Browsing by Subject "anxiety"

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  • Pulkkinen, Maria; Jousela, Irma; Sintonen, Harri; Engblom, Janne; Salanterä, Sanna; Junttila, Kristiina (2021)
    Aims: To explore the effectiveness of a new perioperative practice model on anxiety and health-related quality of life in patients undergoing total hip arthroplasty and total knee arthroplasty under spinal anaesthesia. Design: A randomized clinical trial. Methods: Control group participants (N = 222) received standard perioperative care, meaning they were cared for by various nurses during their perioperative process without postoperative visits. Intervention group participants (N = 231) were assigned one named anaesthesia nurse during their entire perioperative process who visited them postoperatively. Both groups responded to two self-reported questionnaires: the generic 15D health-related quality of life instrument and the State-Trait Anxiety Inventory (STAI) measuring anxiety two to three weeks pre-operatively and three months postoperatively. Results: There were no statistically significant differences between the groups at baseline or at follow-up in health-related quality of life or anxiety.
  • Ala-Lipasti, Minna (Helsingfors universitet, 2016)
    Goals. Inflammation has been found to be associated with psychological symptoms. Especially in regard to depression, there is broad evidence that depressed people have higher levels of inflammation. Higher inflammation has also been linked to poorer response to SSRI-medication. Anxiety has been found to have stronger association to experienced pain than depression and in earlier studies references to an independent association between anxiety and inflammation has emerged. The purpose of this study was to explore if a connection between anxiety and inflammation can be found and what factors are possibly contributing to that connection. Goal was to find factors that can help maintain and improve individual's quality of life and ability to work. Methods. Data used in this study belonged to the biomarker project (project 4), which was part of the second stage of the Midlife in the United States (MIDUS) longitudinal study. The mean age of participants was 57.32 (sd. 11.55) years. As a measure of inflammation serum levels of cytokine interleukin-6 (IL-6) were collected from the blood of participants. Anxiety was measured by Spielberger Trait Anxiety Inventory (STAI). The association between anxiety and inflammation was explored by a linear regression analysis. Sociodemographic factors and also a broad range of other factors related to inflammation and anxiety were controlled in the models. In addition the possible moderating role of inner self-control was studied by a hierarchical linear regression analysis. The sub factor cognition control of the self-control scale was used as a measure of inner self-control. Results and conclusions. When inflammation was predicted only by anxiety, anxiety was a statistically significant predictor and this association remained significant after sociodemographic factors were controlled. When broad range of other controlled variables was included in the model a connection between anxiety and inflammation could not be found. It seems that the association between anxiety and inflammation is mainly due to other factors. Especially the amount of chronic conditions attenuated the association. Inner self-control did not have a statistically significant effect to the connection between anxiety and inflammation. The best predictor for inflammation in this study was body mass index and also other health behavior related factors had a significant role. In regard to the wellbeing of an individual and individual's ability to work, weight control and healthy lifestyle choices are crucial.
  • Hella, Emilia (Helsingfors universitet, 2015)
    This review focuses on neurotrophic factors, especially CDNF, and Amyotropic lateral sclerosis (ALS). This review finds out which neurotrophic factors have been studied in clinical trials of ALS and what kind of results have been got. Neurotrophic factors are important for development and function of neurons because they prevent apoptosis of neurons. They also play role in differentiation, development and migration of neurons. It is also known that many of the neurotrophic factors have protective and restorative properties. ALS is a rare neurodegenerative disease which causes the destruction of motor neurons and leads to death in three years. The disease degenerate the upper and lower motor neurons. Symptoms are muscle weakness, muscle atrophy, cramps and problems with swallowing. At the moment there is no cure for ALS so it is important to study neurotrophic factors that could prevent the progression of the disease and perhaps to protect or repair destroyed motor neurons. This is why it is important to study potential of CDNF in ALS. The experimental part consists of three different parts. The purpose of the first part study was to determine the distribution of CDNF after intraventricular delivery at different time points. CDNF was labeled with 125I (125I-CDNF). The distribution was determined by gammacounter and autoradiography. To determine the stability of the injected 125-I CDNF we performed SDS-PAGE. The second part studied the diffusion volume of CDNF after intraventricular injection with seven wild type mice. After stereotaxic surgery CDNF-immunohistochemistry staining from coronal sections was done. The last experimental part studied the effect of single intracerebral injection of CDNF on motivation, locomotor activity, anxiety and depression with male and female mice. Light-dark box, open field, rotarod, forced swim test (FST), elevated plus maze and fear conditioning were carried out with male mice. After behavioural tests mice were sacrified for HPLC-analysis. Light-dark box and IntelliCage were carried out with female mice before c-fos staining. Gammacounter and autoradiography shows that 125I-CDNF distributes widely after intracerebroventricular injection. It spread throughout to the brain and also all the way to the spinal cord after one and three hours from injection. After 24 hours 125I-CDNF was cleared so the CDNF signal was very weak. SDS-PAGE showed the stability of radioactive CDNF. CDNF increased locomotor activity and decreased anxiety in male mice. But a statistically significant difference appeared in forced swim test and fear conditioning test. HPLC-analysis supported these results partly. CDNF also increased motivation of female mice in IntelliCage experiment. C-fos staining was observed in CDNF group and PBS group so quantitative analysis should be done from these sections so that reliable conclusions could be done. However, because CDNF distributed to spinal cord and it showed some effect on locomotor activity, motivation and depression it might be potential for ALS disease.
