The Finnish Adoptive Family Study of Schizophrenia: differences in somatic diseases and conditions between adoptees with high or low genetic risk for schizophrenia spectrum disorders.

BACKGROUND AND AIMS: There is some evidence that offspring of patients with schizophrenia have higher somatic morbidity, which is thought to be partially due to genetic links between somatic disorders and schizophrenia. This study explored differences in somatic diseases and conditions of adoptees with high genetic risk (HR) or low genetic risk (LR) for schizophrenia spectrum disorders. MATERIAL AND METHODS: The study is part of the Finnish Adoptive Family Study of Schizophrenia. The adoptive research design used made it possible to examine how the somatic health of adoptees raised in similar adoptive families, is affected by their genetic susceptibility to schizophrenia. The study sample consisted of 373 adoptees, of whom 190 had HR and 183 had LR for schizophrenia spectrum disorders. Data on somatic morbidity were gathered from the hospital records and from the national registers of the Care Register of Health Care and the Social Insurance Institution. RESULTS: The only statistically significant difference found was in genitourinary diseases, the likelihood being twofold higher in HR adoptees compared to LR adoptees (16.8% vs. 8.2%; adj. OR = 2.13, 95% CI 1.06-4.25, p = .033). Adoptees who were female and aged over 40 had a higher prevalence of genitourinary illnesses than non-adoptees. CONCLUSION: The significant prevalence of genitourinary diseases in adoptees at risk for schizophrenia spectrum disorders suggests that some specific somatic diseases and schizophrenia may have a shared hereditary etiology. More research is required for specific somatic diseases in study populations that can differentiate between the effects of genetic and environmental factors.

Associations of Duration of Preadoption Out-of-home Care, Genetic Risk for Schizophrenia Spectrum Disorders and Adoptive Family Functioning with Later Psychiatric Disorders of Adoptees.

The objective was to examine the impacts of duration of preadoption out-of-home care and adoptive family functioning on later psychiatric morbidity of adoptees with high (HR) and low (LR) genetic risk for schizophrenia spectrum disorders. The study uses nationwide data from the Finnish Adoptive Family Study of Schizophrenia. The study population in this substudy consisted of 43 h adoptees and 128 LR adoptees. Of these adoptees, 90 had spent 0-6 months and 81 over 6 months in preadoption out-of-home care. The family functioning of adoptive families was assessed based on Global Family Ratings and psychiatric disorders on DSM-III-R criteria. The results showed that among the adoptees with over 6 months in preadoption out-of-home care, the likelihood for psychiatric disorders was significantly increased in HR adoptees compared to LR adoptees. In adoptees with 6 months or less in preadoption out-of-home care, an increased likelihood for psychiatric disorders was found among those living in adoptive families with dysfunctional processes. These findings indicate that especially for HR children, a well-functioning early caregiving environment is crucial in terms of subsequent mental wellbeing. The results emphasize that when adoption is necessary, early placement and well-functioning adoptive family environment are beneficial to children.

Deficits in adolescent social functioning, dysfunctional family processes and genetic risk for schizophrenia spectrum disorders as risk factors for later psychiatric morbidity of adoptees.

Social functioning deficits during adolescence are associated with later psychiatric morbidity, particularly in offspring at high genetic risk for schizophrenia spectrum disorders. However, a shortcoming of earlier study findings is the lack of control of the impact of the family rearing environment. The study was aimed to examine the association of adoptees' social functioning during adolescence, adoptive family functioning, and adoptees' high (HR) or low (LR) genetic risk for schizophrenia spectrum disorders with adoptees' later psychiatric morbidity. The present subsample from the nationwide Finnish Adoptive Family Study of Schizophrenia included 57 HR and 60 LR adoptees. Adolescent social functioning was assessed using UCLA Social Attainment Survey (UCLA SAS). Adoptive family functioning was based on Global Family Ratings (GFRs) and psychiatric disorders on DSM-III-R criteria. The results indicated that, after controlling for adoptive family functioning and genetic risk for schizophrenia spectrum disorders, deficits in peer relationships during adolescence were associated with an increased likelihood of psychiatric morbidity of adoptees. Our findings highlight social functioning deficits during adolescence, specifically in peer relationships, as plausible independent risk factors for later psychiatric disorders. These results can be utilized in identifying possible at-risk groups and targets for prevention and in developing preventive strategies.

Adolescent Social Functioning Deficits in Association With Adoptive Family Functioning and Genetic Risk for Schizophrenia Spectrum Disorders: The Finnish Adoptive Family Study of Schizophrenia.

