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We report clinical and social outcomes of schizophrenia in the longitudinal, population-based Northern Finland 1966 Birth Cohort, and describe associated demographic, developmental and illness-related factors.
Subjects and methods
Subjects with DSM-III-R schizophrenia (n = 59) were followed prospectively from mid-gestation up to age 35 years. Outcome measures included positive and negative symptoms, psychiatric hospitalisations, social and occupational functioning. Several definitions of good and poor outcome were explored, and developmental, socio-demographic and clinical predictors of outcomes were analysed.
Good clinical outcome varied from 10% to 59%, and good social outcome 15–46%, depending on definition. Poor clinical outcome varied 41–77% and poor social 37–54%. Lack of friends in childhood, father's high social class, lower school performance and earlier age of illness onset predicted poor outcomes.
The outcomes of schizophrenia in this study depended on definitions used but were relatively poor. The age of illness onset, father's social class, school performance and poor social contacts in childhood were only statistically significant predictors.
Definitions of outcome have a major effect on estimates for proportions of good and bad outcomes and on the predictors of outcomes. However, regardless of which definitions were used, the outcome of schizophrenia in this population-based sample was generally bleak.
To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.
Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).
The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).
The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.
There are lacking prospective studies in general population of adolescents about symptoms predicting the onset of first episode psychosis.
Members (N= 9,215) of the Northern Finland 1986 Birth Cohort, an unselected general population cohort, were invited to participate in a field survey during 2001, at ages of 15-16 years. The study included a 21-item PROD-screen questionnaire screening prodromal symptoms for psychosis for last six months (Heinimaa et al. 2003). PROD-screen included nine questions for positive and five questions for negative features. The Finnish Hospital Discharge Register was used to find out new cases of hospital treated mental disorders during 2002-2005.
Of the subjects 17 (0.3%) were treated due to first episode psychosis and 95 (1.5%) due to non-psychotic disorder during the follow-up period. Positive symptoms did not associate with the onset of psychosis, but negative symptoms did. 94% of subjects who got psychosis reported negative symptoms. Respective figure for those who were treated for non-psychotic disorder was 48%, and for those ‘healthy’ without psychiatric hospital treatment 46% (Fisher's exact test: psychosis vs. healthy p<0.001, psychosis vs. non-psychosis p<0.001, and non-psychosis vs. healthy p=0.61).
This study may be the only one exploring prospectively in general population features predicting onset of first episode psychosis. The findings emphasize the importance of negative symptoms in the development of neuropsychiatric disorder of first episode psychosis (Weinberger 1995).
The Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Sigrid Juselius Foundation and the Thule Institute, Finland.
ICD-10 delineates Acute and Transient Psychotic Disorders (ATPD, F 23) as distinct from schizophrenia and affective psychosis. We investigated the descriptive epidemiology of ATPD and predictive validity of the diagnosis, compared its three-year outcomes with affective psychosis and schizophrenia, and explored whether acute onset and early remission identify a distinct good outcome subgroup in non-affective psychoses.
Between 1992-1994, all first-episode psychosis patients in Nottingham were identified and assigned an intake ICD-10 diagnosis. Patients were assessed three years later using established outcome measures and longitudinal diagnosis assigned. Multivariate analyses were conducted to determine whether acute onset and early remission predicted favourable three-year outcome in non-affective psychotic disorders.
Of 168 cases of first-episode psychosis, 112 received an intake diagnosis of non-affective psychoses (F20-29) and 32 (19%) of ATPD (F23). ATPD diagnosis was stable in women over three years, but not in men. Outcomes of ATPD were better than schizophrenia and similar to affective psychosis. In non-affective psychoses, favourable outcomes were a function of gender and good premorbid functioning rather than acute onset and early remission.
ICD-10 ATPD criteria identify a diagnostically unstable group of disorders consisting of ‘good outcome’ schizophrenia, affective psychosis and a very small group of ‘true’ non-affective, non-schizophrenic acute and transient psychoses. Although ATPD have a better outcome than schizophrenia, in non-affective psychoses, acute onset and early remission do not independently predict favourable outcome over three years.
