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Objective: Evidence on the efficacy of social skills training for adolescents with Level 1 Autism Spectrum Disorder (ASD) is unclear., Method: We searched Pubmed, Scopus, and Web of Science until July 27th, 2023, for randomized controlled trials (RCTs) of social skills training for pre-adolescents and adolescents (aged 9-18) with Level 1 ASD. We then pooled data on efficacy from individual RCTs by conducting multivariate mixed-effects meta-analyses in R. We estimated possible bias in the retained RCTs using the RoB2 tool., Results: We retained 36 RCTs (encompassing 2796 participants), including 18 RCTs comparing an experimental treatment to a waiting list, and 18 RCTs comparing it to standard care/control treatment. Meta-analyses showed that experimental treatments were significantly more efficacious than waiting list or standard care/ control treatments in improving social skills (SMD = 0.3745; 95%CI = [0.2396; 0.5093]), as well as reducing behavioral symptoms (0.3154;0.1783, 0.4525) and anxious/depressive symptoms (0.2780; 0.0432, 0.5128). However, for some outcomes there was significant heterogeneity across studies and evidence of publication bias. Subgroup analyses and meta-regressions did not identify any specific clinical or demographic factors as significant predictors of outcome. The most common risk of bias across studies was related to deviations from intended interventions and measurement of the outcomes., Conclusions: At the group level, social skills training for adolescents with Level 1 ASD is efficacious, with small-to-moderate effect size. Future research should focus on personalized medicine approaches, aimed at tailoring interventions to specific characteristics of adolescents with Level 1 ASD., Competing Interests: Competing interests: G.M. was on advisory boards for Angelini, received grants from Lundbeck and Humana, and was a speaker for Angelini, Neuraxpharm, and Otsuka. The other authors had no conflict of interest to disclose., (© 2024 Giovanni Fioriti Editore s.r.l.)

Background: Sleep is a complex phenomenon that affects several aspects of life, including cognitive functioning, emotional regulation, and overall well-being. Sleep disturbances, especially during adolescence, can negatively impact emotional regulation, making it a critical factor in targeting psychopathology., Methods: This study explores the interplay between emotional dysregulation (ED) and sleep patterns in a sample of 90 adolescent patients by means of self- and parent-rated clinical measures., Results: Our findings reveal a bidirectional relationship between ED and sleep problems. Adolescents with higher affective instability experience poorer sleep quality, while those with worse sleep quality exhibit higher internalizing problems. Additionally, emotional reactivity is associated with disrupted circadian rhythms., Conclusions: These results emphasize the significance of addressing sleep problems in the context of psychopathology treatment, potentially leading to improved outcomes. Further research is needed to determine the most effective treatment strategies, including nonpharmacological and pharmacological interventions. Understanding the intricate relationship between sleep problems and emotion regulation offers insights for more targeted and effective treatment approaches for youths struggling with ED.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions 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 ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children's Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD.

Background: Internet Gaming Disorder (IGD) and Internet Addiction (IA) are related clinical conditions often comorbid with Attention-Deficit/Hyperactivity Disorder (ADHD)., Objective: We evaluated the efficacy of MPH for IGD/IA symptoms in ADHD patients., Methods: We enrolled 38 drug-naive patients diagnosed with ADHD (Attention-Deficit/Hyperactivity Disorder) and IGD/IA. At baseline, all patients underwent a clinical assessment for IGD/IA symptoms and then received the most appropriate therapy according to their clinical profile. Twenty-one patients received MPH (methylphenidate) treatment, and 17 patients did not. Patients were re-evaluated after three months of treatment., Results: Findings revealed significant reductions in IGD/IA symptoms over time, while no significant effect of MPH on symptom reduction was found. Clinical predictors of symptom reduction were identified, including IQ (Intelligence Quotient) and comorbid anxiety., Conclusion: This longitudinal prospective study contributes to the understanding of IGD/IA treatment in ADHD patients and highlights the importance of considering individual clinical characteristics when predicting treatment response. However, MPH may not directly impact IGD/IA symptom reduction., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