  • Chen, Zuyue; Wei, Hong; Pertovaara, Antti; Wang, Jianhong; Carlson, Synnöve (2018)
    Paracetamol has recently been suggested to affect emotion processing in addition to alleviating pain in humans. We investigated in adult male Hannover–Wistar rats whether acute intraperitoneally administrated paracetamol affects behavior in tests measuring anxiety, mood, motor activity, and memory. Unoperated rats received saline or a low (50 mg/kg) or high (300 mg/kg) dose of paracetamol, while rats with a spared nerve injury (SNI) model of neuropathy and sham-operated rats received saline or the low dose of paracetamol. Rats were tested on open-field (OFT), elevated plus-maze (EPM), light-dark box (LDB), novel-object recognition (NOR), sucrose preference, rotarod, and monofilament tests. In unoperated rats, both the low and high dose of paracetamol reduced line crossings, and grooming time in the OFT, and novel preference in NOR. The high dose of paracetamol increased the time spent in the closed arm in EPM, reduced the number of rearings and leanings in OFT, the time spent in the light box in LDB, and sucrose preference. Paracetamol had no significant effect on the rotarod test measuring motor activity. The low dose of paracetamol suppressed mechanical pain hypersensitivity in SNI rats, without influencing pain behavior in sham-operated rats. Saline- but not paracetamol-treated SNI rats spent more time than sham-operated rats in the closed arm in the EPM test. Together the results suggest that a high dose of paracetamol increases anxiety-like and anhedonic behavior, and impairs recognition memory in unoperated controls, while in neuropathy, a low dose of paracetamol reduces nerve injury-associated anxiety probably by reducing neuropathic pain.
  • Modabbernia, Mohamad-Jafar; MansourGhanaei, Fariborz; Imani, Ali; MirsafaMoghaddam, SeyedAlireza; SedighRahimabadi, Massih; YousefiMashhour, Mahmoud; Joukar, Farahnaz; AtrkarRoushan, Zahra; Bidel, Siamak (2012)
    BACKGROUND: Psychiatric disorders are common in irritable bowel syndrome (IBS) patients. The prevalence of psychiatric disorders in IBS patients varies in different cultures. We conducted this study to determine the prevalence of psychiatric disorders METHODS: In a cross-sectional study, 256 IBS patients were selected (using the criteria of Rome III) and evaluated for psychiatric disorders. In the first phase, subjects were screened using the General Health Questionnaire 28 (GHQ28). In the second phase, those who had scores ≥ 23 were assessed through semi-structured psychiatric interviews. RESULTS: Thirty out of 256 subjects had no significant psychiatric symptoms after performing GHQ28. In further psychiatric evaluation of the remaining subjects (226) who suffered from some degree of a psychiatric problem, 36 were diagnosed without Anxiety/Depressive disorder. Thus 66 subjects (25.8%) were known as a group without any significant psychiatric problem. A total of 190 subjects (74.2%) with anxiety-depressive problems were diagnosed; 89 were suffering from pure anxiety disorders, 41 were suffering from depressive disorders and 60 had co-morbid anxiety-depressive disorders. When comparing anxiety-depressive patients (n = 190) with normal subjects (n = 66), gender (P = 0.016), occupation (P = 0.002) and intensity of IBS (P < 0.001) showed statistically significant differences. CONCLUSION: The high prevalence of anxiety-depressive disorders in this study indicates the necessity of psychiatric assessment, early diagnosis and treatment of the patients with IBS. It may improve management of the patients suffering from IBS.
