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Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Background: Depression is one of the most widespread diseases worldwide, with the highest rates of disability. Considering its chronic course, over the years several treatment options have been developed and validated, however still with high relapse rates. Therefore, in recent years, the so-called third wave psychotherapies have been developed for the treatment of psychiatric disorders. Among these, the Metacognitive therapy (MCT) has proven to be effective in treating depression. The aim of this review is to evaluate the efficacy of MCT as monotherapy or adjunctive treatment in reducing depressive symptoms in patients suffering from major depression or dysthymia., Methods: From bibliographic research in PubMed until December 2023, we retrieved 12 original studies meeting our research criteria., Results: The total sample of patients undergoing metacognitive therapy (MCT) included 376 individuals, while the control groups comprised 300 subjects, with a gender ratio of the participants of 0.48 %. The results show that metacognitive therapy is an effective approach in reducing depressive symptoms in patients with a diagnosis of depression or dysthymia when used as add-on therapy, with an efficacy comparable to CBT and superior to pharmacotherapy and as monotherapy, with an efficacy comparable to therapy with antidepressants compared to the control group and compared to cognitive-behavioral therapy with higher rates of reduction of depressive symptoms after treatment and at six months. Preliminary data also indicate its efficacy in terms of reduction of depressive symptoms in elderly people, suggesting its possible use in this population., Limitations: The methodological heterogeneity in terms of treatment protocols of MCT and treatment control as well as the clinical heterogeneity of the sample employed may have limited the generalizability of the results., Conclusions: The results suggest that the use of MCT, both as monotherapy and as an add-on treatment, is a valid therapeutic option for major depression, even at the later stages. However, further studies are needed for deeper our comprehension of the efficacy of MCT in depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs., Methods: A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD., Results: BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the default mode network. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities., Limitations: Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings., Conclusions: The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Strategies of prevention for psychiatric disorders need a deep understanding of the aetiological factors involved in the psychopathological processes. Our twin study aims at disentangling the contributions of genes and environment to schizotypal and hypomanic dimensions, considering the role of stressful life events (LEs) and the quality of family relationships., Methods: The Magical Ideation Scale (MIS) and Perceptual Aberration Scale (PAS) were used to assess positive schizotypy, while Hypomanic Personality Scale (HPS) and its sub-scales were used to investigate proneness to affective disorders. 268 twins (54.5 % female; aged 18.0 ± 6.68) were included. Participants filled out a questionnaire on LEs and their parents provided an evaluation of intra-family relationship (Relationship Quality Index, RQI). Classic univariate twin models for quantitative traits were fitted for scales, and the effects of covariates (LEs and RQI) were assessed., Results: For MIS, HPS and its sub-scales, significant common and unique environmental effects were detected, with genetic factors affecting only HPS Social Vitality sub-scale. Unique environment was the only source of variance of PAS score. The number of recent LEs influenced MIS and PAS models, while RQI score affected MIS model., Limitations: The main limitation of the study is the small sample size, which reduces statistical power and may potentially lead to an underestimation of heritability. Additionally, the cross-sectional design limits the possibility to draw causal considerations., Conclusions: Findings provide preliminary evidence for a significant environmental role in modulating states of vulnerability. Moreover, the expression of positive schizotypy resulted influenced by recent stressors and intra-family relationships., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Background: Over the last two decades, ketamine has gained significant interest in psychiatry as a potential treatment for major depressive disorder (MDD), especially in individuals who are resistant to traditional therapies or are at a high risk of suicide. Task-based functional magnetic resonance imaging (fMRI) studies can provide insight into how ketamine alters brain function and contributes to its antidepressant properties., Methods: This mini-review followed the MOOSE guidelines for systematic reviews of observational studies. We conducted a literature search in PubMed, Web of Science, and Scopus aiming at identifying fMRI studies investigating the effect of ketamine on brain function in MDD., Results: Eight articles were included in the