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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.)

Mental imagery plays an important role in cognitive and emotional processes, therefore it might contribute to psychopathology in affective disorders. Distressive intrusive imagery is a core feature of anxiety disorders, but the underlying neurobiology remains unexplored. Here, we examined the functional brain mechanisms involved in state/psychological imagery in individuals with anxiety disorders. Functional Magnetic Resonance Imaging (fMRI) was used to assess the brain circuits involved in state/psychological (vs. action) imagery controlled by letter detection on the same stimuli in 33 individuals with anxiety disorders relative to 33 healthy controls. Patients were faster than controls in processing state/psychological stimuli and in general in the imagery task. We found that the left superior frontal gyrus was differentially activated by the state/psychological (vs. action) imagery (vs. letter detection) in the anxious individuals vs. healthy controls. We suggest that this area, which is involved in processing of state/psychological semantic information, appears deregulated during imagery in subjects with anxiety disorders. Our study provided the first evidence of both behavioral and brain functional alterations during imagery, highlighting a key role of the left superior frontal gyrus., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Deficits in executive functions (EF) and social cognition (SC) are often observed in bipolar disorder (BD), leading to a severe impairment in engaging a functional interaction with the others and the surrounding environment. Therefore, in recent years, resting-state functional magnetic resonance imaging (rs-fMRI) studies on BD tried to identify the neural underpinnings of these cognitive domains by exploring the association between the intrinsic functional connectivity (FC) and the scores in clinical scales evaluating these domains., Methods: A bibliographic search on PubMed and Scopus of studies evaluating the correlations between rs-fMRI findings and EF and/or SC in BD was conducted until March 2022. Ten studies met the inclusion criteria., Results: Overall, the results of the reviewed studies showed that BD patients had FC deficits compared to healthy controls (HC) in selective resting-state networks involved in EF and SC, which include the default mode network, especially the link between medial prefrontal cortex and posterior cingulate cortex, and the sensory-motor network. Finally, it also emerged the predominant role of alterations in prefrontal connections in explaining the cognitive deficits in BD patients., Limitations: The heterogeneity of the reviewed studies, in terms of the cognitive domains explored and the neuroimaging acquisitions employed, limited the comparability of the findings., Conclusions: rs-fMRI studies could help deepen the brain network alterations underlying EF and SC deficits in BD, pointing the attention on the neuronal underpinning of cognition, whose knowledge may lead to the development of new neurobiological-based approaches to improve the quality of life of these patients., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Early-onset bipolar disorder (BD) is a complex psychiatric illness characterized by mood swings, irritability and functional impairments. To improve our understanding of the pathophysiology of the disorder, we collected the existing resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies exploring resting-state functional connectivity (rs-FC) and spontaneous activity alterations in children and adolescents with BD., Methods: A search on PubMed, Web of Science and Scopus was conducted to identify all the relevant rs-fMRI investigations conducted in early-onset BD. A total of 14 studies employing different methodological approaches to explore rs-FC and spontaneous activity in early-onset BD were included (independent component analysis, n = 1; seed-based analysis, n = 7; amplitude of low frequency fluctuations analysis, n = 2; regional homogeneity analysis, n = 4)., Results: Overall, the studies showed abnormalities within the Default Mode Network (DMN) and between the DMN and the Salience Network (SN). Moreover, widespread alterations in rs-FC and spontaneous brain activity within and between cortico-limbic structures, involving primarily the occipital and frontal lobes, amygdala, hippocampus, insula, thalamus and striatum were also reported., Limitations: The small sample sizes, the use of medications, the presence of comorbidities and the heterogeneity in methods hamper the integration of the study findings., Conclusions: Early-onset BD seems to be characterized by selective rs-FC and spontaneous activity dysfunctions in DMN and SN as well as in the cortico-limbic and cortico-striatal circuits, which could explain the emotive and cognitive deficits observed in this disabling psychiatric illness., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cognitive Remediation (CR) is designed to halt the pathological neural systems that characterize major psychotic disorders (MPD), and its main objective is to improve cognitive functioning. The magnitude of CR-induced cognitive gains greatly varies across patients with MPD, with up to 40% of patients not showing gains in global cognitive performance. This is likely due to the high degree of heterogeneity in neural activation patterns underlying cognitive endophenotypes, and to inter-individual differences in neuroplastic potential, cortical organization and interaction between brain systems in response to learning. Here, we review studies that used neuroimaging to investigate which biomarkers could potentially serve as predictors of treatment response to CR in MPD., Methods: This systematic review followed the PRISMA guidelines. An electronic database search (Embase, Elsevier; Scopus, PsycINFO, APA; PubMed, APA) was conducted in March 2021. peer-reviewed, English-language studies were included if they reported data for adults aged 18+ with MPD, reported findings from randomized controlled trials or single-arm trials of CR; and presented neuroimaging data., Results: Sixteen studies were included and eight neuroimaging-based biomarkers were identified. Auditory mismatch negativity (3 studies), auditory steady-state response (1), gray matter morphology (3), white matter microstructure (1), and task-based fMRI (7) can predict response to CR. Efference copy corollary/discharge, resting state, and thalamo-cortical connectivity (1) require further research prior to being implemented., Conclusions: Translational research on neuroimaging-based biomarkers can help elucidate the mechanisms by which CR influences the brain's functional architecture, better characterize psychotic subpopulations, and ultimately deliver CR that is optimized and personalized., (Copyright © 2021. Published by Elsevier B.V.)

