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Association Study of the HTR2C, Leptin and Adiponectin Genes and Serum Marker Analyses in Clozapine Treated Long-Term Patients with Schizophrenia
- J.-P. Klemettilä, O. Kampman, N. Seppälä, M. Viikki, M. Hämäläinen, E. Moilanen, N. Mononen, T. Lehtimäki, E. Leinonen
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- Journal:
- European Psychiatry / Volume 30 / Issue 2 / February 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. 296-302
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Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2 C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2 C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P < 0.001; in men leptin vs. weight gain, P = 0.026, leptin vs. IL-1Ra, P < 0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P = 0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2 C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.
Spousal resemblance for history of major depressive episode in the previous year
- S. LINDEMAN, J. KAPRIO, E. ISOMETSÄ, K. POIKOLAINEN, M. HEIKKINEN, J. HÄMÄLÄINEN, L. HAARASILTA, T. LAUKKALA, H. ARO
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- Journal:
- Psychological Medicine / Volume 32 / Issue 2 / February 2002
- Published online by Cambridge University Press:
- 08 April 2017, pp. 363-367
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Background. There is discrepancy in findings on spousal concordance for major depression. Here we report the risk of depression and its determinants in spouses of persons with or without depression, taking into account several known risk factors for major depression.
Methods. A random sample of non-institutionalized Finnish individual aged 15–75 years was interviewed in the 1996 National Health Care Survey. The sample included 1708 male–female spouse pairs. Major depressive episode (MDE) during the last 12 months was assessed using the Short Form of the University of Michigan version of the Composite International Diagnostic Interview (the UM-CIDI Short Form). Risk factors were assessed in the same interview.
Results. Factors associating with MDE were spouse's MDE, own alcohol intoxication at least once a week and own chronic medical conditions. In addition, there was a strong association between female's current smoking and male's MDE, independently of other risk factors and spousal MDE. The association of MDE with spouses's MDE was not affected by taking into account other assessed risk factors (own or spouse's).
Conclusions. The results indicate elevated spouse concordance for MDE independent of the risk factors assessed in the present study.
Association Study of Arcuate Nucleus Neuropeptide Y Neuron Receptor Gene Variation And Serum Npy Levels in Clozapine Treated Patients With Schizophrenia
- J.-P. Klemettilä, O. Kampman, A. Solismaa, L.-P. Lyytikäinen, N. Seppälä, M. Viikki, M. Hämäläinen, E. Moilanen, N. Mononen, T. Lehtimäki, E. Leinonen
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- Journal:
- European Psychiatry / Volume 40 / February 2017
- Published online by Cambridge University Press:
- 10 November 2016, pp. 13-19
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Background
Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients.
Subjects and methodsAssociations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment.
ResultsThe serum levels of NPY correlated with levels of resistin (r = 0.31, P < 0.001) and age (r = 0.22, P = 0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P < 0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P < 0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P = 0.078).
ConclusionsSerum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.
Trends in work disability with mental diagnoses among social workers in Finland and Sweden in 2005–2012
- O. Rantonen, K. Alexanderson, J. Pentti, L. Kjeldgård, J. Hämäläinen, E. Mittendorfer-Rutz, M. Kivimäki, J. Vahtera, P. Salo
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 26 / Issue 6 / December 2017
- Published online by Cambridge University Press:
- 09 September 2016, pp. 644-654
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Aims
Social workers report high levels of stress and have an increased risk for hospitalisation with mental diagnoses. However, it is not known whether the risk of work disability with mental diagnoses is higher among social workers compared with other human service professionals. We analysed trends in work disability (sickness absence and disability pension) with mental diagnoses and return to work (RTW) in 2005–2012 among social workers in Finland and Sweden, comparing with such trends in preschool teachers, special education teachers and psychologists.
