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Background/objectives: Tic disorders are neurodevelopmental conditions often associated with comorbidities like attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Our aims were: (a) in a sample of youth with tic disorders to explore the clinical and psychopathological characteristics of different phenotypes based on the presence of comorbid ADHD and/or ASD and gender; (b) in a subgroup of patients treated with Aripiprazole, to evaluate symptoms variation over time and to identify potential predictors of response., Methods: A total of 95 subjects with tic disorders (age range 6 to 17.9 years, mean 11.1 ± 2.11 years, 80 males) were naturalistically recruited. Questionnaires and semi-structured interviews were administered to assess the symptomatology and investigate the presence of psychiatric comorbidities (Clinic Global Impression-Severity (CGI-S), Children's Global Assessment Scale (C-GAS), Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), Child Yale-Brown Obsessive Compulsive Scale for Children (CYBOCS), Child Behavior Checklist 6-18 (CBCL 6-18), Conners' Parent Rating Scale-Revised-short form (CRSR-S), Reactivity Intensity Polarity Stability Questionnaire-youth version (RIPoSt-Y), and Social Communication Questionnaire-lifetime version (SCQ); Autism Diagnostic Observation Scale-second version (ADOS-2) and Autism Diagnostic Interview-revised version (ADI-R) were administered where ASD was suspected). A total of 22 subjects treated with Aripiprazole were reassessed through the use of some of the clinical measures used at baseline., Results: The presence of ADHD was associated with higher externalizing problem scores on the CBCL 6-18, while ASD was linked to higher internalizing problem scores. A positive correlation was found between the ADHD-ASD interaction and increased internalizing symptoms on CBCL 6-18 and higher ADOS-2 scores. Patients treated with Aripiprazole showed significant improvement across all scales during follow-up. ADHD was identified as a negative predictor of reduced tic severity on the YGTSS., Conclusions: Comorbid neurodevelopmental disorders, such as ADHD or ASD, result in worse emotional and behavioral functioning in patients with tic disorders. ADHD-ASD interaction may be linked to more internalizing symptoms and autistic behaviors. Aripiprazole improves overall clinical outcomes, although comorbid ADHD may hinder the reduction of tic symptoms.

Background : Lithium is the gold-standard treatment for Bipolar Disorder (BD) in both adults and adolescents, effectively managing mood episodes and reducing suicide risk. While its efficacy in neurotypical youth is well established, its use in adolescents with Autism Spectrum Disorder (ASD) and comorbid BD remains under-researched. Here, we present the protocol for a study aiming to evaluate the efficacy and tolerability of Extended-Release Lithium Salts in treating adolescents with BD and comorbid ASD compared to neurotypical BD patients. Methods : This longitudinal prospective naturalistic comparative study will enroll lithium-naïve adolescents aged 12-18 with BD, with or without comorbid ASD, from the Department of Child and Adolescent Psychiatry and Psychopharmacology. Participants will be followed for six months while receiving Extended-Release Lithium Salts treatment. Primary outcomes will include mood instability, suicidality, emotional dysregulation, and aggression, assessed through a range of clinical rating scales and diagnostic tools at baseline, three months, and six months. Secondary outcomes will focus on the safety and tolerability of Extended-Release Lithium Salts, with measures including side effect ratings, physical exams, and laboratory tests. Results : We hypothesize that Extended-Release Lithium Salts will demonstrate non-inferiority in treating BD symptoms in adolescents with comorbid ASD compared to those without ASD. Conclusions : This study is poised to fill a significant gap in the literature by providing critical data on the use of lithium for adolescents with BD and ASD. Findings will inform clinical practice and future research, potentially guiding more personalized treatment approaches for this complex and vulnerable population.

