The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland

Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) and dysbindin (DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3' region of the NRG1 gene yielded suggestive evidence of association (p=0.012 and p=0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population.     

Liver fat in the metabolic syndrome

BACKGROUND: The liver, once fatty, overproduces components of the metabolic syndrome, such as glucose and lipids. The amount of liver fat in subjects with and without the metabolic syndrome has not been determined. It is unknown which clinically available markers best reflect liver fat content. MEASUREMENTS: Components of the metabolic syndrome as defined by the International Diabetes Federation and liver fat content by proton magnetic resonance spectroscopy were measured in 271 nondiabetic subjects (162 women, 109 men). In addition, other features of insulin resistance (serum insulin, C-peptide), intraabdominal and sc fat by magnetic resonance imaging, and liver enzymes (serum alanine aminotransferase and serum aspartate aminotransferase) were measured. RESULTS: Liver fat was 4-fold higher in subjects with [n = 116; median 8.2% (interquartile range 3.2-18.7%)] than without [n = 155; 2.0% (1.0-5.0%); P < 0.0001] the metabolic syndrome. This increase in liver fat remained significant after adjusting for age, gender, and body mass index. All components of the metabolic syndrome correlated with liver fat content. The best correlate was waist in both women (r = 0.59, P < 0.0001) and men (r = 0.56, P < 0.0001). Liver fat correlated significantly with serum alanine aminotransferase (r = 0.39, P < 0.0001 for women; r = 0.44, P < 0.0001 for men) and aspartate aminotransferase (r = 0.27, P = 0.0005 for women; r = 0.31, P = 0.0012 for men) concentrations. The best correlates of liver fat were fasting serum insulin (r = 0.61; P < 0.0001 for both women and men) and C-peptide (r = 0.62; P < 0.0001 for both women and men). CONCLUSIONS: Liver fat content is significantly increased in subjects with the metabolic syndrome as compared with those without the syndrome, independently of age, gender, and body mass index. Of other markers, serum C-peptide is the strongest correlate of liver fat.     

European initiatives in postgraduate education in gerontology

This paper describes three innovative European initiatives in postgraduate education in gerontology. The first is the European Masters Program in Gerontology (EuMaG), developed as an interdisciplinary joint program, supported and delivered by 22 European universities. Second, the Nordplus initiative to increase mobility of students and staff in the field of gerontology in the European Nordic countries is elaborated. Third, two postgraduate Gerontology and Geriatrics programs offered by the European Centre of Gerontology and Geriatrics, University of Malta are presented. In 1995, the Centre was designated a WHO Collaborating Centre for healthy aging. To provide a context for these initiatives, a short overview is presented of developments in the European Higher Education Area, and the current state and recent developments in gerontology training in Europe is elaborated. The article concludes with discussion of the feasibility and sustainability of European internationalization efforts in education and training in gerontology.     

Implementing child-focused family nursing into routine adult psychiatric practice: hindering factors evaluated by nurses

Aims and objectives. The aim of this study is to describe nurses’ evaluations of factors that are hindering implementation of child‐focused family nursing (CF‐FN) into adult psychiatric practice. In addition, it explains the nurses’ evaluations of the hindering factors related to the hospital organizational structure, the individual nurse, nursing and family. Background. There is an increasing amount of families with dependent children in adult psychiatry. Although these families have long‐term benefits from preventive family interventions, implementation of CF‐FN is not routine mental health practice. Design and methods. Data were collected via a questionnaire‐survey completed by Registered Psychiatric Nurses (n = 223) and practical Mental Health Nurses (n = 88) from 45 adult psychiatric units in five Finnish university hospitals. The response rate was 51%. Results. Family‐related factors, such as families’ fears and lack of time, were considered as ‘most hindering’ to CF‐FN. Nurses who used a family‐centred approach and had further family education considered most of the factors as ‘less hindering’ in comparison to other nurses. Conclusion. To meet the needs of the families in mental health services, it is essential to develop nursing intervention methods such as CF‐FN. There is a need for further education and use of family‐centred care to develop this preventive approach. Relevance to clinical practice. The results of this study could be considered when developing mental health services and family interventions for families with parental mental illness.     

Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food

Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.     

Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques

OBJECT: The use of dural grafts is frequently unavoidable when tension-free dural closure cannot be achieved following neurosurgical procedures or trauma. Biodegradable collagen matrices serve as a scaffold for the regrowth of natural tissue and require no suturing. The aim of this study was to investigate the efficacy and safety of dural repair with a collagen matrix using different fixation techniques. METHODS: A total of 221 patients (98 male and 123 female; mean age 55.6 +/- 17.8 years) undergoing cranial (86.4%) or spinal (13.6%) procedures with the use of a collagen matrix dural graft were included in this retrospective study. The indications for use, fixation techniques, and associated complications were recorded. RESULTS: There were no complications of the dural graft in spinal use. Five (2.6%) of 191 patients undergoing cranial procedures developed infections, 3 of which (1.6%) were deep infections requiring surgical revision. There was no statistically significant relationship between the operative field status before surgery and the occurrence of a postoperative wound infection (p = 0.684). In the 191 patients undergoing a cranial procedure, cerebrospinal fluid (CSF) collection occurred in 5 patients (2.6%) and a CSF fistula in 5 (2.6%), 3 of whom (1.6%) required surgical revision. No patient who underwent an operation with preexisting CSF leakage had postoperative CSF leakage. Postoperative infection significantly increased the risk for postoperative CSF leakage. The collagen matrix was used without additional fixation in 124 patients (56.1%), with single fixation in 55 (24.9%), and with multiple fixations in 42 (19%). There were no systemic allergic reactions or local skin changes. Follow-up imaging in 112 patients (50.7%) revealed no evidence of any adverse reaction to the collagen graft. CONCLUSIONS: The collagen matrix is an effective and safe cranial and spinal dural substitute that can be used even in cases of an existing local infection. Postoperative deep infection increases the risk for CSF leakage.     

Chronic oral nicotine administration affects the circadian rhythm of dopamine and 5-hydroxytryptamine metabolism in the striata of mice

The effect of chronic oral administration of nicotine on the circadian rhythm of striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was studied in mice. Mice receiving nicotine in their drinking water and control mice drinking tap water were killed at 05:00, 11:00, 15:00 or 21:00 hours on the 50th day of chronic administration. The plasma concentrations of nicotine and cotinine, as well the striatal concentrations of DA, 5-HT and their metabolites 3,4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated. The largest plasma concentrations of nicotine and cotinine were found at 05:00, when they were more than double the concentrations found at the other times studied. This indicates that the mice, typically for nocturnal animals, consumed most of their daily drinking water at night. In the control mice, the striatal DA and 3-MT concentrations showed circadian variation and were lowest at 11:00. The 5-HIAA concentrations also varied, being highest at 11:00. In the nicotine-treated mice the circadian variations in striatal monoamines were altered and more pronounced than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5-HIAA concentrations in the nicotine-treated mice were significantly higher at 11:00 and the 5-HT concentrations at 21:00 than in the control mice, and, in contrast to the control mice, in the mice treated with chronic nicotine no circadian rhythm was observed in the 3-MT. No elevation of striatal DA metabolites occurred in the nicotine-treated mice compared with the controls when the plasma nicotine concentration was at its peak at 05:00. This finding suggests development of tolerance to the nicotine-induced changes in striatal DA metabolism. Further, our findings suggest that the chronic administration of nicotine in the drinking water of mice alters the circadian pattern of striatal DA and, to a lesser extent, that of 5-HT, and thus may affect the functions regulated by these transmitters.     

A formative evaluation to develop a school health nursing early intervention model for adolescent substance use

OBJECTIVE: To improve an early intervention (EI) triggered by the Adolescents' Substance Use Measurement (ADSUME) as a method to prevent substance abuse among adolescents. We assessed how ADSUME and EI work in practice and how EI could be improved. DESIGN AND SAMPLE: School health nurses (n=10) tested ADSUME and EI on 14- to 18-year-old adolescents (n=228). Six months later, these nurses and their professional partners were invited to assess EI in focus group interviews. METHODS: Four focus group interviews involving a total of 24 nurses and partners were implemented. Interview data were analyzed with qualitative content analysis. RESULTS: ADSUME concretized assessment, activated profound dialogue, and proved to be an important part of EI. It was important to assess the adolescent's resources in addition to the ADSUME score. EI worked well in confidential dialogues after the adolescent and the PHN reached a consensus on the level of concern about the adolescent's substance use. The recommended EI enabled individual brief intervention in all four stages of substance use, from abstinence or experimental use to hazardous use. CONCLUSIONS: EI was improved practically, and the contents of the intervention were reformulated. It is important to integrate EI with the preventive efforts of the school.