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Biomedical subjects

A Apter

Publications and source records attributed to A Apter.

At least 19 recordsLinked to original sources

Relationships between serotonin transporter promoter polymorphism, platelet serotonin transporter binding and clinical phenotype in suicidal and non-suicidal adolescent inpatients.

Relationships between the serotonin transporter promoter polymorphism (5-HTTLPR), platelet serotonin transporter (SERT) binding and clinical phenotype were examined in 32 suicidal and 28 non-suicidal Ashkenazi Israeli adolescent psychiatric inpatients. The 5-HTTLPR polymorphism was not associated with transporter binding or with suicidality or other clinical phenotypes. However, in the suicidal group, a significant positive correlation between platelet SERT density and anger scores (n=32, r=.40; p=.027) and a negative correlation between platelet count and trait anxiety (n=32, r=-.42; p=.034) were observed.

Adolescent↗

DRD4 receptor gene exon III polymorphism in inpatient suicidal adolescents.

Some studies have suggested possible association of the dopamine receptor subtype 4 (DRD4) gene exon III 48 bp repeat polymorphism with novelty seeking behavior. As suicidal behavior in adolescents is linked to risk taking behavior, we evaluated the association of suicidality with DRD4 polymorphism in Israeli inpatient suicidal adolescents. Sixty-nine inpatient adolescents who recently attempted suicide were assessed by structured interview and rating scales for detailed clinical history, diagnoses, suicide intent and risk, impulsivity, violence, and depression. The frequency of DRD4 alleles was compared between the suicidal inpatients and 167 healthy control subjects. No significant association between the DRD4 polymorphism and suicidal behavior was found. Analysis of the suicide-related measures demonstrated a significant difference in depression severity between suicidal inpatients homozygote and heterozygote for the DRD4 alleles (p=0.003). The relevance of this finding to increased depression severity in suicidal adolescents, if replicated, is as yet unclear.

Adolescent↗

Treating asthma by the guidelines: developing a medication management information system for use in primary care.

The aim of this study was to develop, implement, and assess an automated asthma medication management information system (MMIS) that provides patient-specific evaluative guidance based on 1997 NAEPP clinical consensus guidelines. MMIS was developed and implemented in primary care settings within a pediatric asthma disease management program. MMIS infrastructure featured a centralized database with Internet access. MMIS collects detailed patient asthma medication data, evaluates pharmacotherapy relative to practitioner-reported disease severity, symptom control and model of guideline-recommended severity-appropriate medications and produces a patient-specific "curbside consult" feedback report. A system algorithm translates actual detailed medication data into actual severity-specific medication-class combinations. A table-driven computer program compares actual medication-class combinations to a guideline-based medication-class combinations model. Methodology determines whether the patient was prescribed a "severity-appropriate" amount or an amount "more" or "less" medication than indicated for patient's reported severity. Feedback messages comment on comparison. Missing data, unrecognized amounts of controller medication or unrecognized medication combinations create error cases. Post hoc review analyzed error cases to determine prevalence of non-guideline medicating practices among these practitioners. Proportion of valid and error cases across two clinical visits before and after post hoc clinical review were measured, as well as proportion of severity-appropriate, out-of-severity and non-guideline medications. MMIS produced a valid feedback report for 83% of patient visits. Missing data accounted for 60% of error cases. Practitioners used severity-appropriate medications for 60% of cases. When non-severity-appropriate medications were used they tended to be "too much" rather than "too little" (22%, 5%), suggesting appropriate use of guideline-recommended "step down" therapy by these practitioners.

Anti-Asthmatic Agents↗

Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity.

