The role of income inequality as an ecological determinant of mental health: A nation-wide multilevel analysis on an Italian sample.

INTRODUCTION: Income inequality, a pivotal determinant of general and mental health, operates through intricate mechanisms at various geographical scales. While established at country or region levels, the impact of lower-level (municipal or neighborhood) inequality remains inconsistent. This study explores the influence of regional- and municipal-level income inequality on individual psychological distress during the COVID-19 pandemic in Italy, employing a multilevel data analysis. MATERIALS AND METHODS: In a post hoc analysis of data from the first wave of the pandemic (March to April 2020), three hierarchical levels were considered: individual participants, municipalities, and regions. Depressive and anxiety symptoms were measured using the PHQ-9 and GAD-7 scales, while the Gini coefficient gauged income inequality at municipal and regional levels. The analysis incorporated demographic variables as potential confounders. RESULTS: The study encompassed 21 regions, 3,900 municipalities, and 21,477 subjects. Income inequality at both regional and municipal levels exhibited associations with distress scores, suggesting independent effects. Notably, higher distress scores were identified in southern regions with elevated inequality, despite a more substantial COVID-19 impact in the north. DISCUSSION: Findings contribute to existing literature by emphasizing the independent impact of lower-level (municipal) and higher-level (regional) income inequality on population psychopathology. The study supports theories suggesting diverse pathways through which inequality at different levels influences health, such as potential associations with healthcare system dysfunction at the regional level and welfare dysfunction at the municipal level. The observed north-south gradient in distress scores highlights the need for psychosocial interventions to alleviate income inequality, especially in historically disadvantaged southern regions. Future research should explore the nuanced interplay between income inequality and various ecological variables to provide a comprehensive understanding of its health impact.

Early parathyroid hormone (PTH) level as a predictor of post-surgical hypoparathyroidism.

INTRODUCTION: Post-operative hypocalcemia and postoperative persistent hypoparathyroidism remain the most common complications after thyroidectomy. Many approaches have been developed to prevent them, but actually, a common protocol is not yet individuated. MATERIALS AND METHODS: We retrospectively analyzed the results of a prospectively collected database. We dosed PTH preoperatively and 4 h after surgery (PTH_4); calcium was evaluated preoperatively, on the first (I_POD) and on the second postoperative day (II_POD). Hypocalcemia was defined when calcium <8 mg/dl. PTH_4 and I_POD calcium serum levels are identified to predict postoperative hypocalcemia. RESULTS: Three hundred and forty-eight patients were enrolled, 37 patients resulted as hypocalcemic on I_POD and 41 on the II_POD. PTH_4 is related to I_POD (p < 0.001, r = 0.45) and II_POD (p < 0.001, r = 0.44) calcemia. PTH_4-cut-off predicting I_POD hypocalcemia was 10.50 pg/ml (sensitivity: 78.7%, specificity: 72.7%). A PTH_4 value of 11.5 pg/ml is able to predict hypocalcemia during II_POD (sensitivity: 76.5%, specificity: 69.2%). We set up a combined test to predict II_POD hypocalcemia, using PTH_4 and I_POD calcium (sensitivity: 77.8%, specificity: 89.9%). CONCLUSION: This research shows the association between PTH_4 and postoperative hypocalcemia. The PTH_4 cut-off to predict I_POD-hypocalcemia was 10.5 pg/ml. We analyzed the calcemia trend during the postoperative period and we realized a combined test using PTH_4 and I_POD-calcemia. This test improves the accuracy of the previous test. Further studies, in particular multicentric, with a larger sample are necessary to validate the combined model.

Current experimental and early investigational agents for cardiac fibrosis: where are we at?