Non-suicidal self-injury (NSSI) is deliberate harm to the body surface without suicidal intent, though it may be a predictor of suicide attempts. Our aim was to test the hypothesis that persisting and recovering NSSI may have a different longitudinal risk for suicidal ideation and behavior and that the intensity of Cyclothymic Hypersensitive Temperament (CHT) may increase this risk. Fifty-five patients (mean age 14.64 ± 1.77 years) referred for mood disorders according to the DSM-5 were consecutively recruited and followed-up for a mean of 19.79 ± 11.67 months and grouped according to the presence/absence of NSSI at baseline and follow-up into three groups: without NSSI (non-NSSI; n = 22), with NSSI recovered at follow-up (past-NSSI; n = 19), and with persistent NSSI at follow-up (pers-NSSI; n = 14). At follow-up, both NSSI groups were more severely impaired and failed to improve internalizing problems and dysregulation symptoms. Both NSSI groups reported higher scores in suicidal ideation compared to non-NSSI, but only pers-NSSI presented higher scores in suicidal behavior. CHT was higher in pers-NSSI, followed by past-NSSI and then by non-NSSI. Our data support a continuity between NSSI and suicidality, and they suggest the prognostic validity of persistent NSSI, associated with highest CHT scores.

Evidence from everyday life suggests that differences in social behaviors between males and females exist, both in animal and in humans. These differences can be related to socio-cultural determinants, but also to specialized portions of the brain (the social brain), from the neurotransmitter to the neural network level. The high vulnerability of this system is expressed by the wide range of neuropsychiatric disorders associated with social dysfunctions, particularly social withdrawal. The principal psychiatric disorders with prominent social withdrawal are described, including hikikomori-like syndromes, and anxiety, depressive, autistic, schizophrenic, and personality disorders. It is hypothesized that social withdrawal can be partially independent from other symptoms and likely reflect alterations in the social brain itself, leading to a similar, transdiagnostic social dysfunction, reflecting defects in the social brain across a variety of psychopathological conditions. An overview is provided of gender effects in the biological determinants of social behavior, including: the anatomical structures of the social brain; the dimorphic brain structures, and the modulation of their development by sex steroids; gender differences in "social" neurotransmitters (vasopressin and oxytocin), and in their response to social stress. A better comprehension of gender differences in the phenotypes of social disorders and in the neural bases of social behaviors may provide new insights for timely, focused, innovative, and gender-specific treatments., (© 2021 Wiley Periodicals LLC.)

Background: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by a wide spectrum of symptoms, including the onset of obsessive-compulsive disorder and/or severely restricted food intake, associated with emotional symptoms, behavioral symptoms, developmental regression, and somatic symptoms. Among the possible triggering agents, infectious agents have been extensively explored. More recently, sporadic case reports describe a possible association between PANS and SARS-CoV-2 infection but data on clinical presentation and treatment are still scarce., Methods: We describe a case series (10 children) with acute onset or relapse of PANS symptoms after SARS-CoV-2 infection. Standardized measures (CBCL, CPRS, C-GAS, CGI-S, Y-BOCS, PANSS, and YGTSS) were used to describe the clinical picture. The efficacy of a pulse treatment with steroids for three consecutive months was assessed., Results: Our data suggest that the clinical presentation of the COVID-19-triggered PANS is largely similar to that reported in typical PANS, including acute onset, with OCD and/or eating disorders, and associated symptoms. Our data suggest that treatment with corticosteroids may be beneficial for both global clinical severity and global functioning. No serious adverse effects were observed. Both OCD symptoms and tics consistently improved. Among psychiatric symptoms, affective and oppositional symptoms appeared more sensitive to the steroid treatment than the other symptoms., Conclusion: Our study confirms that COVID-19 infection in children and adolescents could trigger acute-onset neuropsychiatric symptoms. Thus, in children and adolescents with COVID-19, a specific neuropsychiatric follow-up should be routinely included. Even if a small sample size and a follow-up with only two points (baseline and endpoint, after 8 weeks) limit the conclusions, it seems that steroid treatment in the acute phase may be beneficial and well tolerated., 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 © 2023 Berloffa, Salvati, Pantalone, Falcioni, Rizzi, Naldini, Masi and Gagliano.)

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.

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.

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.

