Browsing by Subject "SEX-DIFFERENCES"

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  • Oksman, Elli; Rosenstrom, Tom; Hintsanen, Mirka; Pulkki-Raback, Laura; Viikari, Jorma; Lehtimaki, Terho; Raitakari, Olli Tuomas; Keltikangas-Jarvinen, Liisa (2018)
    Sociability and social domain-related behaviors have been associated with better well-being and endogenous oxytocin levels. Inspection of the literature, however, reveals that the effects between sociability and health outcomes, or between sociability and genotype, are often weak or inconsistent. In the field of personality psychology, the social phenotype is often measured by error-prone assessments based on different theoretical frameworks, which can partly explain the inconsistency of the previous findings. In this study, we evaluated the generalizability of "sociability" measures by partitioning the population variance in adulthood sociability using five indicators from three personality inventories and assessed in two to four follow-ups over a 15-year period (n = 1,573 participants, 28,323 person-observations; age range 20-50 years). Furthermore, we tested whether this variance partition would shed more light to the inconsistencies surrounding the "social" genotype, by using four genetic variants (rs1042778, rs2254298, rs53576, rs3796863) previously associated with a wide range of human social functions. Based on our results, trait (between-individual) variance explained 23% of the variance in overall sociability, differences between sociability indicators explained 41%, state (within-individual) variance explained 5% and measurement errors explained 32%. The genotype was associated only with the sociability indicator variance, suggesting it has specific effects on sentimentality and emotional sharing instead of reflecting general sociability.
  • Karjula, Salla; Arffman, Riikka K.; Morin-Papunen, Laure; Franks, Stephen; Järvelin, Marjo-Riitta; Tapanainen, Juha S.; Miettunen, Jouko; Piltonen, Terhi T. (2022)
    Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 18% of women. Besides metabolic and fertility aspects, attention has lately been directed towards the detrimental effect of PCOS on psychological health. The objective of the study was to investigate whether women with PCOS are at higher risk for psychotic disorders. The study population derives from the Northern Finland Birth Cohort 1966 (N = 5889 women). The women with PCOS were identified by two simple questions on oligo-amenorrhea and hirsutism at age 31. Women reporting both symptoms were considered PCOS (N = 124) and asymptomatic women as controls (N = 2145). The diagnosis of psychosis was traced using multiple national registers up to the year 2016. Symptoms of psychopathology were identified using validated questionnaires at age 31. Women with PCOS showed an increased risk for any psychosis by age 50 (HR [95% CI] 2.99, [1.52-5.82]). Also, the risk for psychosis after age 31 was increased (HR 2.68 [1.21-5.92]). The results did not change after adjusting for parental history of psychosis, nor were they explained by body mass index or hyperandrogenism at adulthood. The scales of psychopathology differed between women with PCOS and non-PCOS controls showing more psychopathologies among the affected women. PCOS cases were found to be at a three-fold risk for psychosis, and they had increased psychopathological symptoms. PCOS should be taken into consideration when treating women in psychiatric care. More studies are required to further assess the relationship between PCOS and psychotic diseases.
  • Kuusi, Tuire; Haukka, Jari; Myllykangas, Liisa; Järvelä, Irma (2019)
    OBJECTIVE. Music practice and listening have been reported to have favorable effects on human health, but empirical data are largely missing about these effects. To obtain more information about the effect of exposure to music from early childhood, we examined the causes of death of professional musicians in the classical genre. METHODS: We used standardized mortality ratios (SMR) for Finnish performing artists (n=5,780) and church musicians (n=22,368) during 1981-2016. We examined deaths from cardiovascular diseases, cancers, and neurodegenerative and alcohol-related diseases. The diagnoses were based on the ICD-10, with data obtained from Statistics of Finland. RESULTS: Overall, SMR for all-cause mortality was 0.59 (95% CI 0.57-0.61) for church musicians and 0.75 (95% CI 0.70-0.80) for performing artists, suggesting a protective effect of music for health. In contrast, we found increased mortality in alcohol-related diseases among female performing artists (SMR 1.85, 95% CI 1.062.95) and in neurodegenerative diseases among male performing artists (1.46, 95% CI 1.13-1.84). Additionally, we found higher SMRs for female than male church musicians for cancers (SMRfemales 0.90, 95% CI 0.83-0.97; SMRmales 0.60, 95% CI 0.54-0.67) and cardiovascular diseases (SMRfemales 0.75, 95% CI 0.68-0.82; SMRmales 0.58, 95% CI 0.54-0.64). CONCLUSIONS: Our results show that the causes of death in performers differ from those in church musicians. Performing artists are not protected from neurodegenerative diseases or alcohol-related deaths. The findings call for further study on the life-long effects of music in musicians.
