Possible association between attention deficit hyperactivity disorder and attempted suicide in adolescents - a pilot study.

OBJECTIVE: Both adolescent suicide and attention deficit hyperactivity disorder (ADHD) are troubling phenomena with high comorbidity, including impulsivity, depression and personality disorders (PD). Studies on the association between these two phenomena are relatively rare. This pilot study's aim was to estimate the rate of ADHD in adolescents attempting suicide. METHOD: Subjects constituted consecutive admissions to the psychiatric emergency room (ER) who were admitted as a result of attempting suicide. Assessment included the use of the Kiddie-SADS, Strengths and Difficulties Questionnaire (SDQ) and the Conners' Rating Scale (CRS). Those diagnosed as suffering from ADHD were assessed by a standardized Continuous Performance Test (Test of Variables of Attention [TOVA]) that included methylphenidate (MPH) challenge. Twenty-three (23) adolescents completed the study. M:F ratio was 5:18, respectively. RESULTS: Of the 23 participants who completed the study, 65% were diagnosed with ADHD, 43.5% with depression and 39% with cluster B PD. ADD/ADHD ratio was 66%:34%. Only five of the patients were formerly diagnosed as ADHD, only three had been medicated and 14 out of 15 adolescents responded well to MPH challenge. CONCLUSION: These preliminary results suggest a significant association between ADHD and suicidal behavior in adolescents. Further study is needed to establish this association and assess the causality.

Assessing mental disability in minors.

Forensic psychiatry devotes a great deal of attention to the "imprecise" and "insufficiently scientific" nature of psychiatric disability assessment, and, for this reason, it is vitally important to establish a reliable method of assessing different levels of disability. The assessment of mental disability in minors is unique in that it involves developmental aspects, which affect the formation and outcome of the disability. The relationship between disability and development is reciprocal: disability can affect development, thereby intensifying the degree of disability, while development affects integration of the disability into the personality and self-image, thereby preventing or reducing the transformation of disability into handicap. Only an understanding of both the psychopathological structure and its interaction with developmental elements can lead to an accurate assessment of the degree of disability. Such an understanding is vital to the proper practice of forensic psychiatry. We hereby propose a new formula for disability quantification which provides an arithmetical means for the calculation of disability percentages in minors, and we recommend its use in the assessment of demands for National Insurance benefits and compensation claims. The relationship between this new formula and the existing Children's Global Assessment Scale (CGAS) functional scale, when tested retrospectively on 50 clinical reports composed by the writers of this article, showed a good correlation in the results obtained independently by each writer. Two case studies are presented here. A further evaluation by objective evaluators is necessary in order to construct a model for a final objective evaluation of disability in children and adolescents.

Relations between parents' interactive style in dyadic and triadic play and toddlers' symbolic capacity.

Play has a major role in the evaluation and treatment of young children referred to mental health clinicians. The present study examined parental correlates of preschoolers' symbolic play during dyadic and triadic play interactions. Boys' play contained more aggressive themes, and girls' contained more nurturing themes. Mothers displayed more caring themes during play with both sons and daughters, and fathers displayed more repair and construction themes. Mothers' and fathers' facilitative- creative interaction style in dyadic play predicted the level of the child's symbolic play. Co-parenting style marked by cooperation and autonomy predicted symbolic play during a triadic family session. Child intelligence predicted symbolic play beyond the parent's style during triadic but not dyadic interactions. The findings have implications for early intervention directed at increasing symbolic play in young children.

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.

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.

Informed consent: myth or reality.

The rapidly growing awareness and respect of the social needs and legal rights of the patient in many countries is a sign of cultural maturity of society at large. However, the implementation of these achievements is especially arduous in the field of psychiatry because often mental patients have cognitive restrictions and/or emotional distress both of which may interfere with the exercise of their civil rights. One focus of this paper is the challenging process of obtaining legally valid consent from a severely ill psychiatric patient for diagnostic procedures and for treatment and also for participation in research projects. This paper also analyzes and discusses the new developments in the health legislation in Israel and focuses on the questions that arise in its application to the field of psychiatry. A recommendation for practical assessment of competence is presented. Systematic studies ofthe application of legal regulation and appropriate modifications are needed.

The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA).

