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Background: Diagnostics and care for people with intellectual disabilities (ID) and psychiatric disorders need to be improved. This can be done by using assessment instruments to routinely measure the nature and severity of psychiatric symptoms. Up until now, in the Netherlands, assessment measures are seldom used in the psychiatric care for this population. The objective of the present paper is to evaluate the use of the Brief Symptom Inventory (BSI), a widely used standardised questionnaire in general psychiatry, in a well-defined sample of people with borderline intellectual functioning or mild ID diagnosed with one or more psychiatric disorders. Methods: A total of 224 psychiatric outpatients with either borderline intellectual functioning or mild ID participated in this study. All participants were new patients of Kristal, Centre for Psychiatry and Intellectual Disability in the Netherlands, in the period between 1 April 2008 and 1 October 2009. All participants were assessed by a multidisciplinary team, including a certified psychiatrist. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria were applied. The mean total intelligence quotient was measured with the Wechsler Adult Intelligence Scale (WAIS-III). The BSI was administered in an assisted fashion. Utility and psychometric properties of the BSI were investigated. Internal consistency coefficients (Cronbach's alphas) were computed. Bivariate correlations between the sub-scales were computed to assess differentiation between the scales. Mean sub-scale scores were compared between different DSM-IV-TR subgroups to investigate the discriminant abilities of the scales. A confirmatory factor analysis was conducted. Results: The results suggest that the BSI is practically useful. Internal consistencies ranged from 0.70 to 0.96 and thus are considered good to adequate. Sub-scale inter-correlations showed there is a degree of differentiation between the sub-scales. Discriminant validity was shown for the sub-scales "depression," "anxiety" and "phobic anxiety." Confirmatory factor analysis showed that the underlying structure of the BSI could be described by the same nine-factor model as reported in previous studies. Conclusions: As a result of the psychometric properties illustrated, this study supports the use of the BSI as a screener for psychopathology and a general outcome measure in people with ID. (Contains 3 tables and 4 figures.)

Purpose: Sociodemographic and socioeconomic characteristics of participants in antidepressant and psychotherapy efficacy trials (AETs and PETs) for major depressive disorder (MDD) may limit the generalizability of the results. We compared trial participants with daily practice patients. We subsequently assessed the influence of socio-demographic and socioeconomic status on treatment outcome in daily practice. Methods: Data on daily practice patients were derived through routine outcome monitoring (ROM). We included 626 patients with MDD according to the MINIplus. Distributions of age, gender, race, marital status and employment status were compared with participants in 63 selected AETs and PETs. Influence of these features on treatment outcome was explored through multivariate regression analysis. Results: Trial participants were older, more often male (diff. 4 %, p = 0.05), white (diff. 4 %, p < 0.001) and not married (diff. 7 %, p = 0.003). Although significant, most differences were relatively small. However, the difference in employment status was striking: 34 % of the ROM patients were currently working versus 68 % of the trial participants (diff. 34 %, p < 0.001). Being employed contributed to a positive treatment outcome: OR 1.8 for response [50 % reduction of Montgomery Asberg Rating Scale for Depression (MADRS)], OR 1.9 for remission (MADRS ≤10). Conclusions: Employment status should be taken into account while interpreting results from randomized controlled trials and as predictor of treatment success in daily practice. [ABSTRACT FROM AUTHOR]

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples. [ABSTRACT FROM AUTHOR]

Routine outcome monitoring (ROM) is a method devised to systematically collect data on the effectiveness of treatments in everyday clinical practice. ROM involves documenting the outcome of treatments through repeated assessments. Assistants are employed who perform a baseline assessment comprising a standardized diagnostic interview, administration of rating scales and completion of several self-report measures by the patient. At fixed time intervals, assessments are repeated. Dedicated Web-based software has been developed to assist in this task. ROM informs therapists and patients on the severity of the complaints at intake, and the waxing and waning of symptoms over the course of treatment. Researchers can use ROM for effectiveness research, and managers can use it for benchmarking. The use of ROM for research is illustrated by presenting data on the diagnostic status of patients participating in ROM and data on treatment outcome of a subgroup of patients (with panic disorder) in our database. The results show that implementation of ROM is feasible, and after some initial reservations, most therapists now consider ROM to be a necessary and important adjunct to the clinical treatment. In addition, ROM furthers research as the data can be used to study the phenomenology of psychiatric disorders and the outcome of treatments delivered in everyday practice. Copyright © 2010 John Wiley & Sons, Ltd. • A form of tracking the progress of treatment through routine outcome monitoring (ROM) is described. • Implementation of ROM appears feasible and can be carried out in large institutions as well as smaller practices. • Providing feedback about outcome in an appealing format is highly valued by both therapists and patients. • ROM data enable investigation of the effectiveness of treatments in everyday clinical practice. [ABSTRACT FROM AUTHOR]

