The relationship between sex, personality traits, and the hypothalamic-pituitary-adrenocortical axis.

The aim of our study was to examine whether there are sex-based differences in the relationship between personality traits and hypothalamic-pituitary-adrenal (HPA) axis measures. A total of 106 healthy volunteers (56.6% women; age: 48.0 ± 15.8 years) were studied. The revised temperament and character inventory (TCI-R) and the Childhood Trauma Questionnaire (CTQ) were administered. HPA axis function was assessed using three dynamic measures: the cortisol awakening response (CAR), the diurnal cortisol slope, and the cortisol suppression ratio with 0.25 mg of dexamethasone (DSTR). Female sex was associated with an increased CAR and a more flattened diurnal cortisol slope, although a negative significant interaction between harm avoidance and female sex was found. Regarding the DSTR, perseverance was associated with increased cortisol suppression after dexamethasone; sex did not affect this association. Our study suggests that the relationship between specific personality traits (harm avoidance) and HPA axis measures (CAR, diurnal slope) differs according to sex.

A conserved C-terminal peptide of sorghum phosphoenolpyruvate carboxylase promotes its proteolysis, which is prevented by Glc-6P or the phosphorylation state of the enzyme.

MAIN CONCLUSION: A synthetic peptide from the C-terminal end of C4-phosphoenolpyruvate carboxylase is implicated in the proteolysis of the enzyme, and Glc-6P or phosphorylation of the enzyme modulate this effect. Phosphoenolpyruvate carboxylase (PEPC) is a cytosolic, homotetrameric enzyme that performs a variety of functions in plants. Among them, it is primarily responsible for CO2 fixation in the C4 photosynthesis pathway (C4-PEPC). Here we show that proteolysis of C4-PEPC by cathepsin proteases present in a semi-purified PEPC fraction was enhanced by the presence of a synthetic peptide containing the last 19 amino acids from the C-terminal end of the PEPC subunit (pC19). Threonine (Thr)944 and Thr948 in the peptide are important requirements for the pC19 effect. C4-PEPC proteolysis in the presence of pC19 was prevented by the PEPC allosteric effector glucose 6-phosphate (Glc-6P) and by phosphorylation of the enzyme. The role of these elements in the regulation of PEPC proteolysis is discussed in relation to the physiological context.

Development and assessment of an active strategy for the implementation of a collaborative care approach for depression in primary care (the INDI·i project).

BACKGROUND: Primary care is the principal clinical setting for the management of depression. However, significant shortcomings have been detected in its diagnosis and clinical management, as well as in patient outcomes. We developed the INDI collaborative care model to improve the management of depression in primary care. This intervention has been favorably evaluated in terms of clinical efficacy and cost-effectiveness in a clinical trial. Our aim is to bring this intervention from the scientific context into clinical practice. METHODS: Objective: To test for the feasibility and impact of a strategy for implementing the INDI model for depression in primary care. DESIGN: A quasi-experiment conducted in primary care. Several areas will be established to implement the new program and other, comparable areas will serve as control group. The study constitutes the preliminary phase preceding generalization of the model in the Catalan public healthcare system. PARTICIPANTS: The target population of the intervention are patients with major depression. The implementation strategy will also involve healthcare professionals, primary care centers, as well as management departments and the healthcare organization itself in the geographical areas where the study will be conducted: Camp de Tarragona and Vallès Occidental (Catalonia). INTERVENTION: The INDI model is a program for improving the management of depression involving clinical, instructional, and organizational interventions including the participation of nurses as care managers, the efficacy and efficiency of which has been proven in a clinical trial. We will design an active implementation strategy for this model based on the PARIHS (Promoting Action on Research Implementation in Health Services) framework. MEASURES: Qualitative and quantitative measures will be used to evaluate variables related to the successful implementation of the model: acceptability, utility, penetration, sustainability, and clinical impact. DISCUSSION: This project tests the transferability of a healthcare intervention supported by scientific research to clinical practice. If implementation is successful in this experimental phase, we will use the information and experience obtained to propose and plan the generalization of the INDI model for depression in the Catalan healthcare system. We expect the program to benefit patients, the healthcare system, and society. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03285659 ; Registered 12th September, 2017.

Phosphoenolpyruvate carboxylase (PEPC) and PEPC-kinase (PEPC-k) isoenzymes in Arabidopsis thaliana: role in control and abiotic stress conditions.

