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The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM-III-R disorders.

BACKGROUND: The Great Smoky Mountains Study of youth focuses on the relationship between the development of psychiatric disorder and the need for and use of mental health services. METHODS: A multistage, overlapping cohorts design was used, in which 4500 of the 11758 children aged 9, 11, and 13 years in an 11-county area of the southeastern United States were randomly selected for screening for psychiatric symptoms. Children who scored in the top 25% on the screening questionnaire, together with a 1 in 10 random sample of the rest, were recruited for 4 waves of intensive, annual interviews (n = 1015 at wave 1). In a parallel study, all American Indian children aged 9, 11, and 13 years were recruited (N = 323 at wave 1). RESULTS: The 3-month prevalence (+/-SE) of any DSM-III-R axis I disorder in the main sample, weighted to reflect population prevalence rates, was 20.3% +/- 1.7%. The most common diagnoses were anxiety disorders (5.7% +/- 1.0%), enuresis (5.1% +/- 1.0%), tic disorders (4.2% +/- 0.9%), conduct disorder (3.3% +/- 0.6%), oppositional defiant disorder (2.7% +/- 0.4%), and hyperactivity (1.9% +/- 0.4%). CONCLUSIONS: The prevalence of psychiatric disorder in this rural sample was similar to rates reported in other recent studies. Poverty was the strongest demographic correlate of diagnosis, in both urban and rural children.

Adolescent↗

Eye-movement tics in children.

Tics are relatively common in childhood, especially between the ages of six to 12 years. While eye-blinking and eye-winking tics are well recognised, eye-movement tics are not. Three children with conjugate eye-movement tics, occurring alone or in combination with other tics, are described and the differential diagnosis is discussed. Treatment of tics in the first instance comprises reassurance and explanation. Detailed further investigation is not indicated, but follow-up is desirable while tics persist, since some children may go on to develop Tourette syndrome or chronic tic disorder.

Adolescent↗

[The treatment of the resistant obsessive-compulsive disorder: an update].

Although the majority of patients with obsessive compulsive disorder (OCD) can be helped significantly by modern pharmacotherapy with serotonin uptake inhibitors (SUIs), usually in combination with behavioral techniques of exposure and response prevention, complete cure occurs infrequently and some remain very ill and refractory to treatment. In open-label reports, the addition of agents that enhance serotonin neurotransmission, such as lithium, tryptophan, fenfluramine, buspirone, clonazepam and other SUIs or tricyclic antidepressants to ongoing treatment in SUI-refractory patients has yielded encouraging results. However, the anti-obsessive efficacy of SRI-lithium and SRI-buspirone has not been confirmed in recent controlled trials. Preliminary evidence suggests that addition of low-dose dopamine antagonists appears to be a potentially useful strategy for the specific subgroup of OCD patients with a comorbid chromic tic disorder and possibly for those with concurrent psychotic spectrum disorders. Mono Amino oxidase Inhibitors (MAOIs) have also had promising results in open studies. New and experimental drugs are briefly reviewed. Other biological approaches (e.g., electroconvulsive therapy and psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant OCD.

Antidepressive Agents, Tricyclic↗

Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance.

To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for approximately 40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader, phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.

Adolescent↗

[Comorbidity of compulsive disorders in childhood and adolescence].

OBJECTIVE: The cross-sectional comorbidity of child and adolescent inpatients with obsessive-compulsive disorder (OCD) was assessed. METHODS: The hospital records of all inpatients treated for OCD since 1976 (31 girls, 46 boys) were compared with data from a prospective epidemiological longitudinal study (90 girls, 84 boys) in two age cohorts (< 15 years; > or = 15 years) with regard to comorbid psychiatric diagnoses. Additionally, psychiatric Axis I diagnoses of patients with a supplementary diagnosis of compulsive symptoms (n = 45) were descriptively assessed in the client population. RESULTS: In the subgroup of OCD patients < 15 years, boys showed a higher incidence of tic disorders. OCD girls > or = 15 years showed a tendency toward more frequent comorbid affective disorders and a significant result regarding concurrent eating disorders. Eighteen of 27 female patients with supplementary compulsive symptoms requiring clinical intervention had an Axis I diagnosis of eating disorder. CONCLUSIONS: Due to different criteria of classification, diverging definitions of comorbidity and different age cohorts and samples, studies on comorbidity in OCD patients are difficult to compare. The frequency of comorbid psychiatric disorders may be over-estimated if the general prevalence of psychiatric disorders in terms of gender and age is not taken into account.

Adolescent↗

Reactivity of tic observation procedures to situation and setting.

