Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.

Proteomics Insights into Medullary Sponge Kidney Disease: Review of the Recent Results of an Italian Research Collaborative Network.

BACKGROUND: Medullary sponge kidney (MSK) disease is a rare and neglected congenital condition typically associated with nephrocalcinosis/nephrolithiasis, urinary concentration defects, and cystic anomalies in the precalyceal ducts that, although sporadic in the general population, is relatively frequent in renal stone formers. The physiopathologic mechanism associated with this disease is not fully understood, and omics technologies may help address this gap. SUMMARY: The aim of this review was to provide an overview of the current state of the application of proteomics in the study of this rare disease. In particular, we focused on the results of our recent Italian collaborative studies that, analyzing the MSK whole and extracellular vesicle urinary content by mass spectrometry, have displayed the existence of a large and multifactorial MSK-associated biological machinery and identified some main regulatory biological elements able to discriminate patients affected by this rare disorder from those with idiopathic calcium nephrolithiasis and autosomal dominant polycystic kidney disease (including laminin subunit alpha 2, ficolin 1, mannan-binding lectin serine protease 2, complement component 4-binding protein ß, sphingomyelin, ephrins). KEY MESSAGES: The application of omics technologies has provided new insights into the comprehension of the physiopathology of the MSK disease and identified novel potential diagnostic biomarkers that may replace in future expensive and invasive radiological tests (including CT) and select novel therapeutic targets potentially employable, whether validated in a large cohort of patients, in the daily clinical practice.

Metabolic Fingerprinting of Fabry Disease: Diagnostic and Prognostic Aspects.

Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype-phenotype correlation. In the early stages, FD could involve the peripheral nervous system (acroparesthesias and dysautonomia) and the ski (angiokeratoma), but later kidney, heart or central nervous system impairment may significantly decrease life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. In this narrative review, we will focus on the main metabolomic studies, which have underscored the importance of detecting biomarkers for a diagnostic and prognostic purpose in FD. These investigations are potentially useful to explain the wide clinical, biochemical and molecular heterogeneity found in FD patients. Moreover, the quantitative mass spectrometry methods developed to evaluate concentrations of these biomarkers in urine and plasma will be described. Finally, the complex metabolic biomarker profile depicted in FD patients will be reported, which varies according to gender, types of mutations, and therapeutic treatment.

Oxidative Stress and Ischemia/Reperfusion Injury in Kidney Transplantation: Focus on Ferroptosis, Mitophagy and New Antioxidants.

Although there has been technical and pharmacological progress in kidney transplant medicine, some patients may experience acute post-transplant complications. Among the mechanisms involved in these conditions, ischemia/reperfusion (I/R) injury may have a primary pathophysiological role since it is one of the leading causes of delayed graft function (DGF), a slow recovery of the renal function with the need for dialysis (generally during the first week after transplantation). DGF has a significant social and economic impact as it is associated with prolonged hospitalization and the development of severe complications (including acute rejection). During I/R injury, oxidative stress plays a major role activating several pathways including ferroptosis, an iron-driven cell death characterized by iron accumulation and excessive lipid peroxidation, and mitophagy, a selective degradation of damaged mitochondria by autophagy. Ferroptosis may contribute to the renal damage, while mitophagy can have a protective role by reducing the release of reactive oxygen species from dysfunctional mitochondria. Deep comprehension of both pathways may offer the possibility of identifying new early diagnostic noninvasive biomarkers of DGF and introducing new clinically employable pharmacological strategies. In this review we summarize all relevant knowledge in this field and discuss current antioxidant pharmacological strategies that could represent, in the next future, potential treatments for I/R injury.

mTOR inhibitors improve both humoral and cellular response to SARS-CoV-2 messenger RNA BNT16b2 vaccine in kidney transplant recipients.

