Browsing by Subject "STRESS"

Sort by: Order: Results:

Now showing items 1-20 of 211
  • Haghighi, Mona; Johnson, Suzanne Bennett; Qian, Xiaoning; Lynch, Kristian F.; Vehik, Kendra; Huang, Shuai; TEDDY Study Grp; Knip, Mikael (2016)
    Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
  • Kaukonen, Riikka; Lehto, Elviira; Ray, Carola; Vepsäläinen, Henna; Nissinen, Kaija; Korkalo, Liisa; Koivusilta, Leena; Sajaniemi, Nina; Erkkola, Maijaliisa; Roos, Eva (2019)
    Although evidence exists of the association between children's temperament and weight, only few studies have examined how temperament is associated with actual food consumption among preschoolers. We examined concurrent associations between children's temperament and the consumption of different foods, and investigated whether the association between children's temperament and vegetable consumption is mediated by vegetable-related parenting practices. We utilized the data from the cross-sectional DAGIS study of 864 preschool children aged between three to six and their families, conducted between 2015 and 2016 in Finland. The parents reported their children's temperament, food consumption, and their vegetable-related parenting practices. Adjusted logistic regression analyses found positive associations between surgency and vegetable consumption as well as between effortful control and vegetable consumption. Both associations were mediated by one examined vegetable-related parenting practice: enhanced availability and autonomy support. No associations were found between children's negative affectivity and food consumption or vegetable-related parenting practices. In conclusion, children's temperament may be an important factor behind food-related parenting practices and children's diet. However, further longitudinal research and research covering different food-related parenting practices and home environment factors is necessary to better understand the complex associations between temperament and food consumption among young children.
  • West, Gun; Turunen, Minttu; Aalto, Anna; Virtanen, Laura; Li, Song-Ping; Heliö, Tiina; Meinander, Annika; Taimen, Pekka (2022)
    Lamins A and C are nuclear intermediate filament proteins that form a proteinaceous meshwork called lamina beneath the inner nuclear membrane. Mutations in the LMNA gene encoding lamins A and C cause a heterogenous group of inherited degenerative diseases known as laminopathies. Previous studies have revealed altered cell signaling pathways in lamin-mutant patient cells, but little is known about the fate of mutant lamins A and C within the cells. Here, we analyzed the turnover of lamins A and C in cells derived from a dilated cardiomyopathy patient with a heterozygous p.S143P mutation in LMNA. We found that transcriptional activation and mRNA levels of LMNA are increased in the primary patient fibroblasts, but the protein levels of lamins A and C remain equal in control and patient cells because of a meticulous interplay between autophagy and the ubiquitin-proteasome system (UPS). Both endogenous and ectopic expression of p.S143P lamins A and C cause significantly reduced activity of UPS and an accumulation of K48-ubiquitin chains in the nucleus. Furthermore, K48-ubiquitinated lamins A and C are degraded by compensatory enhanced autophagy, as shown by increased autophagosome formation and binding of lamins A and C to microtubule-associated protein 1A/1B-light chain 3. Finally, chaperone 4-PBA augmented protein degradation by restoring UPS activity as well as autophagy in the patient cells. In summary, our results suggest that the p.S143P-mutant lamins A and C have overloading and deleterious effects on protein degradation machinery and pharmacological interventions with compounds enhancing protein degradation may be beneficial for cell homeostasis.
