Jonathan Sever

A Comparison of Life Events Between Suicidal Adolescents With Major Depression and Borderline Personality Disorder

The current study compared the correlations of different types of stressful life events (SLE) between suicidal adolescents with major depressive disorder (MDD) and suicidal adolescents with borderline personality disorder (BPD). Both groups were referred following an attempted suicide. Twenty adolescents with MDD and 20 adolescents with BPD who were consecutively referred to an outpatient clinic following a suicide attempt were evaluated. A community control group of adolescents with no lifetime history of suicidal behavior was also assessed. The following measurements were employed: the Suicide Risk Scale (SRS) Beck Depression Inventory (BDI), the Life Events Checklist (LEC), and the Childhood Sexual Abuse Questionnaire (CSEQ). Both groups of suicidal subjects reported more SLE in general and more physical abuse than community controls in the 12 months before the suicide attempt. The MDD adolescents had more lifetime death-related SLE than the BPD and control groups, while the BPD adolescents reported more lifetime sex abuse-related SLE than the other two groups. Thus, suicidal behavior in general may be related to the amount of SLE. However, different disease-specific life events may precipitate suicide attempts in adolescents with MDD and BPD.

Neurosteroids in child and adolescent psychopathology.

Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes. There is accumulating evidence on their role in adult psychopathology, including Alzheimer disease, schizophrenia, mood disorder, anxiety disorders and post-traumatic stress disorder. Little is known, however, about the possible role of neurosteroids in child and adolescent psychopathology although there is increasing evidence for their critical role from the early stages of brain development until adolescence. In this review we focus on the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents. Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit. The complex interaction between neurosteroids, neurodevelopment, life-events, genetics and mental disorders in children and adolescents merits further investigation.

Low-dose quetiapine for adolescents with autistic spectrum disorder and aggressive behavior: open-label trial.

Background Atypical antipsychotics may be useful in treating aggression associated with autistic spectrum disorder (ASD). We evaluated the effectiveness of low-dose quetiapine treatment in ASD adolescent patients with aggressive behavior. Method Eleven adolescent patients (8 boys and 3 girls) diagnosed with ASD, aged 13 to 17 years, were treated with quetiapine in an open-label study over an 8-week period. The severity of ASD, aggressive behavior, and sleep disturbances were assessed using the Clinical Global Impression—Severity (CGI-S), Overt Aggression Scale, and Child Sleep Habits Questionnaire, respectively. Results Nonsignificant changes were obtained in autistic behavior after quetiapine treatment (CGI-S: 4.0 ± 0.6 vs CGI-S after: 3.1 ± 1.1; 2-tailed paired t = 1.93; df = 10; P = 0.08). Severity of aggressive behavior decreased significantly after quetiapine treatment (Overt Aggression Scale: 2.1 ± 0.94 vs 1.3 ± 0.64, respectively; 2-tailed paired t = 2.37; df =10; P = 0.028). Sleep disturbances improved significantly (Child Sleep Habits Questionnaire: 49.0 ± 12 vs 44.1 ± 9.6; 2-tailed paired t = 2.98; df =10; P = 0.014) and a positive correlation was found between the improvements in aggression and sleep (Spearman correlation: r = 0.43; N = 11; P = 0.013). Quetiapine was well tolerated. Conclusion Short-term low-dose quetiapine treatment may reduce aggression levels and improve sleep quality in adolescents with ASD.

Methylphenidate in the treatment of female adolescents with cooccurrence of attention deficit/hyperactivity disorder and borderline personality disorder : a preliminary open-label trial

Recent studies reported symptomatic overlap between attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD). Methylphenidate (MPH) is the most efficient treatment for ADHD. We assessed the efficacy and tolerability of MPH treatment in adolescent females who met the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for both disorders. Fourteen BPD/ADHD female adolescents aged 14–19 years were treated with MPH for 12 weeks, targeting ADHD, BPD symptoms, and aggressive behavior, as rated by ADHD-rating scale (ADHD-RS) and Clinical Global Impression-Severity (CGI-S) scale for BPD and aggressive behavior severity. A significant improvement was detected in both ADHD and BPD severity (baseline vs. end point, ADHD-RS: 33.1±4.8 vs. 17.6±5.2, P<0.001; BPD CGI-S: 4.6±0.8 vs. 3.4±0.8, P<0.0005, respectively) as well as in aggressive behavior (Aggression CGI-S: 3.5±1.3 vs. 1.8±0.5, P<0.001). MPH was well tolerated. MPH may be useful and well tolerated in treating some shared symptoms of ADHD and BPD among female adolescents. Controlled studies are needed to substantiate these findings.

