Association of adoptive child's thought disorders and schizophrenia spectrum disorders with their genetic liability for schizophrenia spectrum disorders, season of birth and parental Communication Deviance.

Joint effects of genotype and the environment have turned out to be significant in the development of psychotic disorders. The purpose of the present study was to assess the association of an adoptive child׳s thought and schizophrenia spectrum disorders with genetic and environmental risk indicators and their interactions. A subgroup of the total sample used in the Finnish Adoptive Family Study was considered in the present study. The subjects were 125 adoptees at a high (n=53) or low (n=72) genetic risk of schizophrenia spectrum disorders and their adoptive parents. The risk factors evaluated were the adoptive child's genetic risk for schizophrenia spectrum disorders, winter or spring birth and parental Communication Deviance (CD). Thought disorders in the adoptees were assessed using the Thought Disorder Index and diagnoses were made according to DSM-III-R criteria. The adoptive child׳s Thought Disorder Index was only associated with parental Communication Deviance. The adoptive child's heightened genetic risk or winter or spring birth or parental CD or their interactions did not predict the adoptee's schizophrenia spectrum disorder. The results suggest that studies taking several risk indicators and their interactions into account may change views on the mutual significance of well-known risk factors.

Stability in MMPI among adoptees with high and low genetic risk for schizophrenia and with low Communication Deviance of their adoptive parents.

Stability has been considered an important aspect of vulnerability to schizophrenia. The temporal stability of the scales in the Minnesota Multiphasic Personality Inventory (MMPI) was examined, using adoptees from the Finnish Adoptive Family Study of Schizophrenia. Adoptees who were high-risk (HR) offspring of biological mothers having a schizophrenia spectrum disorder (n=28) and low-risk (LR) controls (n=46) were evaluated using 15 MMPI scales at the initial assessment (HR, mean age 24 years; LR, mean age 23 years) and at the follow-up assessment after a mean interval of 11 years. Stability of the MMPI scales was also assessed in the groups of adoptees, assigned according to the adoptive parents'(n=44) communication style using Communication Deviance (CD) scale as an environmental factor. Initial Lie, Frequency, Correction, Psychopathic Deviate, Schizophrenia, Manifest Hostility, Hypomania, Phobias, Psychoticism, Religious Fundamentalism, Social Maladjustment, Paranoid Schizophrenia, Golden-Meehl Indicators, Schizophrenia Proneness and 8-6 scale scores significantly predicted the MMPI scores at the follow-up assessment indicating stability in the characteristics of thinking, affective expression, social relatedness and volition. Low CD in the family had an effect on the stabilization of personality traits such as social withdrawal and restricted affectivity assessed by Correction and Hostility.

Communication Deviance in parents of families with adoptees at a high or low risk of schizophrenia-spectrum disorders and its associations with attributes of the adoptee and the adoptive parents.

Communication Deviance (CD) in rearing parents is a known indicator of a psychopathology risk in the offspring, but the direction of the effects of these two factors on each other has remained an unresolved question. The purpose of the present study was to clarify this issue by assessing the relationship of CD in adoptive parents with certain attributes of the adoptee and adoptive parents themselves. The subjects were 109 adoptees at a high or low risk of schizophrenia-spectrum disorders and their adoptive parents. Communication Deviance was measured in individual, spouse and family Rorschach situations. Thought disorders in the adoptees were assessed using the Thought Disorder Index. The variability of CD in the adoptive parents in individual Rorschach situations was not significantly explained by any characteristics of the child. The variability in parental CD in family Rorschach situations was most closely associated with the characteristics of the parents themselves. The results strongly support the hypotheses that the frequency of Communication Deviance is an enduring trait rather than a fluctuating state and that frequent CD in parent's speech may impair the growing child's cognitive development and predispose him/her to schizophrenia-spectrum disorders.

Genetic vulnerability and premature death in schizophrenia spectrum disorders: a 28-year follow-up of adoptees in the Finnish Adoptive Family Study of Schizophrenia.

