Ancient Philosophers on Mental Illness

This dissertation is about ancient philosophers notions of mental illness, from Plato onwards. Mental illness here means disorders that, in ancient medical thought, were believed to originate in the body but to manifest themselves predominantly through mental symptoms. These illnesses were treated by physical means, which were believed to address the bodily cause of the illness, conceived of as an elemental imbalance or a state of cephalic stricture , for example. Sometimes the mental symptoms were addressed directly by psychotherapeutic means. The first and most important question explored concerns how the ancient philosophers responded to the medical notion of mental illness, and how they explained such illnesses in their theories of physiology and psychology. Although the illnesses are seldom discussed extensively, the philosophers were well aware of their existence and regarded their occurrence an indication of the soul s close dependence on the body. This called for a philosophical account. The second question addressed has to do with the ancient philosophers role as experts in mental problems of a non-medical kind, such as unwanted emotions. These problems were dubbed diseases of the soul , and the philosophers thus claimed to be doctors of the soul. Although the distinction between mental illnesses and diseases of the soul was often presented as rather obvious, there was some vagueness and overlap. There is still a third question that is explored, concerning the status of both mental illnesses and diseases of the soul as unnatural conditions, the role of the human body in the philosophical aetiologies of evil, and the medico-philosophical theories of psycho-physiological temperaments. This work consists of an introduction and five main chapters, focusing on Plato, Aristotle, the Stoics and Galen, and the Sceptics, the Epicureans and later Platonists. The sources drawn on are the original Greek and Latin philosophical and medical texts. It appears that the philosophers accepted the medical notion of mental illness, but interpreted it in various ways. The differences in interpretation were mostly attributable to differences in their theories of the soul. Although the distinction between mental illness and diseases of the soul was important, marking the boundary between the fields of expertise of medicine and philosophy, and of the individual s moral responsibilities, the problematic aspects of establishing it are discussed rather little in ancient philosophy. There may have been various reasons for this. The medical descriptions of mental illness are often extreme, symptoms of the psychotic type excluding the possibility of the condition being of the non-medical kind. In addition, the rigid normativeness of ancient philosophical anthropologies and their rigorous notion of human happiness decreased the need to assess the acceptability of individual variation in their emotional and intellectual lives and external behaviour.

Finnish Homicides and Mental Disorders: An investigation of offense and offender characteristics

Although the majority of people with mental illness are not violent, scientific studies over the last decades show that certain psychiatric disorders increase the risk of violent behavior, including homicide. This thesis examined crime scene behaviors and offender background characteristics among mentally ill Finnish homicide offenders. Previously, homicide crime scene behaviors have been investigated in relation to offender demographic characteristics, whereas this study compares the behaviors of offenders with various mental illnesses. The study design was a retrospective chart review of the forensic psychiatric statements of Finnish homicide offenders. The work consists of four substudies. The aims of the study were as follows: To describe differences in the childhood and family backgrounds as well as in the adolescent and adult adjustment of Finnish homicide offenders belonging to different diagnostic categories (schizophrenia, personality disorder, alcoholism, drug addiction or no diagnosis). Further, the study examined associations between the crime scene behaviors and mental status of these offenders. Also, the distinguishing characteristics between two groups of offenders with schizophrenia were examined: early starters, who present antisocial behavior before the onset of schizophrenia, and late starters, who first offend after the onset of mental disorder. Finally, it was investigated how the use of excessive violence is associated with clinical and circumstantial variables as well as offender background characteristics among homicide offenders with schizophrenia. The main findings of the study can be summarized as follows. First, offenders with personality disorder or drug addiction had experienced multiple difficulties in their early environments: both family and individual problems were typical. Offenders with schizophrenia were relatively well-adjusted in childhood compared to the other groups. However, in adolescence and adulthood, social isolation, withdrawal and other difficulties attributable to these offenders illness became evident. In several aspects, offenders with alcohol dependency resembled offenders with no diagnosis in that these offenders had less problematic backgrounds compared to other groups. Second, the results showed that crime scene behaviors, victim gender and the victim-offender relationship differ between the groups. In particular, offenders with a diagnosis of schizophrenia or drug addiction have some unique features in their crime scene behaviors and choice of victims. Offenders with schizophrenia were more likely to kill a blood relative, to use a sharp weapon and to injure the victim s face. Drug addiction was associated with stealing from the victim and trying to cover up the body. Third, the results suggest that the offense characteristics of early- and late-start offenders with schizophrenia differ only modestly. However, several significant differences between the groups were found in characteristics of offenders: early starters had experienced a multitude of problems in their childhood surroundings and also later in life. Fourth, violent acts where the offender did not commit the offense alone or had previous homicidal history were predictive of excessive violence among offenders with schizophrenia. Positive psychotic symptoms did not predict the use of excessive violence. Nearly one third of the cases in the sample involved multiple and severe violence, including features such as sadism, mutilation, sexual components or extreme stabbing. In sum, mentally disordered homicide offenders are heterogeneous in their offense characteristics as well as their background characteristics. Empirically based information on how the offender s mental state is associated with specific crime scene behaviors can be utilized within the police force in developing methods of prioritizing suspects in unsolved homicide cases. Also, these results emphasise the importance of early interventions for problem families and children at risk of antisocial behavior. They may also contribute to the development of effective treatment for violent offenders.