Background: The failure to regulate emotions, namely emotional dysregulation (ED), is a relevant construct in adolescent psychiatry, in terms of prognostic and developmental implications. We developed and validated a novel self-report questionnaire for the assessment of ED, the RIPoSt-Y, both in clinical and non-clinical samples., Methods: Items selection and subscales construction were conducted on healthy controls (n=374), while test-retest reliability was evaluated in a subsample (n=72); internal consistency was examined both in the control group and in two clinical samples, respectively including patients with Bipolar Spectrum Disorders (BSD; n=44) and ADHD (n=34). Construct, concurrent and convergent validity were also assessed., Results: Thirty-one items were finally retained, and three subscales were identified (Affective Instability, Emotional Reactivity, Interpersonal Sensitivity). Test-retest was significant for each subscale with moderate-to-good correlations, and internal consistency showed good-to-excellent coefficients. Construct validity was supported by significant differences between patients and controls and gender-related differences. Concurrent validity was confirmed through significant associations with two subscales of the CHT-Q, while convergent validity proved to be significant with the CBCL/YSR dysregulation-profile. Cut-offs were also computed to discriminate clinically significant scores of ED., Limitations: The use of a school-based survey to recruit controls could have biased our results; gender distributions between clinical and non-clinical samples were significantly different., Conclusions: Our novel questionnaire proved to be a valid and reliable tool able to assess the presence of ED in youths and to characterize this fundamental construct in its multidimensional facets., (Copyright © 2021. Published by Elsevier B.V.)

Background: Severe suicide ideation or attempts and non-suicidal self-injury (NSSI) present both differences and relevant overlaps, including frequent co-occurrence and shared risk factors. Specific categorical diagnoses, namely bipolar disorder (BD), may affect clinical features and natural histories of suicidal or not suicidal self-harm behaviour. Our study aimed to compare suicidality (severe suicidal ideation or suicidal attempts) and NSSI in referred bipolar adolescents., Methods: The sample included 95 bipolar adolescents (32 males, 63 females) aged 11 to 18 years. Thirty adolescents with suicide attempts/suicidal ideation and BD (SASIB) were compared with structured measures to 35 adolescents with NSSI and BD, without suicidal ideation or attempts (NSSIB), and to 30 adolescents with BD, without suicidal ideation or attempts or NSSI (CB)., Results: Compared to CB, suicidality and NSSI were both associated with female sex, borderline personality disorder and self-reported internalizing disorders, anxiety/depression and thought disorders. The NSSI were specifically associated with somatic problems. Severe suicidal ideation and suicide attempts were associated with adverse life events, immigration, bullying, eating disorders, social problems, depressive feelings, performance and social anxiety, and feelings of rejection., Conclusions: Both shared and differential features between suicidal and not suicidal adolescents may represent possible targets for diagnostic and preventative interventions.

LEGO ® -based therapy is a social skills development program aimed at children with autism spectrum disorder (ASD). A systematic review of the literature was conducted using PRISMA guidelines. PubMed, Scopus and Web of Science bibliographic databases were searched from their date of inception to August 2020. The review included 19 studies. Studies were classified according to experimental designs (e.g., Randomized Control Trial, Non-Randomized Studies of Interventions and case report and series) and a narrative synthesis of each was provided, along with a critical discussion of the strengths and weaknesses of the available literature on the topic. Although LEGO ® -based therapy appears a promising treatment for social interaction in ASD, the findings of LEGO ® -based therapy studies should be interpreted and generalized with caution, due to the low quality of the studies and the small sample sizes.

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.