Reduced platelet vesicular monoamine transporter density in Tourette's syndrome pediatric male patients

The vesicular monoamine transporter (VMAT2) plays a major role in the synaptic accumulation and quantal release of monoamines. In this study, we assessed high affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2, in a group of untreated male Tourettes syndrome (TS) patients (age: 8-17.5 years, n=9) and in a group of age- and sex-matched healthy controls (age: 9-16 years, n=16). Significantly decreased platelet VMAT2 density (B(max)) (-23%, p=0.016) was observed in the TS patients. The affinity (K(d)) of the ligand to platelet VMAT2 was similar in both groups. If the lower platelet VMAT2 density also occurred in the brain, it may have serve as an adaptive mechanism geared to decrease dopamine storage in the presynaptic neurons and thereby to attenuate the dopaminergic overactivity and ameliorate the movement disorder.

Methylphenidate treatment in children with attention deficit hyperactivity disorder and comorbid social phobia.

The aim of this study was to assess the response of social phobia (SP) symptoms to methylphenidate (MPH) treatment in children with attention deficit hyperactivity disorder (ADHD). Twenty-one ADHD patients with SP, aged between 8 and 18 years, received 12 weeks of MPH treatment. The severity of SP symptoms were assessed by the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA), and the severity of ADHD symptoms was assessed by the ADHD Rating Scale at baseline and at endpoint. MPH treatment was associated with a significant decrease in the ADHD Rating Scale scores (P<0.0001) and in the total LSAS-CA scores (P=0.013), as well as the school-related items of LSAS-CA (P=0.011). A significant correlation was found between the reductions in ADHD score and total LSAS-CA score (P=0.038), especially in school-related SP. The improvement in ADHD symptoms because of MPH treatment correlates with a parallel improvement in SP. MPH treatment appears to be safe and effective in ADHD/SP children.

Short-Term Effects of Lithium on White Blood Cell Counts and on Levels of Serum Thyroid-Stimulating Hormone and Creatinine in Adolescent Inpatients: A Retrospective Naturalistic Study

OBJECTIVE The purpose of this study was to determine if the known side effects of lithium in adults may be generalized to younger patients with psychiatric disorders. METHODS A retrospective naturalistic study design was used. Data were collected from the database of a tertiary pediatric medical center covering the years 1994-2010. Included were patients hospitalized for bipolar and non-bipolar disorders and treated with lithium, alone or in combination with other medications. The electronic medical files were reviewed for changes in thyroid and kidney function and for hematological parameters during the course of treatment. RESULTS Sixty-one patients 12.5-20.4 years of age (mean 16.94±1.66) met the study criteria: 33 with bipolar disorder and 28 with a non-bipolar disorder. Mean duration of lithium treatment (mean lithium blood level, 0.73±0.24 mEq/L) was 193.68±254.35 days. Mean levels of thyroid-stimulating hormones (TSH) rose significantly from baseline to last measurement (3.16±2.68 vs. 1.52±0.92 mU/L; paired t=-5.19, df=50, p<0.001); in 25% of patients, TSH levels at the last measurement were above normal (≥4 mU/L). Only one patient developed TSH values >10 mU/L (the threshold considered clinically significant). Positive correlation was found between pre- and posttreatment TSH levels (Pearsons r=0.60; n=51, p<0.05). White blood cell count (WBC) also increased significantly following lithium treatment (7195±2151 vs. 7944±2096 cells/mm(3); t=2.83, df=60, p=0.006). No significant changes were noted in serum creatinine levels. There was no difference in these parameters between patients treated with lithium alone or in combination with other medications. CONCLUSIONS Lithium treatment in adolescents with bipolar or non-bipolar disorders is associated with a significant increase in blood TSH levels and WBC count. Lithium-treated adolescent inpatients with a high basal TSH level may be at risk of developing pituitary-thyroid axis dysregulation. Therefore, baseline measurement of thyroid functions and serial monitoring throughout treatment are recommended.

Reboxetine treatment for autistic spectrum disorder of pediatric patients with depressive and inattentive/hyperactive symptoms: an open-label trial.

