Cigarette Smoking, Alcohol and Cannabis Use in Patients With Pervasive Developmental Disorders.

BACKGROUND AND OBJECTIVES: This study aimed to examine the rates of cigarette smoking, alcohol and cannabis use among patients with pervasive developmental disorder (PDD), in order to determine whether they are relatively protected from developing substance-related addictive behaviors. METHODS: This case-control study included 85 patients diagnosed with PDD and 85 age- and gender-matched nonpsychotic psychiatric patients without PDD. Data were collected from the patients' electronic medical records and included demographic and psychiatric parameters, as well as data on smoking, alcohol, and cannabis use. RESULTS: A lower rate of cigarette smoking was found among patients diagnosed with PDD in comparison to those without PDD [20.0% vs. 52.9% respectively, p < .001). The likelihood of smoking in PDD was found to be 3.57-fold lower than in psychiatric controls [OR = 3.57 (95% CI 1.69-7.14), p = .001]. A multivariate analysis showed that after adjusting for age, comorbid diagnoses and use of an antipsychotic medications, this effect was even more robust with the likelihood of smoking in PDD decreasing even more substantially compared to controls [OR = 8.33 (95% CI 2.86-25), p < .001]. A similar finding was noted when comparing the prevalence of alcohol and cannabis use between the two groups [OR 6.67 (95%CI 1.30-33.33), p = .02 and 5.55 (95%CI 1.30-25), p = .01, respectively]. CONCLUSIONS: PDD is associated with 5-8-fold lower adjusted risk of smoking, alcohol and cannabis use compared to other non-psychotic psychiatric patients. Further research should elucidate the neurobiological and psychosocial mechanisms underlying the apparent addiction protective properties of PDD.

Suicide, Satisfaction With Life, and Insight Capacity Among Adolescents With Mental Disorders.

BACKGROUND: Little is known about the role of insight and satisfaction with life in adolescent suicidal behavior. AIMS: The objective of this study was to examine the relationship between suicide risk, insight, and satisfaction with life among adolescents with mental disorders. METHOD: A total of 30 adolescents were evaluated using self-report measures of insight, satisfaction with life, and suicide risk. Regression analysis was used to assess the contribution of each factor to suicide risk. RESULTS: Positive correlations were found between suicide risk and insight dimensions. Satisfaction with life correlated negatively with suicide risk and insight dimensions. Insight explained 27.3% of suicide risk (p = .003). Both insight and satisfaction with life explained 39.0% of suicide risk (p = .031). CONCLUSION: Among adolescents with mental disorders, insight is a risk factor, whereas satisfaction with life is a protective factor for suicidality. Insight affects suicide risk of adolescents with mental disorders via reduction of satisfaction with life.

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 (Pearson's 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.

The beneficial effect of methylphenidate in ADHD with comorbid separation anxiety.

The objective of this study was to assess the response of subsyndromal separation anxiety (SSSA) symptoms to methylphenidate (MPH) treatment in patients with attention-deficit/hyperactivity disorder (ADHD). A group of patients with ADHD and SSSA (n=42), aged 8-17 years, received 12 weeks of MPH treatment. The severity of SSSA symptoms was assessed using appropriate scales including the Screen for Child Anxiety Related Emotional Disorders and the specially designed Child and Adolescent Separation Anxiety Scale (CASAS). The severity of ADHD symptoms was assessed using the ADHD Rating Scale. The severity of ADHD and separation anxiety reduced significantly and significant positive correlations were found between the changes in ADHD Rating Scale and the total CASAS scores (P=0.012), as well as other relevant subscales of Screen for Child Anxiety Related Emotional Disorders and CASAS. The MPH-related attenuation in the severity of ADHD was associated with a corresponding improvement in separation anxiety related to school. SSSA symptomatology may be secondary to ADHD and thus the alleviation in ADHD symptoms achieved by MPH treatment results in corresponding relief in separation anxiety.

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.

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

BACKGROUND: Reboxetine 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. METHOD: Eleven 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. RESULTS: Significant, 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 (Δ, 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. CONCLUSIONS: Reboxetine treatment may reduce, modestly but significantly, depressive and ADHD symptoms in adolescents with ASD. High rate of adverse effects requires close monitoring.

Handshaking as a measure of social responsiveness in patients with autistic spectrum disorder.

BACKGROUND: Children with autistic spectrum disorder (ASD) have difficulties understanding and using nonverbal communication. Handshaking is an expressive gesture that requires adequate skills for social interaction and, because of its highly emotional characteristic for patients with ASD, may reflect their ability for social responsiveness. Unlike eye contact or complex social behavior, this gesture has not been studied in the past. We developed a rating scale intended to evaluate social responsiveness through handshaking, in patients with ASD. METHOD: A group of patients with ASD (n = 20), aged 9 to 18 years, was compared with 2 age-matched groups, one of patients with attention deficit/hyperactivity disorder (n = 20) and the other is of patients with mild (IQ, 55-70) mental retardation (n = 20). To rate the handshaking behavior, we designed a Handshaking Assessment Scale (HAS) that includes 8 Yes/No items. The predefined cutoff point was a minimum of 4 "Yes" answers. RESULTS: Significantly more patients with ASD (13/20) had abnormal HAS (Yes answers, ≥4) than either in the attention deficit/hyperactivity disorder group (1/20; P < .0001) or in the mental retardation group (5/20; P < .025). CONCLUSION: There seems to be a strong association between poor handshaking skills and autistic psychopathology, as compared with the 2 control groups. As was demonstrated by the brief and easy-to-administer HAS assessment tool, it may be advisable to use handshaking more widely as a diagnostic procedure for ASD or include it in larger diagnostic batteries. Large-scale studies are needed to substantiate our observation.