study. Results showed that ketamine affects brain activity in MDD, especially in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, and amygdala. Interestingly, the majority of the reviewed studies showed a correlation between the changes in brain activity induced by ketamine and improvements in clinical depressive symptoms. These correlations involved the prefrontal cortex, ACC, and cortico-cerebellar circuits., Limitations: Lack of longitudinal data on the lasting effects of ketamine on brain activity and the small number of studies., Conclusions: This review identifies key research areas that can enhance our understanding of ketamine's effects on the brain in MDD. It calls for studies on ketamine's mechanisms of action, long-term impact, dose-response optimization, and comparisons with other fast-acting antidepressants. Addressing these areas can optimize ketamine's therapeutic use and reveal new treatment targets., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Postpartum Depression (PPD) exerts a substantial negative effect on maternal well-being post-delivery, particularly among Cesarean Section (C/S) recipients. In this study, we aimed to review the efficacy of perioperative esketamine, the S-enantiomer of ketamine, in preventing PPD incidence and depressive symptoms as measured with the Edinburgh Postnatal Depression Scale (EPDS) after C/S., Methods: A systematic search for relevant articles was conducted in Scopus, PubMed, Web of Sciences, and PsycINFO until April 6, 2024. Meta-analyses were conducted using random-effect models to compare the PPD incidence and EPDS scores via log odds ratio and Hedge's g, respectively, during the first week post-C/S and at 42 days post-C/S in the esketamine and control group., Results: Fourteen studies, including 12 randomized controlled trials and 2 retrospective cohorts, were reviewed. Our meta-analyses found lower PPD incidence during the first week (log odds ratio: -0.956 [95 % confidence interval: -1.420, -0.491]) and at day 42 post-C/S (log odds ratio: -0.989 [95 % confidence interval: -1.707, -0.272]) among patients administered esketamine compared to controls. Additionally, EPDS scores for the esketamine group were significantly lower than controls during the first week (Hedge's g: -0.682 [95 % confidence interval: -1.088, -0.276]) and at day 42 post-C/S (Hedge's g: -0.614 [95 % confidence interval: -1.098, -0.129])., Limitations: Presence of various concomitant medications and heterogeneous study designs., Conclusion: Our review highlights the potential impact of esketamine in PPD prevention, as well as in alleviating depressive symptoms post-C/S, regardless of PPD occurrence, therefore suggesting the benefits of adding esketamine to peri-C/S analgesic regimen., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is associated with increased morbidity/mortality. Adverse outcome prediction might help with the management of patients with BD., Methods: We systematically reviewed the performance of machine learning (ML) studies in predicting adverse outcomes (relapse or recurrence, hospital admission, and suicide-related events) in patients with BD. Demographic, clinical, and neuroimaging-related poor outcome predictors were also reviewed. Three databases (PubMed, Scopus, and Web of Science) were explored from inception to July 2023., Results: Eighteen studies, accounting for >30,000 patients, were included. Support vector machine, decision trees, random forest, and logistic regression were the most frequently used ML algorithms. ML models' area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity ranged from 0.71 to 0.98, 72.7-92.8 %, and 59.0-95.2 % for relapse/recurrence prediction (4 studies (3 on relapses and 1 on recurrences). The corresponding values were 0.78-0.88, 21.4-100 %, and 77.0-99.7 % for hospital admissions (3 studies, 21,266 patients), and 0.71-0.99, 44.4-97.9 %, and 38.9-95.0 % for suicide-related events (10 studies, 5558 patients). Also, one study addressed a combination of the interest outcomes. Adverse outcome predictors included early onset BD, BD type I, comorbid psychiatric or substance use disorder, circadian rhythm disruption, hospitalization characteristics, and neuroimaging parameters, including increased dynamic amplitude of low-frequency fluctuation, decreased frontolimbic functional connectivity and aberrant dynamic functional connectivity in corticostriatal circuitry., Conclusions: ML models can predict adverse outcomes of BD with relatively acceptable performance measures. Future studies with larger samples and nested cross-validation validation should be conducted to reach more reliable results., Competing Interests: Declaration of competing interest There are no financial/personal relationships with any people or organizations that could inappropriately influence this study. There are no potential competing interests including employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Psychiatric disorders in patients with inflammatory bowel disease (IBD) represent a significant but uncertain facet of the disease, with unsolved questions regarding their overall magnitude, their impact on intestinal disease, and the whole burden of psychiatric manifestations., Aim: This systematic review summarizes the evidence