Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF:a family based association study

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): Reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia

Background: Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages). Methods: Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity. Results: Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains. Conclusion: Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies. Copyright © 2010 International Psychogeriatric Association.

Neuropsychiatric symptoms in the prodromal stages of dementia

Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.

Examining carer stress in dementia: the role of subtype diagnosis and neuropsychiatric symptoms

INTRODUCTION: Caring for people with dementia incurs significant stress for carers. Stress has been related to the duration of caring role, the number of weekly hours provided and severity of cognitive impairment. What remains less clear is the impact of neuropsychiatric symptoms and subtype of dementia on carer stress and this study aimed to examine these. METHODS: Dementia carers were recruited for people with a range of dementia subtypes. Carers were interviewed using the Neuropsychiatric Inventory with the Carer Distress Scale. Cognitive fluctuations were assessed using the Dementia Cognitive Fluctuations Scale. All patients were also examined with The Cambridge Assessment for mental disorders in the elderly. RESULTS: Dementia diagnostic subtype, the presence of cognitive fluctuations and some neuropsychiatric symptoms (psychosis and mood disturbance) did predict carer stress (all at p < 0.01) but age, gender and severity of cognitive impairment did not (all p > 0.33). Carers of people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) experienced more stress than those caring for patients with Alzheimer's disease and vascular dementia. Carer stress was associated with higher levels of psychosis, mood disturbances, daytime sleep and cognitive fluctuations in the person with dementia. CONCLUSIONS: This study identified the significant impact on carers of providing care for people with DLB and PDD dementia subtypes and also highlighted the significant impact of providing care for patients with high levels of psychosis, mood disturbances and cognitive fluctuations.

Glial reduction in the subgenual prefrontal cortex in mood disorders

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann’s area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.

Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Anthropometric characteristics and the burden of altered nutritional status among neuropsychiatric patients at Zomba Mental Hospital in Zomba, Malawi

Objective To determine the prevalence of overnutrition and undernutrition among neuropsychiatric inpatients and outpatients at Zomba Mental Hospital in Zomba, Malawi. Methods In this analytical cross-sectional study (n = 239), data were collected from psychiatric patients who were either inpatients (n = 181) or outpatients (n = 58) at Zomba Mental Hospital, which is the largest mental health facility in Malawi. Information was collected about patient demographics, anthropometric data, dietary information, and tobacco and alcohol use, among other variables. Data were entered and analysed in SPSS 16.0 (SPSS Inc., Chicago, IL, USA). Means were generated and compared between male and female patients, and between inpatients and outpatients. Results The study recruited 158 male and 81 female patients, with mean ages of 31.24 ± 11.85 years and 33.08 ± 15.18 years (p = 0.328), respectively. Male patients were significantly taller (165.27 ± 7.25 cm) than female patients (155.30 ± 6.56 cm) (p < 0.001); were significantly heavier than females (60.02 ± 10.56 kg versus 55.64 ± 10.53 kg); and had a significantly lower mean body mass index (BMI) than females (21.87 ± 3.21 vs. 23.01 ± 3.78) (p = 0.016). Overweight and obese patients comprised 17.6% of the participants, and 8.8% were underweight. There were no significant differences in the prevalence of overweight, obesity, and underweight between male and female participants, or between inpatients and outpatients. Conclusion Our study—the first one of its kind in Malawi—characterised the anthropometry of neuropsychiatric patients at a major metal health facility in Malawi, and has shown a high proportion of overweight patients and a notable presence of underweight patients among them. Being overweight or obese is a risk factor for metabolic disorders. Being underweight may aggravate mental illness or disturb the effect of medication. There is need, therefore, to include nutrition screening and therapeutic or supplementary feeding as part of a comprehensive care and treatment plan for neuropsychiatric patients.