Tic frequency was assessed and compared across home and clinic as well as three experimentally-manipulated situations in order to assess the phenomenon of tic reactivity. Forty-three youngsters with chronic tic disorder recruited from two geographically-distinct sites were videotaped over three weekly laboratory visits under each of the following conditions: (1) alone/camera present, (2) other present/camera present, and (3) alone/camera hidden. Contrary to expectation, more tics were observed during overt as compared to covert observation, while the presence of another person had no overall impact on tic expression. Mean tic counts obtained from clinic observation did not significantly differ from those obtained at home collected either one day before or after. Tic frequency counts were remarkably stable over the three weekly assessments both at home and clinic. Study findings are consistent with past observations that tic expression can be influenced by environmental factors and suggest the stability of tic frequency may exhibit greater temporal and setting stability than previously thought. The clinical and research implications of these results are discussed.

Adolescent↗

Case series: clonidine has no systematic effects on PR or QTc intervals in children.

This study retrospectively examined the effects of clonidine, both alone and combined with psychostimulants, on the electrocardiograms (ECGs) of children and adolescents. Two pediatric cardiologists, blinded to treatment condition, examined pre- and posttreatment ECGs in 42 subjects treated with clonidine for attention-deficit/hyperactivity or tic disorder. While ECG variability was found, it did not appear to be related to any systematic effect of clonidine, either alone or in combination with psychostimulants. These data do not rule out the possibility of rare idiosyncratic reactions to clonidine with or without psychostimulants, though none occurred in this sample.

Adolescent↗

Psychiatric morbidity of second and third grade primary school children in Korea.

This study was undertaken to identify psychiatric morbidity among Korean second and third elementary school children using an objective diagnostic interview tool. Data from 5,118 (2,723 boys, 2,395 girls; mean age = 8.41 years (SD = 0.66)) second and third grade schoolchildren were drawn from 28 elementary schools. After initial screening assessments using the 28-item Child Problem-Behavior Screening Test for parents, 672 primary caregivers were subjected to secondary screening using the Korean version of the CBCL. Two hundred and seventy-one high-risk children selected according to the K-CBCL results, 138 (50.9%) children and their primary caregivers were interviewed using the Korean version of K-SADS-PL for objective DSM-IV psychiatric diagnoses. Sixty-four (46.4%) of the hundred and thirty eight children were determined to have at least one psychiatric disorder. More boys were diagnosed as psychiatric patients than girls (46 males, 18 females; OR = 2.21). The most frequently diagnosed disorder was ADHD (46/64; 71.9%), followed by tic disorder, anxiety disorders, mental retardation, oppositional defiant disorder, and separation anxiety disorder. Two or more comorbid psychiatric disorders were found in 22 (34.4%) of the 64 patients. The computed crude percentage of psychiatric patients in this study was 4.12%, which is similar to previously published data.

Child↗

B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome?

OBJECTIVE: It has been hypothesized that Sydenham's chorea, a major manifestation of rheumatic fever, may provide a medical model for obsessive-compulsive disorder and associated conditions, such as Tourette's syndrome. Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in nearly all patients with rheumatic fever and is thought to be a trait marker for susceptibility to this complication of group A streptococcal infection. The authors investigated whether D8/17 expression is greater than normal in some forms of obsessive-compulsive disorder and Tourette's syndrome. METHOD: By immunofluorescence techniques, 31 patients with childhood-onset obsessive-compulsive disorder and/or Tourette's syndrome or chronic tic disorder and 21 healthy comparison subjects were evaluated for percentage of D8/17-positive B cells. None had rheumatic fever or Sydenham's chorea. Levels of antineuronal antibodies and streptococcal antibodies were also determined. RESULTS: The average percentage of B cells expressing the D8/17 antigen was significantly higher in the patients (mean = 22%, SD = 5%) than in the comparison subjects (mean = 9%, SD = 2%). When classified categorically, all patients but only one comparison subject were D8/17 positive. No difference between groups in the presence of antineuronal antibodies or high streptococcal titers was found. CONCLUSIONS: Patients with childhood-onset obsessive-compulsive disorder or Tourette's syndrome had significantly greater B cell D8/17 expression than comparison subjects despite the absence of documented Sydenham's chorea or rheumatic fever. These findings suggest that D8/17 may serve as a marker for susceptibility among some forms of childhood-onset obsessive-compulsive disorder and Tourette's syndrome, as well as rheumatic fever or Sydenham's chorea.

Adolescent↗

Biological approaches to treatment-resistant obsessive compulsive disorder.

Biological approaches to the patient with treatment-resistant obsessive compulsive disorder are briefly reviewed. The most commonly employed strategy involves combining a potent serotonin reuptake inhibitor (SRI) (e.g., clomipramine or fluvoxamine) with another medication that may exert effects on the brain serotonin system. Open-label reports regarding the addition of tryptophan, fenfluramine, lithium, or buspirone to ongoing SRI therapy of obsessive compulsive disorder are encouraging. However, the anti-obsessive compulsive efficacy of SRI-lithium and SRI-buspirone combination therapy has not been confirmed in recent controlled trials. Preliminary evidence suggests that addition of neuroleptic may benefit SRI-refractory obsessive compulsive disorder patients who have a comorbid chronic tic disorder. Other biological approaches (e.g., electroconvulsive therapy and psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant obsessive compulsive disorder. Finally, an algorithm is proposed for those patients with obsessive compulsive disorder who fail to respond to an adequate trial with a potent SRI.