Background: Major depressive disorder (MDD) is a severe psychiatric condition characterized by selective cognitive dysfunctions. In this regard, functional Magnetic Resonance Imaging (fMRI) studies showed, both at resting state and during tasks, alterations in the brain functional networks involved in cognitive processes in MDD patients compared to controls. Among those, it seems that the attention network may have a role in the disease pathophysiology. Therefore, in this review we aim at summarizing the current fMRI evidence investigating sustained attention in MDD patients., Methods: We conducted a search on PubMed on case-control studies on MDD employing fMRI acquisitions during Go/No-Go and continuous performance tasks. A total of 12 studies have been included in the review., Results: Overall, the majority of fMRI studies reported quantitative alterations in the response to attentive tasks in selective brain regions, including the prefrontal cortex, the cingulate cortex, the temporal and parietal lobes, the insula and the precuneus, which are key nodes of the attention, the executive, and the default mode networks., Limitations: The heterogeneity in the study designs, fMRI acquisition techniques and processing methods have limited the generalizability of the results., Conclusions: The results from the included studies showed the presence of alterations in the activation patterns of regions involved in sustained attention in MDD, which are in line with current evidence and seemed to explain some of the key symptoms of depression. However, given the paucity and heterogeneity of studies available, it may be worthwhile to continue investigating the attentional domain in MDD with ad-hoc study designs to retrieve more robust evidence., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Major depressive disorder (MDD) is a severe and pervasive psychiatric condition with a lifetime prevalence of 15-25%. Numerous Magnetic Resonance Imaging (MRI) studies employing scans at field strengths of 1.5T or 3T have been carried out in the last decades, providing an unprecedented insight into the neural correlates of MDD. However, in recent years, MRI technology has largely progressed and the use of scans at ultra-high field (≥ 7T) has improved the sensitivity and the resolution of MR images. In this context, with this review we aim to summarize evidence of structural and functional brain mechanisms underlying MDD obtained with ultra-high field MRI., Methods: We conducted a search on PubMed, Scopus and Web of Science of neuroimaging studies on MDD patients, which employed ultra-high field MRI. We detected six structural MRI studies, two Diffusion Tensor Imaging (DTI) studies and five functional MRI (fMRI) studies., Results: Overall, the MRI and DTI studies showed volumetric and structural connectivity alterations in the hippocampus and, to a lesser extent, in the amygdala. In contrast, more heterogeneous results were reported by fMRI studies, which, though, described functional abnormalities in the cingulate cortex, thalamus and several other brain areas., Limitations: The small sample size and the heterogeneity in patients' samples, processing and study design limit the conclusion of the present review., Conclusions: Studies employing scans at ultra-high magnetic field may provide a useful contribution to the mixed body of literature on MDD. This preliminary but promising evidence confirms the importance of performing ultra-high field MRI investigations in order to detect and better characterize subtle brain abnormalities in MDD., (Copyright © 2021. Published by Elsevier B.V.)

Background: Schizophrenia (SCZ) and Bipolar Disorder (BD) are severe psychiatric illnesses often characterized by mild-to-severe cognitive deficits. Since available pharmacotherapy showed poor efficacy in treating these cognitive impairments, new strategies are needed. Repeated Transcranial Magnetic Stimulation (rTMS) represents a safe non-invasive technique that has been hypothesized to improve cognitive symptoms in these pathologies. Therefore, our brief review aims at summarizing the results of Randomized Controlled Trials (RCTs) using rTMS for improving cognitive symptoms in SCZ and BD., Methods: We performed a bibliographic research on PubMed, Google Scholar and Medline of RCTs conducted in patients with BD and SCZ, which evaluated cognitive outcomes after rTMS treatment., Results: The inclusion criteria were met by fifteen RCTs, twelve in SCZ and three in BD. Regarding patients with SCZ, the results showed that rTMS seemed to have poor effects on improving cognitive performances, with mixed results also observed for schizoaffective patients. In BD, overall the RCTs showed that rTMS in these patients seemed to improve cognitive domains in euthymic patients, while its effect during acute phases, especially depression, appeared limited., Limitations: Studies employed different rTMS protocols and evaluated different cognitive domains., Conclusions: Although the available evidence from RCTs evaluating the efficacy of rTMS on cognitive deficits in SCZ and BD are still mixed and heterogenous, overall they suggest that rTMS represents a potential clinical tool that could ameliorate cognitive symptoms, especially in specific patients' subtypes. However, standardized protocols and further research are still necessary to evaluate the real efficacy of rTMS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS)., Methods: During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference., Results: The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions., Limitations: Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too., Conclusions: Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas., (Copyright © 2020. Published by Elsevier B.V.)