on the prevalence and impact of psychiatric disorders, including depression, anxiety, bipolar disorder (BD), and schizophrenia, among patients with IBD., Methods: A systematic search across PubMed/MEDLINE, Embase, and Scopus databases from January 2010 to January 2023 was performed to identify relevant studies. The focus was on studies exploring the prevalence of specific psychiatric disorders in IBD patients compared to the general population and that reported specific outcome measures. A subsequent meta-analysis (MA) assessed the strength of the association between IBD and these psychiatric disorders, with data reliability ensured through rigorous extraction and quality assessment., Results: Out of 3,209 articles, 193 met the inclusion criteria and only 26 provided complete data for comprehensive analysis. These studies showed a significantly higher overall prevalence of psychiatric comorbidities in IBD patients compared to the general population. The MA showed a significant association between IBD and depression (pooled OR 1.42, 95% CI = 1.33-1.52, P < .0001) and anxiety (pooled OR 1.3, 95% CI = 1.22-1.44, P < .0001). The association between IBD and BD was significant (pooled OR 1.64, 95% CI = 1.20-2.24, P < .0001) but showed considerable heterogeneity (I2 = 94.01%). Only 3 studies examined the association between schizophrenia and IBD, providing widely heterogeneous results, with an inconclusive OR, estimated at 0.93 (95% CI = 0.62-1.39, P = .73)., Conclusions: This MA highlights the high prevalence of psychiatric disorders, particularly depression and anxiety, in IBD patients, which exceeds rates in the general population. BD in IBD is proving to be an important but under-researched area. The sparse and contradictory data on schizophrenia requires further investigation. These findings highlight the need for better understanding, early detection, and tailored mental health interventions in the management of IBD to significantly improve patients' quality of life., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Diffusion neuroimaging has emerged as an essential non-invasive technique to explore in vivo microstructural characteristics of white matter (WM), whose integrity allows complex behaviors and cognitive abilities. Studying the factors contributing to inter-individual variability in WM microstructure can provide valuable insight into structural and functional differences of brain among individuals. Genetic influence on this variation has been largely investigated in twin studies employing different measures derived from diffusion neuroimaging. In this context, we performed a comprehensive literature search across PubMed, Scopus and Web of Science of original twin studies focused on the heritability of WM. Overall, our results highlighted a consistent heritability of diffusion indices (i.e., fractional anisotropy, mean, axial and radial diffusivity), and network topology among twins. The genetic influence resulted prominent in frontal and occipital regions, in the limbic system, and in commissural fibers. To enhance the understanding of genetic influence on WM microstructure further studies in less heterogeneous experimental settings, encompassing all diffusion indices, are warranted., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions., (© 2024. The Author(s).)

Introduction: Cerebellar alterations, including both volumetric changes in the cerebellar vermis and dysfunctions of the corticocerebellar connections, have been documented in psychotic disorders. Starting from the clinical observation of a bipolar patient with cerebellar hypoplasia, the purpose of this review is to summarize the data in the literature about the association between hypoplasia of the cerebellar vermis and psychotic disorders [schizophrenia (SCZ) and bipolar disorder (BD)]., Methods: A bibliographic search on PubMed has been conducted, and 18 articles were finally included in the review: five used patients with BD, 12 patients with SCZ and one subject at psychotic risk., Results: For SCZ patients and subjects at psychotic risk, the results of most of the reviewed studies seem to suggest a gray matter volume reduction coupled with an increase in white matter volumes in the cerebellar vermis, compared to healthy controls. Instead, the results of the studies on BD patients are more heterogeneous with evidence showing a reduction, no difference or even an increase in cerebellar vermis volume compared to healthy controls., Conclusions: From the results of the reviewed studies, a possible correlation emerged between cerebellar vermis hypoplasia and psychotic disorders, especially SCZ, ultimately supporting the hypothesis of psychotic disorders as neurodevelopmental disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992., Objectives: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari., Materials and Methods: We adopted the health surveillance protocol, which was validated at the national level in 2018., Results: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%., Conclusion: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 De Maria, Pentimone, Cavone, Caputi, Sponselli, Fragassi, Dicataldo, Luisi, Delvecchio, Giannelli, Cafaro, Sole, Ronghi, Zagaria, Loiacono, Sifanno, Ferri and Vimercati.)