The importance of environment in the regulation of brain, behaviour and physiology has long been recognized in biological, social and medical sciences. Animals maintained under enriched conditions have clearly been shown to have better learning abilities than those maintained under standard conditions. However, the effects of environmental enrichment (EE) on immunity and emotionality have been less documented and remain questionable. Therefore, we investigated the effect of EE on natural killer (NK) cell activity, psychological stress responses and behavioural parameters. Male C3H mice were housed either in enriched or standard conditions for 6 weeks. Behaviour was then examined by the grip-strength test, staircase and elevated plus maze, and corticosterone levels and NK cell activity were measured. Furthermore, animals exposed to the stress paradigm, achieved by electric shock with reminders, were tested for freezing time in each reminder. Corticosterone levels were also measured. The EE mice showed decreased anxiety-like behaviour and higher activity compared to standard mice, as revealed by a greater percentage of time spent in the open arms of the elevated plus maze, and a higher rate of climbing the staircase. A shorter freezing time in the stress paradigm and no corticosterone level reactivity were measured in EE mice. In addition, NK cell activity in spleens of EE mice was higher than that demonstrated in those of standard mice. Thus, EE has a beneficial effect on anxiety-like behaviour, stress response and NK cell activity. The effect on NK cell activity is promising, due to the role of NK cells in host resistance.

Animals↗

Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia.

OBJECTIVES: To evaluate and compare the drug response and side effects of adolescents with schizophrenia treated with olanzapine, risperidone, and haloperidol. METHODS: Forty-three patients were treated with olanzapine (n = 19), risperidone (n = 17) and haloperidol (n = 7) for 8 weeks in an open clinical trial. Clinical improvement was evaluated with the Positive and Negative Syndrome Scale (PANSS), and side effects with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. RESULTS: Significant clinical improvement was observed by week 4 for all medications. Olanzapine and haloperidol induced fatigability more frequently than risperidone. Haloperidol was associated with a higher frequency of depression and more severe extrapyramidal symptoms. CONCLUSIONS: To the best of our knowledge this is the first study in adolescents to compare the efficacy and side effects of three most commonly prescribed antipsychotic medications. Olanzapine, risperidone and haloperidol appear to be equally effective for the treatment of schizophrenia in adolescent inpatients but have different side effect profiles.

Adolescent↗

Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study.

Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN because alleles with longer repeats have been found to be associated with mental disorders. Forty Israeli AN family trios were genotyped for the hSKCa3 CAG repeat polymorphism using the haplotype relative risk (HRR) method. The distribution of alleles transmitted to the patients was found to be significantly different from that of the non-transmitted parental alleles, with the longer alleles being over-represented in the patients (Wilcoxon rank test, P = 0.008). The transmission disequilibrium test (TDT) revealed that longer (>19) repeat alleles were preferentially transmitted to AN patients (McNemar's chi(2) = 10.31, P = 0.0013). These results were corroborated by comparing the distribution of alleles between patients and healthy controls (Mann-Whitney test, P = 0.005). Our study suggests that the longer repeat alleles of the hSKCa3 gene may contribute to the genetic susceptibility to AN.

Adolescent↗

Case control and family-based studies of tryptophan hydroxylase gene A218C polymorphism and suicidality in adolescents.

The association of suicidality with polymorphism A218C in intron 7 of tryptophan hydroxylase (TPH) gene remains controversial. The aim of this study was to use family-based methods to examine this association in adolescents in order to eliminate the difficulty of sampling a control group from the same ethnic population. Eighty-eight inpatient adolescents who recently attempted suicide were assessed by structured interview for detailed clinical history, diagnoses, suicide intent, suicide risk, impulsivity, aggression, and depression. DNA samples were collected from all subjects, from both biological parents of 40 subjects and from one parent of 9 subjects; TPH allele frequencies were calculated and tested for association to phenotype, stratified by severity, using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods (n = 49). The frequencies were also compared for all the Jewish subjects (n = 84) to the known frequencies of these alleles in healthy Jewish populations. There was no significant allelic association of A218C polymorphism with suicidal behavior or other phenotypic measures according to the HRR method (chi-square = 0.094; P = 0.76), the TDT (chi-square = 0.258; P = 0.61), or association analysis to known population frequencies (chi-square = 1.667, P = 0.19 for Ashkenazi, and chi-square = 0.810, P = 0.37 for non-Ashkenazi). Analysis of variance with the Scheffè test demonstrated a significant difference between CC and AA genotypes in suicide risk and depression among the patients (n = 88). The findings suggest that polymorphism A218C has no major relevance to the pathogenesis of adolescent suicidal behavior, but may have a subtle effect on some related phenotypes.