BACKGROUND: Excess mortality is widely reported among schizophrenia patients, but rarely examined in adoption study settings. AIM: We investigated whether genetic background plays a role in the premature death of adoptees with schizophrenia. METHODS: Mortality among 382 adoptees in the Finnish Adoptive Family Study of Schizophrenia was monitored from 1977 to 2005 through the national causes-of-death register. The sample covered 190 adoptees with a high genetic risk of schizophrenia (HR) and 192 with a low risk (LR). RESULTS: Overall mortality among the adoptees did not differ between the HR and LR groups, as 10% and 9% respectively had died during the follow-up, at mean ages of 45 and 46 years. Schizophrenia spectrum disorder was the most significant predictor of premature death in both groups, with dysfunction in the rearing family environment associated with mortality, unnatural deaths and suicides in the HR but not in the LR group. All the suicides involved HR cases. CONCLUSIONS: Mortality among the adoptees was not related to genetic factors but to environmental ones. The association of unnatural deaths and suicides with dysfunction in the rearing environment among the HR adoptees may indicate that they had a greater genetically determined vulnerability to environmental effects than their LR counterparts. The genetic and rearing environments can be disentangled in this setting because the biological parents give the offspring their genes and the adoptive parents give them their rearing environment. Our findings add to knowledge of the factors associated with the premature death of adoptees in mid-life.

How to use bibliometric methods in evaluation of scientific research? An example from Finnish schizophrenia research.

We present bibliometric methods that can be utilized in evaluation processes of scientific work. In this paper, we present some practical clues using Finnish schizophrenia research as an example and comparing the research output of different institutions. Bibliometric data and indicators including publication counts, impact factors and received citations were used as tools for evaluating research performance in Finnish schizophrenia research. The articles and citations were searched from the Web of Science database. We used schizophrenia as a keyword and defined address Finland, and limited years to 1996-2005. When we analysed Finnish schizophrenia research, altogether 265 articles met our criteria. There were differences in impact factors and received citations between institutions. The number of annually published Finnish schizophrenia articles has tripled since the mid-1990s. International co-operation was common (43%). Bibliometric methods revealed differences between institutions, indicating that the methods can be applied in research evaluation. The coverage of databases as well as the precision of their search engines can be seen as limitations. Bibliometric methods offer a practical and impartial way to estimate publication profiles of researchers and research groups. According to our experience, these methods can be used as an evaluation instrument in research together with other methods, such as expert opinions and panels.

MMPI measures as signs of predisposition to mental disorder among adoptees at high risk for schizophrenia.

The DSM-III-R diagnoses of a group of adoptees were predicted by the MMPI (Minnesota Multiphasic Personality Inventory) schizophrenia-related scales in the Finnish Adoptive Family Study. The sample consisted of 60 high-risk (HR) adopted-away offspring of biologic mothers with a diagnosis of broad schizophrenia spectrum and 76 low-risk (LR) control adoptees. They were assessed with the MMPI before the onset of any psychiatric disorder at a mean age of 24 years. High scores on the Psychopathic Deviate scale predicted psychiatric disorder at 11-year follow-up. Furthermore, LR adoptees', but not HR adoptees', mental disorders could be predicted with the MMPI scales Psychopathic Deviate and Golden-Meehl Indicators. These scales measure schizophrenia-related personality traits, including a social behavior, anhedonia, ambivalence, interpersonal aversiveness, and formal thought disturbances.

Interaction of genetic vulnerability to schizophrenia and Communication Deviance of adoptive parents associated with MMPI schizophrenia vulnerability indicators of adoptees.

The aim of this study was to establish possible genotype-environment interaction in high-risk and low-risk adoptees' vulnerability to schizophrenia. The study population consisted of a subgroup of 41 adoptive families with a high genetic risk adoptee and 58 families with a low genetic risk adoptee from the Finnish Adoptive Family Study of Schizophrenia. Communication style was assessed based on the Communication Deviance (CD) of the adoptive parents, and the adoptees' vulnerability indicators were measured with the Minnesota Multiphasic Personality Inventory (MMPI). Taken separately, only the genetic liability to schizophrenia, but not the communication style of the adoptive parents, was significantly associated with the Lie, Correction and Hostility scales in the MMPI of the adoptees. Analyses of the genotype-environment interactions showed that the high-risk adoptees with high-CD rearing parents had an increased risk of vulnerability on the MMPI Social Maladjustment scale compared with the corresponding low-risk adoptees. Genetic vulnerability to schizophrenia and genotype-environment interaction are manifested in adoptees' MMPI.

Differentiation of adoptees at high versus low genetic risk for schizophrenia by adjusted MMPI indices.

The aim of this study was to find potential signs of genetic vulnerability to schizophrenia. The differences between adoptees at high genetic risk for schizophrenia (their biological mother had a schizophrenia spectrum disorder) and control adoptees of non-schizophrenia spectrum biological mothers were assessed. The comparisons between these groups were based on the Minnesota Multiphasic Personality Inventory (MMPI) test's subscale scores adjusted by gender, age at MMPI assessment, age at placement into the adoptive family and social class. The subjects were a subsamples of a total of 182 tested adoptees and 136 mentally healthy adoptees in the Finnish Adoptive Family Study. The high-risk group was found to be distinguishable from the low-risk group based on deviant scores on the Hostility, Hypomania and Lie scales. These scales may measure genetic vulnerability and also possibly be indicative of psychometric deviance predicting future onset of schizophrenia.