A recently developed oral serotonergic challenge test consisting of 5-Hydroxytryptophane (5-HTP, 200 mg) combined with carbidopa (CBD, 100 mg + 50 mg) exhibited dose-related neuroendocrine responsiveness and predictable pharmacokinetics. However, its applicability is limited by nausea and vomiting. A randomized, double-blind, placebo-controlled, four-way crossover trial was performed in 12 healthy male volunteers. The 5-HTP/CBD-challenge was combined with two oral anti-emetics (granisetron, 2 mg or domperidone, 10 mg) to investigate its reliability when side-effects are suppressed. The neuroendocrine response (serum cortisol and prolactin), the side-effect profile [Visual Analogue Scale Nausea (VAS)] and vomiting subjects per treatment were the main outcome measures. Compared to 5-HTP/CBD/placebo, 5-HTP/CBD/ granisetron had no impact on cortisol [% change with 95% confidence interval: -7.1% (18.9; 6.5)] or prolactin levels [-9.6% (-25.1; 9.1)]; 5-HTP/CBD/domperidone increased cortisol [+13.0% (-4.2; 33.4)], and increased prolactin extensively [+336.8% (245.7; 451.9)]. Compared to placebo, VAS Nausea increased non-significantly with granisetron [+7.6 mm (-1.3; 16.5)], as opposed to domperidone [+16.2 mm (7.2; 25.2)] and 5-HTP/CBD/placebo [+14.7 mm (5.5; 23.8)]. No subjects vomited with granisetron, compared to two subjects treated with 5-HTP/CBD/placebo and five subjects with domperidone. Compared with 5-HTP/CBD/placebo, granisetron addition decreased Cmax of 5-HTP statistically significantly different (from 1483 to 1272 ng/ml) without influencing AUC0-∞. Addition of granisetron to the combined 5-HTP/CBD challenge suppresses nausea and vomiting without influencing the neuroendocrine response or pharmacokinetics, enhancing its clinical applicability in future psychiatric research and drug development. [ABSTRACT FROM AUTHOR]

The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of depression and correlating plasma AVP and cortisol concentrations. The data support the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression. The aim of the present study was to test whether above-normal plasma AVP concentration in depression is related to personality characteristics reflecting a specific social behaviour style. The data of 78 patients from a previously investigated sample were reanalysed. Fifty-eight patients were available after 2 years, 15 of whom with initially above-normal plasma AVP. The dimensions of the Temperament and Character Inventory (TCI) were scored, with particular focus on the dimensions of Cooperativeness (CO) and Reward-dependence (RD). Normative subjects and other depressed subjects were used as controls. After full remission, patients with initially above-normal AVP had low CO compared with normal and patient controls. During depression, these patients had both low CO and low RD compared with normal controls and low RD compared with patient controls. Low CO is a presumably premorbid trait and reduced RD a state-dependent characteristic in depression with above-normal plasma AVP. The low CO further supports the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression. [ABSTRACT FROM AUTHOR]

5-hydroxytryptophan (5-HTP) is a direct 5-hydroxytryptamine (5-HT) precursor used to assess central serotonergic function. Its use has been limited by a narrow window between neuroendocrine changes and side effects, and variable kinetics related to inconsistent administration modes. By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT. A doubleblind, placebo-controlled, single rising dose, four-way crossover trial with placebo randomisation was performed in 15 healthy male volunteers to investigate the neuroendocrine dose-response relationship at various 5-HTP levels; the tolerability and subjective effects of oral 5-HTP at 100, 200 and 300mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge. Dose-dependent increases in average cortisol concentrations were observed. Mean response (area-under-thecurve) over the first 4 hours (SD): 172.0nmol/L (22.3) for placebo, 258.3nmol/L (72.6) for 100mg, 328.47nmol/L (84.6) for 200mg and 387.3nmol/L (82.4) for 300mg 5-HTP. Similar dose-dependent increases for prolactin were seen while adreno-corticotrophic hormone response was more variable. 5-HTP kinetics were adequately described using a one-compartment model with first-order absorption and a lag time (mean oral clearance 28 L/h ± interindividual coefficient of variation 31%). Nausea and vomiting occurred dose-dependently as most frequent side effects, resulting in dose-related dropout of 6.6% at 100mg and 45.5% at 300mg 5-HTP. Orally administered 5-HTP combined with CBD is an effective serotonergic challenge test, exhibiting dose-related plasma concentrations and neuroendocrine responsiveness. Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100mg. [ABSTRACT FROM AUTHOR]