INTRODUCTION: Myocardial fibrosis (MF) is induced by factors activating pro-fibrotic pathways such as acute and prolonged inflammation, myocardial ischemic events, hypertension, aging process, and genetically-linked cardiomyopathies. Dynamics and characteristics of myocardial fibrosis development are very different. The broad range of myocardial fibrosis presentations suggests the presence of multiple potential targets. AREA COVERED: Heart failure treatment involves medications primarily aimed at counteracting neurohormonal activation. While these drugs have demonstrated efficacy against MF, not all specifically target inflammation or fibrosis progression with some exceptions such as RAAS inhibitors. Consequently, new therapies are being developed to address this issue. This article is aimed to describe anti-fibrotic drugs currently employed in clinical practice and emerging agents that target specific pathways, supported by evidence from both preclinical and clinical studies. EXPERT OPINION: Despite various preclinical findings suggesting the potential utility of new drugs and molecules for treating cardiac fibrosis in animal models, there is a notable scarcity of clinical trials investigating these effects. However, the pathology of damage and repair in the heart muscle involves a complex network of interconnected inflammatory pathways and various types of immune cells. Our comprehension of the positive and negative roles played by specific immune cells and cytokines is an emerging area of research.

Situs viscerum inversus and abdominal aortic aneurysm: A systematic review of a rare association.

Situs viscerum inversus (SVI) is a very rare condition in that abdominal and thoracic organs are located reversed. Abdominal aortic aneurysm (AAA) is a life-threatening pathology due to progressive aortic enlargement until the rupture. The association between SVI and AAA is very infrequent. The aim of this study is to identify the surgical procedures available to treat AAA in SVI. We performed a literature review of all studies about AAA in SVI patients, analyzing PubMed/MEDLINE, EMBASE, Web of Science (WOS), Google Scholar databases. The survey includes all publications until June 2023. The outcomes include demographic findings, type of surgical procedure, intraoperative and postoperative complications, follow-up. A total of 12 studies, including 12 patients, were considered eligible for the review. AAA mean size was 70.5 mm (range: 55-90 mm); the most common localization was in the infrarenal aortic portion. 6 studies reported data on elective surgery, and 6 on emergency procedures. In one case endovascular treatment was performed. No intraoperative complications are reported; 3 postoperative complications are registered. Medium follow-up period was 13.5 months (range: 3-60). According to the available literature, the treatment of AAA in SVI is feasible and does not show an incremented morbidity compared to patients with a normal visceral configuration. This treatment seems to be effective also in case of endovascular treatment. AAA treatment in SVI should be performed (especially in elective settings) in high volume centers where it is possible to bring on collaboration across different surgical specialists.

Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol.

INTRODUCTION: Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs. AIM:  Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. AIM: Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. METHODS: We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers. CONCLUSIONS: Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement.

Divergent emotional and autonomic responses to Cyberball in patients with opioid use disorder on opioid agonist treatment.

The perception of social exclusion among patients with opioid use disorder (OUD) could be affected by long-term opioid use. This study explores the emotional and cardiac autonomic responses to an experience of ostracism in a sample of participants with OUD on opioid agonist treatment (OAT). Twenty patients with OUD and twenty healthy controls (HC) performed a ball-tossing game (Cyberball) with two conditions: Inclusion and Ostracism. We measured self-reported ratings of perceived threat towards one's fundamental needs and respiratory sinus arrhythmia (RSA) immediately after the game and 10 min after Ostracism (Reflective stage). Following ostracism, participants with OUD self-reported blunted feelings of threat to the fundamental need to belong. RSA levels were significantly suppressed immediately after ostracism and during the Reflective stage in comparison with HC, indicating an autonomic alteration in response to threatening social situations. Finally, only among HC higher perceived threats towards fundamental needs predicted increases in RSA levels, suggesting an adaptive vagal regulation in response to a perceived threat. Conversely, among patients with OUD the subjective response to ostracism was not associated with the autonomic reaction. OAT may have a protective effect against negative feelings of ostracism. However patients with OUD on OAT present poor autonomic regulation in response to social threats, which could reflect their trait hypersensitivity to social rejection.

Editorial: What is computational psychopathology, and why do we need it?

Computational Psychopathology is an emerging discipline, which is based around the theoretical and mechanistic focus of explanatory psychopathology and computational psychiatry, and reflects the general move in psychiatric research away from whole disorders to component symptoms or transdiagnostic processes. In this Editorial, we present a brief summary of these disciplines and how they combine together to form a 'Computational Psychopathology', and present a brief possible taxonomy. We highlight the papers that form part of this Special Issue, along with their place in our putative taxonomy. We conclude this Editorial by highlighting the benefits of a Computational Psychopathology for research into mental health.

