Browsing by Subject "anxiety"

Depressive disorders and especially Major Depressive Disorder (MDD) have recently raised a lot of concerns. According to Bains & Abdijadid, (2022), in 2030 MDD will be the most common concern in terms of mental well-being and Kessler & Bromet (2013) pointed out that MDD “has one of the highest lifetime prevalence among psychiatric disorders”, and for this reason MDD results in a significant burden from an individual and societal perspective (Lépine & Briley, 2011). Anhedonia which is a core symptom of MDD (Gorwood 2008, Liang et al. 2022) can be defined as the “inability to enjoy experiences or activities that normally would be pleasurable” (APA Dictionary of Psychology, n.d.-c). Its effects on cognitive processes such as reward responsiveness has been the interest of various studies. Pizzagalli et al. (2008) demonstrated in their study that individuals suffering from MDD and experiencing anhedonic symptoms have a blunted reward responsiveness compared to some healthy subjects. This master thesis aimed to replicate Pizzagalli et al. (2008) study to reinvestigate anhedonia´s impact on reward responsiveness as well as anxiety´s role since individuals suffering from MDD also face anxiety or anxiety disorder (Xin et al. 2015).Two groups were formed, a clinical group (N=29) based on the DSM-IV criteria and a control group (N=20), and both groups were given the Face Game or the Probabilistic Reward Task (Pizzagalli et al. 2008) to measure reward responsiveness. Reward responsiveness was computed as “response bias” and the perceived difficulty of the task as “discriminability”. The results showed no significant difference in response bias scores between the depressed and healthy participants, and no significant correlations were found between depression scores, anhedonia scores, anxiety scores, and response bias scores. An effect of the experimental task’s blocks on response bias and discriminability scores was found, but no interaction effect (group * block) was found for the response bias and discriminability scores. Thus, we cannot argue in favor of the results obtained by Pizzagalli et al, (2008) that individuals suffering from MDD and especially experiencing anhedonic symptoms are more likely to have a blunted reward sensitivity compared to some healthy subjects. The statistically non-significant results were attributed to the small sample size, the complexity of the task and its design. Therefore, further investigations should focus on getting larger clinical and control groups and they also should redefine some aspects of the experimental task to make it more sensitive to any changes to reward responsiveness among individuals suffering from MDD and experiencing anhedonic symptoms.

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.

Chronic stress has been linked to the pathogenesis of various disorders, such as generalized anxiety disorder, depression, and post-traumatic stress disorder (PTSD). Stress-induced hyperexcitability of the basolateral amygdala (BLA) has implications in anxiety-like behavior. Promising evidence points to the direction of GluK1 subunit containing kainate receptors (KARs) having a role in the modulation of GABAergic transmission in the lateral amygdala (LA). The aim of the present study was to investigate whether dysfunction of KARs contribute to stress-induced amygdala hyperexcitability and anxiogenesis in mice. Chronic restraint stress (CRS) is an animal model simulating chronic psychological stress. An in situ hybridization experiment was performed to investigate how CRS affects expression levels of GluK1 in the different neuronal populations in the LA. These data show that CRS leads to downregulation of GluK1 expression in the parvalbumin-positive (PV+) interneurons specifically. Patch clamp recordings of spontaneous inhibitory postsynaptic currents showed that CRS did not affect synaptic GABAergic transmission to the principal neurons in the LA. Lastly, conditional knock-out (cKO) mice that have the Grik1 gene knocked out selectively in the PV-expressing interneurons showed no change in anxiety-like behavior after CRS while their wild-type counterparts demonstrated an increase in anxiety-like behavior observable in the elevated plus maze test. Thus, ablation of GluK1 in PV+ interneurons affects the stress-induced anxiogenesis. Due to low number of animals, it cannot be confirmed yet whether the deletion leads to stress resilience or a phenotype where even regular handling is an aversive experience comparable to physical restraint. GluK1 KAR modulation of PV+ interneuron excitability and its susceptibility to stress-related alterations is only a recently discovered phenomenon, and even though this study provides some insight into the underlying mechanism, further research is needed. Systematic characterization of the mechanism could provide a novel tool for understanding and treating stress-related pathological anxiety, possibly helping patients suffering from anxiety disorders resistant to current treatments available.

