RESUMEN
A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress.
RESUMEN
BACKGROUND: Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania. METHODS: A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study. RESULTS: Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition. CONCLUSIONS: Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.