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The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4 ) that may in turn influence infants’ behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants’ temperament at 3 months.

•IGF-tuned cerebellar tACS enhances visuomotor precision.•tACS reduces cortical silent period, indexing GABAB-mediated disinhibition.•Theta power increases post-tACS, suggesting cross-frequency modulation. The cerebellum plays a key role in motor control, yet its oscillatory dynamics remain poorly understood due to anatomical and methodological constraints. Transcranial alternating current stimulation (tACS) has emerged as a promising tool to modulate cerebellar activity, particularly when tailored to individual neural oscillations. This study examined the effects of EEG-guided gamma-frequency cerebellar tACS—matched to each participant’s individual gamma frequency (IGF)—on motor performance and neurophysiological markers in healthy adults. Forty-four male and female participants completed a visuomotor task while undergoing either real or sham tACS across two sessions. Critically, EEG activity was recorded before and immediately after the stimulation while participants performed the visuomotor task to assess electrophysiological changes in power spectrum density. Measures of corticospinal excitability and inhibition were collected via transcranial magnetic stimulation (TMS) protocols following each stimulation session. tACS at IGF enhanced motor precision during challenging task conditions and reduced corticospinal inhibition, without affecting corticospinal excitability. EEG analyses revealed IGF-dependent increases in theta-band power post-stimulation in motor regions, suggesting cross-frequency interactions. These findings highlight the potential of personalized cerebellar tACS to enhance motor performance and modulate inhibitory cortical dynamics, supporting its use as a precision neuromodulation tool in both research and clinical settings.

•Motor and visuospatial functions are predictors of social skills in IDD children.•Deviation from typical development of cortical thickness might impair cognition.•Fronto-parietal areas impact social skills via attention and visuospatial abilities.•Early visuospatial rehabilitation may improve social skills in IDD. Different theoretical perspectives emphasize the significance of sensorimotor and visuospatial functions in shaping social perception, including theory of mind (ToM) and affect recognition (AR) abilities. This study aimed to investigate where in the brain cortical thickness (CT) predicts social perception, and which cognitive functions mediate such relationship. To these aims, we used a hierarchical analytical plan: Step 1 identified brain areas’ CT that correlate with cognitive measures; Step 2 used stepwise regression to predict social perception outcomes (ToM and AR) from brain areas’ CT; Step 3 assessed whether cognitive measures mediate the link between CT and social perception outcomes. The results showed that the CT of the left inferior frontal gyrus (IFG; pars triangularis) predicted both ToM and AR, while the CT of the right superior parietal gyrus (SPL) and of the right anterior occipital sulcus (AOcs) predicted only AR. Mediation models unveiled that visuo-constructive abilities and visual attention mediated the relationship between CT in these areas and social perception outcomes. These findings align with the role of the IFG in mentalizing abilities and underscore the involvement of SPL in visuospatial functions, including mental object rotation and spatial perspective-taking, which are essential for advanced social skills; the role of the AOcs in face processing was also highlighted. Importantly, the findings suggest that fronto-parietal areas are indirectly involved in social perception thorough their involvement in visuo-constructive abilities and visual attention.

Congenital or acquired cerebellum alterations are associated with a complex pattern of motor, cognitive and social disorders. These disturbances may reflect the involvement of the cerebellum in generating and updating the internal models that sub-serve-the prediction of sensory events. Here, we tested whether the cerebellar involvement in using contextual expectations to interpret ambiguous sensory sceneries is specific for social actions or also extends to physical events. We applied anodic, cathodic and sham cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of an adult sample in two tasks requiring the prediction of social actions or moving shapes. For both tasks, in an earlier implicit-learning phase (familiarization), we manipulated the probability of co-occurrence between a particular action/shape and contextual elements, which could provide either strongly or moderately informative expectations. The use of these expectations was then tested when participants had to predict the unfolding of temporally occluded videos, in situations of perceptual uncertainty (testing). Results showed that in the testing, but not in the familiarization phase, cathodic as compared to anodic and sham ctDCS hindered participants’ sensitivity in predicting actions embedded in strongly, but not moderately, informative contexts. Conversely, anodic as compared to sham ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. We observed no ctDCS effects for the shape prediction task, thus pointing to a specific involvement of the cerebellum in forming expectations related to social events. Our results encourage the exploration of rehabilitative effects of ctDCS in patients with social perception deficits.

Adolescent suicidality represents a major and persistent public health concern, with sustained increases in suicidal ideation and behaviors observed in recent years. Although suicide risk is widely conceptualized as a complex and multifactorial phenomenon, biological vulnerability factors remain insufficiently integrated into adolescent clinical assessment frameworks. In particular, neuroinflammatory processes, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and alterations in blood-brain barrier integrity have emerged as potentially relevant but underexplored contributors to suicidality. This prospective clinical cohort study adopts an integrative, multi-method approach to enhance the characterization of suicidality among help-seeking adolescents. We hypothesize that adolescents with suicidal ideation or suicidal behaviors will show distinct peripheral biomarker profiles compared with adolescents without suicidal concerns. The primary analyses focus on group differences at baseline in inflammatory cytokines, markers of systemic inflammation, HPA-axis activity, and blood-brain barrier-related biomarkers, as well as measures of suicidality severity and global functioning. Secondary outcomes include associations between biomarker levels and psychopathological severity and functioning, and longitudinal changes in biological and clinical measures, including transitions in suicidality status, over a 2-month follow-up. Participants will undergo a comprehensive psychodiagnostic assessment and standardized peripheral blood sampling at baseline and follow-up. By integrating biological measures with detailed psychological and behavioral profiling within a longitudinal design, this protocol aims to establish a framework for biomarker-informed risk stratification of high-risk adolescents, ultimately informing more precise and developmentally sensitive suicide prevention strategies.

