Deconstructing the 'black box' of the Camberwell assessment of need score in mental health services evaluation.

OBJECTIVE: The aim of the study was to examine an alternative way of scoring the Camberwell Assessment of Need (CAN) for the purpose of service evaluation, using the by us defined Social Services (SI) and Psychiatric Services (PI) subindices. METHODS: CAN assessments in 1997 and 1999 of 262 outpatients (mean age 45 years, 77.1% psychotic disorders) were reanalysed to fit the SI and the PI, which were compared to the full CAN. RESULTS: The mean total needs on the full CAN decreased from 6.65 to 6.22 (P = 0.007), as did the mean unmet needs (1.55-1.81, P = 0.049). The mean total needs on the PI decreased from 2.42 to 2.22 (P = 0.006), as did the mean unmet needs (1.66-0.57, P < 0.001). No changes in mean needs occurred on the SI. CONCLUSIONS: All significant changes occurred on the PI, indicating a more beneficial outcome of the psychiatric care than the social care in terms of meeting needs, a result impossible to discern from the total scores of the CAN. Thus, output scores on subindices of the CAN might be useful as outcome measures in service evaluation.

Functional characterization of tyrosine transport in fibroblast cells from healthy controls.

Human fibroblast cells are an advantageous model to study the transport of amino acids across cell membranes, since one can control the environmental factors. A major problem in all earlier studies is the lack of precise and detailed knowledge regarding the expression and functionality of tyrosine transporters in human fibroblasts. This motivated us to perform a systematic functional characterization of the tyrosine transport in fibroblast cells with respect to the isoforms of system-L (LAT1, LAT2, LAT3, LAT4), which is the major transporter of tyrosine. Ten (n=10) fibroblast cell lines from healthy volunteers were included in the study. Uptake of L-[U-14C] tyrosine in fibroblasts was measured using the cluster tray method in the presence and absence of excess concentrations of various combinations of inhibitors. This study demonstrated that LAT1 is involved in 90% of total uptake of tyrosine and also around 51% of alanine. Not more than 10% can be accounted for by LAT2, LAT3 and LAT4 isoforms. LAT2 seems to be functionally weak in uptake of tyrosine while LAT3 and LAT4 contributed around 7%. 10% could be contributed by system-A (ATA2 isoform). Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine transport through the LAT1 isoform has a higher affinity compared to system-L. In conclusion, the LAT1 isoform is the major transporter of tyrosine in human fibroblast cells. Competition between tyrosine and alanine for transport is shown to exist, probably between LAT1 and LAT2 isoforms. This study established fibroblast cells as a suitable experimental model for studying amino acid transport defects in humans.

Aberrant amino acid transport in fibroblasts from children with autism.

Autism is a developmental, cognitive disorder clinically characterized by impaired social interaction, communication and restricted behaviours. The present study was designed to explore whether an abnormality in transport of tyrosine and/or alanine is present in children with autism. Skin biopsies were obtained from 11 children with autism (9 boys and 2 girls) fulfilling the DSM-IV diagnostic criteria for autistic disorder and 11 healthy male control children. Transport of amino acids tyrosine and alanine across the cell membrane of cultured fibroblasts was studied by the cluster tray method. The maximal transport capacity, V(max) and the affinity constant of the amino acid binding sites, K(m), were determined. Significantly increased V(max) for alanine (p=0.014) and increased K(m) for tyrosine (p=0.007) were found in children with autism. The increased transport capacity of alanine across the cell membrane and decreased affinity for transport sites of tyrosine indicates the involvement of two major amino acid transport systems (L- and A-system) in children with autism. This may influence the transport of several other amino acids across the blood-brain-barrier. The significance of the findings has to be further explored.

The Camberwell assessment of need as an outcome measure in routine mental health care.

BACKGROUND: Subsidiary findings in several studies indicate that the standard summary scores (total number of needs, met needs and unmet needs) of the Camberwell Assessment of Need (CAN) may conceal important differences among patient populations at the item level of the measure. The aim of this study was to investigate whether changes in need and need status at the item level are adequately reflected by changes in the summary scores. METHODS: In a longitudinal design assessments of need in 1997 and 2003 of 192 outpatients (mean age 45.4 years, 78.1% psychotic disorders) in routine mental health care were compared. RESULTS: None of the summary scores changed between 1997 and 2003. This result, however, was contradicted by significant changes in needs at the item level. CONCLUSIONS: The summary scores conceal changes in need on the underlying items and thus is recommended not to be used as dependent measures when comparisons among populations or between points in time are of interest.

Support for limited brain availability of tyrosine in patients with schizophrenia.