  • Lieslehto, Johannes; Rantanen, Noora; Oksanen, Lotta-Maria A. H.; Oksanen, Sampo A.; Kivimäki, Anne; Paju, Susanna; Pietiäinen, Milla; Lahdentausta, Laura; Pussinen, Pirkko; Anttila, Veli-Jukka; Lehtonen, Lasse; Lallukka, Tea; Geneid, Ahmed; Sanmark, Enni (2022)
    During the COVID-19 pandemic, healthcare workers (HCWs) have faced unprecedented workloads and personal health risks leading to mental disorders and surges in sickness absence. Previous work has shown that interindividual differences in psychological resilience might explain why only some individuals are vulnerable to these consequences. However, no prognostic tools to predict individual HCW resilience during the pandemic have been developed. We deployed machine learning (ML) to predict psychological resilience during the pandemic. The models were trained in HCWs of the largest Finnish hospital, Helsinki University Hospital (HUS, N = 487), with a six-month follow-up, and prognostic generalizability was evaluated in two independent HCW validation samples (Social and Health Services in Kymenlaakso: Kymsote, N = 77 and the City of Helsinki, N = 322) with similar follow-ups never used for training the models. Using the most predictive items to predict future psychological resilience resulted in a balanced accuracy (BAC) of 72.7-74.3% in the HUS sample. Similar performances (BAC = 67-77%) were observed in the two independent validation samples. The models' predictions translated to a high probability of sickness absence during the pandemic. Our results provide the first evidence that ML techniques could be harnessed for the early detection of COVID-19-related distress among HCWs, thereby providing an avenue for potential targeted interventions.
  • Raevuori, Anu; Vahlberg, Tero; Korhonen, Tellervo; Hilgert, Outi; Aittakumpu-Hyden, Raija; Forman-Hoffman, Valerie (2021)
    Background: Meru Health Program (MHP) is a therapist-guided, 8-week intervention for depression delivered via smartphone. The aim was to test its efficacy in patients with clinical depression in a Finnish university student health service.& nbsp; Methods: Patients (n=124, women 72.6%, mean age 25y) were stratified based on antidepressant status, and randomized into intervention group receiving MHP plus treatment as usual (TAU), and control group receiving TAU only. Depression, measured by the Patient Health Questionnaire-9 (PHQ-9) scale, was the primary outcome. After baseline (T0), follow-ups were at mid-intervention (T4), immediately post-intervention (T8); 3 months (T20), and 6 months (T32) post-intervention.& nbsp; Results: The intervention group and control group did not have significant differences in depression outcomes throughout end of treatment and follow-up. Among secondary outcomes, increase in resilience (d=0.32, p=0.03) and mindfulness (d=0.57, p=0.002), and reduction in perceived stress (d=-0.52, p=0.008) were greater in MHP+TAU versus TAU at T32; no differences were found in anxiety, sleep disturbances, and quality of life between groups. Post-hoc comparisons of patients on antidepressants showed significantly greater reduction in depression at T32 for MHP+TAU versus TAU (d=-0.73, p=0.01); patients not on antidepressants showed no between-group differences.& nbsp; Limitations: Limitations include unknown characteristics of TAU, potential bias from patients and providers not being blinded to treatment group, and failure to specify examination of differences by antidepressant status in the protocol.& nbsp; & nbsp;Conclusions: Most outcomes, including depression, did not significantly differ between MHP+TAU and TAU. Exploratory analysis revealed intervention effect at the end of the 6-month follow-up among patients on anti-depressant medication.
  • Acosta, H.; Tuulari, J. J.; Kantojärvi, K.; Lewis, J. D.; Hashempour, N.; Scheinin, N. M.; Lehtola, S. J.; Fonov, V. S.; Collins, D. L.; Evans, A.; Parkkola, R.; Lahdesmaki, T.; Saunavaara, J.; Merisaari, H.; Karlsson, L.; Paunio, T.; Karlsson, H. (2021)
    Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.
  • Niittynen, Taru; Riihonen, Veera; Moscovice, Liza; Koski, Sonja (2022)
    Ensuring horse welfare is a central aim in equestrian activities. Training is an important context for welfare, as horses form long-lasting representations of people and actions at a young age. However, only a few studies have addressed horses' emotional responses during early training with humans. In this study, we followed N = 19 young horses, including naive yearlings and more experienced two-to three-year-olds, through five foundation training sessions over nine months. Our goal was to combine physiological and behavioral measures to assess emotional responses to early foundation training. Specifically, we measured salivary oxytocin (sOXT) in N = 100 samples and salivary cortisol (sCORT) in N = 96 samples before and after training sessions. We also recoded behavioral responses during training. Changes in sOXT during training predicted individual variation in behavioral responses: Horses who showed more affiliative human-directed behaviors during training had in-creases in sOXT, while horses who showed more behavioral indicators of discomfort during training had de-creases in sOXT. Salivary cortisol was not related to individual behavioral responses, but experienced horses had lower sCORT concentrations both before and after training, and all horses showed decreases in sCORT and in behaviors indicative of fear or discomfort as training progressed. In addition, sCORT increased during longer training sessions, consistent with the established role of cortisol in responding to physical stressors. We conclude that individual variation in positive or negative behavioral responses to foundation training corresponds with acute changes in sOXT concentrations in young horses, suggesting that sOXT may be useful as a non-invasive indicator of emotional responses in young horses.