Anhedonia and sensitivity to punishment in schizophrenia, depression and opiate use disorder.

BACKGROUND: From a behavioural perspective anhedonia is defined as diminished interest in the engagement of pleasurable activities. Despite its presence across a range of psychiatric disorders, the cognitive processes that give rise to anhedonia remain unclear. METHODS: Here we examine whether anhedonia is associated with learning from positive and negative outcomes in patients diagnosed with major depression, schizophrenia and opiate use disorder alongside a healthy control group. Responses in the Wisconsin Card Sorting Test - a task associated with healthy prefrontal cortex function - were fitted to the Attentional Learning Model (ALM) which separates learning from positive and negative feedback. RESULTS: Learning from punishment, but not from reward, was negatively associated with anhedonia beyond other socio-demographic, cognitive and clinical variables. This impairment in punishment sensitivity was also associated with faster responses following negative feedback, independently of the degree of surprise. LIMITATIONS: Future studies should test the longitudinal association between punishment sensitivity and anhedonia also in other clinical populations controlling for the effect of specific medications. CONCLUSIONS: Together the results reveal that anhedonic subjects, because of their negative expectations, are less sensitive to negative feedbacks; this might lead them to persist in actions leading to negative outcomes.

Psychopathology, Personality and Depression after Acute Coronary Syndrome: A Network Analysis in an Italian Population.

Several biopsychosocial factors are associated with the onset of a Major Depressive Episode (MDE) after cardiovascular events. However, little is known of the interaction between trait- and state-like symptoms and characteristics and their role in predisposing cardiac patients to MDEs. Three hundred and four subjects were selected among patients admitted for the first time at a Coronary Intensive Care Unit. Assessment comprised personality features, psychiatric symptoms and general psychological distress; the occurrences of MDEs and Major Adverse Cardiovascular Events (MACE) were recorded during a two-year follow-up period. Network analyses of state-like symptoms and trait-like features were compared between patients with and without MDEs and MACE during follow-up. Individuals with and without MDEs differed in sociodemographic characteristics and baseline depressive symptoms. Network comparison revealed significant differences in personality features, not state-like symptoms: the group with MDEs displayed greater Type D personality traits and alexithymia as well as stronger associations between alexithymia and negative affectivity (edge differences between negative affectivity and difficulty identifying feelings was 0.303, and difficulty describing feelings was 0.439). The vulnerability to depression in cardiac patients is associated with personality features but not with state-like symptoms. Personality evaluation at the first cardiac event may help identify individuals more vulnerable to development of an MDE, and they could be referred to specialist care in order to reduce their risk.

Heart Rate Fractality Disruption as a Footprint of Subthreshold Depressive Symptoms in a Healthy Population.

Objective: Psychopathology (and depression in particular) is a cardiovascular risk factor independent from any co-occurring pathology. This link is traced back to the mind-heart-body connection, whose underlying mechanisms are still not completely known. To study psychopathology in relation to the heart, it is necessary to observe the autonomic nervous system, which mediates among the parts of that connection. Its gold standard of evaluation is the study of heart rate variability (HRV). To investigate whether any association exists between the HRV parameters and sub-threshold depressive symptoms in a sample of healthy subjects. Method: In this cross-sectional study, two short-term HRV recordings (5 min - supine and sitting) have been analyzed in 77 healthy subjects. Here we adopted a three-fold approach to evaluate HRV: a set of scores belonging to the time domain; to the frequency domain (high, low, and very low frequencies) and a set of 'nonlinear' parameters. The PHQ-9 (Patient Health Questionnaire-9) scale was used to detect depressive symptoms. Results: Depressive symptoms were associated only with a parameter from the non-linear approach and specifically the long-term fluctuations of fractal dimensions (DFA-α2). This association remained significant even after controlling for age, gender, BMI (Body-Mass-Index), arterial hypertension, anti-hypertensive drugs, dyslipidemia, and smoking habits. Moreover, the DFA-α2 was not affected by the baroreflex (postural change), unlike other autonomic markers. Conclusions: Fractal analysis of HRV (DFA-α2) allows then to predict depressive symptoms below the diagnostic threshold in healthy subjects regardless of their health status. DFA-α2 may be considered as an imprint of subclinical depression on the heart rhythm.