Background: Non-suicidal self-injury (NSSI) and Feeding or Eating Disorders (FEDs) often coexist during adolescence with reciprocal influences on their clinical picture. The present study aimed to identify differences and similarities in the clinical presentation of young patients with both conditions compared to those with the two non-comorbid disorders., Methods: We consecutively recruited forty-five female patients aged between 11 and 18 at our third-level hospital and subdivided them into three groups (NSSI: n = 15; FED: n = 15; NSSI + FED: n = 15). Patients underwent a full clinical assessment., Results: Based on our results, the NSSI + FED group was characterized by higher rates of binging/purging behaviors, greater prevalence of Cyclothymic Disorder, and a more severe clinical presentation compared to the non-comorbid groups. Moreover, higher levels of suicidal ideation were found in the NSSI + FED group. Pharmacological treatment patterns also differed, with SSRI being prescribed more frequently to NSSI + FED patients while mood stabilizers were prescribed more frequently to NSSI ones. A Principal Component Analysis identified four main dimensions: "Body Image" impairment was more pronounced in NSSI + FED patients, indicating negative attitudes towards their own body; "Metacognition" deficits were higher in NSSI than FED., Conclusions: The present study underscores distinctive clinical features in patients with comorbid NSSI and FED, emphasizing the urgent need for tailored intervention strategies focusing on specific symptom domains.

Severe social withdrawal, including staying alone in one's bedroom, non-attendance at school or work, and minimal or absent social contacts, sometimes only through electronic devices, can be found in several psychiatric disorders, or in a 'primary' form, firstly defined in Japan as 'Hikikomori'. The distinction between primary and secondary forms is questionable, as it prevalently depends on the quality of psychiatric assessment. To date, few studies specifically explored Hikikomori in an adolescent population outside Japan. The aim of the present study is to describe clinical features of a consecutive group of 80 referred youth (13 to 18 years, 57 males) with social isolation, of which 40 were followed up on for 4-6 months, to characterize clinical features and outcome. All the participants presented psychiatric comorbid disorders, prevalently anxiety disorders, mood disorders, and autism spectrum disorder. Suicidality (ideation and behavior) was reported in 32.5% of the participants, and 20% of the participants attempted suicide. More than half of the participants exceeded the cut-off of the Internet Addiction Test, and 42.4% met the criteria for the Internet Gaming Disorder. At the follow-up appointment, an improvement of social withdrawal was reported in 75% of the sample; 67.5% of the participants significantly improved according to the CGI-improvement scale; and 55% of the participants had an improvement of functioning according to the C-GAS. Our findings suggest that Hikikomori is a transnosographic entity, with high rates of suicidality and Internet addiction, and that can it improve when it is timely diagnosed and treated.

Liver transplantation (LT) represents the primary curative option for HCC. Despite the extension of transplantation criteria and conversion with down-staging loco-regional treatments, transplantation is not always possible. The introduction of new standards of care in advanced HCC including a combination of immune checkpoint inhibitor-based therapies led to an improvement in response rates and could represent a promising strategy for down-staging the tumor burden. In this review, we identify reports and series, comprising a total of 43 patients who received immune checkpoint inhibitors as bridging or down-staging therapies prior to LT. Overall, treated patients registered an objective response rate of 21%, and 14 patients were reduced within the Milan criteria. Graft rejection was reported in seven patients, resulting in the death of four patients; in the remaining cases, LT was performed safely after immunotherapy. Further investigations are required to define the duration of immune checkpoint inhibitors, their minimum washout period and the LT long-term safety of this strategy. Some randomized clinical trials including immunotherapy combinations, loco-regional treatment and/or tyrosine kinase inhibitors are ongoing and will likely determine the appropriateness of immune checkpoint inhibitors' administration before LT.

Psychopathic traits in community and referred youths are strongly associated with severe externalizing problems and low prosocial behavior. However, less is known about the mechanisms that may link youth psychopathy and these outcomes. Social dominance orientation (SDO), defined as the general individual orientation toward unequal and dominant/subordinate relationships, might represent a valuable construct to explore to better understand the association between psychopathic traits, externalizing problems, and prosocial behavior. Based on this, the current study aimed to investigate the relationship between psychopathic traits, SDO, externalizing problems, and prosocial behavior in a community sample ( N = 92, 45.57% females, mean age = 12.53, and SD = 0.60) and in a clinical ( N = 29, 9% female, mean age = 12.57, and SD = 0.57) samples of adolescents with Oppositional Defiant Disorder or Conduct Disorder. Results showed that SDO mediated the relationship between psychopathic traits and externalizing problems and between psychopathic traits and prosocial behavior only in the clinical sample. These findings can provide valuable information on psychopathic trait correlates in youths with aggressive behavior disorders; treatment implications are discussed.