  • Salmela-Aro, Katariina; Upadyaya, Katja; Vinni-Laakso, Janica; Hietajärvi, Lauri (2021)
    This longitudinal study examined school engagement and burnout profiles among early and middle adolescents before and during COVID-19, and within-class latent change and stability in students' socio-emotional skills the profiles. The longitudinal data were collected in fall 2019 and 2020 from 1381 5th to 6th, and 1374 7th to 8th grade students. Using repeated measures latent profile analyses based on school engagement and burnout we identified five study well-being change profiles in both samples showing structural similarity: normative (53% sample 1; 69% sample 2), moderate-decreasing (4%; 5%), high-decreasing (17%; 10%), low-increasing (6%;7%) and moderate-increasing (20%; 10%) groups. The groups with increasing study well-being showed simultaneous increase in intrapersonal socio-emotional competencies but showed less changes in interpersonal outcomes.
  • Mikkola, Tuija M.; Kautiainen, Hannu; Mänty, Minna; von Bonsdorff, Mikaela B.; Kröger, Teppo; Eriksson, Johan G. (2021)
    Background Evidence on family caregivers' health is conflicting. Aim To investigate all-cause and cause-specific mortality in Finnish family caregivers providing high-intensity care and to assess whether age modifies the association between family caregiver status and mortality using data from multiple national registers. Methods The data include all individuals, who received family caregiver's allowance in Finland in 2012 (n = 42,256, mean age 67 years, 71% women) and a control population matched for age, sex, and municipality of residence (n = 83,618). Information on dates and causes of death between 2012 and 2017 were obtained from the Finnish Causes of Death Register. Results Family caregivers had lower all-cause mortality than the controls over the follow-up (8.1 vs. 11.6%) both among women (socioeconomic status adjusted hazard ratio [HR]: 0.64, 95% CI 0.61-0.68) and men (adjusted HR: 0.73, 95% CI 0.70-0.77). When modelling all-cause mortality as a function of age, younger caregivers had only slightly lower or equal mortality to their controls, but older caregivers had markedly lower mortality than their controls, up to more than 10% lower. Caregivers had a lower mortality rate for all the causes of death studied, namely cardiovascular, cancer, neurological, external, respiratory, gastrointestinal and dementia. The lowest risk was for dementia (subhazard ratio = 0.29, 95% CI 0.25-0.34). Conclusions Older family caregivers had lower mortality than the age-matched general population while mortality did not differ according to caregiver status in young adulthood. This age-dependent advantage in mortality is likely to reflect the selection of healthier individuals into the family caregiver role.