Background: Social anxiety disorder (SAD) is a psychiatric condition characterized by impaired social functioning that negatively impacts individuals' quality of life. Previous neuroimaging studies have revealed morphological and functional changes in various brain regions associated with SAD. Recent advances in diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) have enabled the investigation of microstructural white matter (WM) alterations in SAD. This study aims to provide an overview of DTI/DWI studies exploring WM microstructure changes in SAD., Methods: A systematic search on PubMed, Scopus, Web of Science, and PsycINFO was conducted for relevant records on July 8, 2023. An exploratory meta-analysis was also performed., Results: Eight studies were reviewed. Consistent findings indicated reduced fractional anisotropy and increased diffusivity measures in different WM tracts in SAD patients compared to healthy controls. These alterations were mostly observed within regions of the fronto-limbic network, like uncinate fasciculus (UF) and superior and inferior longitudinal fasciculi (SLF and ILF). Finally, our exploratory meta-analysis on four studies utilizing a voxel-wise analytic approach yielded no significant differences between SAD patients and controls., Limitations: Limited number of studies, small sample sizes, and heterogeneity in analysis methods., Conclusions: Patients with SAD exhibited altered WM integrity, particularly in the UF, SLF, and ILF, compared to healthy controls. However, due to the limited number of included studies, our meta-analysis yielded no significant differences between SAD patients and controls. Therefore, future research is crucial to unravel the link between altered WM structure and the involvement of other limbic and cortical structures in SAD pathogenesis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gian Maria Cavallini, Tommaso Verdina, Matteo Forlini, Veronica Volante, Michele De Maria, Giulio Torlai, Caterina Benatti, Giancarlo Delvecchio Institute of Ophthalmology, University of Modena and Reggio Emilia, Modena, Italy Purpose: To determine the efficacy of bimanual microincision cataract surgery (B-MICS) performed by surgeons in training, evaluating clinical results, posterior capsule opacification (PCO) incidence, and clear corneal incision (CCI) architecture in a long-term follow-up and comparing results with those obtained by experienced surgeons. Patients and methods: Eighty eyes of 62 patients operated on by three surgeons in training who used B-MICS technique for the first time were included in the study (Group A). Eighty eyes of 59 patients who underwent B-MICS by three experienced surgeons were included as a control group (Group B). Best corrected visual acuity, astigmatism, corneal pachymetry, and endothelial cell count were evaluated before surgery and at 1 month and 18 months after surgery. Anterior segment optical coherence tomography images were obtained to study the morphology of CCIs. PCO incidence was evaluated using EPCO2000 software. Results: Out of 160 surgeries included in the study, mean best-corrected visual acuity improvement at 18 months was 0.343±0.246 logMAR for Group A, and 0.388±0.175 logMAR for Group B, respectively. We found no statistically significant induced astigmatism nor corneal pachymetry changes in either group, while we noticed a statistically significant endothelial cell loss postoperatively in both groups (P

Machine learning (ML) has emerged as a promising tool to enhance suicidal prediction. However, as many large-sample studies mixed psychiatric and non-psychiatric populations, a formal psychiatric diagnosis emerged as a strong predictor of suicidal risk, overshadowing more subtle risk factors specific to distinct populations. To overcome this limitation, we conducted a systematic review of ML studies evaluating suicidal behaviors exclusively in psychiatric clinical populations. A systematic literature search was performed from inception through November 17, 2022 on PubMed, EMBASE, and Scopus following the PRISMA guidelines. Original research using ML techniques to assess the risk of suicide or predict suicide attempts in the psychiatric population were included. An assessment for bias risk was performed using the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines. About 1032 studies were retrieved, and 81 satisfied the inclusion criteria and were included for qualitative synthesis. Clinical and demographic features were the most frequently employed and random forest, support vector machine, and convolutional neural network performed better in terms of accuracy than other algorithms when directly compared. Despite heterogeneity in procedures, most studies reported an accuracy of 70% or greater based on features such as previous attempts, severity of the disorder, and pharmacological treatments. Although the evidence reported is promising, ML algorithms for suicidal prediction still present limitations, including the lack of neurobiological and imaging data and the lack of external validation samples. Overcoming these issues may lead to the development of models to adopt in clinical practice. Further research is warranted to boost a field that holds the potential to critically impact suicide mortality., (© 2024. The Author(s).)

