Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway... Show moreIntroduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship. Show less
Please note this dissertation was updated in 2024. I refer to the Cover Note (2024) for details about these updates. ------------------------------------------------------------------ Cognitive... Show morePlease note this dissertation was updated in 2024. I refer to the Cover Note (2024) for details about these updates. ------------------------------------------------------------------ Cognitive enhancement reflects the use of any (legitimate) means such as for example food supplements to reach one’s personal best, and has gained great interest over the past years. The increasing costs of the welfare offer one explanation, the second is that both Eastern and Western societies are continuously driven towards more individualism pushing the idea that an individual is the director of his or her own life.In this dissertation, I attempted to explain how and why enhancement techniques such as brain stimulation, videogaming, and food supplements (e.g. tyrosine and tryptophan) are promising and inexpensive ways to enhance cognition. That is, clear ideas about the underlying mechanisms of these effects are needed before these techniques can be applied outside the field of science. Our findings have important societal and economic implications and go hand-in-hand with the ideological individualistic trend in society. More research is needed in order to gain better insights into the underlying mechanisms and the role of individual differences in modulating the observed effects. However, the discussed techniques do have promising potential, not only in possibly delaying cognitive decline in elderly, but also enhancing (social) cognitive functioning and mental well-being in healthy humans. Show less
In this thesis, we report on our investigations regarding the involvement of several neurotransmitter and hormonal systems in generalized social anxiety disorder (gSAD), one of the most common... Show moreIn this thesis, we report on our investigations regarding the involvement of several neurotransmitter and hormonal systems in generalized social anxiety disorder (gSAD), one of the most common psychiatric disorders. We found evidence of the involvement of serotonin, dopamine, and noradrenaline/the autonomic nervous system, but not the hypothalamic-pituitary-adrenal-axis, in the neurobiology of gSAD. As a result of our studies, we hypothesize that serotonin and dopamine function is decreased in gSAD, that there is hyperfunctioning of the autonomic nervous system, and that the other part of the stress system, the hypothalamic-pituitary-adrenal-axis function is not concordant with autonomic nervous system activation, as we saw in basal conditions, and in stress conditions following manipulation of the serotonergic system. We also think that there are indications that the female gonadal hormones also have a modulatory role in gSAD in a subgroup of women. This exploration of the neurobiology of gSAD leads to the conclusion that a variety of brain systems are involved in gSAD in a complex way.involvement of several neurotransmitter and hormonal systems in gSAD. Show less
In Chapter 2, results of a study are reported in which remitted depressed patients are compared to healthy controls to investigate possible residual cognitive impairments that persist into the... Show moreIn Chapter 2, results of a study are reported in which remitted depressed patients are compared to healthy controls to investigate possible residual cognitive impairments that persist into the euthymic phase. Chapter 3 will describe the effects of an alpha-lactalbumin enriched diet on cognitive performance in unmedicated recovered depressed patients and healthy controls. In Chapter 4 the effects of alpha-lactalbumin on mood and stress-induced cortisol response in unmedicated recovered depressed patients and healthy controls are reported. Chapter 5 describes the effects of low-dose and high-dose ATD on mood and neutral as well as emotional information processing in medicated remitted depressed patients. In Chapter 6, the effects of low-dose and high-dose tryptophan depletion on individual plasma tryptophan levels and the ratio tryptophan/LNAA will be discussed. In Chapter 7 the effects of ATD on heart rate variability in medicated remitted depressed patients are reported. A literature overview of studies investigating the effects of serotonin manipulations on emotional information processing and mood is given in Chapter 8. Also, evidence for a possible sequential link between serotonin induced changes in emotional information processing and mood is evaluated. Chapter 9 contains a summary and integration of the main findings, as well as methodological strengths and limitations, directions for future research and clinical implications of the findings reported in this thesis Show less