Background: Serious mental illnesses may be characterized by accelerated biological aging, and over the last years the research on the topic has been stimulated by studies exploring the molecular underpinnings of senescence., Methods: In the present manuscript we propose that measuring frailty, a general product of organismal ageing, through the "Frailty Index" (FI), a recently-emerged macroscopic indicator of functional status and biological age, adds an important marker to the measurements currently implemented in the study of accelerated biological age in psychiatric illnesses., Results: The FI quantifies functional negative health attributes and measures their cumulative effect, thus providing a useful estimate of the individual's biological age and risk profile. Recent studies in older adults have observed significant associations between FI and molecular measures of aging., Limitations: High FI values can be driven by causes different from aging per se, so FI may be a sensitive but not specific measure of biological aging., Conclusions: FI, which is extensively used in geriatrics and gerontology but it has rarely been used in relation to mental health, may be of relevance in the evaluation of age-related phenomena associated with psychiatric diseases., Competing Interests: Declaration of Competing Interest All authors have no actual or past potential conflict of interest to disclose, including any financial, personal or other relationships with other people or organizations that could inappropriately have influenced the results presented in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: Transcranial Magnetic Stimulation (TMS) has emerged as a valid therapeutic option in the treatment of depression, especially in cases of inadequate response to antidepressant agents. Despite the recognized efficacy of this technique, its mechanisms of action are still debated and optimal protocols have not yet been established., Methods: The present review focuses on TMS protocols that either engage the targeted brain circuits or synchronize the stimulation frequency to individual neuronal oscillations to increase the antidepressant efficacy., Results: TMS efficacy was found to be enhanced by preliminary or concomitant modulation of the functional state of the targeted brain networks. Conversely, there is not enough evidence of higher efficacy of TMS protocols with individual selection of the stimulation frequency compared to standard ones., Limitations: Most studies included small patient samples., Conclusions: Our results suggest that a good option to enhance rTMS efficacy might be to follow synaptic potentiation and depression rules., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Background: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in self-controlling attention, behavior, and emotions. In recent years, noninvasive optical techniques, such as near infrared spectroscopy (NIRS), have been used to measure the neural correlates of pharmacological-therapy outcomes in children and adolescents with ADHD., Methods: We reviewed a short series of articles that investigated the results of functional NIRS (fNIRS) on developmental-age ADHD. The review was limited to fNIRS studies that investigated the cortical responses that occurred during neuropsychological tasks in ADHD patients who received methylphenidate or atomoxetine., Results: The majority of the reviewed studies revealed the presence of increased oxygenated hemoglobin concentrations in the prefrontal cortex following pharmacotherapy in ADHD samples. A higher frequency of right-lateralized results was found., Limitations: The considered studies are characterized by substantial methodological heterogeneity in terms of the patients' medication status and washout period, explored cerebral regions, and neuropsychological tasks., Conclusions: fNIRS seems to be a promising tool for the detection of pharmacological-treatment biomarkers in samples of children and adolescents with ADHD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a major psychiatric illness characterized by heterogeneous symptoms including psychotic features. Up until now, neuroimaging studies investigating cerebral morphology in patients with BD have underestimated the potential impact of psychosis on brain anatomy in BD patients. In this regard, psychotic and non-psychotic BD may represent biologically different subtypes of the disorder, being possibly associated with specific cerebral features., Methods: In the present study, magnetic resonance imaging (MRI) at 3T was used to identify the neuroanatomical correlates of psychosis in an International sample of BD patients. A large sample of structural MRI data from healthy subjects (HC) and BD patients was collected across two research centers. Voxel based morphometry was used to compare gray matter (GM) volume among psychotic and non-psychotic BD patients and HC., Results: We found specific structural alterations in the two patient groups, more extended in the psychotic sample. Psychotic patients showed GM volume deficits in left frontal cortex compared to HC, and in right temporo-parietal cortex compared to both HC and non-psychotic patients (p < 0.001, > 100 voxels). Psychotic patients also exhibited enhanced age-related GM volume deficits in a set of subcortical and cortical regions., Limitations: The integration of multiple datasets may have affected the results., Conclusions: Overall, our results confirm the importance of classifying BD based on psychosis. The knowledge of the neuronal bases of psychotic symptomatology in BD can provide a more comprehensive picture of the determinants of BD, in the light of the continuum characteristic of major psychoses., (Copyright © 2017 Elsevier B.V. All rights reserved.)