Biomedical subjects

F Poustka

Publications and source records attributed to F Poustka.

At least 19 recordsLinked to original sources

PubMed2006

Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism.

Autism has a strong genetic background with a higher frequency of affected males suggesting involvement of X-linked genes and possibly also other factors causing the unbalanced sex ratio in the etiology of the disorder. We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism. We have obtained evidence that the amino-acid substitutions L206M and H213Q at the C-terminal end of RPL10 confer hypomorphism with respect to the regulation of the translation process while keeping the basic translation functions intact. This suggests the contribution of a novel, possibly modulating aberrant cellular function operative in autism. Previously, we detected high expression of RPL10 by RNA in situ hybridization in mouse hippocampus, a constituent of the brain limbic system known to be afflicted in autism. Based on these findings, we present a model for autistic disorder where a change in translational function is suggested to impact on those cognitive functions that are mediated through the limbic system.

Amino Acid Substitution↗

PubMed2006

[Suicidality in depressive children and adolescents during treatment with selective serotonin reuptake inhibitors. Review and meta-analysis of the available randomised, placebo controlled trials].

Due to concerns that selective serotonin reuptake inhibitors (SSRI) might be associated with an increased risk of suicidal ideation and suicide attempts in depressive children and adolescents, treatment with these drugs is controversial. All available data from randomised controlled trials on SSRIs treating depression in these age groups were examined regarding efficacy and suicidality. Results suggest that fluoxetine and, less clearly, sertraline are effective in such treatment. A meta-analysis yielded no statistically significant difference between treatment with SSRI and placebo with regard to the occurrence of suicidal behavior. Following evidence-based criteria, the risk:benefit ratio is favourable for fluoxetine and sertraline. Their use in the pharmacotherapy of depressive children and adolescents is indicated.

Adolescent↗

PubMed2005

[Arbutin, salicin: the possibilities of their biotechnological production].

The paper aimed to transform exogenous precursors with in vitro cultures of Datura meteloides, Coronilla varia, Leuzea carthamoides and Schisandra chinensis. These cultures were added the precursors of arbutin and salicin (phenylalanine, cinnamic, p-coumaric, p-anisoic, o-coumaric, salicylic acids, salicylaldehyde, helicin), not yet tested by the present authors. The culture of Schisandra chinensis was also added, besides the above-mentioned precursors, hydroquinone, because this culture had not been employed for biotransformation purposes yet. The precursors tested were used in a concentration of 100 mg x l(-1) and the period of their action was 6; 12; 24; 48, and 168 hours. Positive results (both TLC and HPLC) in arbutin production were obtained in the culture of Schisandra chinensis after an addition of hydroquinone. The largest amount of arbutin in callus cultures was measured after a week's cultivation with hydroquinone (5.08 %). In this experimental variant, arbutin was released also to the culture medium. Our results revealed salicylaldehyde to be the optimal precursor of salicin. It was transformed by the culture of Datura meteloides after 6; 24, and 168 hours and by the culture of Coronilla varia after 6 hours. In comparison with arbutin, its amount was smaller.

Arbutin↗

PubMed2004

[Diagnostic Observation Scale for Autistic Disorders: initial results of reliability and validity].

OBJECTIVE: To examine the psychometric properties of the German version of the Autism Diagnostic Observation Schedule (ADOS). METHODS: Interrater and retest reliability, internal consistency, convergent and diagnostic validity were determined in a total sample of 137 subjects with autism, 23 with atypical autism or pervasive developmental disorder not otherwise specified, 16 with Asperger-syndrome and 13 with other psychiatric disorders. RESULTS: Interrater and retest reliability on the level of diagnosis (kappa w = 1.00 and .62) and raw-scores (ru = .84 and .79) were good. Likewise, the internal consistency of the algorithm scale communication and social interaction of modules 1 to 4 was fair (ru = .78 to .89). The categorical convergence for autism between the ADOS and the Autism Diagnostic Interview-Revised (ADI-R) reached 79% (kappa = .23), with their corresponding subscales correlating moderately (rtc = .31 to .45). The concordance of the ADOS judgment and the clinical consensus diagnosis was 77% (kappa w = .37), with a sensitivity of the ADOS of 90.4% and a specificity of 48.1% regarding the discrimination of autism and other autistic disorders. CONCLUSIONS: The ADOS is a reliable and sufficiently sensitive diagnostic tool in the assessment of autistic disorders. For ICD-10/DSM-IV classification and to ensure a high specificity of diagnosis additional information concerning repetitive, stereotyped behavior and early development (e.g. taken from the ADI-R) has to be collected.

