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Background: Cyclothymic-hypersensitive temperament (CHT) has been related to both depression and bipolarity, as well as to suicidality. Recently, a psychometrically sound way of assessment has been validated in youth (Cyclothymic-Hypersensitive Temperament Questionnaire, CHTQ), but data on clinical populations are still scant. Aim of our study is to further explore the structure and other psychometric properties of the revised version of CHTQ and its clinical implications in clinical samples., Methods: The study is based on a dataset of patients with unipolar depression, bipolar disorder and attention deficit and hyperactivity disorder (ADHD) (243 patients, 135 males, mean age 14.22 ± 2.16 years, age range 9-18 years), compared to a community sample of adolescents (398 subjects, 95 boys, mean age 15.47 ± 1.96 years, age range 10-18 years) RESULTS: The two-correlated factor structure of CHT has been confirmed, with a moodiness/hypersensitiveness factor, correlated with internalizing symptoms, and an impulsiveness/emotional dysregulation factor, correlated with externalizing symptoms. All CHTQ scores correlate with global functioning. CHTQ total scores discriminate patients from healthy controls. Only CHTQ impulsiveness/emotional dysregulation subscale score is higher in bipolar patients, compared to unipolar depression and ADHD, whereas neither CHTQ moodiness/hypersensitiveness subscale score nor CHTQ total score discriminate between clinical groups., Limitation: Data on current mood states are unavailable. Patients were recruited in a third level clinic. The unipolar depression group is relatively small., Conclusion: CHT may be a rapid and reliable screening and diagnostic tool in the clinical practice with youth, exploring the cyclothymic dimension in different psychiatric disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Increasing attention has been recently paid to precursors of bipolar disorder (BD). Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been reported among the most common prodromes of BD. The aim of this study was to estimate the risk of BD in youths affected by ADHD based on prospective studies., Methods: A systematic review was conducted according to the PRISMA guidelines. A meta-analysis of single proportions was performed to compute the overall occurrence of BD in ADHD individuals. Binary outcome data were used to calculate risk estimates of BD occurrence in ADHD subjects versus Healthy Controls (HC)., Results: An overall proportion of BD occurrence of 10.01% (95%-confidence interval [CI]: 6.47%-15.19%; I 2  = 82.0%) was found among 1248 patients with ADHD over 10 prospective studies. A slightly higher proportion was found when excluding one study based on jack-knife sensitivity analysis (11.96%, 95%-CI: 9.15%-15.49%; I 2  = 54.1%) and in three offspring studies (12.87%, 95%-CI: 8.91%-18.23%). BD occurrence was not significantly associated with mean follow-up duration (p-value = 0.2118). A greater risk of BD occurrence in ADHD versus HC from six studies was found (risk ratio: 8.97, 95%-CI: 4.26-18.87, p-value < 0.0001)., Limitations: Few prospective studies have been retrieved in our search and most were not specifically aimed at assessing BD in followed-up ADHD patients., Conclusions: Greater clinical attention should be paid to ADHD as an early precursor of BD since a substantial proportion of ADHD patients is expected to be diagnosed with BD during the developmental age., (Copyright © 2021. Published by Elsevier B.V.)

Background: Lithium is a first-line treatment for bipolar disorder in adults, but its mechanism of action is still far from clear. Furthermore, evidences of its use in pediatric populations are sparse, not only for bipolar disorders, but also for other possible indications., Objectives: To provide a synthesis of published data on the possible mechanisms of action of lithium, as well as on its use in pediatric samples, including pharmacokinetics, efficacy, and safety data., Methods: Clinical trials in pediatric samples with at least one standardized measure of efficacy/ effectiveness were included in this review. We considered: i) randomized and open label trials, ii) combination studies iii) augmentation studies iv) case series including at least 5 patients., Results: Different and non-alternative mechanisms of action can explain the clinical efficacy of lithium. Clinical studies in pediatric samples suggest that lithium is effective in managing manic symptoms/episodes of bipolar disorder, both in the acute phase and as maintenance strategy. Efficacy on depressive symptoms/phases of bipolar disorder is much less clear, while studies do not support its use in unipolar depression and severe mood dysregulation. Conversely, it may be effective on aggression in the context of conduct disorder. Other possible indications, with limited published evidence, are the acute attacks in Kleine-Levin syndrome, behavioral symptoms of X-fragile syndrome, and the management of clozapine- or chemotherapy- induced neutropenia. Generally, lithium resulted relatively safe., Conclusions: Lithium seems an effective and well-tolerated medication in pediatric bipolar disorder and aggression, while further evidences are needed for other clinical indications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions.

Two Child Behaviour Checklist (CBCL) profiles were correlated to poor self-regulation, Deficient Emotional Self-Regulation (DESR) (elevation between 1 and 2 Standard Deviations (SD) in Anxiety/Depression, Aggression, Attention subscales), and Dysregulation Profile (DP) (elevation of 2 Standard Deviations or more). We explored youths with Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) whether these profiles are associated with specific clinical features. The sample included 57 patients with DESR profile and 41 with DP profile, ages 9 to 15 years, all assigned to a non-pharmacological Multimodal Treatment Program. No differences resulted between groups in demographic features, diagnosis ratio, and comorbidities with Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), and Anxiety Disorder. The DP group was associated with higher scores in Withdrawn, Social Problem, Thought, Rule Breaking, and Somatic CBCL subscales, and higher scores in Narcissism and Impulsivity (but not Callous-Unemotional (CU)), according to the Antisocial Process Screening Device (APSD). After treatment, patients with DESR improved their personality traits (Narcissistic and Callous-Unemotional, but not Impulsivity), while changes in CBCL scales were modest. Patients with DP improved scales of Attention, Aggression, Anxiety-Depression, Rule Breaking, Withdrawal, Social Problem and Thought, while personality features did not change. These results suggest diagnostic implications of CBCL profiles, and indications for targeted treatment strategies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (p<0.0001). Nine out of the 16 patients with suicidality (56.3%) had a reduction in this severe symptom during the follow-up. Nonresponders were more frequently males, and more frequently had an attention-deficit/hyperactivity disorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