  • Mehmood, Shiraz; Din, Israr Ud; Ullah, Izhar; Mohamed, Heba; Basit, Abdul; Khan, Mudassar Nawaz; Shah, Syed Saad Hussain; Rehman, Attiq ur (2021)
    Background Knowledge of the genetic diversity and population structure of germplasm collections is an important foundation for crop improvement. Rice production across a broad range of rice-growing environments results in a diverse array of local rice varieties. Many rice varieties have been lost as a result of biodiversity loss and are now grown in Pakistan. Methods and results To protect the biodiversity of rice varieties, an experiment was carried out to check the genetic and morphological variations between 8 exotic and 7 local rice genotypes, using 5 different SSR markers, i.e., RM3, RM259, RM341, RM520, and RM11943. The analysis of morphological and quality traits of rice observed significant variation across genotypes. The results revealed that genotype Irri-Pak attained the highest plant height and primary branch plant-1, while genotype Mushkan produced a higher number of productive tillers and obtained a higher fertility factor (%). Similarly, the highest value for panicle length was observed for genotype Faker-e-Malakand, 1000-grains weight in genotype Calmochi, and maximum days to maturity was noticed in genotype Swati-2014. Moreover, the genotype Brio attained the highest value of stem diameter, while maximum seed length was noted in the genotype Sug Dasi. The highest number of primary branches plant(-1) in genotype Ibge-I and secondary branches plant(-1) in genotype Calmochi were noticed. A higher concentration of sodium and potassium was observed for the genotype Marte, while the genotype Muskan attained the maximum content of copper. Moreover, the highest concentration of iron in genotype Originario, zinc in genotype JP-5, and cadmium content were noticed in genotype Ibge. Similarly, the dendrogram analysis for quantitative parameters showed three clusters at 74.13% similarities. Whereas all the genotypes of European origin formed a separate cluster. A set of 5 simple sequence repeat primers, covering four chromosomes, amplified a total of 14 alleles and showed 100% polymorphism with an average PIC value ranging from 0.39 to 0.91. The UPGMA cluster analysis separated the 15 rice genotypes into 3 main groups based on 32.5% similarities and the highest genetic distance (45.1%) was observed between two genotypes (Fakher-e-malakand and Musa), having different geographical origins. There was no genetic distance between the genotypes Marte and Brio, irrespective of having the same origin. Conclusions The maximum genetic distances were noted for genotype, Fakhre-e-Malakand and Musa having a different origin, while the minimum genetic distance was shown by genotypes, Marte and Onice, from the same origin.
  • Grotell, Milo; den Hollander, Bjornar; Jalkanen, Aaro; Törrönen, Essi; Ihalainen, Jouni; de Miguel, Elena; Dudek, Mateusz; Kettunen, Mikko I.; Hyytiä, Petri; Forsberg, Markus M.; Kankuri, Esko; Korpi, Esa R. (2021)
    Mephedrone (4-MMC), despite its illegal status, is still a widely used psychoactive substance. Its effects closely mimic those of the classical stimulant drug methamphetamine (METH). Recent research suggests that unlike METH, 4-MMC is not neurotoxic on its own. However, the neurotoxic effects of 4-MMC may be precipitated under certain circumstances, such as administration at high ambient temperatures. Common use of 4-MMC in conjunction with alcohol raises the question whether this co-consumption could also precipitate neurotoxicity. A total of six groups of adolescent rats were treated twice daily for four consecutive days with vehicle, METH (5 mg/kg) or 4-MMC (30 mg/kg), with or without ethanol (1.5 g/kg). To investigate persistent delayed effects of the administrations at two weeks after the final treatments, manganese-enhanced magnetic resonance imaging brain scans were performed. Following the scans, brains were collected for Golgi staining and spine analysis. 4-MMC alone had only subtle effects on neuronal activity. When administered with ethanol, it produced a widespread pattern of deactivation, similar to what was seen with METH-treated rats. These effects were most profound in brain regions which are known to have high dopamine and serotonin activities including hippocampus, nucleus accumbens and caudate-putamen. In the regions showing the strongest activation changes, no morphological changes were observed in spine analysis. By itself 4-MMC showed few long-term effects. However, when co-administered with ethanol, the apparent functional adaptations were profound and comparable to those of neurotoxic METH.
  • Wang, Shunbin; Guo, Peng; Li, Xiaoxiao; Wu, Minggen; Overmyer, Kirk; Liu, Shenkui; Cui, Fuqiang (2020)
    Sporadic and unpredictable extreme hot weather events associated with global warming have been an increasingly serious problem and are difficult to test under natural field conditions. In this study, we used subtropical summer to mimic extreme hot weather under realistic field conditions to test for heat tolerance in the cold-adapted emergent oil crop, Camelina sativa. Utilizing a forward genetic screen, Camelina was screened for heat-adapted genotypes, resulting in the identification of three subtropical summer tolerant (sst) mutants. The sst mutants were late flowering and exhibited altered expression of the key flowering genes FLOWER LOCUS C and FLOWER LOCUS T. With RNA-seq assay, it was found that redox and defense related genes were significantly enriched in the up-regulated genes of the sst mutants. Consistently, reduced hydrogen peroxide production and enhanced resistance to a fungal pathogen were observed. Overall, our results suggested that to breed temperate crops to adapt to the subtropics, flowering time, antioxidant ability, and defense signaling could be the potential targets.