MethodsRecords of work disability (>14 days) with mental diagnoses (ICD-10 codes F00–F99) from nationwide health registers were linked to two prospective cohort projects: the Finnish Public Sector study, years 2005–2011 and the Insurance Medicine All Sweden database, years 2005–2012. The Finnish sample comprised 4849 employees and the Swedish 119 219 employees covering four occupations: social workers (Finland 1155/Sweden 23 704), preschool teachers (2419/74 785), special education teachers (832/14 004) and psychologists (443/6726). The reference occupations were comparable regarding educational level. Risk of work disability was analysed with negative binomial regression and RTW with Cox proportional hazards.
ResultsSocial workers in Finland and Sweden had a higher risk of work disability with mental diagnoses compared with preschool teachers and special education teachers (rate ratios (RR) 1.43–1.91), after adjustment for age and sex. In Sweden, but not in Finland, social workers also had higher work disability risk than psychologists (RR 1.52; 95% confidence interval 1.28–1.81). In Sweden, in the final model special education teachers had a 9% higher probability RTW than social workers. In Sweden, in the final model the risks for work disability with depression diagnoses and stress-related disorder diagnoses were similar to the risk with all mental diagnoses (RR 1.40–1.77), and the probability of RTW was 6% higher in preschool teachers after work disability with depression diagnoses and 9% higher in special education teachers after work disability with stress-related disorder diagnoses compared with social workers.
ConclusionSocial workers appear to be at a greater risk of work disability with mental diagnoses compared with other human service professionals in Finland and Sweden. It remains to be studied whether the higher risk is due to selection of vulnerable employees to social work or the effect of work-related stress in social work. Further studies should focus on these mechanisms and the risk of work disability with mental diagnoses among human service professionals.
Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors
- K. Räikkönen, A.-K. Pesonen, J. R. O'Reilly, S. Tuovinen, M. Lahti, E. Kajantie, P. Villa, H. Laivuori, E. Hämäläinen, J. R. Seckl, R. M. Reynolds
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- Journal:
- Psychological Medicine / Volume 45 / Issue 15 / November 2015
- Published online by Cambridge University Press:
- 22 June 2015, pp. 3217-3226
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Background.
Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and ‘programming’ of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors.
Method.Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days.
Results.Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13–0.69, p = 0.005], HSD1B11 (0.30, 0.03–0.57, p = 0.03), NR3C1 (0.44, 0.19–0.68, p = 0.001) and SLC6A4 (0.26, 0.00–0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05).
Conclusions.Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.
Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity
- R. M. Reynolds, A.-K. Pesonen, J. R. O'Reilly, S. Tuovinen, M. Lahti, E. Kajantie, P. M. Villa, H. Laivuori, E. Hämäläinen, J. R. Seckl, K. Räikkönen
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- Journal:
- Psychological Medicine / Volume 45 / Issue 10 / July 2015
- Published online by Cambridge University Press:
- 28 January 2015, pp. 2023-2030
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Background
Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.
MethodWe studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11β-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies.
ResultsIn adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01–0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01–0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2–3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses).
ConclusionsOur findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.