Several mechanisms have been suggested to account for altered dopaminergic neurotransmission in schizophrenia. The brain is the only organ for which amino-acid transport is limited and competition for transport over the blood-brain barrier (BBB) occurs at physiological plasma concentrations. One line of research suggests that patients with schizophrenia have altered brain levels of the essential amino acid tyrosine, the precursor for the synthesis of dopamine. The most common hypothesis is that less tyrosine is available because of competition with elevated levels of other amino acids. By consequence, the synthesis of dopamine in the brain will decrease. In contrast, another line of evidence suggests a change in the affinity for one of the transport proteins. A limitation of this research has been that the systems for amino-acid transport across the BBB have not been fully characterized at a molecular or functional level. The L system is the major system for transport of tyrosine across cell membranes including the BBB. The A system is also involved in this transport. Earlier in-vitro studies using fibroblasts have demonstrated a normal L system in schizophrenia but nevertheless reduced tyrosine transport. The combination of molecular research, fibroblast techniques, and brain imaging provides a new basis for clinical research on the role of amino-acid membrane transport in schizophrenia.

Tyrosine transport in fibroblasts from healthy volunteers and patients with schizophrenia.

Aberrant tyrosine transport across the fibroblast membrane, as measured by lower Vmax and/or lower Km is a repeated finding in patients with schizophrenia. The aim of this study was to investigate the importance of two major transporters, the L- and A-systems and tyrosine transport in fibroblast cell lines from patients with schizophrenia and healthy volunteers. Fibroblast cell lines, n=6 from healthy volunteers and n=6 from patients with schizophrenia, were included in the study. Uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in absence and presence of inhibitors. The uptake of tyrosine by the L-system was evaluated with the inhibitor 2-aminobicyclo heptane-2-carboxylic acid (BCH) and the A-system with the inhibitor nonmetabolized methyl-aminoisobutyric acid (MeAIB). Using [14-C] MeAIB the functionality of system A isoform 2, ATA2, was tested. BCH inhibited the uptake of tyrosine with 90%, showing that tyrosine transport in fibroblasts is mainly transported by the L-system. Not more than 10% could be contributed by the A-system. Excess of MeAIB did not influence tyrosine kinetics. Moreover, MeAIB kinetics did not differ between the patients and the controls. In conclusion, aberrant tyrosine transport observed in patients with schizophrenia is probably linked to the one of the L-systems and does not seem to involve the ATA2 transporter.

The Need of Support and Service Questionnaire (NSSQ): a brief scale to assess needs in clients with long-term mental disabilities.

We present the Need of Support and Service Questionnaire (NSSQ), a new instrument developed to provide professionals in psychiatric care and community social services with a tool to assess needs of support and service in mentally disabled clients. The final version of the instrument was designed after comments from professionals in psychiatric care, community social services, and the clients and their relatives. A reliability study (test-retest, n=77), inter-rater (n=69) and a validity study (n=529) were performed. In the validity study, comparisons were done with the Camberwell Assessment of Need (CAN) scale, the Global Assessment of Functioning (GAF) scale and the Social and Occupational Functioning Assessment Scale (SOFAS). The test-retest and inter-rater reliability were 0.86 and 0.76, respectively. The percentage of agreement on the individual items ranged from 83.1% to 100.0% (test-retest) and 76.8% to 100.0% (inter-rater reliability). The corresponding kappa coefficients ranged from 0.63 to 1.00 (test-retest) and 0.33 to 1.00 (inter-rater reliability). The comparison between NSSQ and CAN items demonstrated high sensitivity and specificity as well as satisfactory likelihood ratios (LRs). The correlations between GAF and SOFAS scores and the number of needs of support, number of needs of service and the total number of needs of support and service were -0.49, -0.32 and -0.47, and -0.48, -0.26 and -0.45, respectively. All correlations were statistically significant (P<0.01). The results demonstrated that the psychometric characteristics of the NSSQ were satisfactory. Moreover, professionals without any formal training easily used it.

Needs assessed by psychiatric health care and social services in a defined cohort of clients with mental disabilities.

BACKGROUND: The identification of needs for support and service in clients with long-term mental disabilities is usually not done by staff personnel from both psychiatric care and social services. However, such a process is probably necessary in order to provide adequate psychiatric care and social services. AIMS: To estimate the prevalence of mentally disabled clients and investigate whether staff from psychiatric care and social services identified the same individuals and the same number of needs in the same areas. METHODS: Clients from a defined catchment area were identified during a three-month period. A questionnaire was developed to collect socio-demographic information and to assess needs for support and service. RESULTS: The study identified 1,290 clients with needs with a prevalence of 5.72/1000 inhabitants. More than half of the clients needed support in activities of daily living. Only 18.1% of the clients were identified by both organizations. In general, the staff from psychiatric care and social services identified the same needs at a group level. However, at the individual level, agreement was quite low. CONCLUSIONS: The staffs from both psychiatric care and social services are necessary to evaluate the needs of support and services in clients with mental disabilities.

Kinetics of tyrosine transport and cognitive functioning in schizophrenia.

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.

Factor structure in the Camberwell Assessment of Need.