Major Depressive Disorder (MDD) is a severe psychiatric disorder characterized by selective impairments in mood regulation, cognition and behavior. Although it is well-known that antidepressants can effectively treat moderate to severe depression, the biochemical effects of these medications on white matter (WM) integrity are still unclear. Therefore, the aim of the study is to review the main scientific evidence on the differences in WM integrity in responders and non-responders to antidepressant medications. A record search was performed on three datasets (PubMed, Scopus and Web of Science) and ten records matched our inclusion criteria. Overall, the reviewed studies highlighted a good efficacy of antidepressants in MDD treatment. Furthermore, there were differences in WM integrity between responders and non-responders, mainly localized in cingulate cortices, hippocampus and corpus callosum, where the former group showed higher fractional anisotropy and lower axial diffusivity values. Modifications in WM integrity might be partially explained by branching and proliferation as well as neurogenesis of axonal fibers mediated by antidepressants, which in turn may have positively affected brain metabolism and increase the quantity of the serotonergic neurotransmitter within synaptic clefts. However, the reviewed studies suffer from some limitations, including the heterogeneity in treatment duration, antidepressant administration, medical posology, and psychiatric comorbidities. Therefore, future studies are needed to reduce confounding effects of antidepressant medications and to adopt longitudinal and multimodal approaches in order to better characterize the differences in WM integrity between responders and non-responders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Videtta, Squarcina, Prunas, Brambilla and Delvecchio.)

Introduction: Bipolar disorder (BD) is a severe mental disorder characterized by high heritability rates. Widespread brain cortical alterations have been reported in BD patients, mostly involving the frontal, temporal and parietal regions. Importantly, also unaffected relatives of BD patients (BD-RELs) present abnormalities in cortical measures, which are not influenced by disease-related factors, such as medication use and illness duration. Here, we collected all available evidence on cortical measures in BD-RELs to further our knowledge on the potential cortical alterations associated with the vulnerability and the resilience to BD., Methods: A search on PubMed, Web of Science and Scopus was performed to identify neuroimaging studies exploring cortical alterations in BD-RELs, including cortical thickness (CT), surface area (SA), gyrification (GI) and cortical complexity. Eleven studies were included. Of these, five assessed CT, five examined CT and SA and one explored CT, SA and GI., Results: Overall, a heterogeneous pattern of cortical alterations emerged. The areas more consistently linked with genetic liability for BD were the prefrontal and sensorimotor regions. Mixed evidence was reported in the temporal and cingulate areas., Limitations: The small sample size and the heterogeneity in terms of methodologies and the characteristics of the participants limit the generalizability of our results., Conclusions: Our findings suggest that the genetic liability for BD is related to reduced CT in the prefrontal cortex, which might be a marker of risk for BD, and increased CT within the sensorimotor cortex, which could represent a marker of resilience., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)