Background: Bipolar Disorders (BD) in youth are a heterogeneous condition with different phenomenology, patterns of comorbidity and outcomes. Our aim was to explore the effects of gender; age at onset (prepubertal- vs. adolescent-onset) of BD; and elements associated with attention deficit hyperactivity disorder (ADHD) and Substance Use Disorder (SUD) comorbidities, severe suicidal ideation or attempts, and poorer response to pharmacological treatments., Method: 117 youth (69 males and 57 females, age range 7 to 18 years, mean age 14.5 ± 2.6 years) consecutively referred for (hypo)manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders , 54th ed (DSM 5) were included., Results: Gender differences were not evident for any of the selected features. Prepubertal-onset BD was associated with higher rates of ADHD and externalizing disorders. SUD was higher in adolescent-onset BD and was associated with externalizing comorbidities and lower response to treatments. None of the selected measures differentiated patients with or without suicidality. At a 6-month follow up, 51.3% of the patients were responders to treatments, without difference between those receiving and not receiving a psychotherapy. Clinical severity at baseline and comorbidity with Conduct Disorder (CD) and SUD were associated with poorer response. Logistic regression indicated that baseline severity and number of externalizing disorders were associated with a poorer outcome., Conclusions: Disentangling broader clinical conditions in more specific phenotypes can help timely and focused preventative and therapeutic interventions.

Background: Although lithium is currently approved for the treatment of bipolar disorders in youth, long term data, are still scant. The aim of this study was to describe the safety and efficacy of lithium in referred bipolar adolescents, who were followed up at the 4th (T1) and 8th (T2) month of treatment., Methods: The design was naturalistic and retrospective, based on a clinical database, including 30 patients (18 males, mean age 14.2±2.1 years)., Results: Mean blood level of lithium was 0.69±0.20 mEq/L at T1 and 0.70±0.18 mEq/L at T2. Both Clinical Global Impression-Severity (CGI-S) and Children Global Assessment Scale (C-GAS) scores improved from baseline (CGI-S 5.7±0.5, C-GAS 35.1±3.7) to T1 (CGI-S 4.2±0.70, C-GAS 46.4±6.5; P <0.001), without significant differences from T1 to T2. Thyroid-stimulating hormone significantly increased from 2.16±1.8 mU/mL at baseline to 3.9±2.7 mU/mL at T2, remaining within the normal range, without changes in T3/T4 levels; two patients needed a thyroid hormone supplementation. Creatinine blood level did not change. No cardiac symptoms and electrocardiogram QTc changes occurred. White blood cell count significantly increased from 6.93±1.68 10 3 /mmc at baseline to 7.94±1.94 10 3 /mmc at T2, and serum calcium significantly increased from 9.68±0.3 mg/dL at baseline to 9.97±0.29 mg/dL at T2, both remaining within the normal range; all the other electrolyte levels were stable and normal during the follow-up. The treatment with lithium was well tolerated, probably due to the relatively low lithium blood levels. Gastrointestinal symptoms (16.7%), sedation (9.7%) and tremor (6.4%) were the most frequently reported side effects., Conclusion: Lithium was effective and safe in adolescent bipolar patients followed-up for eight months., Competing Interests: Disclosure Dr GM was in the advisory boards for Eli Lilly, Shire and Angelini, has received research grants from Eli Lilly, Shire and Lundbeck and has been speaker for Eli Lilly, Shire and FB Health. The other authors report no conflicts of interest in this work.

