Cognitive Functioning in Alcohol and Other Substance Use Disorders in Young Adulthood : A Genetic Epidemiological Study

Alcohol and other substance use disorders (SUDs) result in great costs and suffering for individuals and families and constitute a notable public health burden. A multitude of factors, ranging from biological to societal, are associated with elevated risk of SUDs, but at the level of individuals, one of the best predictors is a family history of SUDs. Genetically informative twin and family studies have consistently indicated this familial risk to be mainly genetic. In addition, behavioral and temperamental factors such as early initiation of substance use and aggressiveness are associated with the development of SUDs. These familial, behavioral and temperamental risk factors often co-occur, but their relative importance is not well known. People with SUDs have also been found to differ from healthy controls in various domains of cognitive functioning, with poorer verbal ability being among the most consistent findings. However, representative population-based samples have rarely been used in neuropsychological studies of SUDs. In addition, both SUDs and cognitive abilities are influenced by genetic factors, but whether the co-variation of these traits might be partly explained by overlapping genetic influences has not been studied. Problematic substance use also often co-occurs with low educational level, but it is not known whether these outcomes share part of their underlying genetic influences. In addition, educational level may moderate the genetic etiology of alcohol problems, but gene-environment interactions between these phenomena have also not been widely studied. The incidence of SUDs peaks in young adulthood rendering epidemiological studies in this age group informative. This thesis investigated cognitive functioning and other correlates of SUDs in young adulthood in two representative population-based samples of young Finnish adults, one of which consisted of monozygotic and dizygotic twin pairs enabling genetically informative analyses. Using data from the population-based Mental Health in Early Adulthood in Finland (MEAF) study (n=605), the lifetime prevalence of DSM-IV any substance dependence or abuse among persons aged 21—35 years was found to be approximately 14%, with a majority of the diagnoses being alcohol use disorders. Several correlates representing the domains of behavioral and affective factors, parental factors, early initiation of substance use, and educational factors were individually associated with SUDs. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUDs were found to be largely independent of factors from other domains, whereas daily smoking and low education were still associated with SUDs after adjustment for behavioral and affective factors. Using a wide array of neuropsychological tests in the MEAF sample and in a subsample (n=602) of the population-based FinnTwin16 (FT16) study, consistent evidence of poorer verbal cognitive ability related to SUDs was found. In addition, participants with SUDs performed worse than those without disorders in a task assessing psychomotor processing speed in the MEAF sample, whereas no evidence of more specific cognitive deficits was found in either sample. Biometrical structural equation models of the twin data suggested that both alcohol problems and verbal ability had moderate heritabilities (0.54—0.72), and that their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). The relationship between educational level and alcohol problems, studied in the full epidemiological FT16 sample (n=4,858), was found to reflect both genetic correlation and gene-environment interaction. The co-occurrence of low education and alcohol problems was influenced by overlapping genetic factors. In addition, higher educational level was associated with increased relative importance of genetic influences on alcohol problems, whereas environmental influences played a more important role in young adults with lower education. In conclusion, SUDs, especially alcohol abuse and dependence, are common among young Finnish adults. Behavioral and affective factors are robustly related to SUDs independently of many other factors, and compared to healthy peers, young adults who have had SUDs during their life exhibit significantly poorer verbal cognitive ability, and possibly less efficient psychomotor processing. Genetic differences between individuals explain a notable proportion of individual differences in risk of alcohol dependence, verbal ability, and educational level, and the co-occurrence of alcohol problems with poorer verbal cognition and low education is influenced by shared genetic backgrounds. Finally, various environmental factors related to educational level in young adulthood moderate the relative importance of genetic factors influencing the risk of alcohol problems, possibly reflecting differences in social control mechanisms related to educational level.