  • Direk, Nese; Williams, Stephanie; Smith, Jennifer A.; Ripke, Stephan; Air, Tracy; Amare, Azmeraw T.; Amin, Najaf; Baune, Bernhard T.; Bennett, David A.; Blackwood, Douglas H. R.; Boomsma, Dorret; Breen, Gerome; Buttenschon, Henriette N.; Byrne, Enda M.; Borglum, Anders D.; Castelao, Enrique; Cichon, Sven; Clarke, Toni-Kim; Cornelis, Marilyn C.; Dannlowski, Udo; De Jager, Philip L.; Demirkan, Ayse; Domenici, Enrico; van Duijn, Cornelia M.; Dunn, Erin C.; Eriksson, Johan G.; Esko, Tonu; Faul, Jessica D.; Ferrucci, Luigi; Fornage, Myriam; de Geus, Eco; Gill, Michael; Gordon, Scott D.; Grabe, Hans Joergen; van Grootheest, Gerard; Hamilton, Steven P.; Hartman, Catharina A.; Heath, Andrew C.; Hek, Karin; Hofman, Albert; Homuth, Georg; Horn, Carsten; Hottenga, Jouke Jan; Kardia, Sharon L. R.; Kloiber, Stefan; Koenen, Karestan; Kutalik, Zoltan; Ladwig, Karl-Heinz; Lahti, Jari; Levinson, Douglas F.; Lewis, Cathryn M.; Lewis, Glyn; Li, Qingqin S.; Llewellyn, David J.; Lucae, Susanne; Lunetta, Kathryn L.; MacIntyre, Donald J.; Madden, Pamela; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Milaneschi, Yuri; Montgomery, Grant W.; Mors, Ole; Mosley, Thomas H.; Murabito, Joanne M.; Mueller-Myhsok, Bertram; Nothen, Markus M.; Nyholt, Dale R.; O'Donovan, Michael C.; Penninx, Brenda W.; Pergadia, Michele L.; Perlis, Roy; Potash, James B.; Preisig, Martin; Purcell, Shaun M.; Quiroz, Jorge A.; Raikkonen, Katri; Rice, John P.; Rietschel, Marcella; Rivera, Margarita; Schulze, Thomas G.; Shi, Jianxin; Shyn, Stanley; Sinnamon, Grant C.; Smit, Johannes H.; Smoller, Jordan W.; Snieder, Harold; Tanaka, Toshiko; Tansey, Katherine E.; Teumer, Alexander; Uher, Rudolf; Umbricht, Daniel; Van der Auwera, Sandra; Ware, Erin B.; Weir, David R.; Weissman, Myrna M.; Willemsen, Gonneke; Yang, Jingyun; Zhao, Wei; Tiemeier, Henning; Sullivan, Patrick F. (2017)
    BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 x 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 x 10(-9)). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
  • Rantonen, O.; Alexanderson, K.; Clark, A. J.; Aalto, P.; Sonden, A.; Bronnum-Hansen, H.; Hougaard, C. O.; Rod, N. H.; Mittendorfer-Rutz, E.; Kivimäki, M.; Oksanen, T.; Salo, P. (2019)
    Background: Social workers have an elevated risk for mental disorders, but little is known about their antidepressant treatment. Aims: To examine any and long-term antidepressant treatment among social workers in Finland, Sweden and Denmark. Methods: We linked records from drug prescription registers to three prospective cohorts: the Finnish Public Sector study, years 2006-2011, and nation-wide cohorts in Sweden and Denmark, years 2006-2014, including a total of 1.5 million employees in (1) social work, (2) other social and health care professions, (3) education and (4) office work. We used Cox proportional hazards models to estimate hazard ratios for any and long-term (>6 months) antidepressant treatment among social workers compared to the three reference occupational groups and carried out meta-analyses. Results: During follow-up, 25% of social workers had any prescriptions for antidepressants (19-24% reference occupations) and 20% for long-term treatment (14-19% reference occupations). The pooled effects for any and long-term treatment showed that probabilities were 10% higher in social workers compared to other health and social care professionals and 30% higher compared to education and non-human service professionals. Probabilities for any treatment in the three countries were relatively similar, but for long-term treatment social workers in Finland had a greater risk compared with other human service professions. Limitations: There were differences between the cohorts in the availability of data. Specific diagnoses for the antidepressant treatment were not known neither adherence to treatment. Conclusion: Social workers have a higher risk for any and long-term antidepressant treatment than other human and non-human service professionals.
