Association of aggressive behaviours with psychiatric disorders, age, sex and degree of intellectual disability: a large-scale survey.

BACKGROUND: The link between aggression and mental disorders has been the focus of diverse studies in persons with and without intellectual disabilities (ID). Because of discrepancies in the finding of studies in persons with ID to date, and because of differences in research design, instruments used and the population studied, more research is needed. The purpose of this study was to delineate any significant association between certain psychiatric disorders and specific domains of aggressive behaviours in a large sample of persons with ID controlling for sex, age, autism and degree of ID. METHOD: Data from the present study were obtained from 47% of all persons with ID receiving services from New York State agencies, using the Institute for Basic Research - Modified Overt Aggression Scale (IBR-MOAS between 2006 and 2007). The IBR-MOAS was completed by the chief psychologists of 14 agencies based on information from the participants' files. Demographic information obtained included the psychiatric diagnosis made by the treating psychiatrist as well as information on age, sex and degree of ID. Data from 4069 participants were analysed. RESULTS: Impulse control disorder and bipolar disorder were strongly associated with all five domains of aggressive behaviour in the IBR-MOAS. Psychotic disorder was highly associated with four domains except for physical aggression against self (PASLF), which was of borderline significance. Anxiety was most associated with PASLF and verbal aggression against self (VASLF); depression with VASLF; obsessive compulsive disorder with physical aggression against objects (PAOBJ); personality disorders with verbal aggression against others (VAOTH), VASLF and PASLF; and autism with physical aggression against others (PAOTH), PAOBJ and PASLF. Mild to moderate ID was associated with VAOTH and VASLF and severe to profound ID with PAOBJ and PASLF. Female sex was most associated with VASLF. CONCLUSIONS: Impulse control, mood dysregulation and perceived threat appear to underlie most of the aggressive behaviours reported. Psychosis and depression appeared to have been over-diagnosed in persons with mild to moderate ID and under-diagnosed in persons with severe and profound ID. These findings replicate and extend findings from previous studies. The pattern of associations reported can be used as helpful indicators by professionals involved in the treatment of aggressive behaviours in persons with ID.

Pharmacotherapy for aggressive behaviours in persons with intellectual disabilities: treatment or mistreatment?

BACKGROUND: Antipsychotic medications have been used extensively to treat aggressive behaviours in persons with intellectual disabilities (ID) when the main psychiatric diagnoses given to them in the past were schizophrenia, childhood psychoses and ID with behaviour problems. Today, antipsychotics are still estimated to comprise 30-50% of all the psychotropics prescribed for persons with ID, although the prevalence of psychotic disorders is only 3% in this population. The overuse of antipsychotics in persons with ID could be justified if their aggressive behaviours were associated with mostly psychotic disorders and not other psychiatric disorders or factors and if the anti-aggressive properties of the antipsychotics have been supported by basic research or reviews of clinical studies. Is that so? This article explores these questions. METHODS: The literature on aggressive behaviours, their associations with psychiatric disorders and other contributing factors and the past and current treatment options for aggressive behaviours in persons with and without ID was reviewed. Also, the literature on basic research regarding the brain receptors implicated in aggressive behaviours and the basic research and clinical studies on the anti-aggressive properties of antipsychotics was reviewed. RESULTS: Aggressive behaviours in persons with ID serve different functions and many factors contribute to their initiation, maintenance and exacerbations or attenuation including most of the psychiatric and personality disorders. Genetic disorders, early victimisation, non-enriched and restrictive environments during childhood or later on and traumatic brain injury, which are common in persons with ID, have been associated with aggressive behaviours and with mostly non-psychotic disorders in persons with and without ID. If the factors above and the knowledge derived from studies of domestic violence and premeditated aggression in persons without ID are considered and applied during the evaluation of the most severe aggressive behaviours in persons with ID, more appropriate and effective treatment than antipsychotics can be implemented. Basic research implicates mostly the GABA and the serotonin pre-post synaptic brain receptors influence the initiation, modulation or inhibition of aggression in animals. The anti-aggressive properties of the antipsychotics have not been supported by reviews of clinical studies and basic research is absent. Antipsychotics are the indicated treatment only for psychiatric disorders and for aggressive behaviours associated with psychotic disorders and psychotic features as activation of dopamine receptor leads to defensive aggression. CONCLUSIONS: Most of the persons with ID and aggressive behaviours do not have a diagnosis of psychotic disorder and there is lack of strong evidence supporting the anti-aggressive properties of the antipsychotics. The overuse of antipsychotics in this population may be explained by the old, faulty notion that aggressive behaviour in persons with ID is mostly associated with psychotic disorders. Given the discrediting of this notion, the use of antipsychotics in persons with ID may, in some cases, be considered mistreatment rather than proper treatment. In order to reverse the practice of over-prescribing antipsychotics for aggressive behaviours in persons with ID, basic research information on aggression must be disseminated, the search for the 'quick fix' must be abandoned and the promotion of antipsychotics as anti-aggressive drugs must be discouraged. Matching the treatment with the variables contributing to the aggressive behaviours, seeking a long-term rather than a short-term solution and avoiding the promotion of only one type of treatment for all types of aggression might change the current practice and improve the quality of life for many persons with ID.