  • Peters, Dana (Helsingin yliopisto, 2021)
    Concern about global warming can lead to climate change anxiety, a form of anxiety characterized by excessive worry about the climate crisis and associated consequences on the natural world and human society. It has been suggested by previous research that humor can be used to manage feelings of anxiety. This study seeks to determine if this phenomenon can be applied specifically to climate change anxiety. The research combines a comprehensive literature review with an online survey that leveraged climate change themed internet memes as a proxy for humor to gather opinions about the intersections between these two topics. The survey data supplemented claims made by existing literature, indicating that climate change themed internet memes and humor in general can be useful coping mechanisms to mitigate feelings of climate anxiety. The survey was completed by 93 respondents; most of these participants were women, located in the US, and/or between the ages of 20 and 29. Results from the survey showed that people tend to feel best about their environmental anxiety when they are taking active steps to solve the problem. Conscious decisions such as reducing waste or participating in activist movements are easier to recognize and self-report than more passive coping skills. Reliance on humor was reported as a supplementary coping skill, but many respondents indicated that looking at humorous climate change themed memes did influence their feelings about climate change overall. The scope of this study was relatively small in scale, therefore the results presented in this thesis may not be indicative of broader social trends and likely require further research.
  • Virtanen, Suvi; Kuja-Halkola, Ralf; Mataix-Cols, David; Jayaram-Lindström, Nitya; D'Onofrio, Brian M.; Larsson, Henrik; Ruck, Christian; Suvisaari, Jaana; Lichtenstein, Paul; Latvala, Antti (2020)
    Background Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.
  • Konttinen, Hanna (2006)
    Sosiologist Aaron Antonovsky was among the first who was interested in factors that maintain and enhance health instead of risk factors for different diseases. He developed the sense of coherence (SOC) construct, which is the core concept of his salutogenic theory, to explain how some individuals stay healthy despite the numerous stressful situations they encounter during their life. Sense of coherence is a global orientation towards life that characterizes the extent to which an individual appraises his or her internal and external environments as comprehensible, manageable and meaningful. In previous studies, there has been a strong inverse association between the SOC scale and the measures of depressive symptoms and anxiety. This is in accordance with Antonovsky's theory but the size of the correlations raises the question whether the SOC scale measures similar construct to depression and anxiety measures. The aim of this thesis was to investigate what is the relationship of the SOC scale (short form) with the measures of depressive symptoms (Beck Depression Inventory) and anxiety (Spielberger's State Anxiety Scale), and if they are similarly related to health and health behaviours. The participants of the present study were 25 – 74 years old Finnish men (n=2351) and women (n=2291) from the national cardiovascular risk factor survey (FINRISK) conducted in 1997. The SOC scale had strong and inverse correlations with the measures of depression (r=-0.62 among men and women) and anxiety (r=-0.57 among men and r=-0.54 among women). In addition, sense of coherence was similarly associated with health and health behaviours as depressive symptoms (cognitive and affective) and anxiety. These results suggest that the SOC scale overlaps with depression and anxiety measures. Nevertheless, there were also small differences between these measures: education was related only to sense of coherence, and in factor analysis, items of the each scale defined their own factors. The SOC scale was more normally distributed than the measure of depressive symptoms as depression measure did not create variation among those respondents who did not have depressive symptoms. However, the low end of the SOC distribution was more important in the prediction of different health variables than the high end of the SOC distribution. This finding questions the status of sense of coherence (as measured by the SOC scale) as a protective factor for health that is qualitatively different from risk factors. It is concluded that the items of the 13-item SOC scale should be reconstructed to reflect better the SOC construct and be less confounded with negative emotional states. Most important references: Antonovsky, A. (1987). Unraveling the mystery of health: How people manage stress and stay well. San Francisco: Jossey-Bass. Relevant articles from scientific peer reviewed journals.