  • Koski, Sonja E.; Buchanan-Smith, Hannah M.; Ash, Hayley; Burkart, Judith M.; Bugnyar, Thomas; Weiss, Alexander (2017)
    Increasing evidence suggests that personality structure differs between species, but the evolutionary reasons for this variation are not fully understood. We built on earlier research on New World monkeys to further elucidate the evolution of personality structure in primates. We therefore examined personality in 100 family-reared adult common marmosets (Callithrix jacchus) from 3 colonies on a 60-item questionnaire. Principal components analyses revealed 5 domains that were largely similar to those found in a previous study on captive, ex-pet, or formerly laboratory-housed marmosets that were housed in a sanctuary. The interrater reliabilities of domain scores were consistent with the interrater reliabilities of domain scores found in other species, including humans. Four domainsdmdash; conscientiousness, agreeableness, inquisitiveness, and assertiveness-resembled personality domains identified in other nonhuman primates. The remaining domain, patience, was specific to common marmosets. We used linear models to test for sex and age differences in the personality domains. Males were lower than females in patience, and this difference was smaller in older marmosets. Older marmosets were lower in inquisitiveness. Finally, older males and younger females had higher scores in agreeableness than younger males and older females. These findings suggest that cooperative breeding may have promoted the evolution of social cognition and influenced the structure of marmoset prosocial personality characteristics.
  • Kerkelä, Martta; Gyllenberg, David; Gissler, Mika; Sillanmäki, Lauri; Keski-Säntti, Markus; Hinkka-Yli-Salomäki, Susanna; Filatova, Svetlana; Hurtig, Tuula; Miettunen, Jouko; Sourander, Andre; Veijola, Juha (2021)
    Objective The aim of this study was to explore changes in the incidences of childhood and early adulthood hospital-treated psychiatric disorders in five large Finnish birth cohorts of individuals born between 1966 and 1997. Methods The five birth cohorts were as follows: Northern Finland Birth Cohort 1966 (NFBC 1966) and 1986 (NFBC 1986), 1987 Finnish Birth Cohort (FBC 1987) and 1997 (FBC 1997), and Finnish 1981 Birth Cohort Study (FBCS 1981). Incidences of hospital-treated psychiatric disorders in each cohort were calculated separately for males (N = 71,209) and females (N = 65,190). Poisson regression was used to test difference in proportions of psychiatric disorders in wide range of diagnosis classes separately in childhood and adolescence, and early adulthood. Results The total incidences of psychiatric disorders in childhood and adolescence among males has increased in the birth cohorts over decades (Incidence Rate Ratio, IRR = 1.04 (1.04-1.05); p <0.001). Similar result was seen among females (IRR = 1.04 (1.03-1.04); p <0.001). In early adulthood, there was significant increase among females (IRR = 1.04 (1.03-1.05); p <0.001), but among males, the change was not significant (IRR = 0.99 (0.99-1.00), p = 0.051). Conclusions The main finding was that the cumulative incidence of hospital-treated psychiatric disorders increased over the decades in Finland. The increasing trend in hospital-treated psychiatric disorders in early adulthood was detected in females but not in males. In the youngest cohorts, the cumulative incidence of hospital-treated psychiatric disorders was at the same level in males and females, whereas in oldest cohort, males had higher incidence than females.