One particular candidate gene, the dopamine D4 receptor (DRD4), has been the focus of intense study regarding ADHD since the original investigation by La Hoste et al, an observation confirmed by a recent metaanalysis. However, two previous studies from Israel failed to observe this association. We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test, preferential transmission of the short allele. Additionally, we now report the effect of the DRD4 repeat region on the Test Of Variables of Attention (TOVA), a widely used computerized continuous performance test. Probands with the short exon III repeat performed significantly worse on the TOVA measured both by errors of commission and response time variable. Intriguingly, a 'dose effect' was observed. Increasing repeat size is accompanied by a reduced number of errors of commission and a significant difference is observed between the 2 vs 7 repeats. On the whole, our results lend credence to the notion that the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a neighboring locus.

Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA).

Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands (chi(2) = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission (chi(2) = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P < 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson chi(2) = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype chi(2) = 21.28; P = 0.0032, 3 df and allele chi(2) = 30.88, P= 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.

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.

Effectiveness of dynamic cognitive intervention in rehabilitation of clients with schizophrenia.

OBJECTIVE: To examine the efficacy of dynamic cognitive treatment in rehabilitation of schizophrenic clients. SUBJECTS: Fifty-eight schizophrenic clients that were matched equally into two groups: a study group (n = 29) (treated by Instrumental Enrichment) and a control group (treated with traditional occupational therapy methods). SETTING: The subjects were treated in a day rehabilitation centre in the community. STUDY DESIGN: The programme lasted one year, the same schedule was provided for both groups. Subjects were randomly assigned and assessed before and after intervention with the same battery and at a follow-up six months later, work and residence status were evaluated. MAIN OUTCOME MEASURES: Instruments included: (1) memory and thought processes, measured by a battery of structured tests from the Learning Potential Assessment Device (LPAD), Raven Progressive Matrices and General Aptitude Test Battery (GATB); (2) functional outcomes, instrumental activities of daily living (IADL), measured by a questionnaire; work and residence status; (3) self-concept measured with Fitts questionnaire. RESULTS: Results showed significant differences between the groups on almost all the cognitive tests (MANOVA revealed significant differences between the two groups for both memory and thought process (F(2.52) = 13.75, p < 0.001; and F(1.46) = 7.28, p < 0.001, respectively) as well as in work (chi2 = 14.30, p < 0.001), and residence (chi2 = 3.86, p < 0.05) status. There were no significant differences in IADL questionnaire or the self-concept scale. CONCLUSIONS: The successful outcome points to the importance of including long-term cognitive intervention in rehabilitation of schizophrenic clients. This work suggests that the classic view of schizophrenia as a progressive irreversible decline that cannot be altered may be wrong.

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.

Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder.

Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors. Recently, a common 44-bp deletion in the promoter region of the serotonin transporter (5-HTTLPR) that results in reduced transcription and lower transporter protein levels was described. Toward unraveling a possible role of the 5-HTTLPR polymorphism in childhood disruptive behaviors, we examined this gene in attention deficit hyperactivity disorder (ADHD), a heterogeneous childhood disorder in which three phenotypes are recognized by DSM IV criteria: inattentive (type I), hyperactive-impulsive (type II), and combined type (type III). By using the haplotype relative risk design, a group of 98 triads (both parents and proband child) were tested for a possible association between 5-HTTLPR and ADHD. A significant decrease in the short/short 5-HTTLPR genotype was observed in the ADHD type III combined group (10.29% vs. 30.88%) compared with the HRR-derived control group (likelihood ratio = 9.62, P = 0.008, n = 68 triads). Similar results were observed when allele frequencies were compared (likelihood ratio = 3.81, P = 0.05, n = 136 alleles). These first findings should be interpreted cautiously until replicated in independently recruited clinical samples.

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.

Psychosocial diagnosis in psychiatrically hospitalized adolescents.

This study examines the relevance of a psychosocial diagnostic system developed by the World Health Organization (WHO; International Classification of Diseases [ICD] 10 axis V) for psychiatrically hospitalized inpatient adolescents and assesses the reliability of semistructured interviews for making these psychosocial diagnoses. Seventy-one consecutive patients admitted to an adolescent unit and their parents were interviewed. The semistructured interviews were derived from the criteria for each psychosocial (axis V) diagnosis. Inter-rater and test-retest reliability were measured for both child and parent interviews on a subsample of 57 and 25 subjects, respectively. Results showed high inter-rater reliability (kappa = 0.8 to 1.0). Some test-retest reliabilities were high and others were low (kappa = 0.4 to 1.0). Parent-child agreement was erratic (kappa = 0.2 to 0.7). All of the psychosocial diagnostic entities were common and relevant to our patient population. We conclude that it is possible to make reliable and relevant psychosocial diagnoses in severely ill adolescents.

