Pavel Golubchik

Lowered DHEA-S plasma levels in adult individuals with autistic disorder

The aim of this study was to determine for the first time neurosteroid levels, dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in particular, in a group of adult patients with autistic disorder and compare these levels with normal healthy individuals. Levels of DHEA, DHEA-S and cortisol were compared between 15 adult drug-free patients with autistic disorder and 13 healthy controls. The Ritvo-Freeman Real-Life Rating Scale (RLRS) and the Overt Aggression Scale (OAS) were assessed as a measure of symptom severity. Significant lower DHEA-S levels were observed in the group with autistic disorder as compared to controls (p < 0.05). DHEA-S levels appear to be low in patients with autistic disorder and, while speculative, may play a role in the etiopathophysiology of the disorder.

Low Platelet-Poor Plasma Levels of Serotonin in Adult Autistic Patients

Background: Hyperserotonemia has been reported in about a third of autistic patients. However, most studies have examined whole blood levels of serotonin (5-HT), the vast majority of which is found in platelets. The aim of this study was to determine 5-HT levels in platelet-poor plasma (PPP) in a group of adult patients with autism. Methods: Levels of PPP 5-HT were compared between 10 adult drug-free autistic patients and 12 healthy controls. The Ritvo-Freeman Real-Life Rating Scale and the Overt Aggression Scale (OAS) were administered to the autistic group as a measure of symptom severity. Results: Significantly lower PPP 5-HT levels were observed in the autistic group as compared to the controls (p = 0.03). In addition, PPP 5-HT levels were inversely correlated with OAS scores among subjects with autism (r = –0.64, p < 0.05). Conclusion: PPP 5-HT (‘free’) levels appear to be low in autistic patients and may play a role in the pathophysiology and symptomatology of the 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.

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.

Neurosteroid blood levels in delinquent adolescent boys with conduct disorder

Accumulating data indicates that neurosteroids can modulate aggressive behavior. The aim of the present study was to examine neurosteroid blood levels in delinquent adolescent boys as compared to normal healthy controls. Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) and cortisol blood levels were measured in 16 delinquent adolescent (age 15.72+/-0.95 years) with conduct disorder (CD) and 11 normal controls (16.82+/-1.83 years). Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS). The delinquent adolescents tended to have higher DHEA-S levels than the normal control group (p=0.054). DHEA and cortisol levels did not differ between the two groups. The interaction between neurosteroids ( especial DHEA-S) and genetic, developmental and environmental factors in juvenile delinquency merits further investigation.

Attention-Deficit Hyperactivity Disorder, Methylphenidate, and Primary Encopresis

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Attention-deficit/hyperactivity disorder and comorbid subsyndromal depression: what is the impact of methylphenidate on mood?

BackgroundYouths with attention-deficit/hyperactivity disorder (ADHD) may develop demoralization or depressive or dysthymic symptoms related to chronic social, familial, and academic difficulties that are associated with their ADHD and are at higher risk for developing mood disorders. We assessed the effectiveness of methylphenidate (MPH) on both ADHD and mood symptoms in children and adolescents diagnosed with ADHD and coexistent subsyndromal depression (SSD). MethodsA group of ADHD patients with SSD (n = 47), aged 8 to 18 years, received 12 weeks of MPH treatment. The severity of depressive and ADHD symptoms was assessed using the Child Depression Rating Scale (CDRS) and the Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), respectively. ResultsA highly significant decrease in both ADHD-RS and CDRS scores was obtained in the total group (N = 47) after MPH treatment (P = 0.0001 and P = 0.0001, respectively). A significant positive correlation was found between the changes in the CDRS total scores and the ADHD-RS (r = 0.34, N = 47, P = 0.018). However, no such correlation was found in a subgroup (N = 8) of patients with “possible depression” (baseline CDRS score, 65–74; r = 0.026, P = 0.95). ConclusionsMethylphenidate treatment is effective for both ADHD and SSD symptoms. It seems that ADHD symptoms are less responsive to MPH in patients with relatively high CDRS scores (possible depression) and that those patients may be candidates for selective serotonin reuptake inhibitor treatment as a supplement for MPH. Further, larger, placebo-controlled, double-blind studies are needed to examine the impact of MPH or d-amphetamine on patients with ADHD/SSD and ADHD/major depressive 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.

Platelet poor plasma serotonin level in delinquent adolescents diagnosed with conduct disorder

OBJECTIVE Accumulating data indicate the involvement of the serotonergic system in adolescent aggression. The aim of this study was to examine the platelet-poor plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with conduct disorder (CD) in comparison with normal controls. METHOD PPP 5-HT levels were measured in 16 male delinquent CD adolescents from a correctional facility and in 14 normal male adolescent controls. Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS). RESULTS Delinquent CD adolescents had higher PPP 5-HT levels (about 3-fold) than the normal controls (27.68+/-32.29 vs. 7.76+/-4.23 ng/ml, respectively, p=0.027). In the delinquent CD adolescents a significant correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive scores (r=0.68, p=0.0034 and r=0.59, p=0.016, respectively). CONCLUSIONS Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT neurotransmission may have a role in the symptomatology and treatment of severe adolescent CD.