Catatonia is a complex neuropsychiatric syndrome, occurring in the context of different psychiatric and neurodevelopmental disorders, in neurological and medical disorders, and after substance abuse or withdrawal. The relationship between Autism Spectrum Disorder (ASD), Schizophrenia Spectrum Disorders (SSDs) and catatonia has been previously discussed, with the three disorders interpreted as different manifestations of the same underlying brain disorder (the "Iron Triangle"). We discuss in this paper the diagnostic, clinical and therapeutic implications of this complex relationship in an adolescent with ASD, who presented an acute psychotic onset with catatonia, associated with mixed mood symptoms. Second-generation antipsychotics were used to manage psychotic, behavioral and affective symptoms, with worsening of the catatonic symptoms. In this clinical condition, antipsychotics may be useful at the lowest dosages, with increases only in the acute phases, especially when benzodiazepines are ineffective. Mood stabilizers with higher GABAergic effects (such as Valproate and Gabapentin) and Lithium salts may be more useful and well tolerated, given the frequent association of depressive and manic symptoms with mixed features.

Dramatic events during the COVID-19 pandemic have acutely impacted the psychosocial environment worldwide, with negative implications for mental health, particularly for more vulnerable children and adolescents with severe psychiatric illnesses. Some data suggest that the pandemic waves may have produced different psychopathological consequences, further worsening in the second phase of the pandemic, compared to those in the first lockdown, soon after March 2020. To test the hypothesis of a further worsening of psychiatric consequences of COVID-19 in the second lockdown compared to the first lockdown, we focused our analysis on a consecutive sample of youth referred to a psychiatric emergency unit for acute mental disorders in the time period between March 2019-March 2021. The sample, consisting of 241 subjects (123 males and 118 females, ranging in age from 11 to 17 years), was divided into three groups: Pre-Lockdown Group (PLG, 115 patients); First Lockdown Group (FLG, 65 patients); and Second Lockdown Group (SLG, 61 patients). Patients in the SLG presented more frequently with non-suicidal self-injuries (NSSIs), suicidal ideation, and suicidal behavior, while no significant differences in self-harm were found between PLG and FLG. Eating disorders were more frequent in both the FLG and SLG, compared to the PLG, while sleep problems were higher only in the SLG. Furthermore, patients in the SLG presented with more frequent psychological maltreatments and neglect, as well as with psychiatric disorders in the parents. Adverse traumatic experiences and internalizing disorders were significantly associated with an increased risk of suicidality. Intellectual disability was less represented from the PLG to SLG, and similarly, the rate of ADHD was lower in the SLG. No differences were found for the other psychiatric diagnoses. This information may be helpful for a better understanding and management of adolescents with severe emotional and behavioral disorders after the exposure to long-lasting collective traumas.

Research on the association between callous-unemotional (CU) traits and intelligence yielded contradictory results. Moreover, several previous studies focused on global intelligence scores or verbal vs. nonverbal/performance abilities usually evaluated with short/abbreviated instruments. The current study builds on these previous works and explores the link between CU traits and intelligence using the full version of the Wechsler Intelligence Scale for Children-4th Edition (WISC-IV), which provides four different verbal and nonverbal abilities scores. This guarantees a more detailed evaluation of children's intelligence and its relation to CU traits. The sample included children ( N = 149; age 6-14 years old) with severe behavioral problems. Clinicians administered the WISC-IV, and parents completed questionnaires evaluating the child's externalizing problems and CU traits. Findings showed that CU traits were associated with lower verbal comprehension scores after also controlling for gender, age, externalizing problems, and the other WISC-IV indexes. In addition, CU traits and externalizing problems did not interact in predicting the WISC-IV indexes, and there were no significant differences in the WISC-IV indexes between children with CU traits and high vs. low externalizing problems. The current study suggests the relevance of assessing and addressing verbal abilities in children with behavioral problems and CU traits.