Late potentials in the signal-averaged electrocardiogram in pre-pubertal children with ADHD, before and after methylphenidate treatment.

Reports on sudden cardiac death (SCD) of children and adolescents treated with stimulant agents have raised concerns regarding the need for cardiovascular monitoring and risk stratification schedules. Cardiac ventricular late potentials (LPs) represent delayed ventricular activation that might predispose to fatal ventricular arrhythmias and SCD in cardiac patients. LPs have not previously been measured in children with attention deficit/hyperactivity disorder (ADHD). LPs were measured in 18 physically healthy ADHD children (5 girls and 13 boys, age 11.9 ± 2.5 years, treatment duration 2.6 ± 1.9 years) before and 2 h after oral methylphenidate administration. No significant changes were detected and LPs were found to be within normal ranges. In conclusion, this preliminary small-scale study suggests that methylphenidate in physically healthy children with ADHD was not associated with cardiac ventricular LPs, suggesting the safety of the agent in this age group.

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 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.

Influence of methylphenidate treatment on smoking behavior in adolescent girls with attention-deficit/hyperactivity and borderline personality disorders.

BACKGROUND: Cigarette smoking and nicotine dependence are prevalent among pediatric populations with attention-deficit/hyperactivity disorder (ADHD). We assessed the impact of methylphenidate (MPH)treatment on the smoking behavior of adolescent girls with ADHD/borderline personality disorder (BPD). METHOD: Twelve female adolescent smokers with ADHD/BPD aged 14to 19 years were treated with MPH for an 8-week period. The severity ofADHD was assessed by the ADHD Rating Scale (ADHD-RS), whereas the smoking behavior was rated by Fagerstorm Test for Nicotine Dependence(FTND). RESULTS: Significant improvement was detected in ADHD symptoms(ADHD-RS, mean [SD], baseline vs end point: 33.1 [6.8] vs 19.9 [6.8],t = 6.875, df = 11, P = 0.0001). A decline, as assessed by FTND (baseline vs end point: 4.1 [2.6] vs 2.0 [1.9], t = 4.056, df = 11, P = 0.0019), was observed in the severity of nicotine dependence. No significant correlation was found between changes in the ADHD-RS and the FTND after MPH treatment (r = 0.09935, P = 0.7587). CONCLUSIONS: Methylphenidate may attenuate smoking behavior in female adolescent smokers with ADHD/BPD.

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 Tourette's 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.

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.

Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10-year retrospective study.

OBJECTIVE: The aim of this study was to investigate the link between the use of specific types of substances and suicidality in adolescent inpatients with schizophrenia and schizoaffective disorder. METHODS: We performed a 10-year naturalistic retrospective study of 178 adolescent inpatients diagnosed as suffering from either schizophrenia or schizoaffective disorder. A comparison was made between the suicide-attempting adolescent inpatients and the non-attempting subjects, by the use of specific types of substances, measurements of psychotic, depressive, and aggressive symptoms, and clinical data reported during their hospitalization. RESULTS: The suicide attempters reported considerably greater usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene-dioxy-methylamphetamine (MDMA) were also used significantly more by this group. However, no differences were found in the usage of cannabis, amphetamines, cocaine, and opiates. The suicide-attempting patients were found to have had more previous psychiatric admissions, a greater level of deliberate self-harm behavior, and a higher level of suicide ideation, but a decreased severity of psychotic symptoms. CONCLUSIONS: This study is the first report of the association between specific types of substances and suicidality in the high-risk population of adolescent psychotic inpatients. The strong association between inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide prevention and intervention programs in adolescent-onset schizophrenia.

Balance dysfunction in childhood anxiety: findings and theoretical approach.

A recent special issue of the Journal of Anxiety Disorders, reviewed the experimental and clinical findings related to comorbidity of balance disorders and anxiety [J. Anxiety Disord. 15 (2001) 1.]. The studies mentioned in that issue were based mostly on adult subjects but prevalence of balance disorders in childhood anxiety is yet to be established. We have tested a small sample of children diagnosed for general or separation anxiety disorder and a control group of normal children. Extensive neurological examination revealed no clinically relevant vestibular impairment. Nevertheless, detailed questionnaires and balance tests confirmed an excessive sensitivity of anxiety disordered children to balance-challenging situations. Moreover, balance-challenging tasks triggered more balance mistakes and slower performance in anxiety versus control children. These findings support the notion of subclinical balance disorder in childhood anxiety. Results are discussed in terms of the two-stage theory of learning, which predicts that anxiety disorder may be an offshoot of lasting balance dysfunction.

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 concluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.

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.