonly-used anxiety-like behavior tests, elevated plus maze (EPM) and open field (OF), represent the human sex difference in adult Sprague-Dawley rats. When interpreted by EPM or OF, female rats displayed less anxiety-like behavior compared to males, as they spent twice as much time in the open arms of the EPM or the center of the OF compared to males. However, they also displayed vastly different levels of locomotor activity, possibly confounding interpretation of these locomotion-dependent tests. To exclude locomotion from the assessment, the acoustic startle response (ASR) test was used. When interpreted by the ASR test, females displayed more anxiety-like behavior compared to males, as indicated by a nearly two-fold higher startle amplitude. The observed sex differences were not driven by gonadal steroids. Overall, all but one of the tests fail to mirror the sex difference in anxiety reported in humans. Our findings suggest that the ASR might be a better fit in modelling female anxiety-like behavior.
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| 6. |
- Cedernaes, Jonathan, et al.
(författare)
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Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 74, s. 258-268
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Tidskriftsartikel (refereegranskat)abstract
- Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45–7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.–7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration. © 2016 The Author(s)
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| 7. |
- Cesta, Carolyn E, et al.
(författare)
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Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort.
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 73, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associations. Using the Swedish national registers, we identified all women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings (n=25,921), plus matched individuals (1:10/100) from the general population and their full-siblings. Psychiatric disorder diagnoses were identified including schizophrenia, bipolar disorder, depressive and anxiety disorders, eating disorders, personality and gender identity disorder, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and completed suicide. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression and adjusted ORs (AOR) were determined by adjustment for comorbid psychiatric disorders. Overall, women with PCOS had an increased odds of having at least one psychiatric disorder (OR=1.56 [95CI%, 1.51-1.61]). Crude ORs showed associations with nearly all psychiatric disorders included in this study. Following adjustment for comorbid psychiatric disorders, women with PCOS were still at a significantly increased risk for bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders, personality disorders, with the highest AORs for ASD (AOR=1.55 [95%CI, 1.32-1.81]) and tics (AOR=1.65 [95%CI, 1.10-2.47]). Significantly higher AORs were found for ASD in both brothers and sisters of women with PCOS, and for depressive, anxiety, and schizophrenia spectrum disorders in the sisters only. Notably, the crude ORs for attempted suicide were 40% higher in women with PCOS and 16% higher in their unaffected sisters. However, the AORs were greatly attenuated indicating that underlying psychiatric comorbidity is important for this association. Women with PCOS had higher risks for a range of psychiatric disorders not shown before. Elevated risk in their siblings suggests shared familial factors between PCOS and psychiatric disorders. This study is an important first step towards identifying the underlying mechanisms for risk of psychiatric disorders in women with PCOS. Health professionals treating women with PCOS should be aware that these patients - as well as their family members - are important targets for mental health care.
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| 8. |
- Cesta, Carolyn E, et al.
(författare)
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Polycystic ovary syndrome, personality, and depression: A twin study.
- 2017
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 85, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Women with polycystic ovary syndrome (PCOS) are at elevated risk for suffering from depression. Neuroticism is a personality trait that has been associated with an increased risk for developing major depressive disorder (MDD). The aim of the present study was to quantify and decompose the correlation between neuroticism, PCOS, and MDD into shared and unique genetic and environmental etiologies, by using quantitative genetic methods.In a cohort of 12,628 Swedish female twins born from 1959 to 1985, neuroticism, PCOS identified by symptoms of hyperandrogenemia (i.e., hirsutism) and oligo- and/or anovulation, and lifetime MDD status were determined through questionnaire responses. Structural equation modeling was used to study the genetic and environmental sources of the variation within, and covariation between neuroticism, PCOS, and MDD.Female twins with PCOS (n=752) had significantly higher levels of neuroticism than women without PCOS, and a 2-fold increase in odds for a lifetime prevalence of MDD. The phenotypic correlation between PCOS and MDD was 0.19, with 63% of the correlation attributable to common genetic factors between the two traits. When taking into account neuroticism, 41% was attributable to common genetic factors and 9% attributable to common environmental factors shared between all three traits, with the remainder attributable to components unique to PCOS and MDD.There are common genetic factors between neuroticism, PCOS, and MDD; however, neuroticism shares approximately half of the genetic and environmental components behind the phenotypic correlation between PCOS and MDD, providing some etiological evidence behind the comorbidity between PCOS and depression.
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| 9. |
- Egecioglu, Emil, 1977, et al.
(författare)
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The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:8, s. 1259-1270
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Tidskriftsartikel (refereegranskat)abstract
- Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.
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| 10. |
- Engberg, Hedvig, et al.
(författare)
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Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.
- 2015
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 60, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n=335) born between January 1915 and January 2010 were compared with aged-matched female (n=33500) and male controls (n=33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.
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