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.

Imipramine binding to platelets of children with attention deficit disorder with hyperactivity.

High-affinity [3H]imipramine binding to platelets was investigated in 11 boys with attention deficit disorder and hyperactivity (ADDH) before and after 28 days of methylphenidate (MPH) treatment, and the results were compared to [3H]imipramine binding parameters (Kd, Bmax) of 10 age-matched normal boys. The binding parameters for imipramine binding sites did not differ between ADDH children and controls. Moreover, the beneficial therapeutic effect of MPH was not accompanied by any alteration in the binding values. This study is consistent with other studies that failed to demonstrate involvement of the serotonergic system in the pathophysiology of ADDH and in the therapeutic effect of MPH.

Cold agglutinin titers in psychiatric patients.

Cold agglutinin titers were obtained from the serum of 41 psychiatric patients. The 21 chronic schizophrenic patients tended to have positive cold agglutinin titers; the authors suggest that this immunological finding may be associated with long-term neuroleptic treatment.

Abnormal growth hormone response to LRH and TRH in adolescent schizophrenic boys.

The authors studied the effect of LRH and TRH on HGH in 10 adolescent schizophrenic boys and 9 age-matched normal boys. Before antipsychotic treatment, LRH and TRH induced a marked rise in hGH in 8 of 10 patients and 4 of 6 patients, respectively. No effect on HGH was observed in the normal controls. After 3 months of treatment with chlorpromazine, thioridazine, or haloperidol, LRH failed to induce a rise in HGH in 5 of the 6 patients tested, but TRH induced a significant rise in HGH in 3 of 4 patients tested. The authors postulate that these results indicate a dysfunction in the mechanism regulating HGH secretion in schizophrenia.

Cold agglutinin autoantibodies in psychiatric patients: their relation to diagnosis and pharmacological treatment.

BACKGROUND AND METHOD: The purpose of this study was to compare titers of cold agglutinins in schizophrenic patients with those in patients with major affective disorders and in normal healthy subjects. One hundred sixty-six psychiatric patients and 37 healthy comparison subjects were included in the study. Ninety of the patients suffered from schizophrenia, 54 from bipolar disorder, and 22 from major depression. Venous blood samples were obtained from all subjects between 8:00 and 10:00 a.m. and were immediately tested for cold agglutinin titers. RESULTS: A high frequency (42.2%) of positive cold agglutinin titers was detected in the schizophrenic patients, compared with the bipolar (11.1%) and unipolar (9.0%) patients and the comparison group (8.1%). The investigators did not find any pharmacological effect on these results. CONCLUSIONS: The findings suggest that, at least in this group, positive cold agglutinin titers are associated with schizophrenia. However, this observation cannot provide direct evidence for the involvement of viral or autoimmune factors in schizophrenia.

High-affinity imipramine binding and serotonin uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients.

The authors evaluated high-affinity [3H]imipramine binding and [3H]serotonin uptake to platelets in eight adolescent and 10 adult patients who met DSM-III criteria for obsessive-compulsive disorder in comparison with those of normal control subjects of similar ages. The maximal binding of [3H]imipramine was significantly lower in adults and adolescents with obsessive-compulsive disorder than in the control subjects. No differences between groups in the affinity of [3H]imipramine to its binding sites or in serotonin uptake kinetic measures were detected. The lower density of [3H]imipramine binding sites in platelet membrane in patients with obsessive-compulsive disorder might implicate involvement of the serotonergic system or might represent an adaptive response to a chronic disease.

Effect of chlorpromazine on hypothalamic-pituitary-gonadal function in 10 adolescent schizophrenic boys.

Low basal plasma testosterone levels with normal response to human chorionic gonadotropin (HCG) stimulation and mild hyperprolactinemia and blunted luteinizing hormone (LH) response to luteinizing-releasing hormone (LRH) stimulation were found in 10 adolescent schizophrenic boys who had been treated with chlorpromazine for more than 6 months. These findings may indicate a disturbance of the hypothalamic-pituitary-gonadal function in these patients, probably due to the prolonged administration of chlorpromazine. It remains to be established whether the decrease in basal testosterone secretion is caused directly by chlorpromazine or secondarily by the drug-induced hyperprolactinemia.