"Secoituxesta järjettömäin luondocappalden canssa" : Perversiot, oikeuselämä ja kansankulttuuri 1700-luvun Suomessa

Bestiality was in the 18th century a more difficult problem in terms of criminal policy in Sweden and Finland than in any other Christian country in any other period. In the legal history of deviant sexuality, the phenomenon was uniquely widespread by international comparison. The number of court cases per capita in Finland was even higher than in Sweden. The authorities classified bestiality among the most serious crimes and a deadly sin. The Court of Appeal in Turku opted for an independent line and was clearly more lenient than Swedish courts of justice. Death sentences on grounds of bestiality ended in the 1730s, decades earlier than in Sweden. The sources for the present dissertation include judgment books and Court of Appeal decisions in 253 cases, which show that the persecution of those engaging in bestial acts in 18th century Finland was not organised by the centralised power of Stockholm. There is little evidence of local campaigns that would have been led by authorities. The church in its orthodoxy was losing ground and the clergy governed their parishes with more pragmatism than the Old Testament sanctioned. When exposing bestiality, the legal system was compelled to rely on the initiative of the public. In cases of illicit intercourse or adultery the authorities were even more dependent on the activeness of the local community. Bestiality left no tangible evidence, illegitimate children, to betray the crime to the clergy or secular authorities. The moral views of the church and the local community were not on a collision course. It was a common view that bestiality was a heinous act. Yet nowhere near all crimes came to the authorities' knowledge. Because of the heavy burden of proof, the legal position of the informer was difficult. Passiveness in reporting the crime was partly because most Finns felt it was not their place to intervene in their neighbours' private lives, as long as that privacy posed no serious threat to the neighbourhood. Hidden crime was at least as common as crime more easily exposed and proven. A typical Finnish perpetrator of bestiality was a young unmarried man with no criminal background or mental illness. The suspects were not members of ethnic minorities or marginal social groups. In trials, farmhands were more likely to be sentenced than their masters, but a more salient common denominator than social and economical status was the suspects' young age. For most of the defendants bestiality was a deep-rooted habit, which had been adopted in early youth. This form of subculture spread among the youth, and the most susceptible to experiment with the act were shepherds. The difference between man and animal was not clear-cut or self-evident. The difficulty in drawing the line is evident both in legal sources and Finnish folklore. The law that required that the animal partners be slaughtered led to the killing of thousands of cows and mares, and thereby to substantial material losses to their owners. Regarding bestiality as a crime against property motivated people to report it. The belief that the act would produce human-animal mongrels or that it would poison the milk and the meat horrified the public more than the teachings of the church ever could. Among the most significant aspects in the problems regarding the animals is how profoundly different the worldview of 18th century people was from that of today.

Molecular Genetics of Schizophrenia and Related Intermediate Phenotypes in a Founder Population