Correlation between anthropometric data and preparatory maneuvers difficulties during laparoscopic right liver resections: a single center prospective study.

PURPOSE: The difficulty of laparoscopic right liver resections (LRLR) is mainly associated with their poor accessibility. Anthropometric data rather than BMI was reported to predict transection time and blood loss. Aim of the study was to evaluate the correlation between anthropometric data and preparatory manoeuvres difficulties during LRLR. METHODS: All patients who underwent LRLR requiring full right liver mobilization from November 2019 to March 2021 were prospectively included in the study. Data on surgeons' difficulty perceptions on liver mobilization (LM), isolation of right hepatic vein (RHVI), liver manageability and visibility were rated with a 5-point scale. Data on cranio-caudal liver diameters (CCliv), CHALLENGE Index (CCliv/latero-lateral abdomen diameter), times needed to LM and RHVI were collected. RESULTS: Sixty-five patients (29 wedge and 36 anatomical resections) with a median BMI of 25.5 were analysed. One patient required open conversion due to oncological reason. No correlations between BMI and CCliv or CHALLENGE Index were found. Larger CCliv diameter correlated with longer time for both RHVI (r = 0.589, p = 0.002) and LM (r = 0.222, p = 0.049). Higher CHALLENGE index correlated with longer time for RHVI (r = 0.589, p = 0.002). The CHALLENGE index showed a linear correlation with difficulty to the isolation of RHV (r = 0.327, p = 0.045), whilst the liver manipulation difficulty increased with latero-lateral liver diameter (r = 0.244, p = 0.033). BMI had no correlation with the duration of preparatory maneuvers neither with surgeons' difficulties. CONCLUSIONS: Anthropometric data can help to anticipate the difficulty of preparatory maneuvers during laparoscopic right liver resections.

Adrenocortical carcinoma metastasis. A long story.

INTRODUCTION: Adrenocortical Carcinoma (ACC) is an uncommon adrenal tumor with a predilection for the female population. CASE REPORT: A 55-year-old woman was referred to our attention to undergo laparoscopic cholecystectomy for symptomatic gallstone disease. She underwent a left adrenalectomy for ACC 5 years before; the follow-up was negative for relapse. During the preoperative study an Ultrasound Scanner study demonstrated a liver lesion in S6 - S7, confirmed by a Magnetic Resonance. A PET identified also a lesion on L1 vertebra. The hepatic US-guided biopsy resulted positive for ACC metastasis. After a muldisciplinary evaluation, the patients underwent a local approach to treat both hepatic and vertebral lesions. Laparoscopic cholecystectomy was performed in order to prevent biliary and pancreatic complications. The minimally invasive technique was adopted in order to reduce surgical trauma in oncological patients, even the previous abdominal surgery and percutaneous hepatic treatment. The patient is alive, with no recurrence after 12 months from local treatments. CONCLUSION: This is a very unusual case of double ACC metastases, discovered after the end of standard follow-up and locally treated. The patient is recurrence-free 12 months after these procedures. Minimally invasive approach to treat symptomatic cholecystectomy was used in order to avoid pancreato-biliary complications. This study emphasized the necessity to realize tailored protocols for the follow-up of rare neoplasia, as ACC. KEY WORDS: Adrenocortical carcinoma, Cholecystectomy, Liver metastasis, Thermoablation.

Malondialdehyde as a candidate biomarker for bipolar disorder: A meta-analysis.

Malondialdehyde (MDA) represents one of the final products of lipid peroxidation that is thought to be enhanced and accelerated in patients affected by bipolar disorder (BD). Purpose of the present article is to critically summarize the available data about MDA as a candidate biomarker for BD. First, we carried out a systematic review of the literature selecting those papers that evaluated MDA levels in BD. Then, we performed two separate meta-analyses: one of the studies that compared healthy controls (HC) with unmedicated BD and one with the studies that assessed MDA levels before and after treatment in BD, showing that bipolar patients experience more oxidative stress than healthy subjects and that treatment is effective in reducing MDA levels. In the first set of studies, we also explored through a meta-regression whether age, gender and experiencing an episode specifically influenced the difference between BD and HC in MDA levels. Bipolar patients compared to healthy subjects had higher MDA levels (SMD: 0.94, 95% CI: 0.23-1.64). Age (p < 0.01), gender (p < 0.01) and the presence of a current mood episode (p < 0.01) significantly influenced MDA plasma/serum levels. Specifically, studies that included more female, older subjects and more BD in euthymia were more likely to have higher MDA levels. Finally, patients after treatment had lower levels of MDA compared to baseline (SMD: -0.52, 95% CI: -0.85 -0.19). More studies are needed to draw definitive conclusions.