  • Diniz, Cassiano Ricardo Alves Faria; Casarotto, Plinio C.; Fred, Senem M.; Biojone, Caroline; Castrén, Eero; Joca, Sâmia R.L. (2018)
    The renin-angiotensin system (RAS) is associated with peripheral fluid homeostasis and cardiovascular function, but recent evidence also suggests a functional role in the brain. RAS regulates physiological and behavioral parameters related to the stress response, including depressive symptoms. Apparently, RAS can modulate levels of brain-derived neurotrophic factor (BDNF) and TRKB, which are important in the neurobiology of depression and antidepressant action. However, the interaction between the BDNF/TRKB system and RAS in depression has not been investigated before. Accordingly, in the forced swimming test, we observed an antidepressant-like effect of systemic losartan but not with captopril or enalapril treatment. Moreover, infusion of losartan into the ventral hippocampus (vHC) and prelimbic prefrontal cortex (PL) mimicked the consequences of systemically injected losartan, whereas K252a (a blocker of TRK) infused into these brain areas impaired such effect. PD123319, an antagonist of AT2 receptor (AGTR2), also prevented the systemic losartan effect when infused into PL but not into vHC. Cultured cortical cells of rat embryos revealed that angiotensin II (ANG2), possibly through AGTR2, increased the surface levels of TRKB and its coupling to FYN, a SRC family kinase. Higher Agtr2 levels in cortical cells were reduced after stimulation with glutamate, and only under this condition an interaction between losartan and ANG2 was achieved. TRKB/AGTR2 heterodimers were also observed, in MG87 cells GFP-tagged AGTR2 co-immunoprecipitated with TRKB. Therefore, the antidepressant-like effect of losartan is proposed to occur through a shift of ANG2 towards AGTR2, followed by coupling of TRK/FYN and putative TRIG transactivation. Thus, the blockade of AGTR1 has therapeutic potential as a novel antidepressant therapy. (C) 2018 The Author(s). Published by Elsevier Ltd.
  • Saltychev, Mikhail; Juhola, Juhani; Ervasti, Jenni; Kivimäki, Mika; Pentti, Jaana; Myllyntausta, Saana; Vahtera, Jussi (2021)
    Objectives To investigate the association between changes in lifestyle risk factors and changes is sleep difficulties. Design Longitudinal repeated measures cohort study. Setting University and national institute of occupational health. Participants Participants of the Finnish Public Sector study with information on sleep and lifestyle-related risk factors collected in five repeat surveys with 4-year intervals from 2000 to 2017. The participants were those, who had responded at least twice and had a change in sleep difficulties (having sleep difficulties vs not) (142 969 observations from 38 400 respondents (mean age 45.5 (SD 9.2) years, 83% women). Primary and secondary outcome measures Changes in sleep quality over time. Longitudinal fixed effects analysis, a method that accounts for time-invariant confounders by design, was used. Results At first available response, sleep difficulties were experienced by 13 998 (36%) of the respondents. Respectively, the mean age was 44.3 (10.0) years, 7526 (20%) were obese, 13 487 (35%) reported low physical activity, 3338 (9%) extensively drinking and 6547 (17%) were smoking. Except for smoking, the changes in the studied modifiable risks were associated with changes in sleep difficulties. The ORs for having sleep difficulties were 1.41 (95% CI 1.35 to 1.48) for obesity, 1.10 (95% CI 1.06 to 1.13) for low physical activity and 1.43 (95% CI 1.35 to 1.51) for heavy drinking. For smoking, the association was negative with OR 0.81 (95% CI 0.76 to 0.86). Including all four modifiable risks into model changed the estimates only little. Conclusions The results of this longitudinal study suggest that changes in sleep quality are interconnected with changes in lifestyle.