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P−). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan’s nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12–40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81–0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87–0.96) and poor specificity (0.58, 95% CI: 0.50–0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81–2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06−0.21) for developing psychosis. Fagan’s nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1–25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.

Computerized cognitive training programs (CCTP) are based on the assumption that cognitive abilities may be boosted by repetitively performing challenging tasks. The integration of game-like features in these programs, associated with the goal of amusing or rewarding participants, may contribute to generate cognitive benefits. Indeed, reinforcement contingencies have been reported to produce positive effects on performance and motivation, especially in children. This meta-analysis was aimed at providing a quantitative summary of the effectiveness of CCTP with game-like features in school-aged children with typical and atypical development. A total of 24 studies, with the cognitive and behavioral outcome data of 1547 participants, were selected for inclusion in the meta-analysis. Subgroup analyses were performed to identify the sources of the observed methodological heterogeneity. A robust variance estimation model, after removal of study outliers, yielded a small-to-moderate significant effect size. Final results pointed out smaller but more precise estimate effect sizes according to methodological aspects related to cognitive domain of outcomes, standardization of measures and type of control applied. Alongside supporting the use of CCTP for rehabilitating cognitive functions, the present results shed light on how different methodological choices are able to shape research findings in the field of children’s cognitive rehabilitation.

A previous study showed that about 80% of Italian adolescents reported isolated symptoms of acute or post-traumatic stress during the first lockdown in Italy. We proposed a new questionnaire to investigate the presence of symptoms related to anxiety, panic, depression, eating disorders, sleep disorders, social withdrawal, stress disorders, psychotic symptoms, anti-conservative thoughts, and self-harming acts aggravated by COVID-19 restrictions and possible differences between males and females. 500 adolescents (12–18 years) completed an online survey created using validated scales. 41% of the respondents felt more stress than during the first lockdown. 1.85% showed suprathreshold symptoms for post-traumatic stress disorder and 21% showed isolated symptoms of acute or post-traumatic stress due to the pandemic. In addition, we found psychotic symptoms (16%), panic (25% suprathreshold), anxiety (46.8% suprathreshold), depression (18.7% suprathreshold), eating-related symptoms (51%), sleep difficulties (57%), a tendency to social withdrawal after the pandemic (15%), suicidal ideation (30%), and self-harming behavior (9%). Furthermore, girls showed a more severe level of distress. The results show a high prevalence of symptoms because of the COVID-19 pandemic and confirm the need for easy access to support and treatment service to help contain the bio-psycho-social risk factors prompted by the current pandemic and promptly and effectively manage the consequences.

Although the uneven neuropsychological profile of William Syndrome (WS) is well established, less is known about social perception and how profile characteristics may affect the ability to predict other’s intentions, a main hallmark of social cognition. This study aimed at examining the neuropsychological profile, including social perception, of adolescents and adults with WS, and at verifying which neuropsychological outcome might account for their social prediction ability. Twenty-six individuals with WS were administered a comprehensive neuropsychological assessment, and a virtual reality scenario designed to assess social prediction in a dynamic, everyday life-like context. We found that social perception was a relative strength of the profile, although a dissociation emerged between impaired verbal ToM and relatively spared low-level components. Peaks and valleys were reported in other domains consistently with the expected profile. Both spatial and facial memory were significantly associated with the performance at the social prediction task. Results clarified that social perception per se should not be considered as typically impaired in WS. Weaknesses and strengths in specific abilities, particularly spatial and facial memory, might affect the ability to understand others’ intentions in WS beyond domain-specific mechanisms. These findings might inform future syndrome-specific rehabilitative interventions.

Introduction: Cerebellar transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulatory intervention for addressing motor, cognitive, and socio-affective deficits across a range of clinical populations. Materials and Methods: This systematic review aimed to synthesize recent evidence (2015–2025) on the efficacy, safety, and methodological characteristics of multi-session cerebellar TMS protocols used in rehabilitation settings. Following PRISMA guidelines, a comprehensive search of PubMed and Scopus was conducted to identify peer-reviewed studies applying multi-session cerebellar TMS in clinical populations for motor, cognitive, or affective rehabilitation. A total of 1750 records were screened, and 46 studies met the inclusion criteria. Data extraction included sample characteristics, study design, TMS protocol, targeted symptoms, outcomes, and risk of bias. Results: The results show that repeated sessions of cerebellar TMS are safe, well-tolerated, and associated with functional improvements primarily in motor disorders—such as spinocerebellar ataxia, Parkinson’s disease, multiple system atrophy, essential tremor, and post-stroke deficits—as well as in psychiatric populations, particularly patients with schizophrenia. Discussion: Evidence regarding the effects of cerebellar TMS on cognitive functions remains limited, though promising. Despite overall positive findings, the literature is limited by variability in stimulation parameters, protocol designs, and outcome measures, small sample sizes and potential publication bias. Conclusions: The review highlights the need for further large-scale and well-controlled trials to refine stimulation protocols, explore long-term effects, and clarify the underlying mechanisms of cerebellar TMS across motor, cognitive, and affective domains. This systematic review has been registered on PROSPERO (registration number: CRD420251067308).