Background: Growing evidence supports the comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in children and adolescents. Our aim is to further explore clinical and treatment implications of this comorbidity, as it appears in clinical practice., Method: The sample included 429 consecutive patients with BD and/or OCD as primary diagnoses, followed for a mean period of 6 months (range 4-9 months), 172 with BD (102 males, mean age 13.7±2.9 years), 169 with OCD (118 males, mean age of 13.2±2.7 years) and 88 with comorbid BD+OCD (56 males, mean age 14.2±2.6 years, 52 with BD as the primary diagnosis), followed for a mean period of 6 months (range 4-9 months). The comorbid group was compared to pure BD and OCD groups, to explore differential clinical and treatment features., Results: The BD-OCD comorbidity was found in 33.8% of the BD patients and in 34.2% of the OCD patients. Age at onset of BD and OCD were not different in pure and "comorbid" groups. The comorbid group presented a higher occurrence of BD type II and hoarding symptoms, and more frequently received a psychotherapy and second generation antipsychotics, but it presented the poorest outcome in terms of response to treatments. Severity at baseline (clinical severity and functional impairment), hoarding obsessions and compulsions, and conduct disorder comorbidity were associated with a treatment non-response., Limitations: A selection bias may have increased the rate of comorbidity, as most of the patients were referred to our tertiary hospital for severe BD and/or OCD and pharmacological treatment. We have used CGI-I as an outcome measure, not a specific measure of BD or OCD symptoms' severity and improvement. The short duration of the follow-up may limit our conclusions., Conclusions: The timely identification of BD-OCD comorbidity may have relevant clinical implications in terms of symptomatology, course, treatment and outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Pediatric social anxiety disorder (SAD) is associated with an increased risk of comorbid mental disorders, with implications for prognosis and treatment strategy. The aim of this study is to explore predictors of treatment response, and the role of comorbidity in affecting refractoriness., Methods: One hundred and forty consecutive youths (81 males, 57.9%), ages 7-18 years (mean age 13.7 ± 2.5 years, mean age at onset of SAD 10.6 ± 2.7 years) met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for SAD as primary diagnosis, according to a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]). All received a pharmacological treatment with serotonin reuptake inhibitors (SSRIs) targeted to SAD, associated with additional medications for comorbidities (mood stabilizers in 27.1%, antipsychotics in 12.8%) and 57.9% received an additional psychotherapy., Results: Eighty-nine patients (63.6%) responded to treatments after 3 months, namely 72.8% with psychotherapy plus medication and 50.8% with medication only. Nonresponders had more severe symptoms at baseline in terms of both clinical severity and functional impairment, and had more comorbid disruptive behavior disorders. The backward logistic regression indicated that clinical severity and functional impairment at baseline, comorbid disruptive behavior disorders, and bipolar disorders were predictors of nonresponse., Conclusion: Our data suggest that SSRIs can be effective in pediatric SAD, but that the more severe forms of the disorder and those with heavier comorbidity are associated with poorer prognosis.

Objective: Two main patterns of comorbidity have been described in bipolar disorder in children and adolescents: the first including preexisting attention-deficit/hyperactivity disorder (ADHD) and related disruptive behavior disorders and the second including anxiety disorders, namely, the association of co-occurring multiple anxiety disorders, usually predating the onset of bipolarity. This study was aimed at exploring whether ADHD and multiple anxiety disorders may exhibit different pathways to specific bipolar phenotypes., Method: We compared 49 youths (7 to 18 years) with bipolar disorder + ADHD without anxiety, 76 youths with bipolar disorder + multiple anxiety disorders without ADHD, and 52 youths with bipolar disorder without ADHD or multiple anxiety disorders who were referred to a third-level hospital and diagnosed according to DSM-IV-TR in the period 2005-2011. Subjects were evaluated for current and lifetime Axis I psychiatric disorders by using a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version) and followed up for at least 6 months., Results: Compared to both patients with bipolar disorder + multiple anxiety disorders and patients with bipolar disorder without ADHD and multiple anxiety disorders, patients with bipolar disorder + ADHD without anxiety were more frequently male, were younger, had an earlier onset of bipolar disorder, had a prevalent chronic course and irritable mood, were more likely to present with a bipolar disorder not otherwise specified diagnosis, had a greater clinical severity and functional impairment, had a manic/mixed index episode, had a higher risk of conduct disorder, and were more resistant to treatments, according to the CGI-Improvement scores (P < .0001). Patients with bipolar disorder + multiple anxiety disorders were similar to those with bipolar disorder without ADHD or multiple anxiety disorders, except for a higher rate of diagnosis of bipolar II disorder, more use of antidepressants, and less use of atypical antipsychotics., Conclusions: The presence of comorbid ADHD versus anxiety disorders is indicative of fundamental differences in the phenomenology of bipolar disorder in youth. While ADHD prior to bipolar disorder is associated with a specific bipolar phenotype, bipolar patients with multiple anxiety disorders are similar to "typical" bipolar patients., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Tourette's disorder (TD) in children and adolescents is frequently co-morbid with attention-deficit/hyperactivity disorder (ADHD). Dopamine-blockers are the first line treatment for TD, whereas dopamine-agonists, such as stimulants, are the gold-standard in the treatment of ADHD. These contrasting effects supported concerns about the risk that stimulants for treating ADHD may trigger or worsen co-morbid tics. Aripiprazole, a partial dopamine agonist, acts as an antagonist at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist properties under hypodopaminergic conditions. The present study describes the use of aripiprazole (10.0 ± 4.8 mg/day) in a consecutive group of 28 patients with a primary diagnosis of TD and co-morbid ADHD, combined subtype. The Yale Global Tic Severity Scale (YGTSS) and the ADHD-Rating Scale (ADHD-RS-IV) were used as primary outcome measures and both significantly improved (p<0.001) after the treatment. Global measures of severity (Clinical Global Impressions-Severity) and of functional impairment (Children's Global Assessment Scale) also significantly improved during the treatment (p<0.001). At the YGTSS there was a reduction of 42.5%, in motor tics, of 47.9% in phonic tics (44.7% for the combined scores), and of 32.3% in tic impairment. Nineteen patients (67.9%) had a reduction of at least 50% of the YGTSS score (motor+phonic tics). The improvement at the ADHD-RS-IV score was 22.5%, 12 patients (42.8%) presented an improvement of 30%, but only 2 (7.1%) an improvement greater than 50%. Using a logistic regression model, a reduction of at least 30% in ADHD-RS-IV score was more likely to occur in the obsessive-compulsive disorder co-morbid group. Aripiprazole was well tolerated and none of the patients discontinued medication because of side effects. In summary, aripiprazole resulted in an effective treatment for TD, but it was only moderately effective on co-occurring ADHD symptomatology. Our preliminary data suggest that aripiprazole may represent a possible therapeutic option, among other possible monotherapies addressing both tics and ADHD.