Schizophrenia, affecting about 1% of population worldwide, is a severe mental disorder characterized by positive and negative symptoms, such as psychosis and anhedonia, as well as cognitive deficits. At present, schizophrenia is considered a complex disorder of neurodevelopmental origin with both genetic and environmental factors contributing to its onset. Although a number of candidate genes for schizophrenia have been highlighted, only very few schizophrenia patients are likely to share identical genetic liability. This study is based on the nation-wide schizophrenia family sample of the National Institute for Health and Welfare, and represents one of the largest and most well-characterized familial series in the world. In the first part of this study, we investigated the roles of the DTNBP1, NRG1, and AKT1 genes in the background of schizophrenia in Finland. Although these genes are associated with schizophrenia liability in several populations, any significant association with clinical diagnostic information of schizophrenia remained absent in our sample of 441 schizophrenia families. In the second part of this study, we first replicated schizophrenia linkage on the long arm of chromosome 7 in 352 schizophrenia families. In the following association analysis, we utilized additional clinical disorder features and intermediate phenotypes – endophenotypes - in addition to diagnostic information from altogether 290 neuropsychologically assessed schizophrenia families. An intragenic short tandem repeat allele of the regional RELN gene, supposed to play a role in the background of several neurodevelopmental disorders, showed significant association with poorer cognitive functioning and more severe schizophrenia symptoms. Additionally, this risk allele was significantly more prevalent among the individuals affected with schizophrenia spectrum disorders. We have previously identified linkage of schizophrenia and its cognitive endophenotypes on the long arms of chromosomes 2, 4, and 5. In the last part of this study, we selected altogether 104 functionally relevant candidate genes from the linked regions. We detected several promising associations, of which especially interesting are the ERBB4 gene, showing association with the severity of schizophrenia symptoms and impairments in traits related to verbal abilities, and the GRIA1 gene, showing association with the severity of schizophrenia symptoms. Our results extend the previous evidence that the genetic risk for schizophrenia is at least partially mediated via the effects of the candidate genes and their combinations on relevant brain systems, resulting in alterations in different disorder domains, such as the cognitive deficits.

The molecular basis of Marinesco-Sjögren syndrome

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia due to cerebellar cortical atrophy, infantile- or childhood-onset bilateral cataracts, progressive myopathy, and mild to severe mental retardation. Additional features include hypergonadotropic hypogonadism, various skeletal abnormalities, short stature, and strabismus. The neuroradiologic hallmarks are hypoplasia of both the vermis and cerebellar hemispheres. The histopathologic findings include severe cerebellar atrophy and loss of Purkinje and granule cells. The common pathologic findings in muscle biopsy are variation in muscle fiber size, atrophic fibers, fatty replacement, and rimmed vacuole formation. The presence of marked cerebellar atrophy with myopathy distinguishes MSS from another rare syndrome, the congenital cataracts, facial dysmorphism, and neuropathy syndrome (CCFDN). Previously, work by others had resulted in the identification of an MSS locus on chromosome 5q31. A subtype of MSS with myoglobinuria and neuropathy had been linked to the CCFDN locus on chromosome 18qter, at which mutations in the CTDP1 gene had been identified. We confirmed linkage to the previously identified locus on chromosome 5q31 in two Finnish families with eight affected individuals, reduced the critical region by fine-mapping, and identified SIL1 as a gene underlying MSS. We found a common homozygous founder mutation in all Finnish patients. The same mutation was also present in patient samples from Norway and Sweden. Altogether, we identified eight mutations in SIL1, including nonsense, frameshift, splice site alterations, and one missense mutation. SIL1 encodes a nucleotide exchange factor for the endoplasmic reticulum (ER) resident heat-shock protein 70 chaperone GRP78. GRP78 functions in protein synthesis and quality control of the newly synthesized polypeptides. It senses and responds to stressful cellular conditions. We showed that in mice, SIL1 and GRP78 show highly similar spatial and temporal tissue expression in developing and mature brain, eye, and muscle. Studying endogenous proteins in mouse primary hippocampal neurons, we found that SIL1 and GRP78 colocalize and that SIL1 localizes to the ER. We studied the subcellular localization of two mutant proteins, a missense mutant found in two patients and an artificial mutant lacking the ER retrieval signal, and found that both mutant proteins formed aggregates within the ER. Well in line with our findings and the clinical features of MSS, recent work by Zhao et al. showed that a truncation of SIL1 causes ataxia and cerebellar Purkinje cell loss in the naturally occurring woozy mutant mouse. Prior to Purkinje cell degeneration, the unfolded protein response is initiated and abnormal protein accumulations are present. MSS thus joins the group of protein misfolding and accumulation diseases. These findings highlight the importance of SIL1 and the role of the ER in neuronal function and survival. The results presented in this thesis provide tools for the molecular genetic diagnostics of MSS and give a basis for future studies on the molecular pathogenesis of MSS. Understanding the mechanisms behind this pleiotropic syndrome may provide insights into more common forms of ataxia, myopathy, and neurodegeneration.