ABSTRACT: Social functioning deficits (SFDs) during adolescence represent potential vulnerability indicators to schizophrenia spectrum disorders, but little is known about how both family environmental and genetic factors contribute to SFDs. The aim of this study was to examine the association of adoptees' adolescent social functioning with adoptive family functioning and adoptees' high (HR) or low (LR) genetic risk for schizophrenia spectrum disorders. The present subsample from the nationwide Finnish Adoptive Family Study of Schizophrenia included 88 HR and 83 LR adoptees. Adolescent social functioning was assessed using UCLA Social Attainment Survey. Assessment of adoptive family functioning was based on Global Family Ratings. Results indicated that dysfunctional family processes and high genetic risk for schizophrenia spectrum disorders contributed approximately equally to adoptees' adolescent social functioning. Our findings underscore the importance of functional family processes in adolescent social functioning, particularly in individuals at high genetic risk for severe psychiatric disorder.

Dysfunctional family functioning in high socioeconomic status families as a risk factor for the development of psychiatric disorders in adoptees: the Finnish Adoptive Family Study of Schizophrenia.

PURPOSE: Earlier findings indicate that socioeconomic status (SES) of family associates with family functioning. This study examined the impacts of family functioning and genetic risk for schizophrenia on psychiatric morbidity of adoptees in families of high SES (HSES) and low SES (LSES). METHODS: The study population is a subgroup of the Finnish Adoptive Family Study of Schizophrenia. Of the adoptees, 152 had high genetic risk for schizophrenia spectrum disorders (HR) and 151 adoptees had low risk (LR). Of the adoptees, 185 (HR = 94, LR = 91) were raised in high-SES (HSES) families and 118 (HR = 58, LR = 60) in low-SES (LSES) families. The family SES was determined by the occupational status of the main provider of the family. The functioning of adoptive families was assessed based on Global Family Ratings (GFRs) and psychiatric disorders on DSM-III-R criteria. RESULTS: In the HSES families, the psychiatric morbidity of the adoptees was emphasized by HR (OR = 4.28, CI 2.14-8.56) and dysfunctional family processes (OR = 6.44, CI 2.75-15.04). In the LSES families, the adoptees´ psychiatric morbidity was almost significantly increased by HR (OR = 2.10, CI 0.99-4.45), but not by dysfunctional family processes (OR = 1.33, CI 0.53-3.34). CONCLUSIONS: This study showed that in HSES families, dysfunctional family processes and HR for schizophrenia increased the likelihoods for the development of psychiatric disorders in adoptees. The results can be utilized in identifying risk factors in the development of psychiatric disorders and focusing preventative strategies on risk groups with acknowledging the importance of family functioning.

Adolescent social functioning in offspring at high risk for schizophrenia spectrum disorders in the Finnish Adoptive Family Study of Schizophrenia.

BACKGROUND: Children and adolescents with a genetic risk for schizophrenia are often found to have poorer social functioning compared to their controls. However, less is known about high-risk offspring who have not been reared by a biological parent with schizophrenia. The purpose of this study was to examine deficits in social functioning in adolescence as a possible factor related to genetic vulnerability to schizophrenia spectrum disorders, and also to examine possible gender differences in these associations. METHOD: The present sample consisted of 88 genetic high-risk (HR) adoptees whose biological mothers were diagnosed with schizophrenia spectrum disorders and 83 genetic low-risk (LR) adoptees with biological mothers with non-schizophrenia spectrum disorders or no psychiatric disorders. Adoptees' social functioning at ages 16-20 was assessed using the UCLA Social Attainment Survey. RESULTS: Compared to LR adoptees, HR adoptees displayed statistically significant deficits in their peer relationships, involvement in activities and overall social functioning during adolescence. HR males were distinguished from LR males by their significantly poorer overall social functioning. Compared to HR females, HR males showed significant deficits in their romantic relationships. Of marginal significance was that HR females displayed more social functioning deficits relative to LR females, mainly in the areas of peer relationships, involvement in activities and overall social functioning. CONCLUSIONS: These results from the adoption and high-risk study design suggest that deficits in social functioning in adolescence may be related to genetic vulnerability to schizophrenia spectrum disorders and that some of these deficits may be gender-specific.

Interaction of genetic vulnerability to schizophrenia and family functioning in adopted-away offspring of mothers with schizophrenia.