Adolescent↗

PubMed2004

Platelet 5-HT uptake in boys with conduct disorder.

Dysregulation of serotonergic function has been found to be associated with aggression in animals, human adults and adolescents. However, studies with children have shown conflicting results. The objective of this study was to investigate whether the kinetic characteristics (Vmax and Km) of 5-HT uptake in platelets are different in children with the diagnosis of conduct disorder according to ICD-10 and healthy age-matched controls. In addition to the standardized assessment of general psychopathology, methods assessing narrowband aggressive symptoms (Child Behavior Checklist) and emotional reactivity to an experimentally induced provocation (Taylor's competitive reaction time task) were used in both groups. We found a trend for a lower mean Vmax of platelet 5-HT uptake in 14 conduct-disordered boys compared with healthy controls (n=15). If, however, 2 patients with a low degree of aggression and emotional reactivity were excluded, the difference became significant (mean=4.27, SD=3.49 in patients and mean=8.45, SD=4.63 in controls). A significant negative correlation was found between parent-rated aggression scores and Vmax (r=-0.41, p < 0.05, n=29). These data suggest that dysfunction of 5-HT transport mechanisms might be associated with specific behavioral symptoms in conduct-disordered children.

Adolescent↗

PubMed2003

Functional imbalance of visual pathways indicates alternative face processing strategies in autism.

OBJECTIVE: To investigate whether autistic subjects show a different pattern of neural activity than healthy individuals during processing of faces and complex patterns. METHODS: Blood oxygen level-dependent (BOLD) signal changes accompanying visual processing of faces and complex patterns were analyzed in an autistic group (n = 7; 25.3 [6.9] years) and a control group (n = 7; 27.7 [7.8] years). RESULTS: Compared with unaffected subjects, autistic subjects demonstrated lower BOLD signals in the fusiform gyrus, most prominently during face processing, and higher signals in the more object-related medial occipital gyrus. Further signal increases in autistic subjects vs controls were found in regions highly important for visual search: the superior parietal lobule and the medial frontal gyrus, where the frontal eye fields are located. CONCLUSIONS: The cortical activation pattern during face processing indicates deficits in the face-specific regions, with higher activations in regions involved in visual search. These findings reflect different strategies for visual processing, supporting models that propose a predisposition to local rather than global modes of information processing in autism.

Adolescent↗

PubMed2002

[Intervention in autistic disorders: status quo, evidence-based, questionable and doubtful techniques].

OBJECTIVE: We describe and critically discuss intervention methods that have been used to modify autistic behaviors. METHODS: Early intervention methods, training of social skills, pharmacological treatment and alternative approaches are reviewed in the light of the empirical evidence. RESULTS: Autism is a persistent and phenotypically heterogeneous disorder for which no cure has been found to date. However, individually composed care and therapies can lead to remarkable quantitative improvement. CONCLUSIONS: Further research is needed to evaluate the true impact of psychological and biological intervention techniques in autistic disorders. Among other things, the therapy studies carried out up to now often lack an adequate diagnostic assessment.

Autistic Disorder↗

PubMed2001

[Speech development and intelligence in autism. How uniform is Asperger syndrome?].

Since the introduction of a separate diagnosis for Asperger's syndrome in the ICD-10 and DSM-IV classification systems, a controversial debate has continued on whether Asperger's syndrome is a specific, clearly distinguishable disorder within the autistic spectrum or whether it represents a milder phenotypical variation of autism. The effect on the amount of autistic symptoms of the variables language delay and level of intelligence was analyzed within a sample of individuals exhibiting autism diagnosed by standardized methods. Both variables showed a significant effect on the degree of autistic symptoms in that impairments in social interaction were less noticeable. In addition, a subsample of individuals exhibited symptoms assumed to be characteristic for Asperger's syndrome. The findings support the assumption that autism and Asperger's syndrome represent "extreme points" on a scale of severity, which leads to the suggestion that the classification of different subtypes of autism could be abandoned in favor of a dimensional (multiaxial) approach.

Adolescent↗

PubMed2001

Discriminant validity of the child behaviour checklist CBCL-4/18 in German samples.

This study examined the discriminant validity of the German version of CBCL in two large samples of referred and non-referred children and adolescents which were matched for age, sex and socio-economic status. The combined sample that was used for statistical analysis consists of 2,058 referred and 2,058 non-referred boys and girls between 4 and 18 years of age (mean age: referred boys= 10.9 years, non-referred boys = 10.9 years, referred girls=11.3 years, non-referred girls=11.1 years). Referral status was used as validity criterion. Statistical procedures included Odds Ratios, Total Predictive Values, ROC analyses and discriminant analyses. Results indicated that the discriminant validity of the German version of CBCL is comparable to the original English version. With the use of CBCL Total Problem Score as predictor (cut-off T > or = 60) 83.8% of children and adolescents could correctly be classified (sensitivity 83.6%, specificity 83.9%). Symptoms of the "Attention Problems Scale" show the highest discriminative power to distinguish between disturbed and undisturbed children and adolescents.