Subjects with family history of psychosis and with prodromal symptoms are at risk for schizophrenia. The aim was to study whether adolescents with familial risk have more commonly prodromal features.
Members (N= 9,215) of the Northern Finland 1986 Birth Cohort, an unselected general population cohort, were invited to participate in a field survey conducted during 2001-2002. At the ages of 15-16 years, the study included a 21-item PROD-screen questionnaire developed for screening prodromal psychotic symptoms with 12 specific questions for psychosis (Heinimaa et al. 2003). The scale measured symptoms for last six months. The Finnish Hospital Discharge Register was used to find out parental psychoses during 1972-2000.
Of the males 24% and 37% of the females were screen positives for prodromal features at the age of 15-16 years. Of the offspring, 1.8% had parents with psychosis. The prevalence of screen positives was 26% in males and 36% in females with familial risk for psychosis.
Prodromal features of psychosis are prevalent in adolescence. It may be difficult to screen adolescent subjects at risk for developing schizophrenia with a questionnaire in a general population, especially as these symptoms do not appear to be more common among subjects with familial risk.
The Academy of Finland, the National Institute of Mental Health, the Signe and Ane Gyllenberg Foundation and the Thule Institute, Finland.
Schizophrenia is considered to be a neurodevelopmental disorder arising as a result of interactions between genetic vulnerability and environmental risk factors. We studied the association between mothers" antenatal depressed mood and schizophrenia in their adult offspring with special consideration to Familial Risk for psychosis.
In the Northern Finland 1966 Birth Cohort mothers of 12,058 children were asked at mid-gestation at the antenatal clinic if they felt depressed. This general population birth cohort of the children was followed up for over 30 years, being record-linked with the Finnish Hospital Discharge Register (FHDR) for detecting psychosis in the subjects. The FHDR was also used for identifying psychosis in the parents. Familial Risk for psychosis was considered as a genetic risk factor and mothers’ depression as an environmental risk factor.
Offspring with both Familial Risk of psychosis and depressed mother had the highest cumulative incidence of schizophrenia, 7.4% (adjusted OR 10.3; 4.6-23.0). Of the offspring with only psychotic parent without antenatal depression, 2.3% got schizophrenia (OR 2.6; 1.2-5.4). In the offspring without Familial Risk of psychosis and with maternal depression the risk of developing schizophrenia was not elevated.
Mothers’ depressed mood during pregnancy per se is unlikely to increase the risk for schizophrenia in the offspring, but may effect in subjects at risk for psychosis. This finding is an example of a gene x environment interaction in the development of schizophrenia.
This work was supported by grants from the Signe and Ane Gyllenberg Foundation and the Academy of Finland.
Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.
Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.
Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.
Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.
Cannabis is a widely used drug, which effects on human health remain controversial. Recent studies have found correlations between cannabis use and brain structural changes that may be related to ageing processes. Eotaxin-1 is a chemokine described as a marker of ageing, which also appear to increase with cognitive deficits and neurogenesis. Here, we aimed at characterising the effect of cannabis in accelerating normal ageing processes, by studying eotaxin-1 plasma levels in people who currently use cannabis, have used cannabis in the past, or have never used cannabis.
A total of 87 healthy volunteers participated in the study. Participants completed the Cannabis Experience Questionnaire, the General Practice Physical Activity Questionnaire, the Sociodemographic, Morphometric, Alcohol and Tobacco Questionnaire, and provided a blood sample. Eotaxin-1 was assessed by ELISA. The three groups were compared using one-way ANOVA to assess levels of eotaxin-1, and nonpaired Student t-tests to assess other factors effects.
Current users of cannabis (n=18) had significantly higher eotaxin-1 plasma levels compared to past users of cannabis (n=33) and individuals who never used cannabis (n=36). The latter two groups had similar eotaxin-1 levels. Higher eotaxin-1 plasma levels were not attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs.