Search For Susceptibility Genes In Schizophrenia

Schizophrenia is a severe mental disorder affecting 0.4-1% of the population worldwide. It is characterized by impairments in the perception of reality and by significant social or occupational dysfunction. The disorder is one of the major contributors to the global burden of diseases. Studies of twins, families, and adopted children point to strong genetic components for schizophrenia, but environmental factors also play a role in the pathogenesis of disease. Molecular genetic studies have identified several potential positional candidate genes. The strongest evidence for putative schizophrenia susceptibility loci relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1), but studies lack impressive consistency in the precise genetic regions and alleles implicated. We have studied the role of three potential candidate genes by genotyping 28 single nucleotide polymorphisms in the DNTBP1, NRG1, and AKT1 genes in a large schizophrenia family sample consisting of 441 families with 865 affected individuals from Finland. Our results do not support a major role for these genes in the pathogenesis of schizophrenia in Finland. We have previously identified a region on chromosome 5q21-34 as a susceptibility locus for schizophrenia in a Finnish family sample. Recently, two studies reported association between the γ-aminobutyric acid type A receptor cluster of genes in this region and one study showed suggestive evidence for association with another regional gene encoding clathrin interactor 1 (CLINT1, also called Epsin 4 and ENTH). To further address the significance of these genes under the linkage peak in the Finnish families, we genotyped SNPs of these genes, and observed statistically significant association of variants between GABRG2 and schizophrenia. Furthermore, these variants also seem to affect the functioning of the working memory. Fetal events and obstetric complications are associated with schizophrenia. Rh incompatibility has been implicated as a risk factor for schizophrenia in several epidemiological studies. We conducted a family-based candidate-gene study that assessed the role of maternal-fetal genotype incompatibility at the RhD locus in schizophrenia. There was significant evidence for an RhD maternal-fetal genotype incompatibility, and the risk ratio was estimated at 2.3. This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia. In conclusion, in this thesis we found evidence that one GABA receptor subunit, GABRG2, is significantly associated with schizophrenia. Furthermore, it also seems to affect to the functioning of the working memory. In addition, an RhD maternal-fetal genotype incompatibility increases the risk of schizophrenia by two-fold.

Psykoottisen mielenterveyspotilaan uskonnonvapaus

Tämän tutkimuksen tarkoituksena on selvittää psykoottisen mielenterveyspotilaan uskonnonvapautta. Tutkimuskysymyksiä on kolme: Millä perusteilla psykoottisen potilaan uskonnonvapaus on turvattu ja millä perusteilla sitä rajoitetaan? Miten psykoottinen ja uskonnollinen todellisuudentulkinta eroavat toisistaan? Vaarantaako psykiatriseen todellisuudentulkintaan perustuva hoito potilaan negatiivisen uskonnonvapauden eli oikeuden elää ilman uskontoa? Tutkimusmetodina on systemaattinen analyysi. Lähteet ovat perustusoikeudet, mielenterveyslaki, potilaslaki, YK:n Principles for the protection of persons with mental illness and the improvement of mental health care, Maailman psykiatriyhdistyksen Madridin julistus ja Suomen mielenterveysseuran Mielenterveyspotilaan oikeudet. Uskonnonvapautta tarkastellaan tässä tutkimuksessa kahden eri vapauskäsityksen näkökulmasta: ulkoisena vapautena, joka edellyttää kompetenssia ja autenttisuutta, sekä ulkoisen ja sisäisen vapauden summana, johon kompetenssi ja autenttisuus sisältyvät. Psykoottisella potilaalla on ihmisyytensä ja kansalaisuutensa perusteella lähtökohtaisesti täysi uskonnonvapaus, mutta sitä voidaan rajoittaa. Jos uskonnonvapaus ymmärretään ulkoiseksi vapaudeksi, rajoittaa psykoottisen potilaan uskonnonvapautta tahdosta riippumattomassa hoidossa hänen terveytensä ja turvallisuutensa suojaaminen. Uskonnonvapauden rajoittaminen voidaan perustella sillä, ettei psykoottinen potilas täytä uskonnonvapauden edellytyksiä eli kompetenssia ja autenttisuutta, sillä, että potilaan terveyteen ja turvallisuuteen liittyvät oikeudet priorisoidaan uskonnonvapauden yläpuolelle sekä sillä, että pyritään terveyshyötyyn. Jos uskonnonvapaus ymmärretään ulkoisen ja sisäisen vapauden summaksi, on psykoosi uskonnonvapautta rajoittava tekijä, koska se tekee yksilöstä epäautenttisen ja puuttuu hänen kompetenssiinsa. Psykoosin (myös tahdosta riippumaton) hoito voidaan ymmärtää tällöin yritykseksi palauttaa uskonnonvapaus. Rajoittamalla ulkoista uskonnonvapautta pyritään maksimoimaan ulkoisen ja sisäisen uskonnonvapauden summa. Vaikka psykoottisella ja uskonnollisella todellisuudentulkinnalla on yhtäläisyyksiä, niiden toisistaan erottaminen on tärkeää, koska yksilöllä, jonka todellisuudentulkinta määritellään psykoottiseksi, on oikeus saada hoitoa, kun taas yksilön uskonnollista todellisuudentulkintaa suojaa uskonnonvapaus eikä sitä saa hoitaa sairautena. Lähteiden mukaan psykoottisen ja uskonnollisen todellisuudentulkinnan toisistaan erottaminen diagnostisten kriteerien ja lääketieteellisen tiedon avulla on lääkärin tehtävä. Tutkimuksessani esitän kaksi periaatetta, joiden avulla todellisuudentulkinnat voidaan erottaa toisistaan. Yksinäinen puu ei pala -periaatteen mukaan yksilön todellisuudentulkinta on uskonnollinen, mikäli se jaetaan jossain yhteisössä. Hedelmistään puu tunnetaan -periaatteen mukaan yksilön todellisuudentulkinta on uskonnollinen, mikäli sen terveydelliset ja sosiaaliset seuraukset ovat hyvät. Antipsykiatrinen kritiikki väittää psykiatrian olevan uskonto. Jos väite on tosi, puututaan tahdosta riippumattomassa hoidossa yksilön oikeuteen elää ilman uskontoa, sillä ko. hoidossa olevan psykoottisen potilaan on pakko suostua siihen, että häntä hoidetaan psykiatrian arvojen ja todellisuudentulkinnan mukaan. Vaikuttaa kuitenkin siltä, että jos psykiatria määritellään uskonnoksi, uskonnon käsite kärsii inflaation. Koska psykoottisen potilaan uskonnonvapaus on pohjimmiltaan eettinen kysymys, on tärkeää myöntää psykiatrian arvosidonnaisuus. Tällöin voidaan tehdä tietoisesti moraalisia päätöksiä ja kantaa moraalinen vastuu esimerkiksi diagnoosin määrittelyssä. Psykiatrian voidaan katsoa perustuvan universaaleihin arvoihin samalla tavalla kuin ihmisoikeuksienkin.