Kidney transplant recipients (KTRs) have been considered as patients at higher risk of SARS-CoV-2-related disease severity, thus COVID-19 vaccination was highly recommended. However, possible interferences of different immunosuppression with development of both humoral and T cell-mediated immune response to COVID-19 vaccination have not been determined. Here we evaluated the association between mTOR-inhibitors (mTOR-I) and immune response to mRNA BNT162b2 (Pfizer-BioNTech) vaccine in KTR. To this aim 132 consecutive KTR vaccinated against COVID-19 in the early 2021 were enrolled, and humoral and T cell-mediated immune response were assessed after 4-5 weeks. Patients treated with mTOR-I showed significantly higher anti-SARS-CoV-2 IgG titer (p = .003) and higher percentages of anti-SARS-CoV-2 S1/RBD Ig (p = .024), than those without. Moreover, SARS-CoV-2-specific T cell-derived IFNγ release was significantly increased in patients treated with mTOR-I (p < .001), than in those without. Multivariate analysis confirmed that therapy with mTOR-I gained better humoral (p = .005) and T cell-mediated immune response (p = .005) in KTR. The presence of mTOR-I is associated with a better immune response to COVID-19 vaccine in KTR compared to therapy without mTOR-I, not only by increasing vaccine-induced antibodies but also by stimulating anti-SARS-CoV-2 T cell response. These finding are consistent with a potential beneficial role of mTOR-I as modulators of immune response to COVID-19 vaccine in KTR.

Is Internet addiction a psychopathological condition distinct from pathological gambling?

AIMS: The behavioural-addiction perspective suggests that Internet addiction (IA) and pathological gambling (PG) could share similar characteristics with substance dependence. Despite the similarities between IA and PG, it is not clear whether these disorders share different or similar psychopathological conditions. The aim of the present study was to test whether IA patients presented different psychological symptoms, temperamental traits, coping strategies and relational patterns compared with PG patients. The hypothesis was that IA patients will show greater interpersonal disengagement than PG patients. METHODS: Two clinical groups (31 IA patients and 11 PG patients) and a control group (38 healthy subjects) matched with the clinical groups for gender and age were enrolled. The clinical groups were gathered in a psychiatric service for IA and PG in a hospital. Anxiety, depression, coping strategies, attachment, temperament, and global assessment of functioning were measured. MANOVAs, ANOVAs and post-hoc comparisons were carried out in order to test the hypothesis. RESULTS: Despite IA and PG showing similar differences with the control group on the levels of depression, anxiety and global functioning, the two clinical groups showed different temperamental, coping and social patterns. Specifically IA patients compared with the PG patients showed a greater mental and behavioural disengagement associated with an important interpersonal impairment. The two clinical groups shared an impulsive coping strategy and socio-emotional impairments. CONCLUSIONS: Despite IA and PG patients presenting similar clinical symptoms, IA condition was characterised by a more relevant mental, behavioural, and social disengagement compared to PG condition.

Adult attention-deficit/hyperactivity disorder in major depressed and bipolar subjects: role of personality traits and clinical implications.

A significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and affective disorders has been consistently reported in adults. Less data regarding the role of personality traits and the influence of ADHD co-occurrence on clinical characteristics and outcome of mood disorders are currently available. One hundred and six remitted major depressed, 102 euthymic bipolar subjects, and 120 healthy controls, homogeneous with respect to demographic characteristics, were included in the study. ADHD diagnosis was based on DSM-IV-TR criteria. Childhood and adult ADHD features were measured with the Wender Utah Rating Scale, the Adult ADHD Self-rating Scale, and the Brown Attention-Deficit Disorder Scale. The Revised NEO Personality Inventory was also administered to the clinical groups, in order to investigate personality dimensions. The occurrence of adult ADHD in subjects with bipolar disorders (BD) or major depressive disorder (MDD) was 15.7 and 7.5 %, respectively, compared to 3.3 % in healthy controls (HC). Significant associations (p < .001) between personality traits (neuroticism, conscientiousness, and extraversion) and ADHD features were observed. Logistic regression analysis of all clinical subjects (n = 208) showed that those with lower levels of neuroticism (OR = 1.031; p = .025) had a lower frequency of ADHD comorbidity. The present study emphasizes the close relationship between affective disorders, especially BD, and ADHD in adults. Our findings support the need to assess subjects with mood disorders in the clinical setting for possible coexisting ADHD and to further investigate personality traits to better understand the etiology of affective disorders and ADHD co-occurrence.

Affective temperaments and psychopathological dimensions of personality in bipolar and cyclothymic patients.