The aim of this study was to assess efficacy of aripiprazole augmentation of serotonin reuptake inhibitor (SRI) treatment in adolescents with obsessive-compulsive disorder (OCD) who did not respond to 2 initial trials with SRI monotherapy. A consecutive series of 39 adolescents (28 males and 11 females; age range, 12 to 18 years; mean age, 14.6 ± 1.2 years), with OCD diagnosed based on a clinical interview and according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were included. The mean final aripiprazole dosage was 12.2 ± 3.4 mg/d. At the endpoint, 27 patients (59.0%) had a Clinical Global Impression (CGI)-Improvement score 1 or 2 (very much or much improved) and a Clinical Global Impression-Severity (CGI-S) score 3 or below and were thus considered responders. The CGI-S improved from 6.0 ± 0.9 at the baseline (severely to extremely severely ill) to 3.5 ± 1.0 (mild to moderately ill) at the end of the follow-up (P < 0.0001), whereas the Children's Global Assessment Scale improved from 39.2 ± 5.8 to 49.8 ± 9.0 (P < 0.0001). Compared with nonresponders, responders were less impaired at the baseline in functional impairment (Children's Global Assessment Scale; P = 0.004) but not in clinical severity (CGI-S). Subtypes of OCD comorbidity and absence of insight did not affect clinical response. Mild transitory agitation (10.3%), mild sedation (10.3%), and sleep disorders (7.7%) were reported, but any of the patients discontinued medication because of adverse effects.In these severely impaired adolescents, aripiprazole augmentation of SRIs was well tolerated and effective in more than half of the patients.

