Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1ß which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

Geometric Reliability of Super-Resolution Reconstructed Images from Clinical Fetal MRI in the Second Trimester.

Fetal Magnetic Resonance Imaging (MRI) is an important noninvasive diagnostic tool to characterize the central nervous system (CNS) development, significantly contributing to pregnancy management. In clinical practice, fetal MRI of the brain includes the acquisition of fast anatomical sequences over different planes on which several biometric measurements are manually extracted. Recently, modern toolkits use the acquired two-dimensional (2D) images to reconstruct a Super-Resolution (SR) isotropic volume of the brain, enabling three-dimensional (3D) analysis of the fetal CNS.We analyzed 17 fetal MR exams performed in the second trimester, including orthogonal T2-weighted (T2w) Turbo Spin Echo (TSE) and balanced Fast Field Echo (b-FFE) sequences. For each subject and type of sequence, three distinct high-resolution volumes were reconstructed via NiftyMIC, MIALSRTK, and SVRTK toolkits. Fifteen biometric measurements were assessed both on the acquired 2D images and SR reconstructed volumes, and compared using Passing-Bablok regression, Bland-Altman plot analysis, and statistical tests.Results indicate that NiftyMIC and MIALSRTK provide reliable SR reconstructed volumes, suitable for biometric assessments. NiftyMIC also improves the operator intraclass correlation coefficient on the quantitative biometric measures with respect to the acquired 2D images. In addition, TSE sequences lead to more robust fetal brain reconstructions against intensity artifacts compared to b-FFE sequences, despite the latter exhibiting more defined anatomical details.Our findings strengthen the adoption of automatic toolkits for fetal brain reconstructions to perform biometry evaluations of fetal brain development over common clinical MR at an early pregnancy stage.

Epicardial Adipose Tissue and Cardiac Arrhythmias: Focus on Atrial Fibrillation.

Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence increases with age. AF is strongly associated with an increased risk of stroke, heart failure and cardiovascular mortality. Among the risk factors associated with AF onset and severity, obesity and inflammation play a prominent role. Numerous recent evidence suggested a role of epicardial adipose tissue (EAT), the visceral fat depot of the heart, in the development of AF. Several potential arrhythmogenic mechanisms have been attributed to EAT, including myocardial inflammation, fibrosis, oxidative stress, and fat infiltration. EAT is a local source of inflammatory mediators which potentially contribute to atrial collagen deposition and fibrosis, the anatomical substrate for AF. Moreover, the close proximity between EAT and myocardium allows the EAT to penetrate and generate atrial myocardium fat infiltrates that can alter atrial electrophysiological properties. These observations support the hypothesis of a strong implication of EAT in structural and electrical atrial remodeling, which underlies AF onset and burden. The measure of EAT, through different imaging methods, such as echocardiography, computed tomography and cardiac magnetic resonance, has been proposed as a useful prognostic tool to predict the presence, severity and recurrence of AF. Furthermore, EAT is increasingly emerging as a promising potential therapeutic target. This review aims to summarize the recent evidence exploring the potential role of EAT in the pathogenesis of AF, the main mechanisms by which EAT can promote structural and electrical atrial remodeling and the potential therapeutic strategies targeting the cardiac visceral fat.

Neurobiologically Based Stratification of Recent-Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes.

BACKGROUND: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures. METHODS: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470). RESULTS: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures. CONCLUSIONS: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostically and improve development of stratified treatments.

Effects of pharmacological treatments on neuroimaging findings in borderline personality disorder: A review of FDG-PET and fNIRS studies.