Cognitive functioning and its heritability in bipolar I disorder

Bipolar I disorder is a severe psychiatric disorder characterized by episodic mood alterations that can be manic, depressive or mixed. Bipolar disorder seems to be highly genetic, but the etiology of this complex disorder has remained elusive. In recent years, studies have found that euthymic patients with bipolar disorder may have impairments particularly in executive functioning, verbal learning and memory. These impairments may be present also among some of the relatives of these patients, who may be vulnerable to the disorder. Using neuropsychological variables as endophenotypes, i.e. intermediate phenotypes between genes and the phenotypes, has been suggested to aid search for the etiological background of the disorder, but evidence is sparse on whether these variables fulfill the criteria for endophenotypes. The present thesis is part of the Genetic Epidemiology and Molecular Genetics of Severe Mental Disorders in Finland project. The specific aim was to investigate whether neuropsychological test variables would indicate genetic liability to the disorder and could therefore be regarded as endophenotypes. Thus, cognitive functions and their heritability were studied in bipolar I disorder patients and in their unaffected first-degree relatives from a population-based sample of families, comparing them to a population-based control group. In order to add homogeneity to the subgroups of bipolar disorder patients and their relatives, cognitive functions and their heritability were further studied in a group of families affected by bipolar I disorder only (bipolar families) and another group of families affected by both bipolar I disorder and schizophrenia or schizoaffective disorders (mixed families). Finally, the effect of processing speed on other cognitive functions was investigated. The study showed that especially executive functioning and processing speed fulfilled the endophenotype criteria. Impairments in these functions were found in bipolar patients and in their relatives irrespective of other severe psychopathology in the family. These functions were highly heritable in these families. Study also showed that generalized impairment in verbal memory may associate more with bipolar disorder than to vulnerability to other psychotic disorders, and be more related to fully developed disease; impairments in verbal learning and memory were found only in patients, and they were not found to be highly heritable. Finally, the most potential endophenotype, i.e. processing speed, seemed to contribute to a range of other cognitive dysfunctions seen in bipolar disorder patients. Processing speed, in particular, has also been shown to be a valid endophenotype in subsequent association analyses in psychiatric genetics in Finland and internationally. Information concerning cognitive impairments and their association with the psychosocial consequences of bipolar disorder is important in planning treatment. It is also important to understand and acknowledge that patients may have cognitive impairments that affect their everyday life. Psychosocial interventions and neuropsychological rehabilitation may supplement other conventional treatments for bipolar patients.

Toiseustarinat : äitinä suomalaisessa yhteiskunnassa

The focus of this study is to analyse the power relations on how our society normalizes motherhood and what kind techniques of power can be found in the motherhood culture. This study is an educational family research, and the aim of this study was to analyse those power frames that try to limit mothers in their motherhoods. There were seven mother participants in this study. They wrote essays about their experiences of motherhood in the Finnish society. The method of the research was qualitative, and the data was analysed by discourse analysis. The theoretical part of the research consists of distinguish in parenthood, family policy in families with children and motherhood in the Finnish society. The methodological approach is Michel Foucault´s analytic of power relations, and in this viewpoint I try to find out the different discourses of motherhood. In this study, mothers process against those assumptions of motherhood, which limit their freedom as acting in their role as mothers. Mothers locate themselves in the position of the Other that differs from those motherhood discourses which mothers were talking about. From the point of the Others , mothers processed their own motherhood, and they feel that they were always distinguished from the motherhood which they were expected to belong. Six categories were found in the motherhood assumptions: the norm of education, the myths of motherhood, the role assumptions in the motherhood, the norm of motherhood and discourse of good parenting, and discourse of project parenting. These discourses of motherhood assumptions make limitations, classifications and difference among motherhood. These assumptions were told by people for example in maternity clinics, first and security houses, judiciary systems, nursery, or by some other people. Mothers in this study made a comparison between the motherhood assumptions and themselves. In this study, mothers also criticize the culture of motherhood in the society and feel incompatible with the norms of motherhood around them. This may also increase mothers exhaustion.