BACKGROUND: In order to define needs for care of people with severe mental illness, the Camberwell Assessment of Need (CAN) is focused on measuring personal and social functioning. However, previous studies of the CAN have given inconsistent results in terms of what variables are actually being measured. AIMS: To investigate the factor structure of the CAN. METHOD: Assessments of 741 out-patients (mean age 45.5 years, 50% females) with severe mental illness (68% schizophrenia or other psychotic disorder) were used in an exploratory maximum likelihood factor analysis. RESULTS: Support was found for a three-factor model, comprising 13 of the 22 variables in the CAN, with the factors corresponding to functional disability (7 variables), social loneliness (3 variables) and emotional loneliness (3 variables). The remaining variables did not load on any factor. CONCLUSIONS: Exploratory factor analysis revealed three homogeneous dimensions in the CAN that may represent functional disability and two aspects of social health.

Clients with long-term mental disabilities in a Swedish county--conditions of life, needs of support and unmet needs of service provided by the public health and social service sectors.

OBJECTIVE: The purpose of the study was to identify and describe conditions of life and needs of support and public service for clients with a mental disability in a Swedish county population. METHODS: Public health care and social service providers identified clients and completed a questionnaire concerning the clients' conditions of life and their special needs. A consecutively recruited sample of clients completed a similar questionnaire. RESULTS: Totally, 1261 clients were identified. The prevalence of clients with mental disabilities was in the urban and rural areas, 6.4/1000 inhabitants and 4.5/1000 inhabitants, respectively. The most prevalent unmet need (42.9%) was to participate in social and scheduled activities. Almost half of the group was reported to need support in activities of daily living. Clients living in urban settings more often needed support with activities of daily living (P < 0.001), whereas clients living in rural settings more often needed support with job training (P < 0.001) or finding work (P < 0.01). Clients and psychiatric care providers reported the needs of the clients in the same areas; however, clients reported a fewer number of needs than did the care providers. CONCLUSIONS: By using both psychiatric care and social service providers, effective case findings of clients with a mental disability were possible to achieve. In general, there was high agreement between psychiatric care providers and clients regarding the clients' number of needs of support and their unmet needs of service. However, at the individual level, the agreement between client and psychiatric care providers was lower.

No association between a putative functional promoter variant in the dopamine beta-hydroxylase gene and schizophrenia.

OBJECTIVE: Disturbances in catecholamine transmission have been implicated in schizophrenia. Dopamine beta-hydroxylase catalyses the conversion of dopamine to norepinephrine in noradrenergic cells. We attempted to investigate a putative functional promoter polymorphism in the dopamine beta-hydroxylase gene (DBH) for association with schizophrenia. METHODS: Unrelated schizophrenic patients (n=155) and control subjects (n=436) were analysed with regard to the DBH -1021 C/T variant. RESULTS: No significant allele or genotype differences were found. CONCLUSIONS: The present results do not support a major involvement of the DBH gene in schizophrenia in the Swedish population investigated.

Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis.

OBJECTIVE: To further evaluate the controversial putative association between a Ser9Gly variant in the first exon of the dopamine D3 receptor gene (DRD3) and schizophrenia. METHODS: Swedish patients with schizophrenia ( n=156) and control subjects ( n=463) were assessed for the DRD3 Ser9Gly variant. Meta-analyses including previous and the present Swedish case-control results were performed. RESULTS: No significant difference between the Swedish patients and controls were found, but there was an association between DRD3 Ser9Gly Ser/Ser and homozygous genotypes and response to anti-psychotic drugs. This finding was supported by an incomplete meta-analysis. In a meta-analysis of all case-control studies comprising 8761 subjects the association between DRD3 Ser9Gly homozygosity and schizophrenia ( =4.96, degree of freedom=1, p <0.05, odds ratio=1.10, 95% confidence interval=1.01-1.20) persisted. However, the previously proposed association between the Ser/Ser genotype and schizophrenia was not significant (chi2 =2.71, degree of freedom=1, p>0.05, odds ratio=1.08, 95% confidence interval=0.99-1.17). CONCLUSIONS: Whereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia. Reasons for the discrepancies between prior studies are discussed.

Association study between dopamine D3 receptor gene variant and personality traits.

Dopamine receptor gene variation has been hypothesized to influence personality traits characterized by novelty seeking and related traits. We analyzed a dopamine D(3) receptor gene (DRD3) variant in a Swedish population (n = 373) investigated with one or more of several personality questionnaires. No significant relationships were found between DRD3 genotypes and any of the 15 Karolinska Scales of Personality (KSP) and five Health-relevant Personality 5 factor inventory (HP5i) scales. The DRD3 variant was associated with some scales related to novelty seeking: the Swedish universities Scales of Personality (SSP) Adventure Seeking and the revised NEO personality inventory (NEO-PI-R) Fantasy (O1) and Order (C2) scales. There were also associations with the Temperament and Character Inventory (TCI) Cooperativeness and Compassion (C4) scales. After correction for multiple testing, however, no significant difference remained. We conclude that the investigated DRD3 polymorphism does not have a major impact on personality in the investigated population.