It is well known that the early removal of basal leaves is a viticultural practice adopted to improve the exposure of clusters to direct sunlight and UV radiation and increase the phenolic compounds and anthocyanin concentration in the berries. The aim of this work was to study the influence of early basal leaf removal on Aglianico wines produced in the Apulia region (southern Italy) during three consecutive seasons. Three vine treatments were carried out, where 100% of the cluster-zone leaves on the north, south and both sides of the canopy were removed. Undefoliated plants were used as a control. The effect of the treatments on the basic chemical parameters, phenol content and volatile composition of wines was investigated using WineScan FT-MIR, spectrophotometry, HPLC-DAD and SPME-GC/MS. Early defoliation increased the amounts of flavonoids (+35-40%), anthocyanins (+15-18%), total polyphenols (+10%), antioxidant activity (+8-14%) and colour intensity (+10%), especially when leaf removal was applied on the south side. Moreover, leaf removal led to a 40% increase in free anthocyanins when applied on the south side of the canopy, while a 24% increase was observed when applied to the north side and 21% when applied to the north and south sides. A negative effect was observed on volatile compounds, which decreased by about 18, 14 and 13% when the treatment was applied on the north, north-south and south sides of the canopy, respectively. In conclusion, early leaf removal treatments allow for the modulation of the phenolic and volatile concentrations of Aglianico wines.

Background: Abnormal sensory reactivity is considered one of the diagnostic criteria for autism spectrum disorders (ASD) and has been associated with autism severity, poorer functional outcomes, and behavioral difficulties across the lifespan. Its early characterization could provide valuable insights into the processes favoring the instantiation of maladaptive behaviors. Objectives: The present study has two aims: (1) to describe the sensory profile of preschool children with ASD compared with an age-matched population of children with a diagnosis of language disorder (DLD) and typically developing (TD) control peers; (2) to explore within each group whether the sensory alterations play a predictive role in the instantiation of emotional and behavioral issues. Methods: The parents of 42 ASD, 18 DLD, and 56 TD filled out the Sensory Processing Measure—Preschool (SPM-P). To gather information on competencies, behaviors, and emotional problems of children, the Child Behavior Checklist 1½-5 (CBCL 1½-5) was also administered. Results: On the SPM-P, ASD and DLD samples generally had scores more compromised than control peers. The contrast between ASD and DLD was reflected in a higher (and highly significant) impairment on the social participation and hearing subscales, suggesting a greater sensitivity and a possible specificity of these scores for ASD. More importantly, linear regression analyses revealed a strong and predictive association for ASD children with SPM total scores explaining more than 50% of the variance of the CBCL 1½-5 total scores (p < 0.001). Conclusions: Our findings reinforce the need to detect the abnormal sensory profiles of ASD already at an early stage and during clinical evaluations. Due to the impact on the emotional and behavioral manifestations, such a procedure has significant clinical and social implications, potentially guiding the development of new interventions relying on multisensory strategies.