Objective: The co-occurrence of conduct disorder (CD) and bipolar disorder (BD) has been frequently reported in referred children and adolescents. We address the implications of this comorbidity in a naturalistic sample of youths with BD, CD, and CD+BD., Methods: The sample consisted of 307 patients (216 males and 91 females, age range 8-18 years, mean age 13.5 +/- 2.6 years) referred during a 5-year period and followed-up for at least 6 months, 106 with CD without BD, 109 with BD without CD, and 92 with CD+BD, diagnosed with a structured clinical interview (K-SADS-PL)., Results: Patients with CD alone were more predominantly males and with the lowest socio-economic status. Patients with CD without BD were the least severe at the baseline, while patients with BD alone presented the greatest improvement during the follow-up, and those with CD+BD had the poorest response. Patients with CD+BD presented higher rates of global aggression at the baseline, namely impulsive aggression, compared with CD alone, and the highest risk of substance abuse. Patients with BD alone presented higher rates of comorbid panic disorder and obsessive compulsive disorder, while patients with CD, with or without BD, had higher rates of ADHD., Conclusions: Bipolar-conduct disorder comorbidity may have meaningful implications in children and adolescents, in terms of presentation, course, and treatments.

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. [ABSTRACT FROM AUTHOR]

Emotional dysregulation (ED) is currently the most frequently used term to describe children with an impaired regulation of emotional states. Recent research studies speculate whether ED may be a neurodevelopmental disorder itself, a shared risk factor, or a common key feature of several psychiatric disorders, including, among others, attention deficit hyperactivity disorder (ADHD), and bipolar spectrum disorders (BSD). The association between ADHD and ED is one of the main reasons of misconceptions in the definition of boundaries between ADHD and BSD, leading to the frequent misdiagnosis of ADHD as BSD. Since ED is a multidimensional concept, a novel instrument—the Reactivity, Intensity, Polarity and Stability (RIPoSt) scale—was recently developed to assess the different dimensions of ED, which could help in detecting specific ED profiles in clinical youths. Our study included 154 patients, aged 13.8 ± 2.3 years, diagnosed with either ADHD, BSD, or comorbid condition, and a school-based sample of 40 healthy control (HC) adolescents, aged 12.5 ± 1.2 years. The RIPoSt scale and the Child Behavior Checklist were administered to both groups. Our results indicate that affective instability and negative emotionality subscales, as well as negative emotional dysregulation, are higher in BSD, both pure and comorbid with ADHD, while emotional impulsivity is higher in the comorbid condition and similar in the ADHD and BSD alone group; all clinical groups scored higher than HC. Conversely, positive emotionality is similar among clinical groups and within them and HC. Our findings also support the validity of the RIPoSt questionnaire, since the instrument proved to have good-to-excellent internal consistency, and strongly significant positive correlations were found with the CBCL-Dysregulation Profile, which is a commonly used, indirect measure of ED. Hence, the five subscales of the RIPoSt can be reliably used as an effective tool to study the emotional dysregulation in different clinical conditions, to help disentangle the complex relationship between ADHD and juvenile BSD and to provide clinicians with crucial evidence for better diagnostic characterization and therapeutic indications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Non suicidal self-injuries (NSSIs) are deliberate self-harm behaviors without suicidal intent, usually starting in adolescence, with increasing rates of occurrence both in epidemiological and clinical samples. Several studies associated cyclothymic-hypersensitive temperament (CHT) with self-harm behaviors and suicidal risk. Aim of this study is to explore the association between NSSIs and CHT in a clinical sample of adolescents. We hypothesized that CHT may differentiate NSSI from non-NSSI adolescents with mood disorders, when other psychopathological features are controlled for.Methods: A consecutive sample of 89 adolescents with mood disorders were assessed for presence and phenomenology of NSSIs, CHT, demographics, comorbid categorical psychiatric diagnoses, dimensional psychopathology, impairment and previous suicide attempts.Results: NSSIs were reported in 52% of the sample, with higher rates in females and in bipolar disorder. Regression analyses showed that CHT, but not age, gender, bipolar vs depression diagnosis, functional impairment, was associated with NSSIs.Discussion: CHT may be in close association with NSSIs in adolescents with mood disorders. An assessment of CHT in adolescents referred for mood disorder may help to detect specific psychological features of NSSIs, which may improve diagnostic and treatment strategies.Limitations: Given the cross-sectional design, a developmental relation between CHT and NSSIs cannot be determined. The small sample size and the selection bias of severely impaired patients limit the generalization of the results. More sophisticated measures of CHT may consent to explore other dimensions of the cyclothymic construct (i.e., emotional intensity, emotional reactivity, emotional stability, positive vs. negative emotions, interpersonal sensitivity, impulsivity). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]