Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment.

Voice analyses using smartphone-based data in patients with bipolar disorder, unaffected relatives and healthy control individuals, and during different affective states

Background Voice features have been suggested as objective markers of bipolar disorder (BD). Aims To investigate whether voice features from naturalistic phone calls could discriminate between (1) BD, unaffected first-degree relatives (UR) and healthy control individuals (HC); (2) affective states within BD. Methods Voice features were collected daily during naturalistic phone calls for up to 972 days. A total of 121 patients with BD, 21 UR and 38 HC were included. A total of 107.033 voice data entries were collected [BD (n = 78.733), UR (n = 8004), and HC (n = 20.296)]. Daily, patients evaluated symptoms using a smartphone-based system. Affective states were defined according to these evaluations. Data were analyzed using random forest machine learning algorithms. Results Compared to HC, BD was classified with a sensitivity of 0.79 (SD 0.11)/AUC = 0.76 (SD 0.11) and UR with a sensitivity of 0.53 (SD 0.21)/AUC of 0.72 (SD 0.12). Within BD, compared to euthymia, mania was classified with a specificity of 0.75 (SD 0.16)/AUC = 0.66 (SD 0.11). Compared to euthymia, depression was classified with a specificity of 0.70 (SD 0.16)/AUC = 0.66 (SD 0.12). In all models the user dependent models outperformed the user independent models. Models combining increased mood, increased activity and insomnia compared to periods without performed best with a specificity of 0.78 (SD 0.16)/AUC = 0.67 (SD 0.11). Conclusions Voice features from naturalistic phone calls may represent a supplementary objective marker discriminating BD from HC and a state marker within BD.

Sharing the Same Perspective. Mental Disorders and Central Serous Chorioretinopathy: A Systematic Review of Evidence from 2010 to 2020

Background: The relevance of the association between mental disorders and other conditions might have been underestimated due to its complexity. Central Serous Chorioretinopathy (CSC) is an ophthalmological disorder associated with many psychiatric factors. The aim of this systematic review is to evaluate the association between mental disorders and CSC. Methods: Articles about studies performed on humans on CSC published in peer-reviewed journals from 1 January 2010 to 31 December 2020 were included in the review. Results: We selected 21 research papers. Nine studies measured stress and anxious depressive symptoms, which are associated with CSC onset and recurrences, emerging as a state marker of the disease. Four out of the five studies focused on sleep disorders suggested a reliable association with CSC. Four studies evaluated other various psychiatric factors. The role of psychopharmacological medication has still not been elucidated (three studies). Conclusion: Multiple pieces of evidence highlights that CSC might arise in the context of systemic disease. This notion, together with the increasing evidence supporting a link between psychiatric disorders and choroidal thickness, suggests that CSC and mental disorders may share some etiopathogenetic pathways. Further research is needed to better investigate possible common etiopathogenetic pathways, especially vascular, immunological and endocrinological systems.

Characteristics and impact of cognitive dysfunction

The chapter characteristics and impact of cognitive dysfunction describes in depth the key features of the domains of cognitive abilities impaired across a broad range of functions. It examines the clinical impact and meta-analytic evidence of cognitive dysfunction both as a state marker of acute depression and a trait marker of depression as an illness. Importantly, it highlights the long-lasting psychosocial and workplace-related impairments in major depressive disorder. In addition to the functional outcomes, it draws the interconnectedness of life domains, subjective experiences of cognitive impairment, and objective measures of cognitive dysfunction, as well as with the course of major depressive disorder.

Inhibition of N-myristoyltransferase Promotes Naive Pluripotency in Mouse and Human Pluripotent Stem Cells

Naive and primed states are distinct states of pluripotency during early embryonic development that can be captured and converted to each other in vitro. To elucidate the regulatory mechanism of pluripotency, we performed a recessive genetic screen of homozygous mutant mouse embryonic stem cells (mESCs) and found that suppression of N-myristoyltransferase (Nmt) promotes naive pluripotency. Disruption of Nmt1 in mESCs conferred resistance to differentiation. Suppression of Nmt in mouse epiblast stem cells (mEpiSCs) promoted the conversion from the primed to the naive state. This effect was independent of Src, which is a major substrate of Nmt and is known to promote differentiation of mESCs. Suppression of Nmt in naive-state human induced pluripotent stem cells (hiPSCs) increased the expression of the naive-state marker. These results indicate that Nmt is a novel target for the regulation of naive pluripotency conserved between mice and humans.

Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.

Olfactory Memory in Depression: State and Trait Differences between Bipolar and Unipolar Disorders

Background: Changes in olfactory recognition memory may constitute sensory markers in depression. Significant differences may exist between unipolar and bipolar depression. Our study compares olfactory memory between control, unipolar, and bipolar patients in depressed and euthymic states in order to identify potential markers of depression. Methods: 176 participants were recruited in 5 groups: depressed bipolar (DB), euthymic bipolar (EB), depressed unipolar (DU), euthymic unipolar (EU), and controls (HC). The participants had a standardized clinical and olfactory assessment (olfactory memory, evaluation of pleasantness, intensity, familiarity, and emotional aspect of smells). Results: DU, DB, and EU patients had a deficit in olfactory memory compared to HC. DB patients had lower capacity to recognize new odors. DB and DU patients had more limited detection of unfamiliar odors than HC. DB patients rated odors as less pleasant compared to the other groups. All groups had lower hedonic ratings than HC. DB patients had lower emotional ratings than EU patients. Conclusions: Olfactory memory is impaired in depressive states, thus constituting a state marker of depression. Impairments in olfactory memory persist after remission of bipolar depression, thus constituting a possible trait marker of bipolarity. Hedonic rating differentiates unipolar from bipolar depression. This is the first study that identifies a sensory marker differentiating between unipolar and bipolar depression.