Peripheral benzodiazepine receptors on platelets in chronic and detoxified alcoholics.

The effect of chronic alcoholism and detoxification treatment with disulfiram on platelet peripheral benzodiazepine receptors was studied in alcoholic males. Chronic consumption of alcohol did not alter the binding values for [3H]PK 11195, as compared to non-alcoholics. Treatment for 3 weeks with disulfiram resulted in a significant increase in the density of peripheral benzodiazepine receptors, with no alteration in the affinity of these sites to the ligand. These results might be relevant to the cellular and metabolic effects of disulfiram.

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.

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.

Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study.

The DRD4 exon III repeat polymorphism has been associated in adults with Novelty Seeking personality traits and in children with attention deficit hyperactivity disorder (ADHD) in some but not all studies. In a previous report we failed to observe preferential transmission of the long DRD4 repeat in ADHD compared to the haplotype relative risk (HRR) derived control group in a group of 49 triads (both parents and ADHD child) recruited in the Jerusalem area. In the current study we independently recruited an additional group of 49 triads from a different geographical location (Petak Tikvah) in Israel but having a similar ethnic background. In contrast to previous findings from a number of groups, in the current study an excess of the long DRD4 alleles was observed in the HRR control group compared to the ADHD subjects (Likelihood ratio = 5.50, P = 0. 02). In the expanded Israeli group of 98 triads so-far examined for the DRD4 repeat polymorphism there is an excess of the long alleles in the HRR control group (Likelihood ratio = 3.81, P = 0.05). These results attest to the complexity of ADHD inheritance and the likelihood that genetic heterogeneity characterizes this disorder especially across ethnic and cultural boundaries.

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.

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.

Paranoid schizophrenia in adolescence.

BACKGROUND: Paranoid schizophrenia is considered to be a rare condition in adolescence. Since this is contrary to the authors' clinical experience, they hypothesized that a controlled study would show that a significant number of adolescents would be diagnosed with paranoid schizophrenia and that scores from the childhood version of the Schedule for Affective Disorders and Schizophrenia (K-SADS) would differentiate between the paranoid schizophrenic adolescents and adolescents with other types of schizophrenia or with affective disorder. METHOD: The authors conducted a prospective study of 120 adolescents admitted consecutively to an adolescent psychiatric inpatient department. Patients were diagnosed on the basis of DSM-III after an 8-week period during which they were evaluated with a structured psychiatric history and psychiatric examination, the K-SADS, repeated nonstructured interviews, and extensive ward observations. RESULTS: Thirty-eight percent of the schizophrenic adolescents and 14% of the total hospitalized population met the DSM-III criteria for paranoid schizophrenia. The symptom profile of the paranoid schizophrenic adolescents clearly distinguished them from adolescents with other psychiatric disorders. CONCLUSIONS: Given the incidence of paranoid schizophrenia in an adolescent population, adolescent psychiatrists are likely to encounter this disorder. DSM-III-R should be used in future studies to further clarify the issue of the prevalence of paranoid schizophrenia in adolescents.

High dose diazepam treatment and its effect on prolactin secretion in adolescent schizophrenic patients.

Thirteen acute schizophrenic patients aged 14-18 years were treated with gradually increasing doses of diazepam to a maximum of 100-400 mg/day/p.o. with a total duration of treatment of 4 weeks. The clinical antipsychotic effect was evaluated by the Brief Psychiatric Rating Scale (BPRS), while the impact on the hypothalamic hypophyseal pathway was evaluated by monitoring the serum prolactin levels (SPL) determined by a highly sensitive homologous radioimmunoassay (RIA). High diazepam doses (100-400 mg/day) caused sedation but no clinical antipsychotic effect was observed. Diazepam treatment with doses up to 250 mg/day caused no significant rise in SPL, while the treatment with doses of higher than 250 mg/day resulted in a mild but still significant increase in SPL. The clinical and laboratory data suggest that diazepam has no direct antidopaminergic activity. The mild hyperprolactinemia achieved with the extremely high doses of diazepam (greater than 250 mg/day) is possibly due to activation of the GABA system which stimulates prolactin release directly or by inhibiting the dopaminergic neurons or alternatively to activation of the endorphinergic system.