Long-term Outcome of DSM-IV Major Depressive Disorder in Psychiatric Care

Much of what we know regarding the long-term course and outcome of major depressive disorder (MDD) is based on studies of mostly inpatient tertiary level cohorts and samples predating the era of the current antidepressants and the use of maintenance therapies. In addition, there is a lack of studies investigating the comprehensive significance of comorbid axis I and II disorders on the outcome of MDD. The present study forms a part of the Vantaa Depression Study (VDS), a regionally representative prospective and naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients (aged 20-59) with a new episode of DSM-IV MDD, and followed-up up to five years (n=182) with a life-chart and semistructured interviews. The aim was to investigate the long-term outcome of MDD and risk factors for poor recovery, recurrences, suicidal attempts and diagnostic switch to bipolar disorder, and the association of a family history of different psychiatric disorders on the outcome. The effects of comorbid disorders together with various other predictors from different domains on the outcome were comprehensively investigated. According to this study, the long-term outcome of MDD appears to be more variable when its outcome is investigated among modern, community-treated, secondary-care outpatients compared to previous mostly inpatient studies. MDD was also highly recurrent in these settings, but the recurrent episodes seemed shorter, and the outcome was unlikely to be uniformly chronic. Higher severity of MDD predicted significantly the number of recurrences and longer time spent ill. In addition, longer episode duration, comorbid dysthymic disorder, cluster C personality disorders and social phobia predicted a worse outcome. The incidence rate of suicide attempts varied robustly de¬pending on the level of depression, being 21-fold during major depressive episodes (MDEs), and 4-fold during partial remission compared to periods of full remission. Although a history of previous attempts and poor social support also indicated risk, time spent depressed was the central factor determining overall long-term risk. Switch to bipolar disorder occurred mainly to type II, earlier to type I, and more gradually over time to type II. Higher severity of MDD, comorbid social phobia, obsessive compulsive disorder, and cluster B personality disorder features predicted the diagnostic switch. The majority of patients were also likely to have positive family histories not exclusively of mood, but also of other mental disorders. Having a positive family history of severe mental disorders was likely to be clinically associated with a significantly more adverse outcome.

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.