Adolescent↗

Family-based association study of serotonin transporter promoter in suicidal adolescents: no association with suicidality but possible role in violence traits.

The serotonin transporter-linked promoter region polymorphism (5-HTTLPR) is thought to be associated with some serotonin dysfunction-related psychopathologies such as depression and anxiety disorders. Suicide and suicide-related behaviors such as violence, aggression, and impulsivity have been reproducibly associated with serotonin dysfunction and are partially genetic. This study examined the association of 5-HTTLPR with suicidal behavior and related traits in Israeli suicidal adolescent inpatients using the haplotype relative risk (HRR) method that controls for artifacts caused by population stratification. Forty-eight inpatient adolescents who recently attempted suicide were assessed by structured interviews for detailed clinical history, diagnoses, suicide intent, suicide risk, impulsivity, violence, and depression. Blood samples were collected and DNA extracted from patients and their biological parents. The 5-HTTLPR allele frequencies were tested for association with suicidality by the HRR method. In addition, the relationship between genotypes and phenotypic severity of several clinical parameters was analyzed. No significant allelic association of the 5-HTTLPR polymorphism with suicidal behavior was found (chi square = 0.023; P = 0.88). Analysis of variance of the suicide-related trait measures for the three genotypes demonstrated a significant difference in violence measures between patients carrying the LL and LS genotypes (9.50+/-4.04 vs. 5.36+/-4.03; P = 0.029). This study suggests that the 5-HTTLPR polymorphism is unlikely to have major relevance to the pathogenesis of suicidal behavior in adolescence but may contribute to violent behavior in this population.

Adolescent↗

Aggravation of food-related behavior in an adolescent with Prader-Willi syndrome treated with fluvoxamine and fluoxetine.

UNLABELLED: Prader-Willi Syndrome is a congenital multisystem disorder, characterized by a typical dysmorphism, mental retardation, hyperphagia due to insatiable appetite, and resultant morbid obesity. Psychiatric symptoms include obsessions and temper tantrums. METHOD: Pharmacotherapy is experimental with a few reports of successful fluoxetine treatment. RESULTS: We report an aggravation in the food-related symptoms and a consequent weight gain in an adolescent with Prader-Willi syndrome, who was treated with fluvoxamine and fluoxetine.

Adolescent↗

Stability of diagnosis: a 20-year retrospective cohort study of Israeli psychiatric adolescent inpatients.

Outcome according to diagnosis and stability of diagnosis were investigated in a follow-back study of 351 adolescents with various psychiatric disorders hospitalized in a closed psychiatric ward. The duration of follow-back was 15-19 years. All diagnoses were based on the ICD-9. Data were collected from the Health Ministry registry and, in the patients who could be located, by structured telephone interview. Special attention was directed at the diagnosis of transient adolescent psychosis (TAP) vs. schizophrenia and prognostic indicators of suicide. The results showed that the most stable diagnosis was anxiety disorder. The stability of the different diagnoses over time was greater between the second and last admission than between the first and last (for patients with three or more admissions). Number of hospitalizations correlated negatively with prognosis. TAP at second admission was an unstable diagnosis; 66% of these patients had a final diagnosis of schizophrenia. However, patients with a diagnosis of TAP at first admission had a higher predictive index score and a higher outcome score than schizophrenic patients. TAP appeared to be a valid diagnostic entity, distinguishable from schizophrenia in course, frequency of suicidal behaviour and social-occupational outcome. Suicide victims had a higher cumulative length of stay than age- and sex-matched non-suicidal patients. Fifty per cent of the suicide victims had a final diagnosis of schizophrenia, compared to 30 per cent for the whole sample. In conclusion, these findings indicate that TAP is associated with a relatively good prognosis and should probably be differentiated from schizophrenia. Further retrospective and prospective studies of adolescent psychiatric inpatients may help delineate the nature and course of psychosis and other psychopathology in this age group.