The psychometric properties of the Multi-Dimensional Observation Scale for Elderly Subjects (MOSES) in middle aged and older populations of people with mental retardation.

OBJECTIVE: To assess the internal consistency, inter-scale correlations and factor structure of the MOSES with older adults with mental retardation. METHOD: A series of outpatients with mental retardation were assessed with the MOSES. 163 middle aged and older adults with mental retardation living in community settings participated. RESULTS: The subscales and total scale of the Multi-Dimension Observation Scale for Elderly Subjects (MOSES) were highly internally consistent. The pattern of correlations between the five scales was very similar to that reported by Dalton et al. (1999). The results of a factor analysis using varimax rotation indicated a three-factor structure corresponding to adaptive behavior, externalizing and internalizing maladaptive behaviors. CONCLUSIONS: The MOSES appears to be was a psychometrically adequate instrument to screen older adults with mental retardation.

Challenging behaviours should not be considered as depressive equivalents in individuals with intellectual disability.

BACKGROUND: Depression is one of the most common forms of psychopathology in people with intellectual disability (ID). The present study evaluated the utility of an expanded assessment of psychiatric symptoms and challenging behaviours, as measured by the Clinical Behavior Checklist for Persons with Intellectual Disabilities (CBCPID). METHODS: The CBCPID was administered to 92 people with ID, 35 of whom were diagnosed with a depressive disorder. RESULTS: Item and factor analysis of the scale indicated that depression was best assessed using the core DSM-IV symptoms of depressive disorder. Challenging behaviours such as self-injury or aggression were not closely associated with depression. Short scales using the core DSM-IV symptoms of depression were highly internally consistent. There was also evidence of the validity of these scales. CONCLUSIONS: This study found no evidence that challenging behaviours were depressive equivalents in this population. The present authors conclude that the assessment of depression in people with ID should focus on the core DSM-IV symptoms of depression.

Effects of macrophage colony-stimulating factor on antifungal activity of neonatal monocytes against Candida albicans.

The effects of recombinant macrophage-colony stimulating factor (M-CSF) on antifungal activities of monocytes (MNC) from healthy neonates and adults against Candida albicans were compared. Pretreatment of adult and neonatal MNC with 15 ng/ml of M-CSF for 4 days significantly increased superoxide anion (O(-2)) production in response to phorbol myristate acetate. While M-CSF-treated MNC from adults produced significantly higher O(-2) in response to Candida blastoconidia, M-CSF-treated neonatal MNC did not show a similar response. Further, M-CSF significantly enhanced phagocytosis of C. albicans by adult MNC but not by neonatal MNC. While M-CSF enhances antifungal activities of adult MNC against C. albicans, it does not appear to affect anticandidal function of neonatal MNC.

Famotidine treatment of children with autistic spectrum disorders: pilot research using single subject research design.

Using single subject research design, we performed pilot research to evaluate the safety and efficacy of famotidine for the treatment of children with autistic spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years old, with a DSM-IV diagnosis of a pervasive developmental disorder, living with their families, receiving no chronic medications, and without significant gastrointestinal symptoms. The dose of oral famotidine was 2 mg/kg/day (given in two divided doses); the maximum total daily dose was 100 mg. Using single-subject research analysis and medication given in a randomized, double-blind, placebo-controlled, cross-over design, 4 of 9 children randomized (44%) had evidence of behavioral improvement. Primary efficacy was based on data kept by primary caregivers, including a daily diary; daily visual analogue scales of affection, reciting, or aspects of social interaction; Aberrant Behavior Checklists (ABC, Aman); and Clinical Global Improvement scales. Children with marked stereotypy (meaningless, repetitive behaviors) did not respond. Our subjects did not have prominent gastrointestinal symptoms and endoscopy was not part of our protocol; thus, we cannot exclude the possibility that our subjects improved due to the effective treatment of asymptomatic esophagitis. The use of famotidine for the treatment of children with autistic spectrum disorders warrants further investigation.

Diagnosis of depression in people with severe/profound intellectual disability.