  • Santavirta, Torsten; Santavirta, Nina; Gilman, Stephen (2018)
    Importance Although there is evidence that adverse childhood experiences are associated with worse mental health in adulthood, scarce evidence is available regarding an emerging concern that the next generation might also be affected. Objective To compare the risk of psychiatric hospitalization in cousins whose parents were vs were not exposed to the Finnish evacuation policy that involved a mean 2-year stay with a Swedish foster family. Design, Setting, and Participants This multigenerational, population-based cohort study of Finnish individuals and their siblings born between January 1, 1933, and December 31, 1944, analyzed the association of evacuee status as a child during World War II in the first generation with the risk of psychiatric hospitalization among offspring in the second generation. Evacuee status during World War II was determined using the Finnish National Archive’s registry of participants in the Finnish evacuation. Data on evacuee status were linked to the psychiatric diagnoses in the Finnish Hospital Discharge Register from January 1, 1971, through December 31, 2012, for offspring (n = 93 391) born between January 1, 1950, and December 31, 2010. Sex-specific Cox proportional hazards regression models were used to estimate hazard ratios for risk of psychiatric hospitalization during the follow-up period. Because offspring of evacuees and their nonevacuated siblings are cousins, the Cox proportional hazards regression models included fixed effects to adjust for confounding factors in families. Data analysis was performed from June 15, 2016, to August 26, 2017. Exposures Parental participation in the evacuation during World War II (coded 1 for parents who were evacuated and placed in foster care and 0 for those not evacuated). Main Outcomes and Measures Offspring’s initial admission to the hospital for a psychiatric disorder, obtained from the Finnish Hospital Discharge Register from January 1, 1971, through December 31, 2012. Results Of the 93 391 study persons, 45 955 (49.2%) were women and 47 436 (50.8) were men; mean (SD) age in 2012 among survivors was 45.4 (6.58) years. Female offspring of mothers evacuated to Sweden during childhood had an elevated risk of psychiatric hospitalization (hazard ratio for any type of psychiatric disorder: 2.04 [95% CI, 1.04-4.01]; hazard ratio for mood disorder: 4.68 [95% CI, 1.92-11.42]). There was no excess risk of being hospitalized for a psychiatric disorder among women whose fathers were exposed to the Finnish evacuation policy during World War II or among men whose mothers or fathers were exposed. Conclusions and Relevance In a prior follow-up study of the Finnish evacuees, girls evacuated to Swedish foster families during World War II were more likely to be hospitalized for a psychiatric disorder—in particular, a mood disorder—in adulthood than their nonevacuated sisters. The present study found that the offspring of these individuals were also at risk for mental health problems that required hospitalization and suggests that early-life adversities, including war-related exposures, may be associated with mental health disorders that persist across generations.