Depressive symptoms and suicidality in physically abused children.

Depressive symptoms and suicidality were assessed in 114 children 6-12 years old, of whom 41 had been physically abused, 38 neglected, and 35 neither abused nor neglected. The physically abused children manifested significantly higher levels of depressive symptomatology and suicidality than did the other two groups. Implications for research and clinical practice are discussed.

Diagnoses and interactive patterns of infants referred to a community-based infant mental health clinic.

OBJECTIVES: To describe the distribution of symptoms and diagnoses in a community-based infant mental health clinic and to compare play and feeding interactions of referred and nonreferred infants. METHOD: The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC 0-3) was used to diagnose 113 referred infants (60% were boys). Thirty additional dyads were matched with 30 nonreferred dyads. Feeding, play interactions, and home environment were compared. RESULTS: Two peaks of referral were found: 0 to 6 and 12 to 18 months. The main reasons for referral were eating problems, sleep problems, aggressive behavior, irritability, and maternal depression. The most common DC 0-3 diagnosis was a combination of primary infant disorder, parent-child relationship disorder, and parental psychopathology. Mothers of referred children provided lower levels of sensitivity, support, and structuring of the interaction, and less optimal home environment. The dyadic relationship showed a lower degree of mutuality and higher negative exchanges. Feeding interactions elicited more negative interactions than play. CONCLUSIONS: Infants referred by community health workers showed less optimal mother-infant interactions and had less optimal environment, compared with nonreferred dyads. Symptoms of emotional distress in infancy are best apprehended when assessed in multi-institutional contexts and formulated in a multiaxial approach.

[Attention deficit disorder in the preschool years: its characteristics and course from infancy to toddlerhood].

Diagnosis of Attention Deficit Disorder with/without hyperactivity in school-age children is based on the presence of the three main symptoms: lack of attention, impulsivity and hyperactivity. In infants and toddlers, these symptoms may very well be contingent to their development stage, but may also signify early signs of attention deficit disorder. Diagnosis in the age group of 2-5 years is very challenging, because reliable criteria are still lacking. The cutpoint between normal developmentally-based lack of attention and impulsivity and "true" attention deficit, is often not clear enough. Also, the very young child's condition often reflects the quality of the early parent-child relationship. Diagnostic criteria, differential diagnoses and treatment relevant to this age group, are presented. An 18 month old boy with signs of irritability, sleep problems, and poor attention span, shows the course of these symptoms, from infancy to toddlerhood under treatment, with modalities that changed over time. We suggest adopting an integrative standpoint of the young child and his/her family in the diagnostic as well as the therapeutic process, while keeping in mind the dynamic and development-dependent nature of the clinical presentation.

Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort.

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. We previously reported an association in 48 ADHD triads (both parents and proband) between the catechol-O-methyl- transferase (COMT) polymorphism (especially the high enzyme activity val allele) and the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) combined category (excluding inattention) of ADHD (however, see erratum, Am. J. Med. Genet. [Neuropsychiatr. Genet.] 96:893). In the current report, we attempted to replicate this finding in an independently recruited group of 70 nuclear families using the haplotype relative risk design. In the current investigation, no evidence for association of the COMT polymorphism and ADHD (or any of the DSM IV subtypes) was observed in either the current cohort or the expanded cohort of 118 Israeli triads. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:858-860, 2000.

A case-study of PTSD in infancy: diagnostic, neurophysiological, developmental and therapeutic aspects.

Post-traumatic Stress Disorder of Infancy has become accepted as a nosological entity. Assessment guidelines and diagnostic criteria have been defined, taking into account the impact of development on the expression of post-traumatic symptoms. Therapeutic reenactment has been considered the cornerstone of the therapeutic process. The issue of deciding what is the optimal time for therapist-induced reenactment of the trauma remains ill-defined. The less verbal and the more avoidant the traumatized infant is, the more directive the therapist needs to be, meaning he will not necessarily get clues from the infant of his readiness for reenactment. The therapist will need to introduce the trauma, at the risk of provoking a massive "flight or fight" reaction, as is illustrated by the case study of a two-and-a-half-year-old post-traumatic preverbal boy and his mother. Issues relating to conditions under which reenactment stops causing reactivation of the trauma and starts being a process of therapeutic desensitization are raised. We suggest that integration of psychodynamic and neurodevelopmental concepts might be useful in deepening the understanding of the impact of therapeutic reenactment in PTSD of Infancy.