MAIN CONCLUSION: Arabidopsis ppc3 mutant has a growth-arrest phenotype and is affected in phosphate- and salt-stress responses, showing that this protein is crucial under control or stress conditions. Phosphoenolpyruvate carboxylase (PEPC) and its dedicated kinase (PEPC-k) are ubiquitous plant proteins implicated in many physiological processes. This work investigates specific roles for the three plant-type PEPC (PTPC) and the two PEPC-k isoenzymes in Arabidopsis thaliana. The lack of any of the PEPC isoenzymes reduced growth parameters under optimal growth conditions. PEPC activity was decreased in shoots and roots of ppc2 and ppc3 mutants, respectively. Phosphate starvation increased the expression of all PTPC and PPCK genes in shoots, but only PPC3 and PPCK2 in roots. The absence of any of these two proteins was not compensated by other isoforms in roots. The effect of salt stress on PTPC and PPCK expression was modest in shoots, but PPC3 was markedly increased in roots. Interestingly, both stresses decreased root growth in each of the mutants except for ppc3. This mutant had a stressed phenotype in control conditions (reduced root growth and high level of stress molecular markers), but was unaffected in their response to high salinity. Salt stress increased PEPC activity, its phosphorylation state, and L-malate content in roots, all these responses were abolished in the ppc3 mutant. Our results highlight the importance of the PPC3 isoenzyme for the normal development of plants and for root responses to stress.

The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

Sleep Disturbances in At-Risk Mental States and First Episode of Psychosis: A Narrative Review on Interventions.

Sleep disturbances are a common yet often overlooked symptom of psychosis that can drastically affect the quality of life and well-being of those living with the condition. Sleep disorders are common in people diagnosed with schizophrenia and have significant negative effects on the clinical course of the illness and the functional outcomes and quality of life of patients. There is a limited number of studies addressing this question in first-episode psychosis (FEP). In this narrative review, we aimed to provide an overview of sleep disorders in populations with FEP and at-risk mental states (ARMS). The review was focused on the various treatments currently used for sleep disorders, including both non-pharmacological and pharmacological treatments. A total of 48 studies were included. We found that sleep disturbances are associated with attenuated psychotic symptoms and other psychopathological symptoms in ARMSs. The association of sleep disturbances with the transition to psychosis has been poorly investigated. Sleep disturbances have an impact on the quality of life and the psychopathological symptoms of people suffering from FEP. The non-pharmacological treatments include cognitive behavioral therapy for insomnia, bright light therapy, cognitive restructuring techniques, sleep restriction therapy, basic sleep hygiene education, and the provision of portable sleep trackers. Other treatments include antipsychotics in acute phases and melatonin. The early intervention in sleep disturbances may improve overall prognosis in emerging psychosis populations.

Schizophrenia: A Review of Social Risk Factors That Affect Women.

Social risk factors are long-term or repeated environmental exposures in childhood and youth that change the brain and may, via epigenetic effects, change gene expression. They thus have the power to initiate or aggravate mental disorders. Because these effects can be mediated via hormonal or immune/inflammatory pathways that differ between men and women, their influence is often sex-specific. The goal of this narrative review is to explore the literature on social risk factors as they affect women with schizophrenia. We searched the PubMed and Scopus databases from 2000 to May 2023 using terms referring to the various social determinants of health in conjunction with "women" and with "schizophrenia". A total of 57 studies fulfilled the inclusion criteria. In the domains of childhood and adult abuse or trauma, victimization, stigma, housing, and socioeconomics, women with schizophrenia showed greater probability than their male peers of suffering negative consequences. Interventions targeting appropriate housing, income support, social and parenting support, protection from abuse, violence, and mothering-directed stigma have, to different degrees, yielded success in reducing stress levels and alleviating the many burdens of schizophrenia in women.

Switching from risperidone to paliperidone palmitate in schizophrenia: Changes in social functioning and cognitive performance.

BACKGROUND: Previous studies suggest that paliperidone might show a better profile for social functioning and cognitive abilities than risperidone. We aimed to study whether switching from risperidone to paliperidone palmitate (PP) is associated with improved cognitive abilities at 3 or 6 months after the switch. METHODS: Thirty-eight patients with a DSM-IV diagnosis of schizophrenia were studied. All patients were treated with oral risperidone or risperidone long-acting injection (RLAI) and had an indication to be switched to PP by their psychiatrists. Statistical analyses were conducted in a final sample of 27 patients who completed the follow-up visits. Three assessments were completed: 1) baseline (preswitch), 2) 3 months postswitch, and 3) 6 months postswitch. Social functioning at each visit was assessed with the Personal and Social Performance Scale. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery. Statistical analyses were performed with R. Linear mixed models were used to explore longitudinal changes in social functioning and cognitive outcomes. RESULTS: PSP scores significantly improved over time after the switch from risperidone to PP. A sensitivity analysis found a significant negative interaction between time and PP maintenance doses (greater improvement in those patients receiving lower doses when compared to higher doses). Regarding longitudinal changes in cognitive functioning, patients improved in 6 out of 10 cognitive tasks involving processing speed, working memory, visual memory, reasoning and problem solving, and attention and vigilance. CONCLUSIONS: Our study suggests that switching from risperidone to PP in patients with schizophrenia is associated with an improvement in social functioning and cognitive performance.

Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders: New Challenges.

For several decades, it has been postulated that dopaminergic pathways explain the neurobiology of schizophrenia, the biological underpinnings of treatment responses and the main mechanisms of action of antipsychotics [...].

Collaboration between Psychiatrists and Other Allied Medical Specialists for the Treatment of Delusional Disorders.

BACKGROUND: There is increasing evidence that individuals with psychosis are at increased risk for cardiovascular disease, diabetes, metabolic syndrome, and several other medical comorbidities. In delusional disorder (DD), this is particularly so because of the relatively late onset age. AIMS: The aim of this narrative review is to synthesize the literature on the necessity for medical collaboration between psychiatrists and other specialists. METHODS: A non-systematic narrative review was carried out of papers addressing referrals and cooperation among specialists in the care of DD patients. RESULTS: Psychiatrists, the primary care providers for DD patients, depend on neurology to assess cognitive defects and rule out organic sources of delusions. Neurologists rely on psychiatry to help with patient adherence to treatment and the management of psychotropic drug side effects. Psychiatrists require ophthalmology/otolaryngology to treat sensory deficits that often precede delusions; reciprocally, psychiatric consults can help in instances of functional sensory impairment. Close collaboration with dermatologists is essential for treating delusional parasitosis and dysmorphophobia to ensure timely referrals to psychiatry. CONCLUSIONS: This review offers many other examples from the literature of the extent of overlap among medical specialties in the evaluation and effective treatment of DD. Optimal patient care requires close collaboration among specialties.

A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.

We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.

Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories.

BACKGROUND: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal treatment and addressing specific health needs of this stage in life will improve outcome. METHODS: Non-systematic narrative review using the PubMed database (1900-July 2021) focusing on randomized controlled trial results addressing our question. Forty-nine studies met our criteria. RESULTS: Premenopausal women show significantly better antipsychotic response than postmenopausal women. Hormone replacement therapies (HRT) should be used in postmenopausal women with schizophrenia with caution. Raloxifene, combined with antipsychotics, is effective for psychotic and cognitive symptoms in postmenopausal women with schizophrenia and related disorders. Medical comorbidities increase after menopause, but the influence of comorbidities on clinical outcomes has been poorly investigated. Preventive strategies include weighing risks and benefits of treatment, preventing medical comorbidities, and enhancing psychosocial support. Ideal treatment settings for this population warrant investigation. CONCLUSIONS: Antipsychotic dose adjustment at menopause is recommended for schizophrenia. Raloxifene may play an important role in permitting dose reduction and lessening adverse effects. Prevention of comorbidities will help to reduce the mortality rate.

The Effect of Child Sexual Abuse on Social Functioning in Schizophrenia Spectrum Disorders.

The objective of this study was to explore social functioning in schizophrenic patients who have suffered child sexual abuse (CSA) in comparison with those who have not suffered from it in a Spanish sample of 50 patients with schizophrenia or schizoaffective disorder. The Quality of Life (QOL) Scale, the Childhood Trauma Questionnaire (CTQ-SF), and the NEO Five Factor Inventory (NEO-FFI) were administered in this study. We found a CSA prevalence of 22% in our sample. Results showed that QOL global scores reduced by 9.34% at a statistically significant level (p = .037) in sexually abused patients in comparison with those who did not report experiencing sexual abuse. Regression analysis in the QOL scales showed no differences in intrapsychic foundation scores or in the social relations scale. Scores in the instrumental role scale were reduced by 4.42 points in patients with CSA (p = .009). Neither neuroticism nor extraversion results differ between the trauma group and those who did not suffer trauma. Clinical implications of these results are discussed.

Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.

Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.

The role of childhood trauma, HPA axis reactivity and FKBP5 genotype on cognition in healthy individuals.

Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.

Cognitive biases are associated with clinical and functional variables in psychosis: A comparison across schizophrenia, early psychosis and healthy individuals.