  • de Miguel, Elena; Vekovischeva, Olga; Elsilä, Lauri V.; Panhelainen, Anne; Kankuri, Esko; Aitta-aho, Teemu; Korpi, Esa R. (2019)
    tTHIP (gaboxadol), a superagonist of the delta subunit-containing extrasynaptic GABA(A) receptors, produces persistent neuroplasticity in dopamine (DA) neurons of the ventral tegmental area (VTA), similarly to rewarding drugs of abuse. However, unlike them THIP lacks abuse potential and induces conditioned place aversion in mice. The mechanism underlying the aversive effects of THIP remains elusive. Here, we show that mild aversive effects of THIP were detected 2 h after administration likely reflecting an anxiety-like state with increased corticosterone release and with central recruitment of corticotropin-releasing factor corticotropin-releasing factor receptor 1 (CRF1) receptors. A detailed immunohistochemical c-Fos expression mapping for THIP-activated brain areas revealed a correlation between the activation of CRF-expressing neurons in the oval nucleus of the bed nuclei of stria terminalis and THIP-induced aversive effects. In addition, the neuroplasticity of mesolimbic DA system (24 h after administration) and conditioned place aversion by THIP after four daily acute sessions were dependent on extrasynaptic GABAA receptors (abolished in delta-GABA(A) receptor knockout mice) and activation of the CRF1 receptors (abolished in wildtype mice by a CRF1 receptor antagonist). A selective THIP-induced activation of CRF-expressing neurons in the oval part of the bed nucleus of stria terminalis may constitute a novel mechanism for inducing plasticity in a population of VTA DA neurons and aversive behavioral states.
  • Sorsa, Minna Anneli; Kylmä, Jari; Bondas, Terese Elisabet (2021)
    Perinatal psychological distress (PPD) may cause delays in help-seeking in the perinatal period, which is crucial for families with small children. Help-seeking theories focus on rational processes of behavior wherein 'help-seeking' is viewed as a decision-making process, in which action is preceded by recognizing a problem. We identified the phase prior to actual help-seeking actions as a life situation and a phenomenon through which to gain a deeper understanding from women's own perspectives. The aim of this study was to integrate and synthesize knowledge of women's experiences of contemplating seeking help for PPD. We chose interpretative meta-ethnography by Noblit and Hare (1988) and implemented eMERGe guidelines in reporting. The search was performed systematically, and the 14 included studies were evaluated with Critical Appraisal Skills Programme checklist (CASP). We identified seven themes and a metaphor in a lines-of-argument synthesis, showing that contemplating help-seeking is a multidimensional phenomenon. We did not observe a straightforward and linear process (as previous research suggests) but instead a complex process of contemplating help-seeking. A clinical implication is that service providers should work with outreach and develop their tools to connect with mothers with PPD. Another suggestion is to improve training in mental health literacy prior to or during pregnancy.
  • 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.
  • Kluger, Nicolas; Pankakoski, Anna; Panelius, Jaana (2020)
    Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. It is also associated with high mortality and poor prognosis due to advanced age of the patients and coexisting comorbidities. There is a dearth of data in the literature regarding depression and anxiety among those patients. The objective of this brief review is to discuss the intertwining relationship between depression and anxiety with bullous pemphigoid.
  • Pihkala, Panu (2020)
    Anxiety and distress about the ecological crisis seems to be a rapidly growing phenomenon. This article analyzes the challenges and possibilities posed by such "eco-anxiety" for environmental education. Variations of eco-anxiety are analyzed, and it is argued that educators should be aware of the multiple forms that the phenomenon has. Eco-anxiety is found to be closely connected with many difficult emotions, such as grief, guilt, anger, and despair. However, anxiety also has an adaptive dimension, which can be called "practical anxiety". Anxiety is connected with expectation, motivation, and hopes. Previous research about eco-anxiety and ecological emotions in various disciplines is discussed, and related studies from various fields of education are brought together. Based on this extensive literature review, theoretical analyses are made, using a philosophical method. It is argued that environmental educators need organizational and peer support both in relation to their own difficult emotions and in order to develop emotional skills in their work. Educators should first practice self-reflection about eco-anxiety, after which they have many possibilities to help their audiences to develop emotional resilience. Potential practical activities related to eco-anxiety are discussed, drawing from various fields of education. These include validation of eco-anxiety and ecological emotions, providing safe spaces to discuss them, and, if possible, providing embodied and creative activities to more fully deliberate on them.