This study reports on the naturalistic pharmacotherapy of 266 youths with bipolar disorder (BP), manic or hypomanic episode (158 males and 108 females, 13.8+/-2.8 years), first treated with monotherapy on valproic acid (VPA) (n=158, 59.4%), lithium (n=90, 33.8%) or atypical antipsychotics (n=18, 6.8%). Among the patients receiving mood stabilizers, 59.5% of those treated with VPA and 47.8% of those receiving lithium did not need other antimanic agents (mood stabilizers and/or atypical antipsychotics). Lower severity was associated with a greater persistence of both VPA and lithium monotherapy. Factors associated with greater persistence of VPA monotherapy were BP II and co-occurring generalized anxiety disorder, separation anxiety disorder and simple phobias. On the contrary, BP I and co-occurring psychotic symptoms and/or conduct disorder were associated with a lower persistence of VPA monotherapy. Factors associated with lower persistence of lithium monotherapy were younger age and the association with attention deficit hyper-activity disorder (ADHD). Type of BP and presence of psychotic symptoms and conduct disorder did not affect the lithium monotherapy. Overall, predictors of non-response (multiple stepwise logistic regression) in both VPA and lithium groups were baseline Clinical Global Impression (CGI) Severity score and comorbid conduct disorder; while psychotic symptoms and absence of comorbid generalized anxiety disorder were predictors of poorer treatment response only in the VPA group, and chronic course, comorbid ADHD and absence of comorbid panic disorder were predictors only in the lithium group. Such naturalistic data from an ordinary clinical setting have relevance to clinical practice., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Few studies have examined the impact of gender, age at onset, phenotype and comorbidity in pediatric obsessive-compulsive disorder (OCD) in children. In this naturalistic study we consider these characteristics of OCD in the framework of the 4 OCD phenotypes (contamination/cleaning, order/symmetry, obsessions/checking and hoarding) proposed by Leckman et al., Sampling and Methods: A consecutive series of 257 patients aged 13.6 +/- 2.8 years, diagnosed using a DSM-IV-based clinical interview (Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime Version), were included., Results: Patients with OCD onset before 12 years of age presented a higher frequency of comorbid tic disorder and disruptive behavior disorders. The type of obsession varied with gender: order/symmetry was more frequent in males, contamination/cleaning in females. Order/symmetry had the highest comorbidity with tics, contamination/cleaning was the least severe according to the Clinical Global Impression Severity, and was associated with a high rate of comorbid anxiety and depression, similarly to sexual-religious obsessions. Hoarding was the severest according to the Clinical Global Impression Severity, and was associated with a high comorbidity with social phobia and bipolar disorder. Tic comorbidity was more prevalent in males, had an earlier onset, and a heavier comorbidity with attention deficit hyperactivity disorder and other disruptive behavior disorders. A comorbid attention deficit hyperactivity disorder was associated with an earlier onset of OCD and a poorer response to treatments., Conclusions: OCD phenotypes and comorbidities may have marked clinical and prognostic implications. Tertiary care population results may not generalize to less impaired juvenile populations., (Copyright 2010 S. Karger AG, Basel.)

Background: Pediatric obsessive-compulsive disorder (OCD) can cause substantial impairment in academic, social and family functioning. Even though cognitive-behavioural therapy (CBT) is an effective treatment, the pharmacological option has to be taken into consideration. Effectiveness of serotonin reuptake inhibitors (SRIs) has been supported by several double-blind, placebo-controlled studies., Objective: To report the response to pharmacotherapy in children and adolescents with OCD naturalistically followed up and treated with SRIs., Methods: From a consecutive series of 257 patients (174 males and 83 females; mean age 13.6+/-2.7 years) diagnosed with OCD following a clinical interview according to DSM-IV criteria, 37 children improved significantly after psychotherapy and were excluded. The remaining 220 patients were included in the study., Results: Eighty-nine patients (40.5%) were managed with SRI monotherapy and 131 with an SRI in combination with another medication. Compared with those who needed polypharmacy, patients managed with SRI monotherapy were younger at the time of the first consultation, had less severe symptoms at baseline, and more frequently presented with co-occurring anxiety and depressive disorders, while patients receiving polypharmacy presented with higher rates of bipolar disorder, tic disorder and disruptive behaviour disorders. 135 patients (61.4%) achieved a positive clinical response and were considered responders. When differences between responders and nonresponders at the end of follow-up were considered, irrespective of the pharmacological treatment (monotherapy or polypharmacy), responders had less severe disease at baseline, were younger at the time of the first consultation, more frequently presented with the contamination/cleaning phenotype and less frequently presented with the hoarding phenotype. Treatment refractoriness was associated with higher rates of conduct disorder and bipolar disorder, and lower rates of generalized anxiety disorder and panic disorder. Forty-three children received therapy with an atypical antipsychotic as an augmenting strategy, and 25 of these children (58.1%) became responders. Responders to augmentation were less severely impaired at baseline, while different subtypes of OCD were similar between responders and nonresponders, as were patterns of co-morbidity., Conclusion: Our study suggests that putative variables associated with response to pharmacological treatment of paediatric OCD can be defined, and can help improve treatment strategies.