Behavior Therapy↗

Treatment of Tourette's syndrome with calcium antagonists.

Six males and one female with chronic tic disorders, whose ages ranged from 12 to 31 years, were evaluated before treatment, after 1 month on placebo, after a single 10 mg nifedipine dose (three patients), and monthly while on flunarizine 10-15 mg (mean dose of 13 mg). None of the patients receiving nifedipine improved, but treatment with flunarizine significantly decreased both motor and phonic tic severity and frequency in all but one patient. Side effects included mild transient headaches in one patient, depression in one, and bradykinesia in two. Although a double-blind study is essential to validate our findings, results suggest that flunarizine is a useful drug in the treatment of Gilles de la Tourette syndrome.

Adolescent↗

Cognitive-pharmacologic functional magnetic resonance imaging in tourette syndrome: a pilot study.

BACKGROUND: Dopamine agonists and antagonists can reduce abnormal movements and vocalizations (tics) in Tourette syndrome (TS); however, dopamine-responsive abnormal function in specific brain regions has not been directly demonstrated in TS. We sought to identify dopamine-modulated brain regions that function abnormally in TS by combining functional magnetic resonance imaging (fMRI), a working memory (WM) task, and infusion of the dopamine prodrug levodopa (while blocking dopamine production outside the brain). METHODS: We obtained complete fMRI data in 8 neuroleptic-naive adults with a chronic tic disorder and in 10 well-matched tic-free control subjects. RESULTS: Different task-sensitive brain regions responded differently to the WM task depending on levodopa status and diagnostic group (analysis of variance [ANOVA], p <.001). Four regions showed interactions with diagnosis (ANOVA, p <.001). In TS subjects, the task induced excessive brain activity in parietal cortex, medial frontal gyrus, and thalamus. Levodopa normalized the excess activity. In left parietal cortex, the degree of normalization was greater in patients with higher levodopa plasma concentrations (n = 6; Spearman's r = -.84, p =.04) and a greater degree of diagnostic confidence of TS (r = -.71, p =.05). CONCLUSIONS: These results are consistent with a dopamine-influenced functional abnormality of brain response in TS and suggest testable hypotheses about the mechanism by which dopamine antagonists and agonists alleviate tics.

Adult↗

Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship.

Previous studies have suggested that obsessive-compulsive symptoms frequently occur among patients with Gilles de la Tourette's syndrome (TS). To examine the relationship between TS and obsessive-compulsive disorder (OCD), data from all first-degree relatives of TS probands were obtained with a semistructured interview designed to collect information on the presence of TS, other tic disorders, and neuropsychiatric illnesses during the lifetime of the individual. The rate of OCD among first-degree relatives was significantly increased over estimates from the general population and a control sample of adoptive relatives. The rates of TS, OCD, and chronic multiple tics (CMT) were virtually the same in families of probands with OCD (TS +/- OCD) when compared with families of probands without OCD (TS - OCD). Finally, the frequency of OCD without TS or CMT among first-degree relatives was significantly elevated in families of both TS + OCD and TS - OCD probands, suggesting that some forms of OCD may represent an alternative expression of the factors responsible for TS and/or CMT.

Adolescent↗

[Tics and Gilles de la Tourette disease].

Clinical characteristics of tic disorders are complex and difficult to ascertain, the pathophysiology remains unknown. Their diagnosis can only be performed clinically they can be classified into two groups with opposite prognosis: transient tics of children with favorable spontaneous evolution, and Gilles de la Tourette disease, a life long disorder with disappointing therapeutic possibilities.

Humans↗

Typical neuroleptics in child and adolescent psychiatry.

This paper reviews the use of typical ("old") neuroleptics in the treatment of child and adolescent psychiatric disorders. Very few methodologically sound papers have been published in the field. It is concluded that typical neuroleptics should be used sparingly and only in severe and incapacitating disorders such as some psychotic conditions and handicaping tic disorders. Side effects have to be very carefully monitored.

Adolescent↗

Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype.

Two common serotonin transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders. We now report an uncommon coding region SERT mutation, Ile425Val, in two unrelated families with OCD and other serotonin-related disorders. Six of the seven family members with this mutation had OCD (n=5) or obsessive-compulsive personality disorder (n=1) and some also met diagnostic criteria for multiple other disorders (Asperger's syndrome, social phobia, anorexia nervosa, tic disorder and alcohol and other substance abuse/dependence). The four most clinically affected individuals--the two probands and their two slbs--had the I425V SERT gene gain-of-function mutation and were also homozygous for 5'-UTR SERT gene variant with greater transcriptional efficacy.

Amino Acid Sequence↗