These results suggest that cannabis use increases eotaxin-1 plasma levels and could result in accelerated brain ageing. However, the effects appear to be reversible when cannabis use ceases. These findings have important implications for treatment and care of mental health disorders, such as schizophrenia.
There are limited amount of studies comparing time trends of incidence and risk factors of psychosis.
To compare time trends of incidence of psychosis in two population samples.
To study 1) onset age and cumulative incidence of psychoses in two Northern Finland Birth Cohorts (NFBC), 2) changes in type of diagnosis and risk factors.
The NFBC 1966 (N=12,058) and NFBC 1986 (N=9,432) are prospective cohorts of the two provinces of Finland with the live born children followed since pregnancy. The data for psychosis and risk factors were collected from variety of nationwide registers and earlier collected data of the NFBCs. The follow-up time was in both cohorts in average 26.5 years.
Proportion of all psychoses was higher in NFBC 1986 than in the NFBC 1966 (1.81% vs 1.0%). There were more affective psychoses in NFBC 1986 (0.5% vs 0.1%), but incidence of schizophrenia was the same (0.4%) in both cohorts. The age of onset was lower in NFBC 1986 than in NFBC 1966 and majority of this cases were females. Only parental psychosis was a significant risk factor predicting psychosis (Hazard Ratios >3.0) in both cohorts.
In conclusion, two birth cohorts within 20 years covering altogether about 40 years showed changes in terms of incidence, age of onset, and type of psychosis.
The effects of long-term antipsychotic medication on cognition in schizophrenia are unclear (Husa A.P. et al., Schizophr. Res. 2014).
Understanding how long-term antipsychotic treatment affects cognition is crucial for the development of safe, evidence-based treatment of schizophrenia.
To analyse the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia at age 43 years in a general population sample.
Sixty (33 males) schizophrenia spectrum subjects from the Northern Finland Birth Cohort 1966 were assessed at age 43 years by California Verbal Learning Test, Visual Object Learning Test, Abstraction Inhibition and Working Memory task, Verbal fluency, Visual series, Vocabulary, Digit Span and Matrix reasoning. Cumulative lifetime antipsychotic dose-years were collected from treatment records and interviews. A factor analysis based on the cognitive tests resulted in one cognitive factor. The association between this cognitive composite score and antipsychotic dose-years was analysed by linear regression.
Higher lifetime antipsychotic dose-years were statistically significantly associated with poorer cognitive composite score at age 43 years (B=-0.32, p>0.001), also when adjusted for gender, onset age, remission and number of hospital treatment days (B=-0.42, p=0.008).
To our knowledge, this is the first report of an association between cumulative lifetime antipsychotic dose and cognition in midlife in schizophrenia. Based on this data, the use of high antipsychotic doses may relate to poorer cognitive functioning in schizophrenia after twenty years of illness. These results do not support the view that antipsychotics prevent cognitive decline or promote cognitive recovery in schizophrenia.
Our aim was to investigate how age of achieving early motor developmental milestones differ among subjects with and without a history of parental psychosis and whether parental psychosis may alter the effects of the age of achievement on the risk of schizophrenia.
The study sample comprised 10,307 individuals from the prospective Northern Finland Birth Cohort 1966. A total of 139 (1.3%) cohort members suffered from schizophrenia by the age of 46 years. Out of them 19 (13.7%) had a parent with a history of psychosis, while among the non-psychotic cohort members this figure was 524 (5.2%).
Out of eight different motor milestones investigated, parental psychosis associated (p>0.05) with later learning of holding head up, grabbing object, and walking without support. In the parental psychosis group, significant risk factors for schizophrenia included later learning of holding head up and touching thumb with index finger. In the non-parental psychosis group risk estimates were lower and statistical significant milestones were different i.e. turning over, sitting without support, standing up, standing and walking without support. Interactions between parental psychosis and touching thumb with index finger and walking without support was found.
Although parental psychosis associated with delays in motor milestones in the first year of life, it does not explain the association between late achievement of motor milestones and later risk for schizophrenia
Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.
Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.
Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.
Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.