  • Kourdougli, Nazim; Varpula, Saara; Chazal, Genevieve; Rivera Baeza, Claudio (2015)
    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20-30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epileptic us (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine-treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down regulation and pathological distribution of the K+-Cl- cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE.
  • Englund, Jonas; Haikonen, Joni; Shteinikov, Vasilii; Amarilla, Shyrley Paola; Atanasova, Tsvetomira; Shintyapina, Alexandra; Ryazantseva, Maria; Partanen, Juha; Voikar, Vootele; Lauri, Sari E. (2021)
    Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.
  • Haapanen, M. J.; Perälä, M. M.; Salonen, M. K.; Kajantie, E.; Simonen, M.; Pohjolainen, P.; Pesonen, A. K.; Räikkönen, K.; Eriksson, J. G.; von Bonsdorff, M. B. (2018)
    Background: Evidence suggests that early life stress (ELS) may extend its effect into adulthood and predispose an individual to adverse health outcomes. We investigated whether wartime parental separation, an indicator of severe ELS, would be associated with frailty in old age. Methods: Of the 972 participants belonging to the present sub-study of the Helsinki Birth Cohort Study, 117 (12. 0%) had been evacuated abroad unaccompanied by their parents in childhood during World War II. Frailty was assessed at a mean age of 71 years according to Fried's criteria. Results: Thirteen frail men (4 separated and 9 non-separated) and 20 frail women (2 separated and 18 non-separated) were identified. Compared to the non-separated men, men who had been separated had an increased relative risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that persisted after adjusting for several confounders. No associations were observed among women (RRR 0.62; 95% CI 0.13, 2.94). Conclusions: These preliminary results suggest that ELS might extend its effects not just into adulthood but also into old age, and secondly, that men may be more vulnerable to the long-term effects of ELS.
  • Elsilä, Lauri; Harkki, Juliana; Enberg, Emma Amanda; Martti, Alvar; Linden, Anni-Maija; Korpi, Esa (2022)
    Background: Psychedelics, like lysergic acid diethylamide (LSD), are again being studied as potential therapies for many neuropsychiatric disorders, including addictions. At the same time, the acute effects of psychedelics on rewarding behaviours have been scarcely studied. Aims: The current study aimed to clarify if LSD decreases binge-like ethanol drinking in mice, and whether the observed acute effects on ethanol consumption are generalizable to a natural reinforcer, sucrose, and if the effects resulted from aversive or reward-attenuating effects caused by LSD. Methods: The effects of acute LSD were examined using 2-bottle choice intermittent ethanol (20%) and sucrose drinking (10%), discrete-trial current-intensity threshold method of intracranial self-stimulation and short-term feeding behaviour assay in C57BL/6 male mice. Results: The results showed that acute 0.1 mg/kg, but not 0.05 mg/kg, dose (i.p.) of LSD reduced 2-h intermittent ethanol drinking transiently without any prolonged effects. No effects were seen in intermittent 2-h sucrose drinking. The tested LSD doses had neither effect on the intracranial self-stimulation current-intensity thresholds, nor did LSD affect the threshold-lowering, or rewarding, effects of simultaneous amphetamine treatment. Furthermore, LSD had small, acute diminishing effects on 2-h food and water intake. Conclusions: Based on these results, LSD decreases binge-like ethanol drinking in mice, but only acutely. This effect is not likely to stem from reward-attenuating effects but could be in part due to reduced consummatory behaviour.