The incidence and outcome of severe sepsis in Finland : The Finnsepsis Study

Severe sepsis is associated with common occurrence, high costs of care and significant mortality. The incidence of severe sepsis has been reported to vary between 0.5/1000 and 3/1000 in different studies. The worldwide Severe Sepsis Campaign, guidelines and treatment protocols aim at decreasing severe sepsis associated high morbidity and mortality. Various mediators of inflammation, such as high mobility group box-1 protein (HMGB1) and vascular endothelial growth factor (VEGF), have been tested for severity of illness and outcome in severe sepsis. Long-term survival with quality of life (QOL) assessment is important outcome after severe sepsis. The objective of this study was to evaluate the incidence, severity of organ dysfunction and outcome of severe sepsis in intensive care treated patients in Finland (study I)). HMGB1 and VEGF were studied in predicting severity of illness, development and type of organ dysfunction and hospital mortality (studies II and III). The long-term outcome and quality of life were assessed and quality-adjusted life years and cost per one QALY were estimated (study IV). A total of 470 patients with severe sepsis were included in the Finnsepsis Study. Patients were treated in 24 Finnish intensive care units in a 4-month period from 1 November 2004 to 28 February 2005. The incidence of severe sepsis was 0.38 /1,000 in the adult population (95% confidence interval 0.34-0.41). Septic shock (77%), severe oxygenation impairment (71.4%) and acute renal failure (23.2%) were the most common organ failures. The ICU, hospital, one-year and two-year mortalities were 15.5%, 28.3%, 40.9% and 44.9% respectively. HMGB1 and VEGF were elevated in patients with severe sepsis. VEGF concentrations were lower in non-survivors than in survivors, but HMGB1 levels did not differ between patients. Neither HMGB1 nor VEGF were predictive of hospital mortality. The QOL was measured median 17 months after severe sepsis and QOL was lower than in reference population. The mean QALY was 15.2 years for a surviving patient and the cost for one QALY was 2,139 . The study showed that the incidence of severe sepsis is lower in Finland than in other countries. The short-term outcome is comparable with that in other countries, but long-term outcome is poor. HMGB1 and VEGF are not useful in predicting mortality in severe sepsis. The mean QALY for a surviving patient is 15.2 and as the cost for one QALY is reasonably low, the intensive care is cost-effective in patients with severe sepsis.

Depressive Disorders in Primary Health Care

The Vantaa Primary Care Depression Study (PC-VDS) is a naturalistic and prospective cohort study concerning primary care patients with depressive disorders. It forms a collaborative research project between the Department of Mental and Alcohol Research of the National Public Health Institute, and the Primary Health Care Organization of the City of Vantaa. The aim is to obtain a comprehensive view on clinically significant depression in primary care, and to compare depressive patients in primary care and in secondary level psychiatric care in terms of clinical characteristics. Consecutive patients (N=1111) in three primary care health centres were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, interview and a retrospective life-chart were used to obtain comprehensive cross-sectional and retrospective longitudinal information. For investigation of suicidal behaviour the Scale for Suicidal Ideation (SSI), patient records and the interview were used. The methodology was designed to be comparable to The Vantaa Depression Study (VDS) conducted in secondary level psychiatric care. Comparison of major depressive disorder (MDD) patients aged 20-59 from primary care in PC-VDS (N=79) was conducted with new psychiatric outpatients (N =223) and inpatients (N =46) in VDS. The PC-VDS cohort was prospectively followed up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the follow-up. Duration of the index episode and the timing of relapses or recurrences were examined using a life-chart. The retrospective investigation revealed current MDD in most (66%), and lifetime MDD in nearly all (90%) cases of clinically significant depressive syndromes. Two thirds of the “subsyndromal” cases had a history of major depressive episode (MDE), although they were currently either in partial remission or a potential prodromal phase. Recurrences and chronicity were common. The picture of depression was complicated by Axis I co-morbidity in 59%, Axis II in 52% and chronic Axis III disorders in 47%; only 12% had no co-morbidity. Within their lifetimes, one third (37%) had seriously considered suicide, and one sixth (17%) had attempted it. Suicidal behaviour clustered in patients with moderate to severe MDD, co-morbidity with personality disorders, and a history of treatment in psychiatric care. The majority had received treatment for depression, but suicidal ideation had mostly remained unrecognised. The comparison of patients with MDD in primary care to those in psychiatric care revealed that the majority of suicidal or psychotic patients were receiving psychiatric treatment, and the patients with the most severe symptoms and functional limitations were hospitalized. In other clinical aspects, patients with MDD in primary care were surprisingly similar to psychiatric outpatients. Mental health contacts earlier in the current MDE were common among primary care patients. The 18-month prospective investigation with a life-chart methodology verified the chronic and recurrent nature of depression in primary care. Only one-quarter of patients with MDD achieved and maintained full remission during the follow-up, while another quarter failed to remit at all. The remaining patients suffered either from residual symptoms or recurrences. While severity of depression was the strongest predictor of recovery, presence of co-morbid substance use disorders, chronic medical illness and cluster C personality disorders all contributed to an adverse outcome. In clinical decision making, beside severity of depression and co-morbidity, history of previous MDD should not be ignored by primary care doctors while depression there is usually severe enough to indicate at least follow-up, and concerning those with residual symptoms, evaluation of their current treatment. Moreover, recognition of suicidal behaviour among depressed patients should also be improved. In order to improve outcome of depression in primary care, the often chronic and recurrent nature of depression should be taken into account in organizing the care. According to literature management programs of a chronic disease, with enhancement of the role of case managers and greater integration of primary and specialist care, have been successful. Optimum ways of allocating resources between treatment providers as well as within health centres should be found.