I. Genotype-environment interaction in the schizophrenia spectrum: genetic liability and global family ratings in the Finnish Adoption Study.

In the Finnish Adoption Study, a national sample of adoptees with high versus low genetic liability for schizophrenia spectrum disorders was indexed by DSM-III-R diagnoses of their biological, adopting-away mothers. The rearing-family environments of the adoptees were independently evaluated from global ratings of directly observed adoptive family relationships. The interaction of high genetic liability and dysfunction of the rearing families predicted highly significantly to schizophrenia spectrum disorder of the adoptees at 21-year follow-up. Either low genetic liability or healthy rearing protected against a spectrum outcomes for the adoptees. Initial adoptive parent diagnosis, as a proxy for rearing family dysfunction, predicted to adoptee outcome only as a trend.

II. Genotype-environment interaction in the schizophrenia spectrum: qualitative observations.

Previous reports from the Finnish Adoptive Family Study of Schizophrenia have documented significant interplay between genetics (G) and family rearing (E), leading to adoptee outcomes of schizophrenia spectrum disorders. Quantitative evidence for this interplay is significantly enhanced when both high genetic liability and severe environmental dysfunction are present. However, when either genetic liability is low or the rearing environment is healthy, the adoptees appear to be resiliently protected against a pathologic outcome. Nevertheless, exceptions to this pattern do occur. Six qualitative vignettes, together with quantitative measures and categorical diagnoses from the same families, illustrate how multiple methods partially confirm one another and also suggest where further exploration of gene-environment interaction is needed.

Observing relationships in Finnish adoptive families: Oulu Family Rating Scale.

Adoption studies were intended to separate genetic from environmental "causal" factors. In earlier adoption studies, psychiatric diagnostic labels for the adoptive parents were used as a proxy for the multiple dimensions of the family rearing environment. In the Finnish Adoption Study, research design provided the opportunity to study directly the adoptive family rearing environment. For this purpose 33 sub-scales were selected creating what we call Oulu Family Rating Scale (OPAS, Oulun PerheArviointiSkaala). In this paper, the manual for scoring of these sub-scales is presented.

Predictors of schizophrenia: evidence from the Northern Finland 1966 Birth Cohort and other sources.

BACKGROUND: Subtle motor, emotional, cognitive and behavioural abnormalities are often present in apparently healthy individuals who later develop schizophrenia, suggesting that some aspects of causation are established before overt psychosis. AIMS: To outline the development of schizophrenia. METHOD: We drew on evidence from The Northern Finland 1966 Birth Cohort supplemented by selected findings from other relevant literature. RESULTS: The main known risk factors in development of schizophrenia are genetic causes, pregnancy and delivery complications, slow neuromotor development, and deviant cognitive and academic performance. However, their effect size and predictive power are small. CONCLUSIONS: No powerful risk factor, premorbid sign or risk indicator has been identified that is useful for the prediction of schizophrenia in the general population.

Predictors of schizophrenia--a review.

Schizophrenia is an aetiologically heterogeneous syndrome that usually becomes overtly manifest in adolescence and early adulthood, but in many cases subtle impairments in neurointegrative function are present from birth; hence it is considered to be a disorder with a neurodevelopmental component. The strongest risk factor that has been identified is familial risk with genetic loading. Other risk factors include pregnancy and delivery complications, infections during pregnancy, disturbances of early neuromotor and cognitive development and heavy cannabis use in adolescence. Unfortunately, to date it has not been possible to utilize the predictors of the disorder that have been identified in primary preventative interventions in a general population. However, some authors have claimed that in future it might be possible to reduce the risk for developing schizophrenia through general health policy. In clinical settings, it is helpful to map out possible early risk factors, at least familial risk for psychosis, especially in child, adolescent and young adult mental patients. Furthermore, in the future we may have predictive models combining data from genetic factors for schizophrenia, antenatal risk factors, childhood and adolescent development and clinical symptomatology, as well as brain structural and functional abnormalities.

Psychometric deviance measured by MMPI in adoptees at high risk for schizophrenia and their adoptive controls.