Objective: According to DSM-IV, bipolar disorders (BDs) include four subtypes, BD I, BD II, cyclothymic disorder, and BD not otherwise specified (NOS). We explore the clinical implications of this subtyping in a naturalistic sample of referred youths with BD I, BD II, and BD-NOS., Method: The sample consisted of 217 patients, 135 males and 82 females, ages between 8 and 18 years (mean age, 13.6 +/- 2.9 years), diagnosed according to historical information, prolonged observations, and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version). The location of the study was the Stella Maris Scientific Institute of Child Neurology and Psychiatry of Pisa (Italy)., Results: Seventy-eight patients (35.9%) had BD I, 97 (44.7%) had BD II, and 42 (19.4%) had BD-NOS. Patients with BD I presented more frequently psychotic symptoms and elated rather than irritable mood. Patients with BD II were less severely impaired, presented more frequently depression as the intake affective episode, and had the highest comorbidity with anxiety disorders. Patients with BD-NOS presented an earlier onset of the disorder, a chronic rather than episodic course, an irritable rather than an elated mood, and a more frequent comorbidity with attention-deficit/hyperactivity disorder and oppositional defiant disorder., Conclusions: DSM-IV categorization of BD may have meaningful implications in youths, but needs to be detailed further.

A substantial portion of patients with juvenile bipolar disorder (BD) have a comorbid panic disorder (PD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. The sample comprised 224 referred children and adolescents with BD, 140 males (62.5%) and 84 females (37.5%), mean age 13.8+/-2.8 years, diagnosed with a clinical interview (K-SADS-PL), and followed up naturalistically for 6 months. Fifty-one BD patients (22.8%) had a lifetime diagnosis of comorbid PD. Subjects with BD+PD and those without BD (BD-noPD) did not differ according to index age, age at onset of BD and bipolar phenotype (episodic vs. continuous course, irritable vs. elated mood). BD+PD was more frequent in females, was less severe at baseline according to the Clinical Global Impression severity score, and was more frequently associated with BD type 2. Moreover, BD+PD presented higher rates of comorbid anxiety disorders (namely separation anxiety disorder) and lower rates of externalizing disorders, namely attention deficit disorder (ADHD) than BD-noPD. However, this different pattern of externalizing comorbidity did not affect severity and improvement. Our findings suggest that PD is frequently comorbid in juvenile BD and can influence severity, pattern of comorbidity and course of BD. The data are compatible with the hypothesis that Panic-BD and ADHD-BD might represent distinct developmental pathways of bipolar disorder. Further research on this question may prove rewarding.

This paper reports on implications of bipolar disorder (BD) co-morbidity in 120 children and adolescents with obsessive-compulsive disorder (OCD) (84 males, 36 females, age 13.7 +/- 2.8 years), diagnosed using a clinical interview according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, and naturalistically followed-up for 12 +/- 6 months. The aim of this naturalistic, retrospective study was to explore the effect of BD co-morbidity, disentangling it from other co-occurring variables, namely the co-morbidity with disruptive behavior disorders. Forty three patients (35.8%) had a bipolar co-morbidity. Compared with OCD patients without BD, they had an earlier onset of OCD, a greater severity and functional impairment, more frequent hoarding obsessions and compulsions, and a poorer response to treatments. They had a higher co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD), and a lower co-morbidity with generalized anxiety disorder (GAD). Finally, they received more mood stabilizers, and 30.2% of them did not receive serotonin-selective reuptake inhibitors (SSRIs) because of pharmacological (hypo)mania. When all the OCD responders and nonresponders were compared, nonresponders (n = 42, 35%) were more severe at baseline and at end of the follow-up, had more frequently hoarding obsessions and compulsions, and had more frequent BD, ODD, and conduct disorder (CD) and less GAD and panic disorder. In the final regression model, hoarding obsessions and compulsions, co-morbidity with ODD, and CD were negative predictors of treatment outcome. This study suggests that even though bipolar co-morbidity is frequent and affects phenomenology and co-morbidity in pediatric OCD, its effect on treatment response seems prevalently accounted for by co-morbidity with disruptive behavior disorders. The significance of the hoarding subtype deserves further research on larger samples of pediatric patients.

Background: This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome., Methods: A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study., Results: Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups., Conclusions: Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.