Health-Related Quality of Life and Mental Disorders in Finland

Quality of life (QoL) and Health-related quality of life (HRQoL) are becoming one of the key outcomes of health care due to increased respect for the subjective valuations and well-being of patients and an increasing part of the ageing population living with chronic, non-fatal conditions. Preference-based HRQoL measures enable estimation of health utility, which can be useful for rational rationing, evidence-based medicine and health policy. This study aimed to compare the individual severity and public health burden of major chronic conditions in Finland, including and focusing on reliably diagnosed psychiatric conditions. The study is based on the Health 2000 survey, a representative general population survey of 8028 Finns aged 30 and over. Depressive, anxiety and alcohol use disorders were diagnosed with the Composite International Diagnostic Interview (M-CIDI). HRQoL was measured with the 15D and the EQ-5D, with 83% response rate. This study found that people with psychiatric disorders had the lowest 15D HRQoL scores at all ages, in comparison to other main groups of chronic conditions. Considering 29 individual conditions, three of the four most severe (on 15D) were psychiatric disorders; the most severe was Parkinson s disease. Of the psychiatric disorders, chronic conditions that have sometimes been considered relatively mild - dysthymia, agoraphobia, generalized anxiety disorder and social phobia - were found to be the most severe. This was explained both by the severity of the impact of these disorders on mental health domains of HRQoL, and also by the fact that decreases were widespread on most dimensions of HRQoL. Considering the public health burden of conditions, musculoskeletal disorders were associated with the largest burden, followed by psychiatric disorders. Psychiatric disorders were associated with the largest burden at younger ages. Of individual conditions, the largest burden found was for depressive disorders, followed by urinary incontinence and arthrosis of the hip and knee. The public health burden increased greatly with age, so the ageing of the Finnish population will mean that the disease burden caused by chronic conditions will increase by a quarter up to year 2040, if morbidity patterns do not change. Investigating alcohol consumption and HRQoL revealed that although abstainers had poorer HRQoL than moderate drinkers, this was mainly due to many abstainers being former drinkers and having the poorest HRQoL. Moderate drinkers did not have significantly better HRQoL than abstainers who were not former drinkers. Psychiatric disorders are associated with a large part of the non-fatal disease burden in Finland. In particular anxiety disorders appear to be more severe and have a larger public health burden than previously thought.