Psychometric deviance in personality traits as assessed by the Minnesota Multiphasic Personality Inventory (MMPI; Dahlstrom, Welsh, & Dahlstrom, 1982) was compared between adopted-away, high-risk (HR) offspring of schizophrenic biologic mothers and low-risk (LR) controls. A subsample of the Finnish Adoptive Family Study (Tienari et al., 2000) included 60 HR adoptees and 76 LR control adoptees who were tested by the MMPI before the onset of any psychiatric disorder at the mean age of 24 years. The HR group was found to be distinguishable based on deviant scores on the scales HOS and HYP, indicating emotional unresponsiveness, restricted affectivity, and decreased energy. These may also be considered possible premorbid and prodromal signs of future schizophrenia among the HR adoptees.

Developmental precursors of psychosis.

Subtle developmental (motor, emotional, cognitive, and behavioral) abnormalities are often present in apparently healthy individuals who later develop psychosis, suggesting that some aspects of causation are established before overt psychosis. These impairments may restrict information processing and social achievements years before manifesting psychosis. The main known risk factors in the development of schizophrenic psychosis are genetic factors, pregnancy and delivery complications, slow neuromotor development, and deviant cognitive and academic performance. However, their effect size and predictive power are small. Developmental precursors are not necessarily specific to schizophrenia, but also common to other psychotic disorders. No powerful risk factor, premorbid sign, or risk indicator has been identified that is useful for prediction of psychoses in the general population.

Early presence of thought disorder as a prospective sign of mental disorder.

The purpose of this study was to assess whether premorbid signs, such as thought disorder, could predict the subsequent manifestation of psychiatric disorders. A group of 75 adoptees at high genetic risk for schizophrenia and 96 low-risk adoptees without any psychiatric disorder at the initial assessment were assessed blindly with the Thought Disorder Index (TDI). Their psychiatric status was re-assessed according to DSM-III-R criteria in a re-interview 11 years later and based on available registers 16 years later. High scores on several TDI variables at the initial assessment predicted a psychiatric disorder of all adoptees at follow-up. Prediction was statistically unsuccessful among the high-risk adoptees because of the small number of cases, but high scores at the 0.50 severity level did predict mental disorders among the low-risk adoptees.

Genotype-environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees.

BACKGROUND: Earlier adoption studies have convincingly confirmed the importance of a genetic contribution to schizophrenia. The designs, however, did not incorporate observations of the rearing-family environment. AIMS: To test the hypothesis that genetic factors moderate susceptibility to environmentally mediated risks associated with rearing-family functioning. METHOD: A Finnish national sample of adopted-away offspring of mothers with schizophrenia-spectrum disorders was compared blindly with adoptees without this genetic risk. Adoptive rearing was assessed using family rating scales based upon extended family observations at initial assessment. Adoptees were independently re-diagnosed after a median interval of 12 years, with register follow-up after 21 years. RESULTS: In adoptees at high genetic risk of schizophrenia, but not in those at low genetic risk, adoptive-family ratings were a significant predictor of schizophrenia-spectrum disorders in adoptees at long-term follow-up. CONCLUSIONS: Adoptees at high genetic risk are significantly more sensitive to adverse v. 'healthy' rearing patterns in adoptive families than are adoptees at low genetic risk.

Interaction of genetic risk and adoptive parent communication deviance: longitudinal prediction of adoptee psychiatric disorders.

BACKGROUND: In the Finnish Adoptive Family Study of Schizophrenia, adoptee thinking disorders have been shown to be a joint effect of genetic liability for schizophrenia spectrum disorders and adoptive rearing-parent communication patterns. However, longitudinal predictions of clinical psychiatric disorders of the adoptees have not been reported. METHOD: Adoptees (n = 109) who had no DSM-III-R disorder at initial assessment (median age 18 years) were selected from the total sample of the Finnish Adoption Study of Schizophrenia. They were defined as at high versus low genetic risk based upon the lifetime diagnoses of their biological, adopting-away mothers - schizophrenia spectrum disorder versus no spectrum disorder. At initial assessment, adoptive rearing parents were independently evaluated from tape-recorded Rorschach protocols scored as manifesting either high or low Communication Deviance (CD), a composite index of communication patterns that distract and befuddle listeners. Adoptees were independently re-diagnosed after a median interval of 14 years and followed-up from national registers for an additional 7 years. RESULTS: The main effects of genetic liability (G) and CD of the adoptive parents (E), each taken separately, predicted significantly for psychiatric disorders of the adoptees as adults. However, when G, E, and their joint interaction effect were entered into the same logistic model, only the interaction effect was significant. The sample included seven adoptees with schizophrenia spectrum disorders, but a separate analysis to predict them was non-significant. CONCLUSION: Genetic liability for schizophrenia spectrum disorder and an adoptive family rearing variable interact, predicting longitudinally and significantly to broadly defined adoptee psychiatric disorder.

Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia.

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.