Towards Unequal Care:reshaping the treatment of schizophrenia spectrum disorders to the male and female body

This thesis challenges if we are doing enough when we treat women with schizophrenia- spectrum disorders (SSD) as if they were equal to men, by investigating the impact of sex and sex hormones on the disorder. While the widespread effects of the female sex hormone estrogen in SSD have been well-established, they have not been translated into current treatment strategies. In women, certain antipsychotics lower estrogen levels, which can affect physical and mental health. Both sex and sex hormones influence the efficacy of antipsychotics in the brain, and the way they are broken down in the body. Current guidelines fail to consider these sex-specific effects, leaving women more susceptible to adverse events. Menopause adds another layer of complexity, being associated with reduced treatment tolerability and effectiveness. The latter was demonstrated in a cohort study showing that women are more vulnerable to be hospitalized for psychosis after reaching menopausal age, suggesting that current antipsychotic treatment options may be insufficient for postmenopausal women. The second part of this thesis conveys a more positive message. Results from a clinical trial demonstrate that addition of the estrogen-like compound raloxifene significantly improves outcomes in women only. This clinical evidence for estrogen’s protective effects was then translated into real-world settings by another cohort study, revealing that estrogen-based menopausal hormone therapy reduces the risk of relapse to psychosis. Overall, this thesis highlights the importance of sex-specific treatment approaches for SSD, showing how estrogen’s protective effects can be harnessed to improve outcomes for female patients

The evolution of photosynthesis in chromist algae through serial endosymbioses

Chromist algae include diverse photosynthetic organisms of great ecological and social importance. Despite vigorous research efforts, a clear understanding of how various chromists acquired photosynthetic organelles has been complicated by conflicting phylogenetic results, along with an undetermined number and pattern of endosymbioses, and the horizontal movement of genes that accompany them. We apply novel statistical approaches to assess impacts of endosymbiotic gene transfer on three principal chromist groups at the heart of long-standing controversies. Our results provide robust support for acquisitions of photosynthesis through serial endosymbioses, beginning with the adoption of a red alga by cryptophytes, then a cryptophyte by the ancestor of ochrophytes, and finally an ochrophyte by the ancestor of haptophytes. Resolution of how chromist algae are related through endosymbioses provides a framework for unravelling the further reticulate history of red algal-derived plastids, and for clarifying evolutionary processes that gave rise to eukaryotic photosynthetic diversity

Towards better care for women with schizophrenia-spectrum disorders

Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than do men at the start of their illness but progress to the same state within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics require dosing and prescription tailored to the female physiology that consider hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. By providing female-specific care, women with schizophrenia-spectrum disorders will have optimal chances to fare well

Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders:a meta-analysis

Background Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. Methods A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition. Results We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains. Conclusions Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention)

The association of prolactin and gonadal hormones with cognition and symptoms in men with schizophrenia spectrum disorder:Divergent effects of testosterone and estrogen

Background: Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication. Methods: This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Results: Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p &lt; .001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r(73) = −0.32, p = .005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p = .007, verbal fluency: β = 0.30, p = .001) and lower symptom scores (total: β = −0.21, p = .001; negative: β = −0.24, p = .002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = −0.22, p &lt; .001) and higher symptoms scores (β = 0.23, p = .010) in men with SSD. Conclusion: The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD.</p

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition

Purpose: Antipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD. Methods: This cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models. Results: In women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β−estradiol = 0.24, βprolactin = -0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r = -0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β−estradiol = -0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027). Conclusions: In women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD

Characterizing speech heterogeneity in schizophrenia-spectrum disorders

Schizophrenia-spectrum disorders (SSD) are highly heterogeneous in risk factors, symptom characteristics, and disease course outcome. Although speech anomalies have long been recognized as a core symptom of SSD, speech markers are an unexplored source of symptom heterogeneity that may be informative in recognizing relevant subtypes. This study investigated speech heterogeneity and its relation to clinical characteristics in a large sample of patients with SSD and healthy controls. Speech samples were obtained from 142 patients with SSD and 147 healthy controls by means of open-ended interviews. Speech was analyzed using standardized open-source acoustic speech software. Hierarchical clustering was conducted using acoustic speech markers. Symptom severity was rated with the Positive and Negative Syndrome Scale, and cognition was assessed with the Brief Assessment of Cognition for Schizophrenia. Three speech clusters could be distinguished in the patient group that differed regarding speech properties, independent of medication use. One cluster was characterized by mild speech disturbances, while two severely impaired clusters were recognized (fragmented speakers and prolonged pausers). Both clusters with severely impaired speech had more severe cognitive dysfunction than the mildly impaired speakers. Prolonged pausers specifically had difficulties with memory-related tasks. Prolonged pausing, as opposed to fragmented speaking, related to chronic active psychosis and refractory psychotic symptoms. Based on speech clustering, subtypes of patients emerged with distinct disease trajectories, symptomatology, and cognitive functioning. The identification of clinically relevant subgroups within SSD may help to characterize distinct profiles and benefit the tailoring of early intervention and improvement of long-term functional outcome. (PsycInfo Database Record (c) 2022 APA, all rights reserved).</p

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition

Purpose: Antipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD. Methods: This cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models. Results: In women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β−estradiol = 0.24, βprolactin= -0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r = -0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β−estradiol = -0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027). Conclusions: In women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD