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Depressive disorders are associated with reduced life satisfaction and ability to work. The waiting time for psychotherapy in Germany is currently between three and six months. Accordingly, there is a need for alternative, evidence-based treatment options that are made accessible to patients at a low threshold. A large number of empirical studies prove the effectiveness of exercise in mild and moderate depression. For further conceptualization and quality assurance of exercise as a treatment option, it is necessary to understand the concrete mechanisms of action. In addition to physiological factors, psychological factors also play a role in the effect. As a meta-theory of human experience and behavior, Self-Determination Theory (SDT) provides a useful frame for understanding psychological mechanisms of action with concrete implications for treatment practice. The conceptual extension of SDT to include the frustration of basic psychological needs in addition to need satisfaction is proving useful in the study of mental illness. The first part of this dissertation consists of two publications that validate relevant measurement instruments in this context. The first questionnaire measures the extent of generally experienced satisfaction and frustration of the basic psychological needs for autonomy, competence, and relatedness. The second questionnaire measures the experienced satisfaction of needs by the instructor (here: exercise therapist). The second part of the dissertation includes two publications that examine and classify the satisfaction and frustration of basic psychological needs in depressive symptoms. Differences in the extent of need satisfaction and need frustration between a sample with depression and a sample without depressive symptoms are examined. Further, the relationship between need frustration and depressive symptoms is placed in the context of established pathological processes (emotional dysregulation, rumination). The main findings of this work show that by adding the dimension of need frustration to Basic Psychological Needs Theory, SDT now covers a broader spectrum on the health-disease continuum. In doing so, SDT focuses on the psychological impact of social environments. In addition to the nonfulfillment of basic psychological needs, it is primarily experienced need frustration that is a general vulnerability factor for the occurrence of psychological illness. Moreover, the unbalanced satisfaction of basic psychological needs possibly indicates a conflicting experience between the needs. For the treatment practice it can be deduced that an autonomy-supporting atmosphere, which enables the balanced satisfaction of all three needs, is central for the treatment success.
The prevalence of depression and anxiety is increased in obese patients compared to healthy humans, which is partially due to a shared pathogenesis, including insulin resistance and inflammation. These factors are also linked to intestinal dysbiosis. Additionally, the chronic consumption of diets rich in saturated fats results in body weight gain, hormonal resistances and unfavorable changes in the microbiome composition. The intake of Lactobacilli has already been shown to improve dysbiosis along with metabolism and mood. Yet, the beneficial role and the underlying mechanism of Lactobacillus rhamnosus GG (LGG) to improve emotional behavior in established diet-induced obese conditions are, so far, unknown. To characterize the role of LGG in diet-induced obesity, female and male C57BL/6N mice were fed a semi-synthetic low-fat diet (LFD, 10 % kcal from fat) or a conventional high-fat diet (HFD, 45 % kcal from fat) for initial 6 weeks, which was followed by daily oral gavage of vehicle or 1x10^8 CFU of LGG until the end of the experiment. Mice were subjected to basic metabolic and extensive behavioral phenotyping, with a focus on emotional behavior. Moreover, composition of cecal gut microbiome, metabolomic profile in plasma and cerebrospinal fluid was investigated and followed by molecular analyses. Both HFD-feeding and LGG application resulted in sex-specific differences. While LGG prevented the increase of plasma insulin, adrenal gland weight and hyperactivity in diet-induced obese female mice, there was no regulation of anxiodepressive-like behavior. In contrast, metabolism of male mice did not benefit from LGG application, but strikingly, LGG decreased specifically depressive-like behavior in the Mousetail Suspension Test which was confirmed by the Splash Test characterizing motivation for ’self-care’. The microbiome analysis in male mice revealed that HFD-feeding, but not LGG application, altered cecal microbiome composition, indicating a direct effect of LGG on behavioral regulation. However, in female mice, both HFD-feeding and LGG application resulted in changes of microbiome composition, which presumably affected metabolism. Moreover, as diet-induced obese female mice unexpectedly did not exhibit anxiodepressive-like behavior, follow-up analyses were conducted in male mice. Here, HFD-feeding significantly altered abundance of plasma lipids whereas LGG decreased branched chain amino acids which associated with improved emotional behavior. In nucleus accumbens (NAcc) and VTA/SN, which belong to the dopaminergic system, LGG restored HFD-induced decrease of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, on gene expression level. Lastly, transcriptome analysis in the NAcc identified gene expression of cholecystokinin as a potential mediator of the effect of LGG on HFD-induced emotional alterations. In summary, this thesis revealed the beneficial effects of LGG application on emotional alterations in established diet-induced obesity. Furthermore, both HFD-feeding and LGG treatment exhibited sex-specific effects, resulting in metabolic improvements in female mice while LGG application mitigated depressive-like behavior in obese male mice along with a molecular signature of restored dopamine synthesis and neuropeptide signaling.
The post-antiretroviral therapy era has transformed HIV into a chronic disease and non-HIV comorbidities (i.e., cardiovascular and mental diseases) are more prevalent in PLWH. The source of these non-HIV comorbidities aside from traditional risk factor include HIV infection, inflammation, distorted immune activation, burden of chronic diseases, and unhealthy lifestyle like sedentarism. Exercise is known for its beneficial effects in mental and physical health; reasons why exercise is recommended to prevent and treat difference cardiovascular and mental diseases in the general population. This cumulative thesis aimed to comprehend the relation exercise has to non-HIV comorbidities in German PLWH. Four studies were conducted to 1) understand exercise effects in cardiorespiratory fitness and muscle strength on PLWH through a systematic review and meta-analyses and 2) determine the likelihood of German PLWH developing non-HIV comorbidities, in a cross-sectional study. Meta-analytic examination indicates PLWH cardiorespiratory fitness (VO2max SMD = 0.61 ml·kg·min-1, 95% CI: 0.35-0.88, z = 4.47, p < 0.001, I2 = 50%) and strength (of remark lowerbody strength by 16.8 kg, 95% CI: 13–20.6, p< 0.001) improves after an exercise intervention in comparison to a control group. Cross-sectional data suggest exercise has a positive effect on German PLWH mental health (less anxiety and depressive symptoms) and protects against the development of anxiety (PR: 0.57, 95%IC: 0.36 – 0.91, p = 0.01) and depression (PR: 0.62, 95%IC: 0.41 – 0.94, p = 0.01). Likewise, exercise duration is related to a lower likelihood of reporting heart arrhythmias (PR: 0.20, 95%IC: 0.10 – 0.60, p < 0.01) and exercise frequency to a lower likelihood of reporting diabetes mellitus (PR: 0.40, 95%IC: 0.10 – 1, p < 0.01) in German PLWH. A preliminary recommendation for German PLWH who want to engage in exercise can be to exercise ≥ 1 time per week, at an intensity of 5 METs per session or > 103 MET·min·day-1, with a duration ≥ 150 minutes per week. Nevertheless, further research is needed to comprehend exercise dose response and protective effect for cardiovascular diseases, anxiety, and depression in German PLWH.