BACKGROUND: Borderline personality disorder (BPD) is a serious mental condition characterized by instability in identity, interpersonal relationships, emotion regulation and impulsivity. These symptoms seem to be associated to specific brain alterations, which have been largely investigated. In particular, positron emission tomography (PET) and functional near-infrared spectroscopy (fNIRS) have demonstrated abnormalities in brain metabolism and hemodynamics in BPD, specifically in the fronto-limbic system. However, the role of medications on brain metabolism and hemodynamics in BPD is still largely unknown. METHODS: We conducted a search on PubMed, Scopus and Web of Science of PET and fNIRS studies exploring the effect of medications on brain metabolism and hemodynamics in BPD. A total of 10 studies met the inclusion criteria. RESULTS: Overall, PET studies showed an effect of psychotropic agents on brain metabolism, especially in frontal and temporal areas. Also, higher metabolic rates in frontal areas were found to correlate with clinical improvements. In contrast, fNIRS investigations reported an inconclusive or absent effects on brain hemodynamics in BPD patients. LIMITATIONS: The small sample size, the elevated percentage of women, the heterogeneity in pharmacological agents and the presence of comorbidities limit the conclusions of the present review. CONCLUSIONS: Serotoninergic agents and second-generation antipsychotics produce changes in frontal and temporal metabolism in BPD, which appear to correlate with clinical improvements. Differently, brain hemodynamics do not seem to be significantly affected by the most commonly prescribed drugs in BPD, suggesting that the therapeutic actions of medications are not mediated by changes in neural hemodynamics.

The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender.

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted ß for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted ß for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted ß for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP­the BDNF rs6265 Met/Met homozygosis­was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Using combined environmental-clinical classification models to predict role functioning outcome in clinical high-risk states for psychosis and recent-onset depression.

BACKGROUND: Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning. AIMS: We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample. METHOD: Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD). RESULTS: Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD. CONCLUSIONS: Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study.

BACKGROUND: Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. MATERIAL AND METHODS: 68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. RESULTS: At baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. CONCLUSIONS: The longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders.

Relationships between global functioning and neuropsychological predictors in subjects at high risk of psychosis or with a recent onset of depression.

OBJECTIVE: Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational functioning, and cognition. METHODS: 102 CHR subjects and 110 patients with recent onset depression (ROD) were recruited. Global assessment of functioning (GAF) related to symptoms (GAF-S) and disability (GAF-D). and global functioning social (GF-S) and role (GF-R), at baseline and of the previous month and year, and a set of neurocognitive measures, were used for classification and regression. RESULTS: Neurocognitive measures related to GF-R at baseline (r = 0.20, p = 0.004), GF-S at present (r = 0.14, p = 0.042) and of the past year (r = 0.19, p = 0.005), for GAF-F of the past month (r = 0.24, p < 0.001) and GAF-D of the past year (r = 0.28, p = 0.002). Classification reached values of balanced accuracy of 61% for GF-R and GAF-D. CONCLUSION: We found that neurocognition was related to psychosocial functioning. More specifically, a deficit in executive functions was associated to poor social and occupational functioning.

ITAlian partnership for psychosis prevention (ITAPP): Improving the mental health of young people.

BACKGROUND: The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. METHODS: An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan-Meier failure function complemented the analyses. RESULTS: The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12-39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3-14.1) at 1 year to 15.9% (95% CI 10.6-23.3) at 2 years, 21.8% (95% CI 14.9-31.3) at 3 years, 34.8% (95% CI 24.5-47.9) at 4 years, and 51.9% (95% CI 36.3-69.6) at 5 years. CONCLUSIONS: The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

Neuroinflammation in Major Depressive Disorder: A Review of PET Imaging Studies Examining the 18-kDa Translocator Protein.

BACKGROUND: Major Depressive Disorder (MDD) is a severe psychiatric disorder whose pathological mechanisms are largely unknown. In the field of immuno-psychiatry, several evidences suggested a prominent role of inflammation in MDD not only in peripheral immune system but also in the brain. To date, brain inflammation is traceable in vivo with Positron Emission Tomography (PET), through the quantification of the expression of 18-kda Translocator Protein (TSPO) by active microglia. In this context, this review aimed to summarize the results of all in vivo PET imaging studies that evaluated microglia activation in MDD. METHODS: A bibliographic search in PubMed up to June 2020 was performed. A total of 9 studies that used first and second generation TSPO radiotracers met our inclusion criteria. RESULTS: Overall the results suggested the presence of TSPO upregulation in MDD, especially in anterior cingulate cortex, prefrontal cortex, hippocampal formation and insula. Notably, from a therapeutic point of view, results suggested that the symptoms amelioration, caused by both antidepressant medication and cognitive behavioural therapy, may be accompanied by reduced inflammatory status in the brain. Finally, a positive effect of the anti-inflammatory treatment with a cyclooxygenase inhibitor has also been observed. LIMITATIONS: The heterogeneity across the studies in experimental designs, sample selection and methods limited the studies comparison. CONCLUSIONS: These findings supported the presence of neuroinflammation in MDD, suggesting that microgliosis may be an important pathophysiological mechanism that merits further investigation as a potential target for novel treatment strategies.