Upper body musculoskeletal disorders among Australian occupational therapy students

Although upper body musculoskeletal disorders (MSDs) represent an increasingly important issue for university students, few if any studies have targeted the occupational therapy faculty. Given this dearth of information, it was considered necessary to investigate a cross-section of Australian occupational therapy students by means of an established questionnaire survey. Completed replies were obtained from 95.7%, 100% and 97.7% (n = 44, 55 and 48) of students in the first, second and fourth years of a large occupational therapy school in northern Queensland, Australia.---------- The 12-month period prevalence of MSDs was as follows: neck (67.4%), shoulder (46.3%) and upper back (39.5%). Three-quarters of all students (75.5%) reported an MSD occurring in at least one of these body regions. Over half (56.5%) reported an MSD over 2 days' duration in the past year. Almost 40% (39.5%) reported an MSD that had affected their daily life, while one-quarter (25.2%) needed some type of treatment.---------- Logistic regression indicated that students aged over 21 years were almost four times more likely to report shoulder-related MSD (OR 3.7, 95%CI: 1.4-10.2). Year of study in the occupational therapy course was another important MSD correlate, with adjusted odds ratios ranging from 3.3 at the upper back (OR 3.3, 95%CI: 1.2-9.6) to 10.9 at the neck (OR 10.9, 95%CI: 3.2-43.8). Computer usage also incurred a certain degree of risk, with students who spent over 5 hours per week on the computer having an increased risk of MSD at the neck (OR 5.0, 95%CI: 1.3-21.5) and shoulder (OR 4.7, 95%CI: 1.4-18.3).---------- Overall, this study suggests that Australian occupational therapy students have a large burden from MSDs in the upper body region, even more so than other student groups and some working populations. Since the distribution of MSD risk is not uniform among them, interventions to help reduce these conditions need to be carefully targeted. Further longitudinal investigations would also be useful in determining the mechanisms and contributory factors for MSDs among this unique student population.

Interventions for co-occurring addictive and other mental disorders (AMDs)

While research on the management of co-occurring addictive and mental disorders (AMDs) has grown substantially in recent years, we still have little guidance on specific strategies. Consideration of epidemiological research and ethical principles can supplement existing clinical trials in providing a way forward. High frequencies of co-occurring disorders, equity of access for affected individuals and potential clashes between services in priorities and procedures, suggest that a stepped model of care by a single service may often be required. Typically, problems are multiple rather than dual, with potential for mutual influence, suggesting a need for interventions that are sensitive to and encompass complex co-occurring problems. Motivational problems are endemic, initial gains are often partial and unstable, and relapses potentially have serious consequences, suggesting a need for long-term, assertive follow-up. Principles such as these provide a solid framework for designing both services and interventions. However, there is a continuing need for controlled trials that unpack effective components of interventions, and increase their impact.

Mailed treatment to augment primary care for alcohol disorders : a randomised controlled trial

Introduction and Aims: Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods: A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3–6. Results: Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions: The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.

Integrated versus non-integrated management and care for clients with co-occurring mental health and substance use disorders : a qualitative systematic review of randomised controlled trials

The purpose of this paper is to conduct a qualitative review of randomised controlled trials in relation to the treatment of adults with co-occurring mental health and substance use disorder (MH/SUD). In particular, integrated approaches are compared with non-integrated approaches to treatment. Ten articles were identified for inclusion in the review. The findings are equivocal with regard to the superior efficacy of integrated approaches to treatment, although the many limitations of the studies need to be considered in our understanding of this finding. Clearly, this is an extremely challenging client group to engage and maintain in intervention research, and the complexity and variability of the problems render control particularly difficult. The lack of available evidence to support the superiority of integration is discussed in relation to these challenges. Much remains to be investigated with regard to integrated management and care for people with co-occurring and MH/SUD, particularly for specific combinations of dual diagnosis and giving consideration to the level of inter-relatedness between the disorders.

Demographic and clinical correlates of comorbid substance use disorders in psychosis : multivariate analyses from an epidemiological sample

Background: While there has been substantial research examining the correlates of comorbid substance abuse in psychotic disorders, it has been difficult to tease apart the relative importance of individual variables. Multivariate analyses are required, in which the relative contributions of risk factors to specific forms of substance misuse are examined, while taking into account the effects of other important correlates. Methods: This study used multivariate correlates of several forms of comorbid substance misuse in a large epidemiological sample of 852 Australians with DSMIII- R-diagnosed psychoses. Results: Multiple substance use was common and equally prevalent in nonaffective and affective psychoses. The most consistent correlate across the substance use disorders was male sex. Younger age groups were more likely to report the use of illegal drugs, while alcohol misuse was not associated with age. Side effects secondary to medication were associated with the misuse of cannabis and multiple substances, but not alcohol. Lower educational attainment was associated with cannabis misuse but not other forms of substance abuse. Conclusion: The profile of substance misuse in psychosis shows clinical and demographic gradients that can inform treatment and preventive research.