Amiodarone in ventricular arrhythmias: still a valuable resource?

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Autonomic vulnerability to biased perception of social inclusion in borderline personality disorder.

BACKGROUND: Individuals with Borderline Personality Disorder (BPD) feel rejected even when socially included. The pathophysiological mechanisms of this rejection bias are still unknown. Using the Cyberball paradigm, we investigated whether patients with BPD, display altered physiological responses to social inclusion and ostracism, as assessed by changes in Respiratory Sinus Arrhythmia (RSA). METHODS: The sample comprised 30 patients with BPD, 30 with remitted Major Depressive Disorder (rMDD) and 30 Healthy Controls (HC). Self-report ratings of threats toward one's fundamental need to belong and RSA reactivity were measured immediately after each Cyberball condition. RESULTS: Participants with BPD showed lower RSA at rest than HC. Only patients with BPD, reported higher threats to fundamental needs and exhibited a further decline in RSA after the Inclusion condition. CONCLUSIONS: Individuals with BPD experience a biased appraisal of social inclusion both at the subjective and physiological level, showing higher feelings of ostracism and a breakdown of autonomic regulation to including social scenarios.

DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization.

Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.

Early parent-child interactions and substance use disorder: An attachment perspective on a biopsychosocial entanglement.

This review aims to elucidate environmental and genetic factors, as well as their epigenetic and neuroendocrine moderators, that may underlie the association between early childhood experiences and Substance Use Disorders (SUD), through the lens of parental attachment. Here we review those attachment-related studies that examined the monoaminergic systems, the hypothalamic pituitary adrenal stress response system, the oxytoninergic system, and the endogenous opioid system from a genetic, epigenetic, and neuroendocrine perspective. Overall, the selected studies point to a moderating effect of insecure attachment between genetic vulnerability and SUD, reasonably through epigenetic modifications. Preliminary evidence suggests that vulnerability to SUDs is related with hypo-methylation (e.g. hyper-expression) of high-risk polymorphisms on the monoaminergic and hypothalamic pituitary adrenal system and hyper-methylation (e.g. hypo-expressions) of protective polymorphisms on the opioid and oxytocin system. These epigenetic modifications may induce a cascade of neuroendocrine changes contributing to the subclinical and behavioural manifestations that precede the clinical onset of SUD. Protective and supportive parenting could hence represent a key therapeutic target to prevent addiction and moderate insecure attachment.

The Relation between the Plasma Concentrations of Long-Acting Atypical Antipsychotics and Clinical Effectiveness in Patients Affected by Schizophrenia or Schizoaffective Disorder: A Comprehensive Overview.

Atypical antipsychotic depot medications are currently recommended for patients with schizophrenia (SCZ) to prevent relapse and ameliorate the long-term prognosis of these patients. This review critically summarizes the available data about the association between the plasma concentrations of long-acting Second- Generation Antipsychotics (SGAs) and the clinical effectiveness of these compounds in patients affected by SCZ or schizoaffective disorder. Our question is if the measurement of these concentrations can be helpful for clinicians in predicting treatment response and clinical stabilization of patients. Bibliographic research on the main databases was performed, and 13 studies were finally included in this review. Contrasting results were found between plasma concentrations of long-acting injectable (LAI) risperidone and clinical amelioration according to rating scale scores. Data are too scanty to draw conclusions for olanzapine and paliperidone. In contrast, despite small sample sizes, data are quite concordant in showing a relation between long-acting SGA plasma concentrations and D2 receptor occupancy. Despite the preliminary encouraging results, particularly for D2 receptor occupancy, future research with larger samples will have to confirm the clinical usefulness of measuring LAI SGA plasma concentrations to predict the clinical response of patients affected by severe mental conditions such as SCZ.