Executive Functions in panic disorder: A mini-review.

BACKGROUND: Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks whose aetiology might be associated with alterations of the prefrontal-amygdala circuitry. The prefrontal cortex is a key region involved in executive functioning (EF) whose disturbance may imply harsh consequences over personal, social, and working aspects of PD patients. Indeed, defining the real involvement of EF in PD could lead to early assessment, better treatment, and rehabilitation options. These could have a substantial impact on the quality of life of these patients and their caregivers, thus reducing long-term health care needs. METHODS: We reviewed findings from different studies that investigated executive functioning in PD patients using standardized neuropsychological measures. The review was conducted with the Preferred Reported Items for Systematic Reviews and Meta-Analysis (PRISMA). In addition, peer-reviewed human-based research articles were selected and twelve studies were retrieved through a search on PubMed. Four uniquely focused on PD patients, two also included a sample of first-degree relatives, while six included a mixed sample of different psychiatric illnesses, including PD. RESULTS: The majority of the studies found no alterations in PD patients, suggesting that EF might not be a core deficit in this disorder. However, some studies (N = 4) found EF deficits in selective domains, which included attention and set-shifting processes, cognitive flexibility, decision-making abilities, and working memory in PD patients and/or in their first-degree relatives. LIMITATIONS: Unbalanced and small samples, unmonitored therapies, and the heterogeneity of cognitive and diagnostic assessment measures might have limited the generalizability of the results. CONCLUSIONS: Overall, the results point towards the hypothesis that PD patients had preserved EF. However, future studies with standardized methodological procedures and with a gold standard assessment of EF will be required to finally exclude its involvement in the disease.

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Heterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach.

Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ2 = 14.874; P < .001; GMV model: χ2 = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ2 = 1.956; P = 0.162; GMV model: χ2 = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.

Facial emotion recognition in panic disorder: a mini-review of behavioural studies.

BACKGROUND: Panic Disorder (PD) is characterized by unexpected and repeated moments of intense fear or anxiety, which manifest themselves through strong cognitive and behavioural symptoms. However, a clear picture of how impairments in recognition and processing of facial emotions affect the everyday life of PD patients has yet to be delineated. This review attempts to provide an overview of behavioural studies of emotion detection from facial stimuli in PD patients. METHODS: A bibliographic research on PubMed of all studies investigating the recognition and processing of facial emotion stimuli in patients with PD and in high-risk offspring was performed, and nine articles (yrs: 2000 to 2019) were discovered. RESULTS: In several of the reviewed studies, PD patients showed significant deficits in detecting (particularly negative) emotions in facial stimuli. These impairments were also found in the offspring of parents with PD and high-risk individuals. LIMITATIONS: Inferences are constrained by methodological heterogeneity, included but not limited to cross-study variability in the stimuli employed, and in the clinical characterization of PD patients. CONCLUSIONS: In general, the results of this survey confirm that deficits in processing facially conveyed negative emotions should be considered a core impairment in PD. However, future larger and more homogenous studies are warranted to better highlight the connection between emotion recognition and PD.

Sexual Dimorphism in the Brain Correlates of Adult-Onset Depression: A Pilot Structural and Functional 3T MRI Study.

Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD-especially in regions involved in attention processing and in the brain default mode-potentially supporting cognitive and symptom differences between sexes.