BackgroundReboxetine is a norepinephrine reuptake inhibitor that may be useful in treating pediatric depression as well as attention-deficit/hyperactivity disorder (ADHD). Both are often comorbid with autistic spectrum disorder (ASD). We evaluated the effectiveness of reboxetine treatment in pediatric patients with ASD with symptoms of depression and ADHD. MethodEleven adolescent patients with ASD (9 boys and 2 girls, aged 12.2 ± 3.6 years) with depressive and ADHD symptoms were treated with reboxetine (maximal dose, 4 mg/d) in an open-label trial during a 12-week period. The severity of depressive and ADHD symptoms was assessed by the Child Depression Rating Scale (CDRS) and Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), respectively. ResultsSignificant, but modest, decreases in the severity of depressive symptoms (CDRS before vs after scores: 65.5 ± 10.8 vs 58.3 ± 8.2; paired t test, 3.1; df, 10; P =0.01) and ADHD symptoms (Attention Deficit/Hyperactivity Disorder Rating Scale before vs after: 36.4 ± 5 vs 32.8 ± 5; paired-t test, 2.94; df, 10; P = 0.015) were obtained after reboxetine treatment. The patients (n = 5) with high baseline scores of CDRS (T score >75) showed a trend toward larger response to reboxetine than those (n = 6) with low (T score <75) basal CDRS scores (&Dgr;, 12.8 ± 5.4 vs 2.3 ± 5.2; P = 0.07).A significant positive correlation was found between the changes in the total scores of the depression and the ADHD severity (Spearman correlation r = 0.65 [95% confidence interval, 0.09–0.9]; n = 11; P = 0.029). Most of the patients (approximately 90%) reported tolerable adverse effects. ConclusionsReboxetine treatment may reduce, modestly but significantly, depressive and ADHD symptoms in adolescents with ASD. High rate of adverse effects requires close monitoring.

Methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder and comorbid trichotillomania: a preliminary report.

Objectives: Trichotillomania (TTM) is a heterogenic mental disorder with a high rate of comorbidity and stressful life events (SLEs). Serotonergic and dopaminergic dysfunction are implicated in the pathophysiology of TTM. As in other impulse control disorders, increased prevalence of attention-deficit/hyperactivity disorder (ADHD) is reported in patients with TTM as well. This study aimed to assess the efficacy and tolerability of methylphenidate (MPH) treatment in children and adolescents who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for both ADHD and TTM. Methods: Nine children and adolescents, aged 6 to 18 years, diagnosed with ADHD and TTM, were treated with MPH for a 12-week period. The severity of ADHD was assessed using the ADHD Rating Scale, and the hair pulling was rated using the Massachusetts General Hospital Hair-Pulling Scale. Additional scales were used for assessing depression and anxiety levels, and history of SLE was recorded. Results: Significant improvement was detected in ADHD after MPH treatment (P < 0.003), but no significant change was observed in hair pulling, as measured by the Massachusetts General Hospital Hair-Pulling Scale (P = 0.096) or in depression and anxiety levels. Lack of response of TTM to MPH (improvement, <50%) was associated with higher rate of positive SLE history (P = 0.047). Conclusions: Some efficacy of MPH treatment was shown in TTM patients with low rate of SLE. A large-scale study is mandatory to evaluate the efficacy of MPH for TTM in ADHD/TTM patients. Trial Registration in www.clinicaltrials.gov. Identifier: NCT00552266.

Attention Patterns in Children with Attention Deficit Disorder with or without Hyperactivity

The objective of this study was to differentiate the attention patterns associated with attention deficit disorder with or without hyperactivity using continuous performance test (CPT). The diagnoses were based on the DSM-III, III-R, and IV criteria and of the 39 children who participated in the study, 14 had attention deficit disorder with hyperactivity (ADDH) and 11 had attention deficit disorder without hyperactivity (ADDWO), while 14 normal children served as a control group. Attention patterns were examined according to the performance of subjects on the CPT and parental scores on the ADHD Rating Scale, the Child Attention Profile, and the Conners Rating Scale. CPT performances were assessed before and after administration of 10 mg methylphenidate. We found as hypothesized that the CPT differentiated between the ADDH and ADDWO groups. However, contrary to our expectations, the ADDH children made more omission errors than the ADDWO children; they also showed more hyperactivity and impulsivity. The performance of both groups improved to an equal degree after the administration of methylphenidate. It is conluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.