Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

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.

Efficacy of Methylphenidate for Internet Gaming Disorder and Internet Addiction in Patients with Attention-Deficit/Hyperactivity Disorder.

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.

Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

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.

Hikikomori (Severe Social Withdrawal) in Italian Adolescents: Clinical Features and Follow-Up.

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.

Persistent Non-Suicidal Self-Injury and Suicidality in Referred Adolescents: A Longitudinal Study Exploring the Role of Cyclothymic Temperament.

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.

Corrigendum: Steroid treatment response to post SARS-CoV-2 PANS symptoms: Case series.

[This corrects the article DOI: 10.3389/fneur.2023.1085948.].

Steroid treatment response to post SARS-CoV-2 PANS symptoms: Case series.

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.

Social withdrawal and gender differences: Clinical phenotypes and biological bases.

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.

Early Sensory Profile in Autism Spectrum Disorders Predicts Emotional and Behavioral Issues.

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 Measure­Preschool (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.

Internet Gaming Disorder in Children and Adolescents with Attention Deficit Hyperactivity Disorder.

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.

Sensory Profiles in School-Aged Children with Autism Spectrum Disorder: A Descriptive Study Using the Sensory Processing Measure-2 (SPM-2).

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.

Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders and Catatonia: The "Iron Triangle" Rediscovered in a Case Report.

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.

Neuroleptic Malignant Syndrome in Children with Autism Spectrum Disorder (ASD): A Case Report and Brief Review of Recent Literature.

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.

A Comparison between Severe Suicidality and Nonsuicidal Self-Injury Behaviors in Bipolar Adolescents Referred to a Psychiatric Emergency Unit.

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.

Could You Give Me the Blue Brick? LEGO®-Based Therapy as a Social Development Program for Children with Autism Spectrum Disorder: A Systematic Review.

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.

A novel multidimensional questionnaire for the assessment of emotional dysregulation in adolescents: Reactivity, Intensity, Polarity and Stability questionnaire-youth version (RIPoSt-Y).

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.

De Novo 1q21.3q22 Duplication Revaluation in a "Cold" Complex Neuropsychiatric Case with Syndromic Intellectual Disability.

Syndromic intellectual disability often obtains a genetic diagnosis due to the combination of first and next generation sequencing techniques, although their interpretation may require revaluation over the years. Here we report on a composite neuropsychiatric case whose phenotype includes moderate intellectual disability, spastic paraparesis, movement disorder, and bipolar disorder, harboring a 1.802 Mb de novo 1q21.3q22 duplication. The role of this duplication has been reconsidered in the light of negativity of many other genetic exams, and of the possible pathogenic role of many genes included in this duplication, potentially configuring a contiguous gene-duplication syndrome.

Autism Spectrum Disorder and Disruptive Behavior Disorders Comorbidities Delineate Clinical Phenotypes in Attention-Deficit Hyperactivity Disorder: Novel Insights from the Assessment of Psychopathological and Neuropsychological Profiles.

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.

A Naturalistic Study of Youth Referred to a Tertiary Care Facility for Acute Hypomanic or Manic Episode.

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.

Lithium treatment in bipolar adolescents: a follow-up naturalistic study.

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±1.68 103/mmc at baseline to 7.94±1.94 103/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.