As the most common mental disorder, anxiety disorders present a major burden to healthcare worldwide and a challenging problem to overcome for the ones suffering from it. Recently, researchers have started to recognize that the relationship between sleep and anxiety disorders is bidirectional; disturbed sleep is a potential risk factor for the progression of anxiety and anxiety can lead to sleep disturbances. However, the neural mechanisms underlying anxiety and sleep problems are still poorly recognized. In this study, we used a chronic sleep fragmentation (SF) paradigm to investigate how disturbed sleep alters anxiety-like behavior in mice and what are the potential underlying neuronal mechanisms. This model was chosen because we wanted to focus on a common form of disturbed sleep in humans rather than total sleep deprivation. We measured anxiety-like behavior in the light-dark box and open field tests right after the 2-week SF period and again after a week of recovery. Additionally, we performed immunohistochemical analysis to study prolonged cell activity (transcription factor ∆FosB), parvalbumin (PV) interneurons and perineuronal net (PNN) structures in the medial prefrontal cortex (mPFC) of the mice. Changes in mPFC activity and related brain areas are associated to anxiety in humans and anxiety-like behavior in rodents alike. Similarly, changes in PV interneurons and PNNs, that regulates PV cell function, are associated to anxiety-like behavior. However, PV interneurons and PNNs have not been previously studied in a setting that combines sleep fragmentation and anxiety-like behavior. We found that chronic SF increases anxiety-like behavior in female mice and that this effect persists at least for a week. Conversely, we did not observe significant increase in anxiety-like behavior in male mice. Both female and male mice showed decrease in ∆FosB in the mPFC suggesting that SF treated mice had lower overall levels of cell activity. Similarly, we found that SF treated mice had decreased PV interneuron intensity in both sexes which could indicate changes in the cell activity. However, the pattern of changes in the IHC results was not identical in males and females. Based on the IHC results, we suggest that SF affects neuronal processes in both sexes but the disparity in them could explain the difference in the behavioral effect. This thesis shows that disturbed sleep can lead to increased anxiety-like behavior in rodent models and recognizes potential targets to study the mechanisms behind the phenomena.

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.

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.

Depression and anxiety are the two most common mental disorders worldwide, and especially common among women of reproductive age. Hence, they are also common problems among pregnant women. Maternal depression and anxiety not only compromise the mother’s quality of life during pregnancy but increase the risk of perinatal complications and poor child neurodevelopment. The biological mechanisms that underpin this transmission remain largely unknown. The placenta, a transient fetal organ functioning as an interface between the mother and the fetus, plays a pivotal role, as the placenta transmits all environmental cues to the fetus. This thesis aims to investigate differential gene expression in the first-trimester chorionic villi and birth placenta samples from women with depression and/or anxiety and healthy controls. Samples are collected and processed as a part of the InTraUterine sampling in early pregnancy (ITU) study and both chorionic villus samples (CVS) collected during the early pregnancy and delivery placenta samples were studied. I defined three different phenotypes based on (i) maternal depression and anxiety disorder diagnosis, (ii) antidepressant and anxiolytic medication purchases, or (iii) self-reported depressive and anxiety symptoms during pregnancy. Genome-wide analysis of differential gene expression was conducted with DESeq2 R-package and further gene set enrichment analysis was performed with a web-based platform FUMA. When comparing mothers with depressive and anxiety symptoms to asymptotic controls, but not those with or without diagnoses or medication purchases, I found 478 genes differentially expressed. In the enrichment analysis these genes related to immune response and inflammation, such as leukocyte and T cell activation, defense response, and cytokine production. Together these results indicate that maternal depressive and anxiety symptoms during pregnancy change the immune system functions in the placenta which may partly explain the adverse effects of maternal depression and anxiety on the developing fetus. These findings may afford a target for timely targeted interventions to prevent perinatal complications and the transmission of maternal depression and anxiety to the next generation.