  • Riekki, Tapani; Svedholm-Häkkinen, Annika M.; Lindeman, Marjaana (2018)
    Using the empathizing-systemizing theory as our framework, we investigated how people with high self-reported empathizing (having good social skills and being interested in people) and systemizing (being interested in physical things and processes) differ in the social information processing of emotionally negative photographs of people during “spontaneous watching” and emotional and cognitive empathy tasks. Empathizers evaluated the pictures as more emotionally touching and the reactions in the photographs more understandable than the systemizers. Compared to the empathizers, systemizers had stronger activations in the posterior cingulate cortex, an area related to cognitive empathy, as well as in the left superior temporal gyrus and middle frontal gyrus when watching emotional photographs spontaneously. During guided emotional and cognitive empathy tasks, these differences disappeared. However, during the emotional empathy task, higher systemizing was associated with weaker activation of the right inferior frontal gyrus /insula. Furthermore, during emotional and cognitive empathy tasks, empathizing was related to increased activations of the amygdala which were in turn related to higher behavioral ratings of emotional and cognitive empathy. The results suggest that empathizers and systemizers engage in social information processing differently: systemizers in more cognitive terms and empathizers with stronger automatic emotional reactions.
  • Arstila, Valtteri; Georgescu, Alexandra L.; Lunn, Daniel; Noreika, Valdas; Falter-Wagner, Christine M.; Pesonen, Henri (2020)
    Essential for successful interaction with the environment is the human capacity to resolve events in time. Typical event timing paradigms are judgements of simultaneity (SJ) and of temporal order (TOJ). It remains unclear whether SJ and TOJ are based on the same underlying mechanism and whether there are fixed thresholds for resolution. The current study employed four visual event timing task versions: horizontal and vertical SJ and TOJ. Binary responses were analysed using multilevel binary regression modelling. Modulatory effects of potential explanatory variables on event timing perception were investigated: (1) Individual factors (sex and age), (2) temporal factors (SOA, trial number, order of experiment, order of stimuli orientation, time of day) and (3) spatial factors (left or right stimulus first, top or bottom stimulus first, horizontal vs. vertical orientation). The current study directly compares for the first time, performance on SJ and TOJ tasks using the same paradigm and presents evidence that a variety of factors and their interactions selectively modulate event timing functions in humans, explaining the variance found in previous studies. We conclude that SJ and TOJ are partially independent functions, because they are modulated differently by individual and contextual variables.
  • Toth, Melinda E.; Sarkozy, Marta; Szucs, Gergo; Dukay, Brigitta; Hajdu, Petra; Zvara, Agnes; Puskas, Laszlo G.; Szebeni, Gabor J.; Ruppert, Zsofia; Csonka, Csaba; Kovacs, Ferenc; Kriston, Andras; Horvath, Peter; Kovari, Bence; Cserni, Gabor; Csont, Tamas; Santha, Miklos (2022)
    Background Metabolic syndrome (MetS) refers to a cluster of co-existing cardio-metabolic risk factors, including visceral obesity, dyslipidemia, hyperglycemia with insulin resistance, and hypertension. As there is a close link between MetS and cardiovascular diseases, we aimed to investigate the sex-based differences in MetS-associated heart failure (HF) and cardiovascular response to regular exercise training (ET). Methods High-fat diet-fed male and female APOB-100 transgenic (HFD/APOB-100, 3 months) mice were used as MetS models, and age- and sex-matched C57BL/6 wild-type mice on standard diet served as healthy controls (SD/WT). Both the SD/WT and HFD/APOB-100 mice were divided into sedentary and ET groups, the latter running on a treadmill (0.9 km/h) for 45 min 5 times per week for 7 months. At month 9, transthoracic echocardiography was performed to monitor cardiac function and morphology. At the termination of the experiment at month 10, blood was collected for serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol measurements and homeostatic assessment model for insulin resistance (HOMA-IR) calculation. Cardiomyocyte hypertrophy and fibrosis were assessed by histology. Left ventricular expressions of selected genes associated with metabolism, inflammation, and stress response were investigated by qPCR. Results Both HFD/APOB-100 males and females developed obesity and hypercholesterolemia; however, only males showed insulin resistance. ET did not change these metabolic parameters. HFD/APOB-100 males showed echocardiographic signs of mild HF with dilated ventricles and thinner walls, whereas females presented the beginning of left ventricular hypertrophy. In response to ET, SD/WT males developed increased left ventricular volumes, whereas females responded with physiologic hypertrophy. Exercise-trained HFD/APOB-100 males presented worsening HF with reduced ejection fraction; however, ET did not change the ejection fraction and reversed the echocardiographic signs of left ventricular hypertrophy in HFD/APOB-100 females. The left ventricular expression of the leptin receptor was higher in females than males in the SD/WT groups. Left ventricular expression levels of stress response-related genes were higher in the exercise-trained HFD/APOB-100 males and exercise-trained SD/WT females than exercise-trained SD/WT males. Conclusions HFD/APOB-100 mice showed sex-specific cardiovascular responses to MetS and ET; however, left ventricular gene expressions were similar between the groups except for leptin receptor and several stress response-related genes.