The aims of the study were: (1) to study possible associations between temperament, personality dimensions, and psychopathological variables in a clinical sample of euthymic patients with bipolar disorder (BD) and cyclothymia; and (2) to assess how Cloninger's temperament and personality dimensions were associated with affective temperaments. Participants, consisting of 60 patients with BD (type I or II) and cyclothymia in the euthymic phase, completed Akiskal's Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Cloninger's Temperament and Character Inventory-revised version (TCI-R). The diagnostic groups differed in past hospitalization, for age at onset of the disorder, and on two affective temperaments: the TEMPS-A Hyperthymia, and the TEMPS-A Irritability. There were six significant associations between affective temperaments and Cloninger's personality dimensions, ranging from 0.26 to 0.54. The measures of Akiskal and of Cloninger tap common behavioral features in patients with bipolar disorder and cyclothymia, yet the differences indicate that the two measures are not redundant. BD and cyclothymic patients differed significantly in temperament and personality, differences that may have important implications for treatment.

Role of substance abuse comorbidity and personality on the outcome of depression in bipolar disorder: harm avoidance influences medium-term treatment outcome.

Comorbid conditions are frequent in bipolar disorder (BD) and may complicate the treatment and course of illness. We investigated the role of substance use disorder (SUD), axis II personality disorders (PD) and continuous personality traits on the medium-term outcome (6 months) of treatment for bipolar depression. One hundred and thirty-nine BD patients meeting criteria for a depressive episode were included in the study. SUD and PD were diagnosed according to structured interviews. Personality dimensions were evaluated by the Temperament and Character Inventory. Depressive severity over time was evaluated by the Hamilton Rating Scale for Depression. Neither PD nor SUD influenced the outcome of depression. Variables independently associated with a poor outcome were a high baseline severity and high scores for the temperamental trait of Harm Avoidance. Though several limitations characterize the present study, neurotic personality traits seem to be associated with a slower recovery from depressive symptoms in BD, independently from their initial severity.

Bipolar disorder: "pure" versus mixed depression over a 1-year follow-up.

OBJECTIVES: To compare two samples of Bipolar (BD) patients presenting "pure" (D) and mixed (Mx) depression to assess any difference in terms of clinical outcome, social functioning and quality of life during a 1-year follow-up. METHODS: A total of 114 depressed outpatients (HDRS > 13) were included. "Pure" depressed (D, n = 76) were divided from "mixed" depressed (Mx, n = 38) by the number of concomitant manic symptoms. All patients were evaluated by the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Young Mania Rating Scale (YMRS), the Global Assessment of Functioning (GAF), the Social Adjustment Self-reported Scale (SASS) and the Quality of Life Scale (QoL), at baseline and after 1, 3, 6 and 12 months of treatment. RESULTS: Mx patients were significantly younger at the onset of BD. Manic features persisted significantly higher in Mx than in D patients all over the follow-up period. Axis I comorbidities had a negative impact on the course of social functioning over the medium term period, while Mx patients showed a faster improvement in social adjustment than "pure" depressed patients. CONCLUSIONS: Mixed features may persist relatively stable throughout a depressive episode, having a negative impact over clinical and functional outcome, but not on social adjustment.

Description and validation of a questionnaire for the detection of meteoropathy and meteorosensitivity: the METEO-Q.

BACKGROUND: There is a growing interest for the effects of weather changes on both healthy and psychiatric individuals. This study aims to validate a short questionnaire (METEO-Q) for the detection of meteoropathy and meteorosensitivity. METHODS: The METEO-Q was administered to 1099 (528 men, 571 women) healthy subjects. Factor analyses, internal consistency, and item analysis were undertaken to examine the factorial structure of the questionnaire. RESULTS: The METEO-Q has satisfactory factorial structure and internal reliability. Our results demonstrate that women have higher scores than man and, therefore, women mostly have meteoropathy. CONCLUSIONS: Our findings support the use of the METEO-Q for collecting information regarding the effects of weather changes on healthy subjects and potentially on psychiatric patients.

Factors associated with the course of symptoms in bipolar disorder during a 1-year follow-up: depression vs. sub-threshold mixed state.