The aim of the study. Subjective time perception is prone to distortions, and one of the factors affecting it is a person's emotional state. Anticipation of unpleasant and threatening situations is of particular importance for coping. Previous research on the relationship between anticipation of unpleasant situations and perceived duration has shown conflicting results. Moreover, the experimental designs have been inadequate. The present study examines the effect of anticipating an unpleasant image and individual anxiety tendency on duration perception. The results are discussed in relation to the attentional gate model, which suggests that the influence of emotionality on perceived duration may be mediated through arousal or attentional allocation. Methods. Subjects (n=39) completed a temporal discrimination task in which the duration of a neutral visual cue stimulus was compared to previously learned short and long comparison durations. The colour of the stimulus indicated whether or not it was followed by an unpleasant image. The experiment consisted of three experimental conditions: (1) an unpleasant image was not anticipated nor presented, (2) an unpleasant image was anticipated but not presented, and (3) an unpleasant image was anticipated and presented. Psychometric functions were generated from the responses to obtain the points of subjective equality. The point refers to a duration that the person cannot distinguish as short or long. The effect of anticipating an unpleasant image and individual self-reported anxiety tendency on the points of subjective equality was analysed using multilevel linear modelling. Results. Anticipation of an unpleasant image led to longer perceived duration. Those reporting more anxiety perceived the duration of the cue stimulus to be longer than those reporting less anxiety. However, anxiety tendency did not moderate the effect of unpleasant image anticipation on perceived duration. Conclusions. Interpreted according to the attentional gate model, the perception of time passing slower is explained by arousal induced by the anticipation of an unpleasant situation, which speeds up the internal clock. In addition, anxious individuals are more aroused during anticipation, which is why they perceive time to pass more slowly than others. The role of attention in the relationship between anticipation of an unpleasant situation and duration perception seems to be more pronounced in situations where the threat is more biologically significant.

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.

Anxiety disorders are the most frequently reported mental health disorder in Europe and treatment outcomes for approximately 30% of patients remains poor. Development of new therapies has been hindered by the fact that neural mechanisms of anxiety disorders are poorly understood. Anxiety is known to be heritable but genetic studies have failed to identify significant gene variants, and it appears that it may not be fully explained by common genetic variation. Recent work has suggested that this 'missing heritability' may in part be explained by epigenetic mechanisms, which include the regulation of transposable elements (TEs). Transposable elements are mobile genetic elements that possess the capability to move their location within a genome. TEs have been found to be specifically repressed in the rodent brain following stress, and also have been found to be overexpressed in human brain tissues and animal models of several neuropsychiatric disorders including schizophrenia and post-traumatic stress disorder. Given the evidence of transposable element overexpression in human patients and animal models of psychiatric disorders, we hypothesized that rodents who underwent psychosocial stress would have differential expression of TEs corresponding to their resilience or susceptibility to anxiety-like behaviors. In this study we examined the expression of transposable elements in C57BL/6Crl and DBA/2Crl inbred mouse strains following chronic social defeat stress. We also examined the baseline levels of six inbred strains (DBA/2J, A/J, 129S/SvImJ, C3H/HeJ, C57BL/6J, and FVB/NJ) that were previously characterized for innate anxiety levels. Overall expression of transposable elements was examined with RNA sequencing, while the expression of Long Interspered Element 1 (LINE-1) family TEs was evaluated with quantitative real-time PCR. We found that following psychosocial defeat, C57BL/6 and DBA/2 animals had strain-specific differences in transposable element expression in the ventral hippocampus but not the medial prefrontal cortex. In the ventral hippocampus, C57BL/6Crl animals resilient to anxiety-like behaviors appeared to have distinctly different transposable element expression profiles compared to control and resilient C57BL/6Crl animals. Conversely, DBA/2Crl animals susceptible to anxiety-like behaviors appeared to have distinctly different transposable element expression profiles from DBA/2Crl controls. We also observed innate strain differences between C57BL/6Crl and DBA/2Crl animals in both the medial prefrontal cortex and the ventral hippocampus and some differences between the six inbred strains in LINE-1 family TE expression. Our findings of differential transposable element expression in the hippocampus following psychosocial stress fits in with the current work on TE activity in the adult brain, which indicates that TE activity in the hippocampus may contribute to adult somatic neural diversity and plasticity. We suggest that a mechanistic effect of variable TE expression may exist that contributes to an individual's susceptibility or resilience to anxiety-like behaviors. Further work identifying de novo TE insertions at the genomic level needs to be done to identify the specific role that differential TE expression may be playing in the neural response to psychosocial stress.