The Marston 30 Symptoms Checklist for detecting depression was used to determine whether or not the notion of 'depressive equivalents' can provide a few of the core characteristics necessary for the diagnosis of depressive disorders in people with severe/profound intellectual disability (ID). Diagnoses of major depression were made by a psychiatrist using the DSM-III-R criteria, combined with information from records, staff, team, parents, behaviour profiles, direct observations, mental status and follow-up visits. Twenty-two people with ID fulfilled the selection criteria from a larger sample of 150 patients who had been evaluated in 350 contact visits. Scores on the checklist for major depression for 15 subjects with severe/profound ID were similar to the core characteristics for diagnosis of major depression by DSM-III-R criteria. Evidence was found for the presence of depressive equivalents in the subjects, but these appeared to be secondary. The 15 participants with severe/profound ID were observed mostly during the depressive phase of bipolar I and bipolar II disorder, and major depression, recurrent type. Melancholic features were prominent in their presentation. Further studies of people with ID are needed to determine whether depressive equivalents are more prominent in cases of major depression with atypical features than in cases of major depression with melancholic features.

Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications.

Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha2 macroglobulin (alpha2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha2M, and the AP proteins c-reactive protein (CRP), alpha1 antitrypsin (alpha1AT), ceruloplasmin (Cp), beta2 Macroglobulin (beta2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha2M and CRP were significantly different in the depressed versus non-depressed groups. The alpha2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.

Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99mTc-dimercaptosuccinic acid scans in neonates with urinary tract infections.

Interleukin (IL)-6 and -8 are important inflammatory cytokines in bacterial infections. Their serum and urine concentrations were measured in 27 neonates with urinary tract infection (UTI) at onset and the second week of therapy, as well as in 23 control neonates. Escherichia coli was isolated in 89% of cases. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scans were performed between the 10th and 90th days after UTI and showed pyelonephritic changes in 15 neonates (56%). Increased IL-6 and IL-8 concentrations were found in urine but not in serum within the first 24 h after presumptive diagnosis of UTI (P=.036 and.010, respectively), suggesting that the neonatal urinary tract can respond to uropathogens by producing inflammatory cytokines. Urine concentrations of IL-6 correlated with findings of renal changes in 99mTc-DMSA scans (P=.012) and thus may serve as a marker of renal parenchymal outcome. All neonates exhibited undetectable urine cytokine levels during the second week of therapy.

5-HTTLPR variants not associated with autistic spectrum disorders.

To determine whether there is an association of polymorphic variants of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) and autistic spectrum disorders, we analyzed the 5-HTTLPR genotypes of 72 autistic subjects, 11 fragile X syndrome patients with autistic behavior, 43 normal subjects, and 49 fragile X syndrome non-autistic subjects. The distribution frequency of 5-HTTLPR long allele (L) and the short allele (S) variants showed no differences between subjects. Our findings do not support the hypothesis that polymorphic 5-HTTLPR variants are a susceptibility factor for autistic disorders.

Identical twins discordant for Sotos syndrome.

The cause of Sotos syndrome is unknown but it usually occurs sporadically. Recent studies have shown no evidence of uniparental disomy. One set of concordant monozygotic twins has been reported. We have identified the Sotos syndrome in one of two 5-year-old male monozygotic twins. Our finding of discordance in these identical twins suggests that a postconceptual mutation, or epigenetic change and/or an environmental factor may be involved in the cause of Sotos syndrome.

Synergistic induction of sister-chromatid exchanges in lymphocytes from normal subjects and from patients under cytostatic therapy by inhibitors of poly(ADP-ribose)polymerase and antitumour agents.

The effects of nicotinamide on SCE rates induced in vitro by chlorambucil (CBC or melphalan (MELPH) or mitomycin C (MMC) was studied. The combined treatments with either CBC or MELPH or MMC and nicotinamide showed the potentiating ability of the latter drug. Theophylline and MELPH were also found to act synergistically on the induction of SCEs. In a combined in vivo and in vitro study, lymphocytes taken from 7 cancer patients who had been given cytoxan by injection 3 h before, were treated with nicotinamide or diphylline (DP) in vitro, and found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved, for monitoring drug combinations that synergistically damage DNA in vivo and in vitro and for identifying interindividual variation in the response to the treatment.

Practical applications of the SCE studies for guiding and improving chemotherapy.

The effect of diphylline (DP) or (1,2-dihydroxy-3-propyl)-theophylline and theobromine (TB) on sister chromatid exchange (SCE) rates induced in vitro by cytosine arabinoside (AraC) was studied in normal human lymphocytes. The combined treatments with AraC plus DP or TB showed the potentiating ability of the latter drugs. In a combined in vivo and in vitro study, lymphocytes taken from 14 patients suffering from various types of cancer who had been given Cytoxan (5 patients) or AraC (9 patients) by injection 3 hr before and then treated with DP or TB in vitro were found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved and for monitoring drug combinations that synergistically damage DNA in vivo and in vitro.