BACKGROUND: Mixed mood states, even in their sub-threshold forms, may significantly affect the course and outcome of bipolar disorder (BD). AIM: To compare two samples of BD patients presenting a major depressive episode and a sub-threshold mixed state in terms of global functioning, clinical outcome, social adjustment and quality of life during a 1-year follow-up. METHODS: The sample was composed by 90 subjects (Group 1, D) clinically diagnosed with a major depressive episode and 41 patients (Group 2, Mx) for a sub-threshold mixed state. All patients were administered with a pharmacological treatment and evaluated for depressive, anxious and manic symptoms by common rating scales. Further evaluations included a global assessment of severity and functioning, social adjustment and quality of life. All evaluations were performed at baseline and after 1, 3, 6 and 12 months of treatment. RESULTS: The two groups were no different for baseline as well as improvement in global severity and functioning. Though clearly different for symptoms severity, the amount of change of depressive and anxiety symptoms was also no different. Manic symptoms showed instead a trend to persist over time in group 2, whereas a slight increase of manic symptoms was observed in group 1, especially after 6 months of treatment. Moreover, in group 1, some manic symptoms were also detected at the Young Mania Rating Scale (n = 24, 26.6%). Finally, improvement in quality of life and social adjustment was similar in the two groups, though a small trend toward a faster improvement in social adjustment in group 1. CONCLUSIONS: Sub-threshold mixed states have a substantial impact on global functioning, social adjustment and subjective well-being, similarly to that of acute phases, or at least major depression. In particular, mixed features, even in their sub-threshold forms, tend to be persistent over time. Finally, manic symptoms may be still often underestimated in depressive episodes, even in patients for BD.

Cardiologic side effects of psychotropic drugs.

Psychotropic drugs can produce cardiovascular side effects associated with a degree of cardiotoxicity. The coexistence of a heart disease complicates the management of mental illness, can contribute to a reduced quality of life and a worse illness course. The co-occurrence of psychiatric disorders in cardiac patients might affect the clinical outcome and morbidity. Moreover, the complex underlying mechanism that links these two conditions remains unclear. This paper discusses the known cardiovascular complications of psychotropic drugs and analyzes the important implications of antidepressive treatment in patients with previous cardiac history.

Sexual behavior in women with bipolar disorder.

INTRODUCTION: There is a lack of studies regarding sexuality and sexual behavior in women with bipolar disorder. The aim of this study is to investigate sexual behavior in women affected by bipolar disorder in order to stimulate interest and debate in this area of care. METHODS: Sixty women (30 BD I and 30 BD II) consent to participate in the study and were included in the sample. Moreover, sixty female healthy subjects without histories of psychiatric disorders were recruited as normal controls. Patients and healthy subjects were given the Sexual Interest and Sexual Performance Questionnaire, a questionnaire devised to explore various aspects of sexual behavior. RESULTS: The results of the present study suggest an increase of sexual interest in patients with BD I as compared both with BD II patients and healthy controls. In women with BD I such increase of interest was detected on some items of section I of the Sexual Interest and Sexual Performance Questionnaire, in particular "Actual Value of Sexuality" and "Implicit Sexual Interest", which implicitly explore sexual interest without overtly focusing upon sexual problems. Moreover, we observed a higher desired frequency of intercourse in women with BD I than BD II and a higher occurrence of repeated sexual intercourse in women with BD I than BD II. CONCLUSIONS: The main finding of the present study was an increase of sexual interest in BD I as compared with BD II female patients and normal controls. This result was detected when sexual interest was explored implicitly. Our study is limited by the small size of our subject groups. Further investigations on larger subject samples are needed to better clarify particular aspects of sexual behavior of BD patients.

Cardiologic side effects of psychotropic drugs / 老年心脏病学杂志（英文版）

Psychotropic drugs can produce cardiovascular side effects associated with a degree of cardiotoxicity.The coexistence of a heart disease complicates the management of mental illness,can contribute to a reduced quality of life and a worse illness course.The co-occurrence of psychiatric disorders in cardiac patients might affect the clinical outcome and morbidity.Moreover,the complex underlying mechanism that links these two conditions remains unclear.This paper discusses the known cardiovascular complications of psychotropic drugs and analyzes the important implications of antidepressive treatment in patients with previous cardiac history.

Behavioural addictions in bipolar disorder patients: role of impulsivity and personality dimensions.