Platelet [3H]imipramine binding in autism and schizophrenia.

[3H]Imipramine binding to platelet membranes was evaluated in ten autistics, eight schizophrenics and seven normal controls. The schizophrenics and eight out of the ten autistics were maintained on chronic neuroleptic treatment. Diagnosis of autism and schizophrenia was established according to the DSM-III criteria. No significant difference in the maximal binding capacity of [3H]imipramine (Bmax) and Kd values could be found among the three groups. It seems that the imipramine binding site is intact both in autism and schizophrenia.

The effect of acute and repeated electroconvulsive treatment on plasma beta-endorphin, growth hormone, prolactin and cortisol secretion in depressed patients.

The effects of single and repeated electroconvulsive treatment (ECT) on beta-endorphin (beta-EP), cortisol, growth hormone (GH) and prolactin (Prl) plasma levels were investigated in nine depressed patients. Blood samples were monitored a day before ECT, the day of the first and sixth ECT (0, 30, 60 and 90 min after seizures), the day afterwards and 4 weeks after termination of the ECT course. A significant elevation of beta-EP levels was achieved immediately with and 24 h after the first and the sixth ECT. A transient increase in basal beta-EP was observed 1 day following the sixth ECT in comparison with pre-treatment level. Peak and 30 min levels of cortisol were increased compared with baseline by the first ECT. The former (peak) but not the latter (30 min) were increased also at the sixth treatment. GH levels were decreased the day after the first ECT in comparison with the pre-treatment levels and immediately following each ECT in comparison with baseline. A trend toward elevation of Prl was observed immediately after the first and sixth ECT, although the rise did not reach significant levels. ECT administration stimulated beta-EP and cortisol secretion and suppressed human GH release, possibly by activation of endorphinergic and/or serotonergic systems. These mechanisms might be involved in the beneficial effect of ECT in depression.

Humoral-endorphin blood levels in autistic, schizophrenic and healthy subjects.

Basal morning humoral (H)-endorphin blood levels were assessed in ten autistic patients, 12 chronic schizophrenic patients and 11 healthy control subjects. Four autistic patients and four schizophrenic patients were drug free for at least 6 months while all other psychiatric patients were under treatment with antidopaminergic agents. Significantly reduced opioid levels were observed in the autistic group (827 +/- 103 vs 1121 +/- 75 pg-eq/ml, P less than 0.025), although the difference was actually only 26% of the control mean. A similar tendency toward low H-endorphin levels was also observed in the schizophrenic patients; however this difference was not significant (919 +/- 129 vs 1121 +/- 75 pg-eq/ml; NS). No significant difference was obtained between subjects suffering from the two psychiatric disorders (827 +/- 103 vs 919 +/- 129 pg-eq/ml; NS). Various interpretations of the decreased secretion of H-endorphin are discussed.

Reduction in serotonin 5HT2 receptor binding on platelets of delinquent adolescents.

The possible involvement of serotonin receptors of the 5HT2 type in aggressive behavior was studied in juvenile delinquents. A group of 28 delinquent adolescents (13-18 years old) who had committed violent crimes was compared with a group of age matched controls. Subjects were drug and medication free during the study. 5HT2 receptors were labeled on platelet membranes using tritiated ketanserin. Receptor binding in the delinquent adolescents was significantly lower than in age matched controls. Mean +/- SD of 76 controls was 32.3 +/- 14.2 fm/mg, compared to 16.6 +/- 8.2 fm/mg in 28 delinquents (P < 0.002, Student's t-test). These results support a role for serotonin in general and 5HT2 receptors in particular in human aggressive behavior.