Borderline personality disorder, metacognition and psychotherapy.

BACKGROUND: Deficits in the ability to think about own mental states and that of others (mindreading) are seen as key aspects of borderline personality disorder (BPD), which could sustain BPD symptoms. Interestingly, some studies showed that in BPD patients metacognition is selectively compromised and could improve during treatments. However, empirical findings are inconsistent, and it is debatable whether BPD presents a specific profile of mindreading impairments that could improve during treatments. METHODS: We performed a bibliographic research on PubMed , Google Scholar and Scopus of all studies investigating a) the metacognitive functioning in the BPD patients and b) the link between psychotherapy, metacognition improvement and BPD symptomatology. A total of 11 studies met our inclusion criteria and considered metacognition following the definition proposed by Semerari. RESULTS: Overall, the results suggest that BPD metacognitive profile mainly includes difficulties in metacognitive sub-domains of integration, differentiation and mastery. The type of treatment most appropriate to improve metacognitive abilities and reduce symptoms seemed to be a long term treatment and specifically focused on metacognitive deficits. LIMITATIONS: Lack of a control group, small sample sizes and heterogeneity in terms of gender, age, comorbidities and other ongoing treatments are the key limits of the original studies reviewed. CONCLUSIONS: The results sustain the hypothesis of a selective and specific metacognitive impairment in BPD patients that could improve during treatments together with their symptomatology. However, more studies are needed to further investigate the role of metacognition in the effectiveness of treatments.

Childhood trauma and substance use underlying psychosis: a systematic review.

Background: Schizophrenia spectrum disorders (SSD) are mental diseases caused by a combination of genetic susceptibility and a number of environmental factors. Among these factors, the role of traumatic events suffered in childhood, as well as that of substance use, have been of particular research interest. Objectives: To conduct a systematic review to clarify whether there is an interaction between childhood trauma and substance use related to the diagnosis or symptoms of SSD. It was also the objective of this review to collate the associations that may exist between the three variables of the study (trauma, substance use and psychosis). Methods: We conducted a systematic search resulting in 240 articles. We considered all of the original articles that explored childhood trauma and substance use in patients suffering from SSD. Results: Twenty-three articles were selected for this review. Several of the reviewed papers found associations between childhood trauma and substance use with SSD, as well as interactions between trauma and drug use on SSD. Conclusions: The results suggest that childhood trauma and substance use may be present at the basis of psychosis. This double hit on the pathogenesis could have clinical implications, since each of these impacts could be considered a window of opportunity for the primary prevention of SSD.

Introducción: Los trastornos del espectro de la esquizofrenia (SSD) son enfermedades mentales que parecen estar provocadas por una combinación de múltiples factores genéticos y ambientales. Entre los factores ambientales desencadenantes, el papel de los eventos traumáticos sufridos en la infancia y el consumo de sustancias resultan de particular interés para la investigación.Objetivos: Aclarar si existe una interacción entre el trauma infantil y el uso de sustancias relacionadas con el diagnóstico o los síntomas de las SSD. También fue el objetivo de esta revisión cotejar las asociaciones que pueden existir entre las tres variables del estudio (trauma, consumo de sustancias y psicosis).Métodos: Se realizó una búsqueda sistemática que resultó en 240 artículos. Consideramos todos los artículos originales que exploraron el trauma infantil y el consumo de sustancias en pacientes que presentaban trastornos psicóticos.Resultados: 23 artículos fueron seleccionados a los efectos de esta revisión. Varios de los artículos revisados encontraron asociaciones entre el trauma infantil y el consumo de sustancias con SSD, además de interacciones entre trauma y consumo en los trastornos psicóticos.Conclusiones: El doble impacto que representan el trauma en la infancia y el consumo de sustancias en la patogénesis de la enfermedad podría tener implicaciones clínicas por la ventana de oportunidad que supone la intervención en estos factores en la prevención primaria de los trastornos psicóticos.

Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative.

BACKGROUND: Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. STRUCTURE: The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/ ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. CONCLUSIONS: The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.