  • Sen, Partho; Qadri, Sami; Luukkonen, Panu K.; Ragnarsdottir, Oddny; McGlinchey, Aidan; Jäntti, Sirkku; Juuti, Anne; Arola, Johanna; Schlezinger, Jennifer J.; Webster, Thomas F.; Oresic, Matej; Yki-Järvinen, Hannele; Hyötyläinen, Tuulia (2022)
    Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. Methods: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using 4 mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. Results: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly those related to bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in females than males. Specifically, we observed PFAS-associated upregulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. The murine exposure study further corroborated our findings, vis-a-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. Conclusions: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. Lay summary: There is increasing evidence that specific environmental contaminants, such as perfluorinated alkyl substances (PFAS), contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts metabolic processes associated with NAFLD, and that the effect is different in females and males. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
  • Vaurio, Olli; Lähteenvuo, Markku; Kautiainen, Hannu; Repo-Tiihonen, Eila; Tiihonen, Jari (2022)
    The mortality of female psychopaths has scarcely been investigated. To estimate the association between psychopathy and mortality, data from subjects having been in forensic psychiatric assessments at Niuvanniemi Hospital during 1984-1993 were linked to the data from the National Death Registry. Sixteen psychopathic females scoring 25 points or higher in the PCL-R scale (psychopaths) were followed up for a median (IQR) 21 (17-25) years and 41 offenders scoring
  • Salminen, Marika; Viljanen, Anna; Eloranta, Sini; Viikari, Paula; Wuorela, Maarit; Vahlberg, Tero; Isoaho, Raimo; Kivelä, Sirkka-Liisa; Korhonen, Päivi; Irjala, Kerttu; Lopponen, Minna; Viikari, Laura (2020)
    Background There is a lack of agreement about applicable instrument to screen frailty in clinical settings. Aims To analyze the association between frailty and mortality in Finnish community-dwelling older people. Methods This was a prospective study with 10- and 18-year follow-ups. Frailty was assessed using FRAIL scale (FS) (n = 1152), Rockwood's frailty index (FI) (n = 1126), and PRISMA-7 (n = 1124). To analyze the association between frailty and mortality, Cox regression model was used. Results Prevalence of frailty varied from 2 to 24% based on the index used. In unadjusted models, frailty was associated with higher mortality according to FS (hazard ratio 7.96 [95% confidence interval 5.10-12.41] in 10-year follow-up, and 6.32 [4.17-9.57] in 18-year follow-up) and FI (5.97 [4.13-8.64], and 3.95 [3.16-4.94], respectively) in both follow-ups. Also being pre-frail was associated with higher mortality according to both indexes in both follow-ups (FS 2.19 [1.78-2.69], and 1.69 [1.46-1.96]; FI 1.81[1.25-2.62], and 1.31 [1.07-1.61], respectively). Associations persisted even after adjustments. Also according to PRISMA-7, a binary index (robust or frail), frailty was associated with higher mortality in 10- (4.41 [3.55-5.34]) and 18-year follow-ups (3.78 [3.19-4.49]). Discussion Frailty was associated with higher mortality risk according to all three frailty screening instrument used. Simple and fast frailty indexes, FS and PRISMA-7, seemed to be comparable with a multidimensional time-consuming FI in predicting mortality among community-dwelling Finnish older people. Conclusions FS and PRISMA-7 are applicable frailty screening instruments in clinical setting among community-dwelling Finnish older people.