Eteva Järvenpään perhepalvelukeskuksen lyhytaikaishoidon suunnittelun kehittäminen

Objectives. The thesis objective was to analyze how person-centred planning is applied to develop short term care in interaction between the disabled children, their families and the workers of the family service centre of Eteva Järvenpää. The thesis contributes to developing the methods of person-centred planning. I applied theoretical frameworks of activity theory and developmental work research, family-based work framework and disability phenomenon. The research questions were: What development needs did the families of disabled children have for the services? How were viewpoints of disabled children, their families and Eteva workers noticed in person-centred planning in the interaction between the disabled children, their families and Eteva workers? What disturbances and development challenges emerged during the person-centred planning? Methods. I first analysed the local history of the disability sector and the short term care to analyse challenges arising from the local history. The actural research material consisted of interviews with four families, two person-centred planning discussions and two discussions where the person-centred planning was reflected by the families.I used interaction voice analysis as defined by the activity theory and developmental work research. From the recorded interviews and discussions I analysed scripts, disturbances, innovation attempts and innovations. From the discussions I analysed also the interaction types (cooperation, coordination and communication). Results and conclusions. As problems, the families considered the scarce resources and the inflexibility of services. The challenges of developing the short term care were how to transfer information from short term care to home, how to develop activities for the children and how to take into account the individual needs of the children in the short term care. Both from the local history analysis and from the family interviews arised the conflict between caring and fulfilling the individual needs. In person-centred planning, the voice of the child was either interpreted by other family members or guided by family members or workers. I modelled the progress of person-centred planning in a two-dimensional coordination. Person-centred planning should be deepened in cooperation between the child, the family and the workers in everyday situations at home and during the short term care. The challenge is to expand person-centred planning to become cross-organizational cooperation connecting the actors of the child s service network in everyday life. Avainsanat Nyckelord - Keywords short term care, activity theory and developmental work research, person-centred planning, disability

Sotalapsuus, äitiys ja isoäitiys : Kertomuksia sotalapsuuden varjossa

War children were sent away to shelter without their parents to other Nordic countries, mainly to Sweden. The phenomenon was remarkable. During the Second World War nearly 80,000 children were sent from their homes by trains or boats. These children travelled to foster homes where they were placed with new parents looking after them. After the conclusion of the peace, for some months or sometimes years later, orders were given to send the children back to their families in Finland. Returning back to Finland and to their biological parents and families was not always easy. Deep bonds between the children and their foster families were created and leaving caused grief to those small travellers once again. In some cases, distances were created in the relations between Mothers and their daughters. Many had forgotten their Finnish, and returning to school proved difficult. Some of the war children felt rootlessness, a result of being torn away from their family and culture. The aim of this study is to describe how former war children became mothers by themselves, and later on grandmothers. The study also explores how they describe the meaning of the war and their childhood in their own parenthood and what were their experiences of time in foster homes. Seven former war children and three daughters were interviewed for this study. Interviews were biographical. A narrative approach and thematic reading (by Riessman 2008) has guided the analysis of the texts. According to the results of this study, the importance of having your own home , family and security in childhood relationships is significant. Caring and having responsibility for disadvantaged others was important for former war children. What come from the detailed experiences of the 'war childhood' most of all were the difficulties they found on returning to Finland. Some of them had become very attached to their foster parents. There were varying degrees of language problems among the returnees. Some of the interviewees had completely forgotten their native language. Given that, starting the school at home was difficult. They also remembered continuous travelling.When asked on the outcome of their relationship with their biological mother, most interviewees were happy, with a few experiencing some distance in this relationship. Security and being available to protect their children were important in their own motherhood and grand motherhood. In difficult family situations like divorce, they wanted to give their time and support for helping with grandchildren. Another important aspect in family life is interaction between all its members. Talking things through in families and also in War Child Associations was highly valued. However, talking of war childhood had been silenced in some families. In conclusion, the experiences of former war children should take in consideration when difficult situations between parents and children or children s positions in war zones are resolved. War children also have a lot to give for further educational study.