Adolescent↗

PubMed2001

[Factor structure of the Autism Diagnostic Interview-Revised (ADI-R): a study of dimensional versus categorical classification of autistic disorders].

OBJECTIVES: This study investigated whether empirically derived dimensions of autistic behavior are consistent with the content-valid construction of the autistic behavior domains according to ICD-10 and DSM-IV (social interaction, communication and repetitive, stereotyped behavior). METHODS: A principal component exploratory factor analysis routine with varimax-rotation and extraction of factors following the Scree criterion was run using data from the Autism Diagnostic Interview-Revised (ADI-R) of N = 262 individuals exhibiting autism or autistic features. RESULTS: A three-factor solution consisting of two socio-communicative and one language dimension and accounting for 46.1% of the total variance was found to best describe the data. These factors yielded only vague correspondence with the idea of behavior domains described in ICD-10 and DSM-IV. In addition, factor loadings of items representing repetitive, stereotyped patterns were generally weak. CONCLUSIONS: The factor-analytic approach to autism indicates a conception of the disorder divergent from that defined in the contemporary psychiatric classification systems, especially regarding the area of repetitive, stereotyped behavior.

Adolescent↗

PubMed2000

Complex segregation analysis of families ascertained through Gilles de la Tourette syndrome.

Although family and twin studies suggest that genetic factors are involved in the etiology of Tourette syndrome and other related tic disorders, further evidence is needed to demonstrate that the familial transmission is consistent with known genetic factors. We performed a complex segregation analysis that allowed for a variable age of onset of Gilles de la Tourette, other tic disorders and obsessive compulsive phenotype information on 108 extended families, each ascertained through one Tourette proband by using regressive models that are able to incorporate additional explanatory variables and major gene effects. A special version of the S.A.G.E. program, REGTLhunt, was used to explore the likelihood surface of all examined models. Results indicated that the pattern of Tourette and other related tic disorders in our data sample is not consistent with Mendelian inheritance even after modelling explanatory variables such as obsessive compulsive symptomatology.

Adolescent↗

PubMed2000

[Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution].

In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies.

Adult↗

PubMed2000

[Utilization of psychological tests for diagnosis in German child and adolescent psychiatry: results of a survey].

92 inpatient and outpatient child and adolescent psychiatric institutions all over Germany were surveyed on practice and attitude towards psychological tests. Leading psychologists were contacted by mail and given a 15 item questionnaire. All institutions reported keeping at least a small test-inventory and using psychological tests in diagnostics. Half of the clinics carried out individual tests obligatory in the routine. Additionally, one third applied self-constructed instruments, which in the minority of cases had been psychometrically investigated or published. Computer-aided testing was established in one third of the institutions. Colleagues, test-compendia, scientific journals and the internet are quite often consulted for test-information. Intelligence measures are the most frequently administered test in child and adolescent psychiatry, while structured interviews are applied rarely. Among the highly frequent used individual tests were the Wechsler-Intelligence-Scales for children and adults, the CFT-scales, the projective Sceno-test and the d2-attention endurance test. One forth of the surveyed clinics reported refusal of individual or groups of tests, including projective and cognitive assessments. Thereby, ethic aspects were never mentioned as a reason for rejection. A range of diagnosticians reported to miss adequate measures for diverse constructs, e.g. learning disabilities. Furthermore, new norms and up-dates for regularly used instruments were often demanded. Some single survey-results also give reason for critically reviewing aspects of test-usage in German child and adolescent psychiatry.

Adolescent↗

PubMed2000

[Mental disorders in hospitalized children of migrant families from the Mediterranean].

