Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks—Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control.

Substance misuse in patients with schizophrenia : Epidemiology and management

Substance misuse in individuals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.

The experience of emotional expression in the context of social relations for people diagnosed with schizophrenia : a phenomenological explication

The experience of emotional expression in the context of social relations is not well understood for people diagnosed with schizophrenia. Early phenomenological research on the experience of people diagnosed with schizophrenia traditionally focussed on self experience in isolation from others, with later research explicating isolated aspects of self experience in relation to others. The current research aimed to focus on the progressive experience of emotional expression of people diagnosed with schizophrenia in relation to others over 12 months, in order to gain a broad spectrum of experience. This study involved unstructured interviews with 7 participants, an average of 4 times each, over a period of 12 months. Due to the unstructured nature of the interviews, a great breadth of experience was explicated. From the interviews there emerged 6 themes grouped together as a transition into, and 5 themes grouped together as a recovery from, symptoms associated with a diagnosis of schizophrenia. Special significance was given to the theme of relational confusion as an experience that provides an understanding of the relationship between social stressors and personal characteristics with responses that are associated with a diagnosis of schizophrenia. It was suggested that participants experienced themselves, including their distancing and isolating responses, as a part of a social system. The breadth of experiences that emerged afforded a framework of experiences within which prior phenomenological research findings on static moments of experience have been located. A more meaningful understanding of the transitioning into and recovery from the experiences associated with a diagnosis of schizophrenia will afford advances in mental health practice.

Schizophrenia Housing and Supportive Relationships

Schizophrenia can be a very disabling illness that affects between 0.5% and 1% of the population. This illness has a great personal impact on the individual sufferer, their family and friends. In addition, it makes significant demands on health services and the community in general. This paper reviews the literature on housing and supportive relationships for people with schizophrenia. The literature reports that people's experience of their schizophrenia is that it not only causes symptoms, but often impacts on their ability to maintain the basic resources in life. These resources include the ability to maintain reasonable quality housing, which seems to further impact negatively on their illness and their ability to maintain supportive social relationships. People with schizophrenia (and people in general) rely on their social relationships and family to maintain their mental health. The loss of social relationships and inability to maintain quality housing seem to be related - if people cannot maintain quality housing, they find it difficult to maintain supportive social relationships.

Non-pharmacological interventions in secondary schizophrenia

Schizophrenia may not be a single disease, but the result of a diverse set of related conditions. Modern neuroscience is beginning to reveal some of the genetic and environmental underpinnings of schizophrenia; however, an approach less well travelled is to examine the medical disorders that produce symptoms resembling schizophrenia. This book is the first major attempt to bring together the diseases that produce what has been termed 'secondary schizophrenia'. International experts from diverse backgrounds ask the questions: does this medical disorder, or drug, or condition cause psychosis? If yes, does it resemble schizophrenia? What mechanisms form the basis of this relationship? What implications does this understanding have for aetiology and treatment? The answers are a feast for clinicians and researchers of psychosis and schizophrenia. They mark the next step in trying to meet the most important challenge to modern neuroscience – understanding and conquering this most mysterious of human diseases.

A DRD2 polymorphism predicts PANSS score variability in schizophrenia patients treated with antipsychotics

Antipsychotic medications act as either antagonists or partial agonists of the dopamine D2 receptor (DRD2) and antipsychotic drugs vary widely in their binding affinity for the D2 receptor (Kapur and Seeman, 2000). The DRD2 957CNT (rs6277) polymorphism has previously been associated with schizophrenia (Lawford et al., 2005) and the T-allele of the 957CNT polymorphism is associated with reduced mRNA stability and synthesis of the dopamine D2 receptor (Duan et al., 2003). The aim of the study was to determine if the rs6277 polymorphism predicts some of the variability of positive and negative symptoms observed in schizophrenia patients being treated with antipsychotic medication.

HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association

Catechol-O-methyl transferase (COMT) encodes an enzyme involved in the metabolism of dopamine and maps to a commonly deleted region that increases schizophrenia risk. A non-synonymous polymorphism (rs4680) in COMT has been previously found to be associated with schizophrenia and results in altered activity levels of COMT. Using a haplotype block-based gene-tagging approach we conducted an association study of seven COMT single nucleotide polymorphisms (SNPs) in 160 patients with a DSM-IV diagnosis of schizophrenia and 250 controls in an Australian population. Two polymorphisms including rs4680 and rs165774 were found to be significantly associated with schizophrenia. The rs4680 results in a Val/Met substitution but the strongest association was shown by the novel SNP, rs165774, which may still be functional even though it is located in intron five. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. This association was slightly improved when males were analysed separately possibly indicating a degree of sexual dimorphism. Our results confirm that COMT is a good candidate for schizophrenia risk, by replicating the association with rs4680 and identifying a novel SNP association.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Schizophrenia and the progression of emotional expression in relation to others

Gaining an improved understanding of people diagnosed with schizophrenia has the potential to influence priorities for therapy. Psychosis is commonly understood through the perspective of the medical model. However, the experience of social context surrounding psychosis is not well understood. In this research project we used a phenomenological methodology with a longitudinal design to interview 7 participants across a 12-month period to understand the social experiences surrounding psychosis. Eleven themes were explicated and divided into two phases of the illness experience: (a) transition into emotional shutdown included the experiences of not being acknowledged, relational confusion, not being expressive, detachment, reliving the past, and having no sense of direction; and (b) recovery from emotional shutdown included the experiences of being acknowledged, expression, resolution, independence, and a sense of direction. The experiential themes provide clinicians with new insights to better assess vulnerability, and have the potential to inform goals for therapy.

Caregiving attachment in mothers with schizophrenia: Child and Youth Mental Health Service, Mater Misericordiae Health Services, South Brisbane, Australia

The assessment of parenting capacity and appropriate provision of services to assist parents with mental illness requires improved understanding of how a mental illness may affect the parent-child relationship. Mothers with mental illness may be defensive when providing self-report accounts of their parenting. Within the framework of attachment theory, this study developed a methodology for investigating the quality and characteristics of caregiving through exploration of the mothers' perceptions and strategies in managing her child at bedtime. Utilising questions derived from caregiving attachment research, five mothers with schizophrenia participated in a semi-structured interview concerning bedtime separation. In addition the mothers completed a modified standardised measure of attachment style, the Parent Bonding Instrument, to provide information regarding how they perceived their parenting style. The mothers demonstrated very poor understanding of their child's bedtime anxiety. They described difficulty being effective with bedtime strategies and attributed it to medication-induced fatigue. The interview data contrasted significantly with the Parent Bonding Instrument data in which the mothers did not identify concerns in themselves as caregivers. This study demonstrated the feasibility of a novel approach to gathering information regarding parenting from mothers with a diagnosis of schizophrenia.

Work-related subjective experiences among community residents with schizophrenia or schizoaffective disorder

Objective: To develop a self-report scale of subjective experiences of illness perceived to impact on employment functioning, as an alternative to a diagnostic perspective, for anticipating the vocational assistance needs of people with schizophrenia or schizoaffective disorders. Method: A repeated measures pilot study (n1 = 26, n2 = 21) of community residents with schizophrenia identified a set of work-related subjective experiences perceived to impact on employment functioning. Items with the best psychometric properties were applied in a 12 month longitudinal survey of urban residents with schizophrenia or schizoaffective disorder (n1 = 104; n2 = 94; n3 = 94). Results: Construct validity, factor structure, responsiveness, internal consistency, stability, and criterion validity investigations produced favourable results. Work-related subjective experiences provide information about the intersection of the person, the disorder, and expectations of employment functioning, which suggest new opportunities for vocational professionals to explore and discuss individual assistance needs. Conclusion: Further psychometric investigations of test-retest reliability, discriminant and predictive validity, and research applications in supported employment and vocational rehabilitation, are recommended. Subject to adequate psychometric properties, the new measure promises to facilitate exploring: individuals' specific subjective experiences; how each is perceived to contribute to employment restrictions; and the corresponding implications for specialized treatment, vocational interventions and workplace accommodations.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

KPNA3 variation is associated with schizophrenia, major depression, opiate dependence and alcohol dependence

KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.