Dissection of the genetic background of childhood onset progressive myoclonic epilepsies

The progressive myoclonic epilepsies (PMEs) are a clinically and etiologically heterogeneous group of symptomatic epilepsies characterized by myoclonus, tonic-clonic seizures, psychomotor regression and ataxia. Different disorders have been classified as PMEs. Of these, the group of neuronal ceroid lipofuscinoses (NCLs) comprise an entity that has onset in childhood, being the most common cause of neurodegeneration in children. The primary aim of this thesis was to dissect the molecular genetic background of patients with childhood onset PME by studying candidate genes and attempting to identify novel PME-associated genes. Another specific aim was to study the primary protein properties of the most recently identified member of the NCL-causing proteins, MFSD8. To dissect the genetic background of a cohort of Turkish patients with childhood onset PME, a screen of the NCL-associated genes PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8 and CTSD was performed. Altogether 49 novel mutations were identified, which together with 56 mutations found by collaborators raised the total number of known NCL mutations to 364. Fourteen of the novel mutations affect the recently identified MFSD8 gene, which had originally been identified in a subset of mainly Turkish patients as the underlying cause of CLN7 disease. To investigate the distribution of MFSD8 defects, a total of 211 patients of different ethnic origins were evaluated for mutations in the gene. Altogether 45 patients from nine different countries were provided with a CLN7 molecular diagnosis, denoting the wide geographical occurrence of MFSD8 defects. The mutations are private with only one having been established by a founder-effect in the Roma population from the former Czechoslovakia. All mutations identified except one are associated with the typical clinical picture of variant late-infantile NCL. To address the trafficking properties of MFSD8, lysosomal targeting of the protein was confirmed in both neuronal and non-neuronal cells. The major determinant for this lysosomal sorting was identified to be an N-terminal dileucine based signal (9-EQEPLL-14), recognized by heterotetrameric AP-1 adaptor proteins, suggesting that MFSD8 takes the direct trafficking pathway en route to the lysosomes. Expression studies revealed the neurons as the primary cell-type and the hippocampus and cerebellar granular cell layer as the predominant regions in which MFSD8 is expressed. To identify novel genes associated with childhood onset PME, a single nucleotide polymorphism (SNP) genomewide scan was performed in three small families and 18 sporadic patients followed by homozygosity mapping to determine the candidate loci. One of the families and a sporadic patient were positive for mutations in PLA2G6, a gene that had previously been shown to cause infantile neuroaxonal dystrophy. Application of next-generation sequencing of candidate regions in the remaining two families led to identification of a homozygous missense mutation in USP19 for the first and TXNDC6 for the second family. Analysis of the 18 sporadic cases mapped the best candidate interval in a 1.5 Mb region on chromosome 7q21. Screening of the positional candidate KCTD7 revealed six mutations in seven unrelated families. All patients with mutations in KCTD7 were reported to have early onset PME, rapid disease progression leading to dementia and no pathologic hallmarks. The identification of KCTD7 mutations in nine patients and the clinical delineation of their phenotype establish KCTD7 as a gene for early onset PME. The findings presented in this thesis denote MFSD8 and KCTD7 as genes commonly associated with childhood onset symptomatic epilepsy. The disease-associated role of TXNDC6 awaits verification through identification of additional mutations in patients with similar phenotypes. Completion of the genetic spectrum underlying childhood onset PMEs and understanding of the gene products functions will comprise important steps towards understanding the underlying pathogenetic mechanisms, and will possibly shed light on the general processes of neurodegeneration and nervous system regulation, facilitating the diagnosis, classification and possibly treatment of the affected cases.

Molecular methods for the epidemiological analysis of methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae

Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae are major health problems worldwide, both found in symptomless carriage but also causing even life-threatening infections. The aim of this thesis was to characterise MRSA and S. pneumoniae in detail by using several molecular typing methods for various epidemiological purposes: clonality analysis, epidemiological surveillance, outbreak investigation, and virulence factor analysis. The characteristics of MRSA isolates from the strain collection of the Finnish National Infectious Disease Register (NIDR) and pneumococcal isolates collected from military recruits and children with acute otitis media (AOM) were analysed using various typing techniques. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and the detection of Panton-Valentine leukocidin (PVL) genes were performed for MRSA isolates. Pneumococcal isolates were analysed using antimicrobial susceptibility testing, serotyping, MLST, and by detecting pilus islet 1 (PI-1) and 2 (PI-2) genes. Several international community- and hospital-associated MRSA clones were recognised in Finland. The genetic diversity among MRSA FIN-4 isolates and among FIN-16 isolates was low. Overall, MRSA blood isolates from 1997 to 2006 were genetically diverse. spa typing was found to be a highly discriminatory, rapid and accurate typing method and it also qualifies as the primary typing method in countries with a long history of PFGE-based MRSA strain nomenclature. However, additional typing by another method, e.g. PFGE, is needed in certain situations to be able to provide adequate discrimination for epidemiological surveillance and outbreak investigation. An outbreak of pneumonia was associated with one pneumococcal strain among military recruits, previously healthy young men living in a crowded setting. The pneumococcal carriage rate after the outbreak was found to be exceptionally high. PI-1 genes were detected at a rather low prevalence among pneumococcal isolates from children with AOM. However, the study demonstrated that PI-1 has existed among pneumococcal isolates prior to pneumococcal conjugate vaccine and the increased antimicrobial resistance era. Moreover, PI-1 was found to associate with the serotype rather than the genotype. This study adds to our understanding of the molecular epidemiology of MRSA strains in Finland and the importance of an appropriate genotyping method to be able to perform high-level laboratory-based surveillance of MRSA. Epidemiological and molecular analyses of S. pneumoniae add to our knowledge of the characteristics of pneumococcal strains in Finland.

Kielellinen erityisvaikeus : oirekuva ja familiaalisuus potilasasiakirjojen perusteella

Goals. Specific language impairment (SLI) has a negative impact on child s speech and language development and interaction. Disorder may be associated with a wide range of comorbid problems. In clinical speech therapy it is important to see the child as a whole so that the rehabilitation can be targeted properly. The aim of this study was to describe the linguistic-cognitive and comorbid symptoms of children with SLI at the age of five, as well as to provide an overwiew of the developmental disorders in the families. The study is part of a larger research project, which will examine paths of development and quality of life of children with SLI as young adults. Methods. The data consisted of patient documents of 100 5-year old children, who were examined in Lastenlinna mainly at 1998. Majority of the subjects were boys, and children s primary diagnosis was either F80.1 or F80.2, which was most common, or both. The diagnosis and the information about the linguistic-cognitive status and comorbid symptoms were collected from reports of medical doctors and experts of other fields, as well as mentions related to familiality. Linguistic-cognitive symptoms were divided into subclasses of speech motor functions, prosessing of language, comprehension of language and use of language. Comorbid symptoms were divided into subclasses of interaction, activity and attention, emotional and behavior problems and neurologic problems. Statistical analyses were based mainly on Pearson s Chi Square test. Results and conclusions. Problems in language processing and speech motor functions were most common of the linguistic-cognitive symptoms. Most of the children had symptoms from two or three symptom classes, and it seemed that girls had more symptoms than boys. Usually children did not have any comorbid symptoms, or had them from one or three symptom classes. Of the comorbid symptoms the most prevalent ones were problems in activity and attention and neurological symptoms, which consisted mostly of motoric and visuomotoric symptoms. The most common of the comorbid diagnoses was F82, specific developmental disorder of motor function. According to literature children with SLI may have problems in mental health, but the results of this study did not confirm that. Children with diagnosis F80.2 had more linguistic-cognitive and comorbid symptoms than children with diagnosis F80.1. The cluster analyses based on all the symtoms revealed four subgroups of the subjects. Of the subjects 85 percent had a positive family history of developmental disorders, and the most prevalent problem in the families was delayed speech development. This study outlined the symptom profile of children with SLI and laid a foundation for the future longitudinal study. The results suggested that there are differences between linguistic-cognitive symptoms of boys and girls, which is important to notice especially when assessing and diagnosing children with SLI.