Mental Disorders among Burn Patients

ABSTRACT Mental disorders and suicide attempts among acute burn patients were investigated in a collaborative research project between National Institute for Health and Welfare and Departments of Psychiatry and Plastic surgery in University of Helsinki in Finland. This project was realized in two parts. The first cohort of burn patients consisted of all burn patients admitted to the Helsinki Burn Centre during 1989 97. In this retrospective cohort, 5.7% (N=46) of the total of 811 burn patients had attempted suicide. The burn severity of suicide attempters was markedly higher than in the other burn patients. Suicide attempters were more often unemployed or on disability pension and had psychiatric history before the injury. The second sample was a prospective cohort of all acute consecutive burn patients admitted to the Helsinki Burn Centre during 18 months in 2006- 2007. All subjects (N=107) of the cohort were interviewed with the Structured Clinical Interview for DSM-IV for Axis I and II mental disorders (SCID-I and SCID-II) at baseline and then 86 % of all (N=92) with SCID-I at the end of six-month follow-up. Most (61%) patients had at least one lifetime mental disorder before burn; 47 % substance-related, 10% psychotic and 23% personality disorders. The overall prevalence of Axis I mental disorders increased significantly from the month prior to burn to acute care but decreased significantly from acute care to six months. However, more than one half (55%) of the cohort suffered from some mental disorder during follow-up. Less than one half of the burn patients with estimated need for psychiatric care received psychiatric care. Burn severity independently and strongly predicted risk for mental disorders during follow-up and pre-burn psychiatric history, severe burns and estimated need for psychiatric care significantly predicted psychiatric care received. The proportion of patients with self-inflicted burns is not high but mental disorders are common among burn patients. Mental disorders may predispose to burns. After burn injury, more than half of the patients suffer from mental disorders and a strong relationship exists between burn severity and some post-burn mental disorders. A minority of the patients with unequivocal need for psychiatric care actually receive it. Psychiatric consultations and care follow mainly the course of acute burn treatment.

Process of burnout: structure, antecedents, and consequences

The major changes that have been witnessed in today's workplaces are challenging the mental well-being of employed people. Stress and burnout are considered to be modern epidemics, and their importance to physical health and work ability has been acknowledged world-wide. The aim of the thesis was to study the concept of burnout as a process proceeding from its antecedents, through the development of the syndrome, and to its outcomes. Several work-related factors considered antecedents of burnout were studied in different occupational groups. The syndrome of burnout is seen as consisting of three dimensions - exhaustion, cynicism and lack of professional efficacy - and different alternatives for the sequential development of these dimensions were tested. Furthermore, several indicators of the severely detrimental health and work ability outcomes of burnout were investigated in a longitudinal study design. The research questions were as follows. 1) Is burnout, as measured with the Maslach Burnout Inventory - General Survey (MBI-GS), a three-dimensional construct and how invariant is the factorial structure across occupations (Finnish) and national samples (Finnish, Swedish and Dutch)? How persistent is exhaustion over time? 2) What is the sequential process of burnout? Is it similar across occupations? How do work stressors relate to the process? 3) How does burnout relate to severe health consequences as well as temporary and chronic work disability according to hospitalization periods, sick-leave episodes and receiving disability pensions? The data were collected between 1986 and 2005. The population of the study consisted of respondents to a company-wide questionnaire survey carried out in 1996-1997 (N=9705, response rate 63%). The participants comprised 6025 blue-collar workers and 3680 white-collar workers. The majority were men (N=7494) and the average age was 43.7 years. In addition, a sample from the population had responded to a questionnaire survey in 1988, which was combined with the 1996 data to form panel data on 713 respondents. The register-based data were collected between 1986 and 2005 from 1) the company's occupational health services' records for a sample of respondents from the 1996 questionnaire survey (sick-leave data), 2) hospitalization records from the Hospital discharge register, and 3) disability pension records from the Finnish Centre for Pensions. These data were combined person by person with the 1996 questionnaire survey data with the help of personal identification numbers which were saved with the study numbers by the researchers. The results showed that burnout consists of three separate but correlating symptoms: exhaustion, cynicism and lack of professional efficacy. As a syndrome, burnout was strongly related to job stressors at work, and seemed to develop from exhaustion through cynicism to lack of professional efficacy in a similar manner among white-collar and blue-collar employees. The results also showed that exhaustion persisted even after eight years of follow-up but did not predict cynicism or lack of professional efficacy after that amount of time. Nor were job stressors longitudinally related to burnout. Longitudinal results were obtained for the severe health-related consequences of burnout. The investigated outcomes represented different phases of health deterioration ranging from sick-leaves and hospitalization periods to receiving work disability pensions. The results showed that burnout syndrome, and its elements of exhaustion and cynicism, were related to future mental and cardiovascular disorders as indicated by hospitalization periods. Burnout was also related to future sick-leave periods due to mental, cardiovascular and musculoskeletal disorders. Of the separate elements, exhaustion was related to the same three categories of disorder, cynicism to mental, musculoskeletal and digestive disorders, and lack of professional efficacy to mental and musculoskeletal disorders. Burnout also predicted receiving disability pensions due to mental and musculoskeletal disorders among initially healthy subjects. Exhaustion was related to receiving disability pensions even when self-reported chronic illness was taken into account. The results suggest that burnout is a multidimensional, chronic, work-related syndrome, which may have serious consequences for health and work ability.