Dominique Piber

Depressive syndromes in neurological disorders

Depressive syndromes represent a common and often characteristic feature in a number of neurological disorders. One prominent example is the development of post-stroke depression, which can be observed in more than one-third of stroke survivors in the aftermath of an ischemic stroke. Thus, post-stroke depression represents one of the most prevalent, disabling, and potentially devastating psychiatric post-stroke complications. On the other hand, depressive syndromes may also be considered as a risk factor for certain neurological disorders, as recently revealed by a meta-analysis of prospective cohort studies, which demonstrated an increased risk for ischemic events in depressed patients. Moreover, depressive syndromes represent common comorbidities in a number of other neurological disorders such as Parkinson’s disease, multiple sclerosis, or epilepsy, in which depression has a strong impact on both quality of life and outcome of the primary neurological disorder.

Effects of mineralocorticoid-receptor stimulation on risk taking behavior in young healthy men and women

Risk taking is influenced by stress, with riskier decisions after exposure to an acute stressor and consecutively elevated cortisol levels. In the brain, cortisol acts on two receptors with different functional profiles: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). In the current study we investigated the effect of MR stimulation on risk taking behavior in 80 young healthy participants (40 women, mean age=23.9). We administered 0.4mg fludrocortisone, a MR agonist, in a between-subjects, placebo controlled design. Subsequently, participants conducted an established risk taking paradigm, the Balloon-Analogue-Risk-Task (BART). We also used two questionnaires to assess risk taking and decision behavior as trait measures. We found a treatment effect with riskier decisions in the fludrocortisone group. Furthermore, we found a sex effect with more risk taking in men. There was no statistically significant interaction between both factors. Our results indicate that acute MR stimulation leads to riskier decisions in women and men. Our findings argue for an important role of the MR in decision making processes.

Sex effects on spatial learning but not on spatial memory retrieval in healthy young adults

OBJECTIVES Sex differences have been found in spatial learning and spatial memory, with several studies indicating that males outperform females. We tested in the virtual Morris Water Maze (vMWM) task, whether sex differences in spatial cognitive processes are attributable to differences in spatial learning or spatial memory retrieval in a large student sample. METHODS We tested 90 healthy students (45 women and 45 men) with a mean age of 23.5 years (SD=3.5). Spatial learning and spatial memory retrieval were measured by using the vMWM task, during which participants had to search a virtual pool for a hidden platform, facilitated by visual cues surrounding the pool. Several learning trials assessed spatial learning, while a separate probe trial assessed spatial memory retrieval. RESULTS We found a significant sex effect during spatial learning, with males showing shorter latency and shorter path length, as compared to females (all p<0.001). Yet, there was no significant sex effect in spatial memory retrieval (p=0.615). Furthermore, post-hoc analyses revealed significant sex differences in spatial search strategies (p<0.05), but no difference in the number of platform crossings (p=0.375). CONCLUSION Our results indicate that in healthy young adults, males show faster spatial learning in a virtual environment, as compared to females. Interestingly, we found no significant sex differences during spatial memory retrieval. Our study raises the question, whether men and women use different learning strategies, which nevertheless result in equal performances of spatial memory retrieval.

Mineralocorticoid receptor stimulation effects on spatial memory in healthy young adults: A study using the virtual Morris Water Maze task

OBJECTIVES Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. METHODS Eighty healthy participants (40 women, 40 men, mean age=23.9years±SD=3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4mg fludrocortisone, a MR agonist, or placebo. RESULTS There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. CONCLUSION In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans.

Depression and neurological diseases

In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinsons disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.

Depression und neurologische Erkrankungen

In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinsons disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.

Insomnia and inflammation: a two hit model of depression risk and prevention: World Psychiatry

tial impact of psychedelic drugs on psychiatry to that of the microscope on biology and, while this analogy may strike some as laughable, let us reflect for a moment that human research with psychedelics has been effectively moribund since the restrictive drug policy reforms of the 1960s-70s, and has only recently been revived. Classic serotonergic psychedelics – such as LSD, psilocybin and dimethyltryptamine – all possess agonist properties at the 5-HT2A receptor subtype, and 5-HT2A receptor agonism is known to be the pharmacological trigger of the “psychedelic experience”. Crucially, there is also a wealth of evidence to implicate 5-HT2A receptor signaling in processes of plasticity, such as neurogenesis, neurodevelopment, learning, extinction learning, cognitiveflexibility andenhancedenvironmental sensitivity. Added to this, the subjective quality of a psychedelic experience is highly susceptible to contextual influence, for example from the environment in which it occurs as well as from the expectations of the “tripper” and those around him or her. Moreover, the quality of an acute psychedelic experience appears to be a highly reliable predictor of subsequent long-term mental health outcomes. Another predictor of long-term psychological outcomes is the degree of increase in the complexity or “entropy” of brain activity recorded during the psychedelic experience, and this brain effect is hypothesized to be relatively unique to psychedelics, and key to an understanding of their exceptional phenomenology and therapeutic potential. Within the last 12 years, a growing body of evidence, albeit from mostly small scale pilot studies, has suggested that psychedelics, combined with contextual manipulation (such as music listening and psychological support), can offer a safe and effective treatment for a range of different psychiatric disorders. Where successful, the treatment effect appears to be rapid and enduring. Moreover, promising outcomes have not just been seen in depression, but in addiction and other disorders as well. That just one or two treatment sessions can yield therapeutic effects lasting for several months is unprecedented in modern psychiatry. Of course, incredible claims require credible evidence but, with large randomized controlled trials beginning with psilocybin for depression, the required roads are being laid. A simple and plausible model of therapeutic mechanisms of psychedelic treatments would greatly complement this ongoing clinical work. The thesis is put forward here that serotonin differentially encodes behavioral and physiological responses to uncertainty. More specifically, it is proposed that the limbic-rich inhibitory postsynaptic 5-HT1A receptor subtype provides basal control during normal conditions, via moderating emotion and anxiety, and promoting a generalized patience. On the other hand, the cortically-rich 5-HT2A receptor subtype is hypothesized to engage more during conditions of crisis, when the above-mentioned default mechanism becomes suboptimal, e.g. when an individual’s internal and/or external milieu becomes so changeable and/or inconsistent with his/her prior beliefs and behaviors that significant revisions becomemandated. Viewed through a Bayesian lens, it is proposed that the principal functional effect of 5-HT2A receptor stimulation is to relax prior assumptions or beliefs, held at multiple levels of the brain’s functional hierarchy: perceptually, emotionally, cognitively and philosophically (e.g., in terms of biases). In so doing, it opens a door to heightened sensitivity to context, an ideal pre-condition for effective change.

Depression und neurologische Erkrankungen@@@Depression and neurological diseases

In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinsons disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.