Koti keskellä kaupunkia : Keskusta lapsiperheen asuinalueena, esimerkkeinä Tukholma ja Helsinki

Families with children have traditionally moved to suburbs. In the last 20 years a modest counter process has however been recognized. Families with an urban lifestyle stay in the city centres. This study looks at the phenomenon through two cases, Stockholm and Helsinki. In the first case it has already been observed that the city centre has grown in popularity among families with children. Therefore it serves as a basis for the study and as well as a point of comparison. Stockholm’s city centre is expanding as new neighbourhoods have been built and are being planned. In the city centre of Helsinki the building of two large neighbourhoods for 30 000 inhabitants will start in a few years. The first aim of the study is to look closer at what has really happened in the city centre of Stockholm, why families choose to live there with their children and how the City of Stockholm has reacted to the change. The main sources of information are secondary sources, statistics and interviews with planners, politicians and experts in the field. The main object is to look at the situation in the city centre of Helsinki. Can a preference for urban residential environments be observed in Helsinki? What are the reasons for a family to choose the city centre as a living place? How does the everyday life of a family in the city centre appear? How are these families taken into account in the planning of the city? The main sources of information here are statistics, interviews with dwellers in the neighbourhood Kruununhaka and interviews with planners. In Stockholm the birth rate has grown constantly during the 2000s and is highest in the city centre. Some of the families still move elsewhere, but many of them do not. One of the most important reasons for living in the city centre is short working distances which give working parents more time with their children. Another reason is a preference of an urban, active lifestyle. Families prefer to live close to everything, childcare, schools, shops and entertainments. The popularity of the city centre among families with children has taken politicians and planners by surprise. Helsinki has not experienced a baby boom like Stockholm. However the negative changes in the birth rate have been more modest in the central areas than in the suburbs. Statistics show, that many families move away from the city centre as the children grow. Families who stay in the city centre especially appreciate closeness to public and private services and good public transportation which means that they are not dependent on using the car. Further they find that the city centre has a tolerant climate and is a safe and beautiful place to live in. The families enjoy the social life of the neighbourhood and feel that it makes a good climate to raise children in. However they are concerned with traffic safety and the lack of stimulus in the playgrounds of the neighbourhood parks. Two large neighbourhoods with homes for about 30 000 inhabitants are now planned in the former Port Districts in the city centre of Helsinki. The other one, Jätkäsaari has been planned to become an attractive alternative for families with children. Traffic safety has been one of the main objects for the planning. The other, Kalasatama, has been planned to attract all groups in society.

The decline of malaria in Finland – the impact of the vector and social variables

Background: Malaria was prevalent in Finland in the 18th century. It declined slowly without deliberate counter-measures and the last indigenous case was reported in 1954. In the present analysis of indigenous malaria in Finland, an effort was made to construct a data set on annual malaria cases of maximum temporal length to be able to evaluate the significance of different factors assumed to affect malaria trends. Methods: To analyse the long-term trend malaria statistics were collected from 1750–2008. During that time, malaria frequency decreased from about 20,000 – 50,000 per 1,000,000 people to less than 1 per 1,000,000 people. To assess the cause of the decline, a correlation analysis was performed between malaria frequency per million people and temperature data, animal husbandry, consolidation of land by redistribution and household size. Results: Anopheles messeae and Anopheles beklemishevi exist only as larvae in June and most of July. The females seek an overwintering place in August. Those that overwinter together with humans may act as vectors. They have to stay in their overwintering place from September to May because of the cold climate. The temperatures between June and July determine the number of malaria cases during the following transmission season. This did not, however, have an impact on the longterm trend of malaria. The change in animal husbandry and reclamation of wetlands may also be excluded as a possible cause for the decline of malaria. The long-term social changes, such as land consolidation and decreasing household size, showed a strong correlation with the decline of Plasmodium. Conclusion: The indigenous malaria in Finland faded out evenly in the whole country during 200 years with limited or no counter-measures or medication. It appears that malaria in Finland was basically a social disease and that malaria trends were strongly linked to changes in human behaviour. Decreasing household size caused fewer interactions between families and accordingly decreasing recolonization possibilities for Plasmodium. The permanent drop of the household size was the precondition for a permanent eradication of malaria.