  • Närvänen, Eija (Helsingin yliopisto, 2020)
    Objective. The FRIENDS programme is a group cognitive behavioural therapy (CBT) programme, developed for the prevention and treatment of child and adolescent anxiety and depression. In the context of prevention, FRIENDS has been extensively researched; however, little research has been conducted on FRIENDS in a treatment setting and with different populations. To help fill this gap, the aim of the present study was to evaluate the effectiveness of the Finnish version of FRIENDS in reducing internalising symptoms in children diagnosed with psychiatric and neuropsychiatric disorders. Methods. The present study was conducted at Helsinki University Hospital (HUS) Child Psychiatry outpatient clinics in the Helsinki metropolitan area, Finland. The participating children (n = 99, mean age = 9.45 years, range 6–13 years, 68.7 % boys) were randomly assigned to either FRIENDS (n = 52) or a waitlist control group (n = 47), which received treatment as usual for a period of 3 months before the intervention. The children’s internalising symptoms were assessed using parent- and teacher-report questionnaires (Child Behavior Checklist and Teacher’s Report Form) at referral to treatment, pre-treatment, post-treatment, and six-month follow-up. Results and conclusions. In both groups, there was a medium-sized statistically significant decrease in parent-reported internalising symptoms immediately after the intervention; however, these improvements were not retained at six-month follow-up. Teacher-reported internalising symptoms followed a similar pattern of decrease during the intervention and increase during follow-up; however, these changes were smaller in magnitude and did not reach statistical significance, possibly due to loss of statistical power caused by missing data. Neither parent- or teacher-reports showed an intervention effect, with children’s internalising symptoms exhibiting similar changes regardless of whether they belonged to the intervention group or the waitlist control group, which received treatment as usual during the wait period. These results raise questions on the durability of treatment effects and the superiority of FRIENDS over active waitlist control conditions or treatment as usual when treating children diagnosed with diverse psychiatric and neuropsychiatric disorders in a community setting where treatment adherence and integrity may not be ideal.
  • Merikanto, Ilona; Partonen, Timo (2021)
    Background Epidemiological data show that having the eveningness associates with poor mental health. For preventive measures it is important to know which underlying factors mediate these associations and the burden posed to public health. This study examines at a population-based level, whether (1) circadian type and the sleep-wake behavior-based phase entrainment similarly associate with mental health problems, (2) there are differences in hospital treatments due to mental disorders between chronotypes, and (3) the association of chronotype with mental health is mediated by insufficient sleep. Methods The study sample (N = 18,039) consisted of population-based sample of Finnish adults, aged 25-74 years, with information on their circadian type and sleep patterns, mental health symptoms, and diagnosis as reported in a health examination survey, as well as hospital treatments as recorded on the national Hospital Discharge Register. Results All the mental health symptoms, diagnoses and hospital treatments were more pronounced among Evening-types, especially when assessed by circadian type. Insufficient sleep mediated most but not all of the associations between eveningness and mental health. Conclusions Eveningness does not increase mental health risks only on symptom or diagnosis level, but also on hospital admission level. A higher prevalence of insufficient sleep among the Evening-types elevates the risk and severity for many of the mental health outcomes. Improving the sleep among Evening-types could help to improve their mental health prospective and ease the health care burden.
  • Helminen, Vilja (Helsingin yliopisto, 2018)
    Objective. The aim of this study was to clarify the relationship between fear and anxiety, and political attitudes. It has been suggested that individual differences in political ideology stem from differences in threat sensitivity and that conservative political ideology acts as a defence mechanism against psychological threats. There is tentative evidence from previous studies that from different threat reactions fear specifically but not anxiety influences political attitudes. It is also unclear whether threat is connected to political ideology more broadly or just attitudes concerning some political matters. In this study I assess whether anxiety disorder symptoms that reflect differences is fearfulness and anxiety predict different political attitudes. Methods. The sample of this study consisted of 5,819 people born in Great Britain in 1958. Symptoms of generalized anxiety disorder, phobia, and panic were assessed at the age of 44, and opinions about political issues six years later. Exploratory factor analysis was used to assess how political opinions were structured into different attitude dimensions, and seven broader political attitudes were formed based on this. Finally, a path model was used to assess whether anxiety disorder symptoms predicted political attitudes. Results and discussion. The anxiety disorder symptoms predicted attitudes towards economic inequality and preservation of the environment. More specifically, those with more generalized anxiety disorder symptoms were more concerned about environmental issues and those with more phobic symptoms were more concerned about economic inequality. This difference between generalized anxiety disorder and phobias might be explained by the fact that the former is connected with anxiousness whereas the latter reflects fearfulness. The results support the notion that fear and anxiety are differently connected to political attitudes. They also call into question threat reactions’ connection with political ideology more broadly.