Background: Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused a worldwide challenging and threatening pandemic. Multinational, placebo-controlled, observer-blinded trials were conducted since the beginning of pandemic because safe and effective vaccines were needed urgently. In most trials of COVID-19 vaccines patients affected by malignancies or on treatment with immunosuppressive drugs were excluded., Patients and Methods: A retrospective monocentric study was conducted at Medical Oncological Unit of Santa Chiara Hospital (Pisa, Italy) in this subset of population to investigate safety and tolerability of COVID-19 vaccines; 377 patients with solid tumor on treatment were enrolled. Vaccine-related adverse events were recorded using a face-to-face questionnaire including a toxicity grading scale. Most of the patients (94%) received mRNA vaccine as indicated by Italian health ministry guidelines. Mean age was 66 years (range 27-87), 62% of the patients were older than 65 years and 68% had at least one additional comorbidity. The majority (86%) of patients were in a metastatic setting and 29% received immunotherapy-based treatment. For statistical analysis, multivariate binary logistic regression models were performed and linear regression models were applied., Results: Adverse events were mild and transient and ended in a few days without any sequelae. No severe or uncommon adverse events were recorded. In multivariate analysis, we found that the female sex was associated with a greater risk of more severe and longer lasting adverse events, and a higher risk of adverse events was found for patients treated with immunotherapy., Conclusions: Our results demonstrate that COVID-19 vaccines were safe and well-tolerated in this population of patients being treated for solid tumors.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion ( p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes ( p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods ( p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Although Attention Deficit Hyperactivity Disorder (ADHD) has been related to an increased risk for behavioral addictions, the relationship between ADHD and Internet Gaming Disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ADHD youth, compared to a normal control group, and by assessing selected psychopathological and cognitive features in ADHD patients with and without IGD. One hundred and eight patients with ADHD (mean age 11.7 ± 2.6 years, 96 males) and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) were included in the study and received structured measures for IGD. In the ADHD group, 44% of the sample were above the IGD cut-off, compared to 9.5% in the NC group. ADHD patients with IGD presented with greater severity and impairment, more severe ADHD symptomatology, more internalizing symptoms, particularly withdrawal/depression and socialization problems, and more prominence of addiction and evasion dimensions. A binary logistic regression showed that the degree of inattention presented a greater weight in determining IGD. These findings may be helpful for identifying, among ADHD patients, those at higher risk for developing a superimposed IGD.

The rising prevalence of Autism Spectrum Disorders (ASD) has led to a quickly increasing need for effective interventions. Several criteria and measures have been developed to critically assess these interventions with particular focus on the evaluation of the efficacy. Given the huge diversity of ASD symptoms and the different levels of severity across individuals, identifying a one size fits all intervention approach is challenging, and the question What works and for whom? Remains still unanswered. Why do we seem to be dragging our feet on this fundamental issue? The main aim of this paper is to answer this question through four non-alternative points. First, there are a scarce number of studies with a solid methodology. Secondly, most trials on intervention efficacy for ASD are designed exclusively in terms of behavioral outcomes. Thirdly, there is a reduced use of biologically oriented outcome measures. Fourthly, in most clinical trials, appropriate practices emerging from research evidence are not systematically applied. A strong effort to improve the methodology of clinical trials is mandatory for the future of autism research. The development of a research-based intervention (RBI) perspective aimed at better integrating: (a) evidence-based approaches; (b) more sensitive behavioral outcome measures; and (c) biomarkers, with the aim of increasing a more detailed clustering of phenotypes, may strongly improve our approach to a precision medicine.

Background: Sensory reactivity is considered one of the diagnostic criteria for Autism Spectrum Disorders (ASD) and has been associated with poorer functional outcomes, behavioral difficulties, and autism severity across the lifespan. The characterization of the sensory processing in ASD has thus become crucial to identify the sensory and motor features influencing the development of personal autonomy. Objectives: The present study has two aims: (1) to compare the sensory processing between school-aged children with ASD and typically developing peers (TD); (2) to evaluate whether, within the ASD sample, the cognitive level and reported sensory symptoms explain the scores exhibited at the Sensory Processing Measure (SPM-2). Methods: The SPM-2 test was administered to the parents of 105 children with ASD and 70 TD. The ASD group was further subdivided into two groups, namely high and low functioning based on their cognitive level (High Functioning (HF), IQ > 80; Low Functioning (LF), IQ < 80). Results: ASD children exhibited higher scores throughout the SPM-2 total score and its multiple subscales. Within ASD, while HF and LF children did not differ in terms of the SPM-2 total score, a significant difference was found for the hearing, social participation, and balance and motion subscales. Conclusions: Aside from classical knowledge that the ASD population suffers from sensory processing disorders, we revealed that different sensory patterns are associated with high or low cognitive functioning. Beyond its neurobiological interest, such knowledge may be of fundamental importance for individualizing psychoeducational interventions in preschool- and school-aged children and later developmental stages.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening, idiosyncratic adverse reaction to antipsychotic drugs. Despite the increasing rates in the prescription of antipsychotics in pediatric patients with autism spectrum disorder (ASD), little is known about the occurrence and hallmarks of NMS in this specific population. NMS appears to be part of the larger catatonia domain, based on the frequent relationship between ASD and catatonia, on the shared, when not overlapping, clinical features with malignant catatonia, and on the effectiveness of catatonia treatments on the NMS/MC symptoms. The intrinsic difficulties of exploring NMS in ASD in controlled studies accounts for the subsequent lack of available information. Based on recent reports and on our case report, clinical features of NMS in the pediatric ASD population appear to be the same as the non-ASD population. Further studies are needed to confirm these results.