From 1.1.1988 to 31.12.1992 928 inpatients at the child- and adolescent psychiatric clinic "Rheinhöhe" were recorded and studied. At that time the service area for this clinic for psychiatric care contained mixed rural/urban localities of four Southhessian sectors including a part of Frankfurt/M. The number of inpatients of Mediterranean origin in relation to German inpatients were significantly lower than expected but higher compared with earlier studies. The pattern of psychiatric disorders differed also in these two populations. The distribution according to sexes showed an moderate higher male rate for both groups (1.2:1). To study the differences in detail, 163 Mediterranean and German patients were matched according to age, gender, school education and SES and subsequently the Mediterranean patients were divided into those with a short- vs. a long-term-assimilation experience. As a result the significant higher rate of psychotic disorders among the Mediterranean treated inpatients counted for the different patterns, especially among the short-term assimilated patients. On the other hand, externalizing disorders were found to be significantly higher among the long-term assimilated Mediterranean inpatients but also among the German inpatients in contrast to the short-term assimilated migrant inpatients from the Mediterranean regions. Suicidal attempts were significantly more frequent among the Mediterranean girls than among their German counterparts. Thus key differences for utilising inpatient services remained; the reasons accounting for these dissimilarities are questionable and noteworthy for psychiatric care.

Acculturation↗

PubMed1999

No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity.

Family and twin studies suggest a genetic contribution to the etiology of anorexia nervosa (AN) and obesity. Genes involved in weight regulation can be considered as candidate genes for AN. The dopaminergic system has been implicated in weight regulation; previous results had suggested a possible involvement of the dopamine D4 receptor gene (DRD4). We screened for alleles of two different polymorphisms (13-bp deletion, 48-bp repeat) in the DRD4. For association tests, allele frequencies were compared between 109 inpatients with AN, 82 underweight students, and 327 extremely obese children and adolescents. For application of transmission disequlibrium tests (TDT) we additionally genotyped 57 and 137 trios comprising a patient with AN or an extremely obese child or adolescent, respectively, and both parents. All genotyping was performed with polymerase chain reaction fragment length polymorphism analyses. None of the association tests or TDT rendered nominal P values below 0.1. An influence of alleles of the DRD4 on the development of AN, underweight, or extreme early onset obesity was not detected. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:594-597, 1999.

Adolescent↗

PubMed1999

Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females

The present French-German investigation of fragile-X syndrome (fra-X) was undertaken to disentangle genetic from environmental effects on cognitive performance as assessed with the following measures: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wisconsin Card Sorting Test, Trail-Making Test, Tower of Hanai, Verbal Fluency Test, Stroop Test, short-term and consolidation memory, and the d2 task. Groups with different genotypes (n = 11 mothers with a full mutation in the FMR-1 gene of fra-X children; n = 65 mothers with a premutation in the FMR-1 gene of fra-X children; n = 18 siblings of these mothers with normal CGG repeats) and with different psychosocial stressors from fra-X families (n = 14 siblings with a premutation but without affected children of their own) were examined. A group of mothers of non-fra-X autistic children (n = 39) formed an external control group. Previous findings were replicated concerning cognitive performance of FMR-1 full-mutation carrier mothers, who were characterized by lower overall IQ and poorer performance than the group of mothers with the FMR-1 premutation in verbal and performance subtests of the WAIS-R, tests of executive-frontal lobe functioning, and tests of sustained attention. Carriers of the FMR-1 premutation, whether they were mothers of affected children or not,performed in a similar way on all neuropsychological tasks to the intrafamilial control group without CGG amplification. On the basis of these results, it is concluded that there is no neuropsychological evidence of reduced cognitive performance of FMR-1 premutation carriers compared with performance of two control groups with normal CGG repeats. Furthermore, the psychosocial burden of raising fra-X children does not exert an environmental effect on neuropsychological test performance.

Journal Article↗

PubMed1999

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects.

RATIONALE: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. OBJECTIVE: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. METHODS: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. RESULTS: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. CONCLUSIONS: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity.

Adult↗

PubMed1999

Tourette syndrome and the norepinephrine transporter gene: results of a systematic mutation screening.

Tourette syndrome (TS) is a complex inherited neuropsychiatric disorder characterized by multiple motor and phonic tics. Involvement of central norepinephrine mechanisms is suggested by central norepinephrinic hyperactivity in patients with TS and by the therapeutic effects of the presynaptic alpha2-adrenergic agonist clonidine. The norepinephrine transporter gene (NET) was systematically screened by single-strand conformation analysis for genetic variants, including the whole coding region and adjacent exon-intron boundaries in 43 patients with TS and 46 healthy controls. We detected 12 DNA sequence variants, among them four missense mutations (Val69Ile, Thr99Ile, Va1245Ile, and Gly478Ser). The observed missense mutations may alter conformational rearrangements during gating of the transporter, assembly of subunits, and norepinephrine-specific uptake affinity. Allele frequency and genotype distribution of the genetic variants showed no differences between TS patients and controls. No mutation of likely functional significance was found that distinguished TS patients from healthy controls, indicating that genetic variants of the NET gene are not causally related to Tourette syndrome.

Adolescent↗