BACKGROUND: Behavioural addictions (BAs) can be understood as disorders characterized by repetitive occurrence of impulsive and uncontrolled behaviours. Very few studies have investigated their association with mood disorders. The present study was undertaken to determine the prevalence of the main behavioural addictions in a sample of bipolar outpatients in euthymic phase or stabilised by medications and to investigate the role of impulsivity and temperamental and character dimensions. METHODS: One-hundred-fifty-eight Bipolar Disorder (BD) (DSM-IV) outpatients were assessed with tests designed to screen the main behavioural addictions: pathological gambling (SOGS), compulsive shopping (CBS), sexual (SAST), Internet (IAD), work (WART) and physical exercise (EAI) addictions. TCI-R and BIS-11 were administered to investigate impulsivity and personality dimensions mainly associated with BAs. The clinical sample has been compared with 200 matched healthy control subjects. RESULTS: In bipolar patients, 33% presented at least one BA respect to the 13% of controls. Significantly higher scores at the scales for pathological gambling (p<.001), compulsive buying (p<.05), sexual (p<.001) and work addictions (p<.05) have been found. Self-Directness (p=.007) and Cooperativeness (p=.014) scores were significantly lower while impulsivity level was significantly higher (p=.007) in bipolar patients with BA than those without BA. CONCLUSIONS: To our knowledge, this is the first study investigating the prevalence of behavioural addictions in BD showing a significant association of these disorders. BAs are more frequent in bipolar patients than in healthy controls and are related to higher impulsivity levels and character immaturity.

Clinical features, response to treatment and functional outcome of bipolar disorder patients with and without co-occurring substance use disorder: 1-year follow-up.

INTRODUCTION: Bipolar disorder patients (BP) with comorbid Substance Use Disorder (SUD) may present clinical features that could compromise adherence and response to pharmacological treatment. The purpose of this study was to examine clinical and psychopathological features of BP with and without comorbid SUD in a real-world setting. METHODS: The sample was composed by 131 affective patients. Sixty-five patients were affected by Bipolar Disorder I (BP-I, 49.2%), 29 by Bipolar Disorder II (BP-II, 22.3%) and 37 by Cyclothymic Disorder (CtD, 28.5%), according to DSM-IV. Sixty-six patients were diagnosed for a comorbid SUD. All patients have been submitted to psychometric assessment with Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Young Mania Rating Scale (YMRS), Global Assessment Scale (GAS), Social Adjustment Self-reported Scale (SASS), Quality of Life Scale (QoL), at baseline and repeated follow-up periods (1, 3, 6, 12 months). RESULTS: BP comorbid for SUD were more likely diagnosed as BP-II and CtD and were less likely to present a moderate-severe manic symptomatology. Furthermore, personality disorders were more frequent in SUD patients than in non-comorbid BP. BP with SUD were not different for primary outcome measure (HDRS, HARS, YMRS, GAS) from non-comorbid BP; however, BP with SUD were significantly more impaired in social functioning (SASS) at any stage of the follow-up and poor functioning increased the risk of relapse in substance use during treatment. Finally, SUD comorbidity did not represent a risk factor for treatment drop-out, while in our sample young age, low treatment dosage and BP-I diagnosis were significantly associated with drop-out. DISCUSSION: The primary finding of this work is that BP with comorbid SUD are significantly more compromised in social functioning. Second, these patients were less likely to be diagnosed for BP-I and to present a severe manic symptomatology. Finally, we found that the diagnosis of SUD, but young age, low treatment dosage and BP-I diagnosis to be risk factors for treatment drop-out. Physicians should be alert to these differences in their clinical practice.

Duloxetine for premenstrual dysphoric disorder: a pilot study.

OBJECTIVE: Premenstrual dysphoric disorder (PMDD) is a complex clinical syndrome that is notoriously difficult to treat. The purpose of the present study was to provide preliminary data on the effectiveness of duloxetine in PMDD. RESEARCH DESIGN AND METHODS: Fifty-five women with PMDD were treated with a 60 mg/day dosage of duloxetine for two menstrual cycles. Responses were assessed at first and second treatment cycle. MAIN OUTCOME MEASURES: Outcome measures included a visual analogue scale, the Zung Self-rating Scale for Depression, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale and the Clinical Global Impressions Scale. RESULTS: Fifty patients completed the trial. All had significant improvement of depression and anxiety and response, defined as a 50% decrease in daily symptom scores, occurred in 39 (78%) patients. The effects of active treatment were marked by the first active cycle of menstruation. CONCLUSIONS: Duloxetine 60 mg/day was effective in reducing PMDD symptoms and generally well tolerated. Limitations of the study were open-label design and lack of placebo control. However, the results appeared to be strong and consistent across measures. Adverse events (nausea, insomnia, poor appetite) were low. Further studies are needed to confirm these results.