This study aimed to further validate the self-reported version of the Proposed Specifiers Conduct Disorder (PSCD) scale, testing the associations between the PSCD with a scale that measures emotional/behavioral difficulties and prosocial behaviors (Strength and Difficulties Questionnaire, SDQ). A total of 536 Italian students (47.76% male; 11-14 years) completed the PSCD, while their caregivers and teachers completed the SDQ. A series of confirmatory factor analyses to test the best fitting model were run. The internal consistency of the PSCD was evaluated, and the correlations between the PSCD self-reported scores and SDQ Parent and Teacher report scores were examined. A bi-factor model was fitted with a refined 19-item version of the scale, which showed adequate fit indices. The PSCD total score was strongly associated with higher parent- and teacher-rated conduct problems, hyperactivity, and lower prosocial behavioral symptoms. In conclusion, this study indicated that the self-report PSCD shows preliminary promise as a reliable, easy-to-use tool, for measuring psychopathic traits in Italian children and young adolescents.

Background: Beside the core symptoms, patients with attention-deficit/hyperactivity disorder (ADHD) frequently show relevant difficulty in developing relationships with peers. Although ADHD symptoms may account for social impairment, deficits in cognitive and/or affective empathy have also been involved. Our aim was to investigate the effect of methylphenidate (MPH) treatment on affective and cognitive empathy., Methods: Sixty-one drug-naïve youths with ADHD (age range 6 to 17 years, mean 10.3 ± 2.8 years, 51 males) naturalistically treated with MPH monotherapy were followed up for 6 months for ADHD symptoms and empathy, measured with the Basic Empathy Scale., Results: After being treated with MPH, the patients showed a significant improvement in affective and cognitive empathy scores. Linear regression models showed that changes in inattention symptoms predicted changes in affective but not in cognitive empathy, while changes in the hyperactivity/impulsivity symptoms did not predict changes in affective or cognitive empathy., Conclusions: Our study provides a further contribution for a better understanding of the possible effects of the MPH on youth's characteristics.

Although childhood-onset psychiatric disorders are often considered as distinct and separate from each other, they frequently co-occur, with partial overlapping symptomatology. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur with each other and with other mental disorders, particularly disruptive behavior disorders, oppositional defiant disorder/conduct disorder (ODD/CD). Whether these associated comorbidities represent a spectrum of distinct clinical phenotypes is matter of research. The aim of our study was to describe the clinical phenotypes of youths with ADHD with and without ASD and/or ODD/CD, based on neuropsychological and psychopathological variables. One-hundred fifty-one participants with ADHD were prospectively recruited and assigned to four clinical groups, and assessed by means of parent-reported questionnaires, the child behavior checklist and the behavior rating inventory of executive functions. The ADHD alone group presented a greater impairment in metacognitive executive functions, ADHD+ASD patients presented higher internalizing problems and deficits in Shifting tasks, and ADHD+ODD/CD subjects presented emotional-behavioral dysregulation. Moreover, ADHD+ASD+ODD/CD individuals exhibited greater internalizing and externalizing problems, and specific neuropsychological impairments in the domains of emotional regulation. Our study supports the need to implement the evaluation of the psychopathological and neuropsychological functioning profiles, and to characterize specific endophenotypes for a finely customized establishment of treatment strategies.