  • Laine, Mikaela A.; Trontti, Kalevi; Misiewicz, Zuzanna; Sokolowska, Ewa; Kulesskaya, Natalia; Heikkinen, Aino; Saarnio, Suvi; Balcells, Ingrid; Ameslon, Pierre; Greco, Dario; Mattila, Pirkko; Ellonen, Pekka; Paulin, Lars; Auvinen, Petri; Jokitalo, Eija; Hovatta, Iiris (2018)
    Anxiety disorders often manifest in genetically susceptible individuals after psychosocial stress, but the mechanisms underlying these gene-environment interactions are largely unknown. We used the chronic social defeat stress (CSDS) mouse model to study resilience and susceptibility to chronic psychosocial stress. We identified a strong genetic background effect in CSDS-induced social avoidance (SA) using four inbred mouse strains: 69% of C57BL/6NCrl (B6), 23% of BALB/cAnNCrl, 19% of 129S2/SvPasCrl, and 5% of DBA/2NCrl (D2) mice were stress resilient. Furthermore, different inbred mouse strains responded differently to stress, suggesting they use distinct coping strategies. To identify biological pathways affected by CSDS, we used RNA-sequencing (RNAseq) of three brain regions of two strains, B6 and D2: medial prefrontal cortex (mPFC), ventral hippocampus (vHPC), and bed nucleus of the stria terminalis (BNST). We discovered overrepresentation of oligodendrocyte (OLG)-related genes in the differentially expressed gene population. Because OLGs myelinate axons, we measured myelin thickness and found significant region and strain-specific differences. For example, in resilient D2 mice, mPFC axons had thinner myelin than controls, whereas susceptible B6 mice had thinner myelin than controls in the vHPC. Neither myelin-related gene expression in several other regions nor corpus callosum thickness differed between stressed and control animals. Our unbiased gene expression experiment suggests that myelin plasticity is a substantial response to chronic psychosocial stress, varies across brain regions, and is genetically controlled. Identification of genetic regulators of the myelin response will provide mechanistic insight into the molecular basis of stress-related diseases, such as anxiety disorders, a critical step in developing targeted therapy.
  • Tikker, Laura; Casarotto, Plinio; Singh, Parul; Biojone, Caroline; Piepponen, T. Petteri; Estartus, Nuri; Seelbach, Anna; Sridharan, Ravindran; Laukkanen, Liina; Castren, Eero; Partanen, Juha (2020)
    Serotonergic neurons in the dorsal raphe (DR) nucleus are associated with several psychiatric disorders including depression and anxiety disorders, which often have a neurodevelopmental component. During embryonic development, GATA transcription factors GATA2 and GATA3 operate as serotonergic neuron fate selectors and regulate the differentiation of serotonergic neuron subtypes of DR. Here, we analyzed the requirement of GATA cofactor ZFPM1 in the development of serotonergic neurons using Zfpm1 conditional mouse mutants. Our results demonstrated that, unlike the GATA factors, ZFPM1 is not essential for the early differentiation of serotonergic precursors in the embryonic rhombomere 1. In contrast, in perinatal and adult male and female Zfpm1 mutants, a lateral subpopulation of DR neurons (ventrolateral part of the DR) was lost, whereas the number of serotonergic neurons in a medial subpopulation (dorsal region of the medial DR) had increased. Additionally, adult male and female Zfpm1 mutants had reduced serotonin concentration in rostral brain areas and displayed increased anxiety-like behavior. Interestingly, female Zfpm1 mutant mice showed elevated contextual fear memory that was abolished with chronic fluoxetine treatment. Altogether, these results demonstrate the importance of ZFPM1 for the development of DR serotonergic neuron subtypes involved in mood regulation. It also suggests that the neuronal fate selector function of GATAs is modulated by their cofactors to refine the differentiation of neuronal subtypes.