  • Kivikangas, J. Matias; Kätsyri, Jari; Järvelä, Simo; Ravaja, Niklas (2014)
  • Rautiainen, M-R; Paunio, T.; Repo-Tiihonen, E.; Virkkunen, M.; Ollila, H. M.; Sulkava, Sonja; Jolanki, O.; Palotie, A.; Tiihonen, J. (2016)
    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N = 370, N = 5850 for controls, GWAS; N = 173, N = 3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR) = 2.19 (1.53-3.14), P = 1.9 x 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR = 1.59 (1.37-1.85), P = 1.6 x 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (beta = 0.68, P = 0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.
  • Kotliarova, Anastasiia; Sidorova, Yulia A. (2021)
    Well-known effects of neurotrophic factors are related to supporting the survival and functioning of various neuronal populations in the body. However, these proteins seem to also play less well-documented roles in glial cells, thus, influencing neuroinflammation. This article summarizes available data on the effects of glial cell line derived neurotrophic factor (GDNF) family ligands (GFLs), proteins providing trophic support to dopaminergic, sensory, motor and many other neuronal populations, in non-neuronal cells contributing to the development and maintenance of neuropathic pain. The paper also contains our own limited data describing the effects of small molecules targeting GFL receptors on the expression of the satellite glial marker IBA1 in dorsal root ganglia of rats with surgery- and diabetes-induced neuropathy. In our experiments activation of GFLs receptors with either GFLs or small molecule agonists downregulated the expression of IBA1 in this tissue of experimental animals. While it can be a secondary effect due to a supportive role of GFLs in neuronal cells, growing body of evidence indicates that GFL receptors are expressed in glial and peripheral immune system cells. Thus, targeting GFL receptors with either proteins or small molecules may directly suppress the activation of glial and immune system cells and, therefore, reduce neuroinflammation. As neuroinflammation is considered to be an important contributor to the process of neurodegeneration these data further support research efforts to modulate the activity of GFL receptors in order to develop disease-modifying treatments for neurodegenerative disorders and neuropathic pain that target both neuronal and glial cells.
  • Rotkirch, Anna; Lyons, Minna; David-Barrett, Tamas; Jokela, Markus (2014)
  • Volanen, S-M.; Lassander, M.; Hankonen, N.; Santalahti, P.; Hintsanen, M.; Simonsen, N.; Raevuori, A.; Mullola, S.; Vahlberg, T.; But, A.; Suominen, S. (2020)
    Background Mindfulness-Based Interventions (MBIs) have shown promising effects on mental health among children and adolescents, but high-quality studies examining the topic are lacking. The present study assessed the effects of MBI on mental health in school-setting in an extensive randomised controlled trial. Methods Finnish school children and adolescents (N=3519), aged 12-15 years (6th to 8th graders), from 56 schools were randomized into a 9 week MBI group, and control groups with a relaxation program or teaching as usual. The primary outcomes were resilience, socio-emotional functioning, and depressive symptoms at baseline, at completion of the programs at 9 weeks (T9), and at follow-up at 26 weeks (T26). Results Overall, mindfulness did not show more beneficial effects on the primary outcomes compared to the controls except for resilience for which a positive intervention effect was found at T9 in all participants (β=1.18, SE 0.57, p=0.04) as compared to the relaxation group. In addition, in gender and grade related analyses, MBI lowered depressive symptoms in girls at T26 (β=-0.49, SE 0.21, p=0.02) and improved socio-emotional functioning at T9(β=-1.37, SE 0.69, p=0.049) and at T26 (β=-1.71, SE 0.73, p=0.02) among 7th graders as compared to relaxation. Limitations The inactive control group was smaller than the intervention and active control groups, reducing statistical power. Conclusions A short 9-week MBI in school-setting provides slight benefits over a relaxation program and teaching as usual. Future research should investigate whether embedding regular mindfulness-based practice in curriculums could intensify the effects.