OBJECTIVE: The aim of this study was to examine the association of family functioning to psychiatric disorders of adoptees with and without genetic vulnerability to schizophrenia. METHODS: The data is based on the Finnish Adoptive Family Study of Schizophrenia. The study sample consisted of 346 adoptive families, of which 175 adoptees had high (HR) and 171 low (LR) genetic risk for schizophrenia. DSM-III-R was used for diagnostic criteria. Family functioning was assessed using the Global Family Ratings. Childhood adversities covered early parental divorce and death occurring before 18 years of age of the adoptees. RESULTS: Approximately two thirds of the adoptees had lived in families with mildly dysfunctional processes (30%) or dysfunctional processes (28.4%). An increased likelihood for psychiatric disorders of the adoptees was related to dysfunctional family processes both in HR (OR = 4.8, 95% CI 2-11.4) and LR (OR = 2.6, 95% CI 1.1-6.3) adoptees, but not to early parental death or divorce. CONCLUSIONS: The risk for psychiatric disorders was increased for adoptees in families with dysfunctional processes, especially for those adoptees with genetic vulnerability to schizophrenia. These results emphasize the importance of policies and practices that aim to strengthen and support family functioning.

How is family interaction analysed as a risk factor for schizophrenia? A cross-method comparison.

In this paper, we compare two methodological approaches - Conversation Analysis (CA) and the Communication Deviance (CD) Scale - in detecting confusing family interaction, which is considered one of the risk factors for schizophrenia. CA is a method for identifying and describing actions in interaction, whereas the CD Scale presents the criteria for identifying communication defects in the field of schizophrenia research. Our aim is to determine whether the approaches resonate with and could complement each other in analysing the same interactional data - i.e., a total of 10.5 hours of audio-recorded Finnish family interaction in a psychological test in which the participants negotiate on mutual Rorschach inkblot interpretations. The data include 585 proposals by the family members. Here we focus on three types of proposal sequences (140 in all) where a proposal is not followed by an acceptance or a rejection. We have earlier shown that from the CA perspective, the family members orient to the discontinuity of these sequences by pursuing an explicit response to a proposal, but very rarely make the 'problematic' nature of the interaction visible to each other or the analyst. In the present paper, we will show that the CD Scale finds communication defects in the sequences under analysis but that the defects do not primarily involve the discontinuity of the sequence. Thus CA and the CD Scale look at interaction from different perspectives and disagree on what is considered an interactional problem.

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.

Pilot evaluation of the impact of structured child-centered interventions on psychiatric symptom profile of parents with serious somatic illness: struggle for life trial.

This is a trial of cancer patients who are seriously somatically ill and of how their distress affects their spouse or children. In the pilot phase the authors examined whether there are changes in psychiatric symptom profile of seriously somatically ill and healthy parents between assessments concerning a situation before the onset of parental illness, in current situation before intervention and 4 months after the intervention. The study is a family cluster, randomized, controlled treatment trial for parents and children in families with a parent who has a serious somatic illness. Global Severity Index (GSI) and psychiatric symptom profile of parents was assessed with the Symptoms Checklist-90 for adults. At pilot evaluation phase of the Struggle for Life trial, a total of 19 families (16 patients, 15 spouses) participated in the baseline assessment conducted before intervention, and 10 families (seven patients, seven spouses) also at the 4-month follow-up after the intervention. The interventions used in this study were the short Let's Talk about Children including two meetings with parents and more intensive Family Talk Intervention consisting of six to eight meetings with parents, children, and whole family. At the 4-month follow-up the GSI score of the patients and spouses was significantly decreased compared to the baseline score. At the baseline the GSI score of the patients was at the same level as that of the psychiatric outpatient sample, whereas at the 4-month follow-up it was at the same level as in the general population. This study lends support to previous studies that recommend that treatment practice should include structured interventions with parents concerning parenting and the wellbeing of children.

Verbal learning and memory and their associations with brain morphology and illness course in schizophrenia spectrum psychoses.

The California Verbal Learning Test and structural brain imaging were administered to 57 subjects with schizophrenia spectrum disorders and 94 controls in a general population sample. Cases had lower semantic cluster scores. Poorer verbal memory strategies were associated with longer duration of illness and heavier use of antipsychotic medication. After controlling for duration of illness, sex, and total gray matter, poorer verbal memory was associated with lower gray matter volume in the cingulate cortex, juxtapositional lobule, right superior temporal gyrus, and precuneus. After controlling for use of antipsychotic medication, there was an association between higher serial clustering and smaller anterior cingulate gyrus and larger intracalcarine cortex.

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.

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.