Use of vitamin D supplements during infancy in an international feeding trial
- Eveliina Lehtonen, Anne Ormisson, Anita Nucci, David Cuthbertson, Susa Sorkio, Mila Hyytinen, Kirsi Alahuhta, Carol Berseth, Marja Salonen, Shayne Taback, Margaret Franciscus, Teba González-Frutos, Tuuli E Korhonen, Margaret L Lawson, Dorothy J Becker, Jeffrey P Krischer, Mikael Knip, Suvi M Virtanen, , Thomas Mandrup-Poulsen, Elias Arjas, Åke Lernmark, Barbara Schmidt, Jeffrey P. Krischer, Hans K. Åkerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Eeva Pajakkala, Marja Salonen, David Cuthbertson, Jeffrey P. Krischer, Linda Shanker, Brenda Bradley, Hans-Michael Dosch, John Dupré, William Fraser, Margaret Lawson, Jeffrey L. Mahon, Mathew Sermer, Shayne P. Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Minna Pekkala, Suvi M. Virtanen, Jacki Catteau, Neville Howard, Patricia Crock, Maria Craig, Cheril L. Clarson, Lynda Bere, David Thompson, Daniel Metzger, Colleen Marshall, Jennifer Kwan, David K. Stephure, Daniele Pacaud, Wendy Schwarz, Rose Girgis, Marilyn Thompson, Shayne P. Taback, Daniel Catte, Margaret L. Lawson, Brenda Bradley, Denis Daneman, Mathew Sermer, Mary-Jean Martin, Valérie Morin, Lyne Frenette, Suzanne Ferland, Susan Sanderson, Kathy Heath, Céline Huot, Monique Gonthier, Maryse Thibeault, Laurent Legault, Diane Laforte, Elizabeth A. Cummings, Karen Scott, Tracey Bridger, Cheryl Crummell, Robyn Houlden, Adriana Breen, George Carson, Sheila Kelly, Koravangattu Sankaran, Marie Penner, Richard A. White, Nancy King, James Popkin, Laurie Robson, Eva Al Taji, Irena Aldhoon, Pavla Mendlova, Jan Vavrinec, Jan Vosahlo, Ludmila Brazdova, Jitrenka Venhacova, Petra Venhacova, Adam Cipra, Zdenka Tomsikova, Petra Krckova, Pavla Gogelova, Ülle Einberg, Mall-Anne Riikjärv, Anne Ormisson, Vallo Tillmann, Päivi Kleemola, Anna Parkkola, Heli Suomalainen, Anna-Liisa Järvenpää, Anu-Maaria Hämälainen, Hannu Haavisto, Sirpa Tenhola, Pentti Lautala, Pia Salonen, Susanna Aspholm, Heli Siljander, Carita Holm, Samuli Ylitalo, Raisa Lounamaa, Anja Nuuja, Timo Talvitie, Kaija Lindström, Hanna Huopio, Jouni Pesola, Riitta Veijola, Päivi Tapanainen, Abram Alar, Paavo Korpela, Marja-Liisa Käär, Taina Mustila, Ritva Virransalo, Päivi Nykänen, Bärbel Aschemeier, Thomas Danne, Olga Kordonouri, Dóra Krikovszky, László Madácsy, Yeganeh Manon Khazrai, Ernesto Maddaloni, Paolo Pozzilli, Carla Mannu, Marco Songini, Carine de Beaufort, Ulrike Schierloh, Jan Bruining, Margriet Bisschoff, Aleksander Basiak, Renata Wasikowa, Marta Ciechanowska, Grazyna Deja, Przemyslawa Jarosz-Chobot, Agnieszka Szadkowska, Katarzyna Cypryk, Malgorzata Zawodniak-Szalapska, Luis Castano, Teba Gonzalez Frutos, Mirentxu Oyarzabal, Manuel Serrano-Ríos, María Teresa Martínez-Larrad, Federico Gustavo Hawkins, Dolores Rodriguez Arnau, Johnny Ludvigsson, Malgorzata Smolinska Konefal, Ragnar Hanas, Bengt Lindblad, Nils-Osten Nilsson, Hans Fors, Maria Nordwall, Agne Lindh, Hans Edenwall, Jan Aman, Calle Johansson, Margrit Gadient, Eugen Schoenle, Dorothy Becker, Ashi Daftary, Margaret Franciscus, Carol Gilmour, Jerry Palmer, Rachel Taculad, Marilyn Tanner-Blasiar, Neil White, Uday Devaskar, Heather Horowitz, Lisa Rogers, Roxana Colon, Teresa Frazer, Jose Torres, Robin Goland, Ellen Greenberg, Maudene Nelson, Holly Schachner, Barney Softness, Jorma Ilonen, Massimo Trucco, Lynn Nichol, Erkki Savilahti, Taina Härkönen, Mikael Knip, Outi Vaarala, Kristiina Luopajärvi, Hans-Michael Dosch
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- Journal:
- Public Health Nutrition / Volume 17 / Issue 4 / April 2014
- Published online by Cambridge University Press:
- 24 June 2013, pp. 810-822
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Objective
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
DesignLongitudinal study.
SettingInformation about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
SubjectsInfants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
ResultsDaily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
ConclusionsMost of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.