Adolescent↗

Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients.

Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution and pharmacological data suggest possible dysfunction of the serotonergic and dopaminergic pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles. Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% chi(2) = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemar's chi(2) = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.

Adolescent↗

Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.

Adult↗

Internalized anger, self-control, and mastery experience in inpatient anorexic adolescents.

OBJECTIVES: To evaluate the implications of internalized anger, self-control and experience of mastery for adolescent girls with severe anorexia nervosa (AN). METHODS: Internalized and externalized anger, internal and external control, mastery, use of methods for self-control, and severity of anorexic symptoms were measured by self-report questionnaires in inpatient anorexic teenagers (N=26), inpatient female adolescent psychiatric patients (N=24), and a normal female comparison group (N=29). RESULTS: Internalized anger was significantly higher in both the anorexic and general psychiatric patients as compared to normal controls, but this difference was significant only for the anorexic patients. Anorexic and general psychiatric patients experienced significantly less mastery than normal controls, but again this difference was significant only in the anorexic group. Within the anorexic group, severity of symptoms correlated significantly with internalized anger, low mastery, and external locus of control, and negative significant correlations among control measures and anger were found. Total length of hospitalization correlated positively with internalized anger only for the anorexics. CONCLUSION: The findings support the notion that internalized anger and defective experience of self-control are important factors in the psychopathology of adolescent anorexic inpatient females The results may have implications for the clinical management of patients with severe AN.

Adolescent↗

Human figure drawings in the evaluation of severe adolescent suicidal behavior.

OBJECTIVE: To evaluate the reliability of using certain indicators derived from human figure drawings to distinguish between suicidal and nonsuicidal adolescents. METHOD: Ninety consecutive admissions to an adolescent inpatient unit were assessed. Thirty-nine patients were admitted because of suicidal behavior and 51 for other reasons. All subjects were given the Human Figure Drawing (HFD) test. HFD was evaluated according to the method of Pfeffer and Richman, and the degree of suicidal behavior was rated by the Child Suicide Potential Scale. RESULTS: The internal reliability was satisfactory. HFD indicators correlated significantly with quantitative measures of suicidal behavior; of these indicators specifically, overall impression of the evaluator enabled the prediction of suicidal behavior and the distinction between suicidal and nonsuicidal inpatients (p < .001). A group of graphic indicators derived from a discriminant analysis formed a function, which was able to identify 84.6% of the suicidal and 76.6% of the nonsuicidal adolescents correctly. Many of the items had a regressive quality. CONCLUSIONS: The HFD is an example of a simple projective test that may have empirical reliability. It may be useful for the assessment of severe suicidal behavior in adolescents.

Adolescent↗

Search for association between suicide attempt and serotonergic polymorphisms.

Serotonergic neurotransmission has been implicated in suicidal behavior. Polymorphisms in the genes coding for tryptophan hydroxylase, serotonin receptor 2A and serotonin transporter were investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No significant differences were found for any of the investigated polymorphisms. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar disorder (n = 45), adjustment disorder (n = 37), substance use disorder (n = 37) and personality disorder, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphisms do not represent a major determinant in suicide attempt. However, a highly significant (P = 0.001; odds ratio, 1.47; 99% confidence interval, 1.42-1.53) allelic association between tryptophan hydroxylase and suicide attempt is indicated after pooling our data with literature data. In light of previous data, a possible association between the tryptophan hydroxylase polymorphism and a phenotype that may become differently stratified within differently selected samples of suicide attempters is discussed.

Adjustment Disorders↗

Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts.

BACKGROUND: Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population. METHODS: We measured [3H] PK 11195 binding to platelet membrane in nine adolescent (age 13-20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS). RESULTS: Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (-35%) compared to the controls (p < 0.005). CONCLUSIONS: Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.

Adolescent↗