Background: Contrary to short-term use, long-term benzodiazepine use is undesirable. Nevertheless, its prevalence is high. To prevent long-term use, it is important to know which short-term users are at risk of becoming long-term users.Objectives: The purpose of the present study was to identify patient-related factors of long-term versus short-term use of benzodiazepines.Methods: A cross-sectional study was carried out in family practices among users of benzodiazepines with regard to DSM-IV diagnosis, coping and psychosocial characteristics,. In a multivariate logistic regression analysis, long-term use of benzodiazepines was the dependent variable.Results: A total of 164 short-term and 158 long-term benzodiazepine users participated in the study. Having a DSM-IV disorder and psychiatric co-morbidity, being older, less educated, lonely and using more avoidance coping behaviour was associated with long-term use of benzodiazepines compared with short-term use.Conclusion: The associations found point to possibilities to reduce long-term benzodiazepine use, for example if patients with these characteristics are treated with the alternatives to benzodiazepines or are monitored closely for a short period after being prescribing benzodiazepines. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition.Aims: To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice, and to evaluate the value of additional group cognitive-behavioural therapy (CBT).Method: A 3-month randomised, 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT, tapering off alone or usual care.Results: Tapering off led to a significantly higher proportion of successful discontinuations than usual care (62% nu. 21%). Adding group CBT did not increase the success rate (58% v. 62%). Neither successful discontinuation nor intervention type affected psychological functioning. Both tapering strategies showed good feasibilityin general practice.Conclusions: Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice. The addition of group CBT is of limited value. [ABSTRACT FROM AUTHOR]

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Background: Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value.Aims: To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor (SSRI) prescribing and to determine the long-term outcome after benzodiazepine withdrawal.Method: Patients went through three phases - change to an equivalent dose of diazepam; subsequent randomisation to either 20 mg of paroxetine or placebo; and gradual reduction of diazepam in depression-free patients - with a follow-up after 2 or 3 years.Results: A total of 230 patients were recruited and 75% in the paroxetine group and 61% in the placebo group were successfully treated after 6 weeks (P:=0.067). After 2 or 3 years 13% of patients were still benzodiazepine free: 26% of those who had successfully tapered off benzodiazepine and 6% of the total group.Conclusions: Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use. The addition of SSRI treatment is of limited value. [ABSTRACT FROM AUTHOR]

Seventy-one subjects with Down's syndrome (DS), between the ages of 29 and 68 years, and 46 matched controls (without DS) were examined for Intelligence, memory (short- and long-term memory, and spatial and temporal orientation), communication (receptive, expressive and written language) and daily living skills (personal, domestic and community daily living skills). All subjects were screened on hearing and visual functions, thyroid functions; depression and dementia. DS-subjects and controls were matched on chronological age, mental age, living conditions and male/female ratio. Comparisons were made between five subgroups (1) non-demented institutionalized subjects with DS (DSi-group; n=35); (2) non-demented institutionalized controls without DS (Ci-group; n=22); (3) demented institutionalized subjects with DS (n= 10); (4) non-demented subjects with DS living in group homes (DSg; n=26); and (5) non-demented controls without DS living in group homes (Cg; n=24). Institutionalized and non-institutionalized subjects, as well as demented and non-demented subjects differed significantly on all functions measured. Multiple regression analysis was performed to examine the influence of age and sensory deficits on adaptive and cognitive functioning. In DSg subjects, significant associations were found between age and mental age, and between age and performances on written language. In (non-demented) DSi subjects, significant relations were found between age and memory functions observed in daily circumstances. Moreover, in the (non-demented) DSi elderly, visual Impairment was significantly related to depressed performance on daily living skills. No age effects were seen in control subjects. Infirmities of old age like dementia and sensory deficits were far more common in people with DS than in controls. Psychiatric and diagnostic aspects of clinical depression and dementia were emphasized in particular. [ABSTRACT FROM AUTHOR]