OBJECTIVE: We investigated the presence of cognitive biases in people with a recent-onset psychosis (ROP), schizophrenia and healthy adolescents and explored potential associations between these biases and psychopathology. METHODS: Three groups were studied: schizophrenia (N=63), ROP (N=43) and healthy adolescents (N=45). Cognitive biases were assessed with the Cognitive Biases Questionnaire for Psychosis (CBQ). Positive, negative and depressive symptoms were assessed with the PANSS and Calgary Depression Scale (ROP; schizophrenia) and with the CAPE-42 (healthy adolescents). Cannabis use was registered. The association between CBQ and psychopathology scales was tested with multiple linear regression analyses. RESULTS: People with schizophrenia reported more cognitive biases (46.1±9.0) than ROP (40±5.9), without statistically significant differences when compared to healthy adolescents (43.7±7.3). Cognitive biases were significantly associated with positive symptoms in both healthy adolescents (Standardized ß=0.365, p=0.018) and people with psychotic disorders (ß=0.258, p=0.011). Cognitive biases were significantly associated with depressive symptoms in healthy adolescents (ß=0.359, p=0.019) but in patients with psychotic disorders a significant interaction between schizophrenia diagnosis and CBQ was found (ß=1.804, p=0.011), which suggests that the pattern differs between ROP and schizophrenia groups (positive association only found in the schizophrenia group). Concerning CBQ domains, jumping to conclusions was associated with positive and depressive symptoms in people with schizophrenia and with cannabis use in ROP individuals. Dichotomous thinking was associated with positive and depressive symptoms in all groups. CONCLUSIONS: Cognitive biases contribute to the expression of positive and depressive symptoms in both people with psychotic disorders and healthy individuals.

Involvement of phospholipase D and phosphatidic acid in the light-dependent up-regulation of sorghum leaf phosphoenolpyruvate carboxylase-kinase.

The photosynthetic phosphoenolpyruvate carboxylase (C(4)-PEPC) is regulated by phosphorylation by a phosphoenolpyruvate carboxylase kinase (PEPC-k). In Digitaria sanguinalis mesophyll protoplasts, this light-mediated transduction cascade principally requires a phosphoinositide-specific phospholipase C (PI-PLC) and a Ca(2+)-dependent step. The present study investigates the cascade components at the higher integrated level of Sorghum bicolor leaf discs and leaves. PEPC-k up-regulation required light and photosynthetic electron transport. However, the PI-PLC inhibitor U-73122 and inhibitors of calcium release from intracellular stores only partially blocked this process. Analysis of [(32)P]phosphate-labelled phospholipids showed a light-dependent increase in phospholipase D (PLD) activity. Treatment of leaf discs with n-butanol, which decreases the formation of phosphatidic acid (PA) by PLD, led to the partial inhibition of the C(4)-PEPC phosphorylation, suggesting the participation of PLD/PA in the signalling cascade. PPCK1 gene expression was strictly light-dependent. Addition of neomycin or n-butanol decreased, and a combination of both inhibitors markedly reduced PPCK1 expression and the concomitant rise in PEPC-k activity. The calcium/calmodulin antagonist W7 blocked the light-dependent up-regulation of PEPC-k, pointing to a Ca(2+)-dependent protein kinase (CDPK) integrating both second messengers, calcium and PA, which were shown to increase the activity of sorghum CDPK.

Data of a meta-analysis on pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia.

The data presented in this paper describe supplementary material to the article entitled "Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: a systematic review and meta-analysis" [1]. Although raw data was published on the original article, additional raw data has been included in the current paper (new tables with socio-demographic and clinical characteristics of the samples of the studies included in the systematic review). Supplementary data also include the PICO scheme of the systematic review, PRISMA checklist, flow diagram, an explanation of the method for obtaining prolactin concentrations from published figures when data was only available in figures, list of the selected studies, risk of bias summary of all five randomized clinical trials evaluating the addition of aripiprazole for lowering prolactin (included in the meta-analysis in the original article). Extra analyses, figures and R code of the meta-analysis have been also included. Meta-analysis of randomized clinical trials (RCTs) considering aripiprazole addition for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia were conducted with two softwares: 1) R and the metaphor package (for the meta-analysis of the primary outcome [prolactin reduction]); 2) MedCalc version 18.11 (for the meta-analysis of the secondary outcome [withdrawal rates]). Data from a sensitivity analysis (repeating the meta-analysis with only placebo-controlled RCTs) has been also included in the current article.