  • Rehman, Sidra; Mansoora, Nida; Al-Dhumri, Sami A.; Amjad, Syeda F.; Al-Shammari, Wasimah B.; Almutari, Mohammad M.; Alhusayni, Fatimah S.; Al Bakre, Dhafer A.; Lalarukh, Irfana; Alshahri, Abdullah H.; Poczai, Peter; Galal, Tarek M.; Abdelhafez, Ahmed A. (2022)
    Heavy metal stress and less nutrient availability are some of the major concerns in agriculture. Both abiotic stresses have potential to decrease the crops productivity. On the other hand, organic fertilizers i.e., activated carbon biochar (ACB) and arbuscular mycorrhizal fungi (AMF) increase nutritional and heavy metal like Nickel (Ni) stress tolerance and provide immunity to plants for their survival in unfavorable environments. Previous studies have only looked at single applications of either ACB or AMF thus far. There is limited evidence of their synergistic effects, especially in plants growing in soil contaminated with nickel (Ni). To cover the knowledge gap of combined use of AMF inoculation (Glomus intraradices) and/or wheat straw biochar amendments on wheat growth, antioxidant activities and osmolytes concentration, present study is conducted. The use of either the AMF inoculant or the ACB alone resulted in improved wheat growth and decreased Ni uptake. Furthermore, sole AMF or ACB also reduced Ni stress effectively, allowing wheat to grow faster and reducing soil Ni transfer into plant tissue. In comparison to a control, adding ACB with AMF inoculant considerably increased fungal populations. The most significant increase in wheat growth and decrease in tissue Ni contents came from amending soil with AMF inoculant and biochar. Inducing soil alkalinization and causing Ni immobilization, as well as decreasing Ni phyto-availability, the combination treatment had a synergistic impact. These findings imply that AMF inoculation in ACB treatment could be used not only for wheat production but also for Ni-contaminated soil phyto-stabilization. (C) 2022 The Author(s). Published by Elsevier B.V.
  • Cooper, Helen M.; Yang, Yang; Ylikallio, Emil; Khairullin, Rafil; Woldegebriel, Rosa; Lin, Kai-Lan; Euro, Liliya; Palin, Eino; Wolf, Alexander; Trokovic, Ras; Isohanni, Pirjo; Kaakkola, Seppo; Auranen, Mari; Lonnqvist, Tuula; Wanrooij, Sjoerd; Tyynismaa, Henna (2017)
    De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G > A (p.G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood. HSP is a clinically and genetically heterogeneous disorder of the upper motor neurons. Symptoms beginning in early childhood may resemble spastic cerebral palsy. The function of ATAD3A, a mitochondrial inner membrane AAA ATPase, is yet undefined. AAA ATPases form hexameric rings, which are catalytically dependent on the co-operation of the subunits. The dominant-negative patient mutation affects the Walker A motif, which is responsible for ATP binding in the AAA module of ATAD3A, and we show that the recombinant mutant ATAD3A protein has a markedly reduced ATPase activity. We further show that overexpression of the mutant ATAD3A fragments the mitochondrial network and induces lysosome mass. Similarly, we observed altered dynamics of the mitochondrial network and increased lysosomes in patient fibroblasts and neurons derived through differentiation of patient-specific induced pluripotent stem cells. These alterations were verified in patient fibroblasts to associate with upregulated basal autophagy through mTOR inactivation, resembling starvation. Mutations in ATAD3A can thus be dominantly inherited and underlie variable neurological phenotypes, including HSP, with intrafamiliar variability. This finding extends the group of mitochondrial inner membrane AAA proteins associated with spasticity.
  • Eerola, Tuomas; Vuoskoski, Jonna K.; Kautiainen, Hannu; Peltola, Henna-Riikka; Putkinen, Vesa; Schafer, Katharina (2021)
    Many people enjoy sad music, and the appeal for tragedy is widespread among the consumers of film and literature. The underlying mechanisms of such aesthetic experiences are not well understood. We tested whether pleasure induced by sad, unfamiliar instrumental music is explained with a homeostatic or a reward theory, each of which is associated with opposite patterns of changes in the key hormones. Sixty-two women listened to sad music (or nothing) while serum was collected for subsequent measurement of prolactin (PRL) and oxytocin (OT) and stress marker (cortisol and adrenocorticotropic hormone) concentrations. Two groups of participants were recruited on the basis of low and high trait empathy. In the high empathy group, PRL and OT levels were significantly lower with music compared with no music. And compared to the low empathy group, the high empathy individuals reported an increase of positive mood and higher ratings of being moved with music. None of the stress markers showed any changes across the conditions or the groups. These hormonal changes, inconsistent with the homeostatic theory proposed by Huron, exhibit a pattern expected of general reward. Our findings illuminate how unfamiliar and low arousal music may give rise to pleasurable experiences.