  • Economides, Marcos; Ranta, Kristian; Nazander, Albert; Hilgert, Outi; Goldin, Philippe R.; Raevuori, Anu; Forman-Hoffman, Valerie (2019)
    Background: Depression is one of the most common mental health disorders and severely impacts one's physical, psychological, and social functioning. To address access barriers to care, we developed Ascend-a smartphone-delivered, therapist-supported, 8-week intervention based on several evidence-based psychological treatments for depression and anxiety. A previous feasibility study with 102 adults with elevated depression reported that Ascend is associated with a postintervention reduction in depression symptoms. Objective: We aimed to examine whether Ascend is associated with a reduction in symptoms of anxiety, and importantly, whether reductions in symptoms of depression and anxiety are maintained up to 12-months postintervention. Methods: We assessed whether the previously reported, end-of-treatment improvements seen in the 102 adults with elevated symptoms of depression extended up to 12 months posttreatment for depression symptoms (measured by the Patient Health Questionnaire-9 [PHQ-9]) and up to 6 months posttreatment for anxiety symptoms (added to the intervention later and measured using the Generalized Anxiety Disorder-7 [GAD-7] scale). We used linear mixed effects models with Tukey contrasts to compare time points and reported intention-to-treat statistics with a sensitivity analysis. Results: The intervention was associated with reductions in symptoms of depression that were maintained 12 months after the program (6.67-point reduction in PHQ-9 score, 95% CI 5.59-7.75; P= 10) reported clinically significant improvement at the 12-month follow-up (at least 50% reduction in PHQ-9 score and postprogram score Conclusions: There is limited evidence on whether outcomes associated with smartphone-based interventions for common mental health problems are maintained posttreatment. Participants who enrolled in Ascend experienced clinically significant reductions in symptoms of depression and anxiety that were maintained for up to 1 year and 6 months after the intervention, respectively. Future randomized trials are warranted to test Ascend as a scalable solution to the treatment of depression and anxiety.
  • Pensola, Tiina (Helsingfors universitet, 2016)
    Objectives. There is a lack of knowledge concerning the contribution of the character traits to the association of work stress and over-commitment with common mental health problems. Primary school teachers are a large, homogenous occupational group that has been related to higher work stress levels and common mental health problems, although to a lesser amount of actual mental disorders. The aim of the study is to examine the extent to which the association between work stress, over-commitment and their interaction with common mental health problems can be attributed to the character traits among primary school teachers. Methods. The data consists of 76 (87% females) primary school teachers from 34 schools randomly selected to a study taking part in the capital area of Finland in 2013-14. There were 1-6 teachers who responded from each school (participation rate 4-33%). Common mental health problems were measured by GHQ-12 (psychological distress) and cognitive anxiety from a state anxiety scale of EMAS (highest tertile vs. two lowest). Work stress and over-commitment (the upper tertile vs. the rest) were measured according to original Siegrist's Effort-Reward-Imbalance Questionnaire. Character traits Self-directness, Cooperativeness, and Self-Transcendence were measured by Cloninger's TCI-questionnaire and each character was dichotomized at median to indicate a higher and lower category of the trait. The control variables were age, working hours and job contract type. The data were analyzed by means of Poisson regression (prevalence ratios, PR, and 90% confidence intervals) and relative rates. Results. Of teachers 30% had common mental health problems. The teachers with high over-commitment in comparison with those with low over-commitment had more often psychological distress (PR=2.5, p=0.018) and cognitive anxiety (PR=2.8, p=0.004). Although work stress was not independently associated with common mental health problems, it was related to the increased psychological distress among those with high over-commitment. Controlling for self-directedness attenuated the association of over-commitment with psychological distress and cognitive anxiety by 29% and 47%, respectively. After all adjustments, an independent association of Self-Directness with cognitive anxiety remained (PR=0.3, p=0.024). The other two character traits didn't have an independent impact on common mental health problems among the primary school teachers, but with the concurrent low self-directedness, low cooperativeness and low Self-Transcendence were related to over-commitment and increased level of cognitive anxiety. Both low cooperativeness and low self-transcendence were related to psychological symptoms. Conclusions: The primary school teachers had higher prevalence of common mental health problems, if they had low self-directedness and were over-committed to their work. Enhancing self-directedness may help in decreasing common mental health problems among overcommitted teachers. In the future the associations of the trait profiles with over-commitment and mental health symptoms should be studied with the larger longitudinal data.