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To describe symptom expression and functional outcome in psychotic disorders in relation with temperament traits assessed with the Temperament and Character Inventory (TCI) in a population-based sample.
As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort, TCI temperament items were filled in by 4349 members of the cohort. In individuals with psychotic disorders, also positive and negative symptoms and outcome variables were assessed in a 35-year follow-up. Information of TCI and outcomes were available for altogether 41 individuals with psychosis.
Reward dependence (RD) (rho = −0.45) and Persistence (P) (rho = −0.52) were significantly correlated with Positive and Negative Syndrome Scale (PANSS) negative symptoms. Higher P scores predicted higher social and occupational functioning (as measured by Social and Occupational Functioning Assessment Scale [SOFAS]), and higher Harm avoidance (HA) predicted a higher likelihood of being on a disability pension.
Results indicate that understanding of personality dimensions support better understanding of outcome and symptom expressions in psychotic disorders.
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.
We study the predictive power and associations of several psychological scales with respect to hospitalisations due to schizophrenic psychoses.
Temperament and Character Inventory, Physical Anhedonia Scale, Social Anhedonia Scale, Perceptual Aberration Scale, Hypomanic Personality Scale, Bipolar II Scale, and Schizoidia Scale were included in the 31-year follow-up survey of the prospective Northern Finland 1966 Birth Cohort (N=4,926). We compared subjects without any previous hospitalisations to those with previous hospital diagnoses (concurrent validity) and to those who in the eight year long follow-up were hospitalised due to schizophrenic psychosis (predictive validity). We also compared the subjects with schizophrenic psychoses and subjects with other psychiatric disorders (discriminant validity).
In most scales, subjects with schizophrenic psychoses differed from healthy subjects. The Perceptual Aberration Scale was the best scales for concurrent (Effect Size, d = 1.89) and discriminant validity (d = 0.64). Subjects having a high score in Hypomanic Personality Scale were in the highest risk for schizophrenic psychoses (OR 10.72; 95% CI 2.87-40.06).
Subjects with schizophrenic psychoses differed in most of the scales from healthy controls and from subjects with other psychiatric disorders. Many of the scales were useful predictors for future hospitalisations due to schizophrenic psychoses; however scales were not very diagnosis specific. The predictive power of the scales is limited, these scales are probably not useful as screening instruments but can be used in several ways when studying e.g. risk factors or genetics of schizophrenic psychoses.
Follow-up studies of schizophrenia have reported divergent rates of outcomes. In addition to definition and measurement challenges, one reason for divergence may be due to sampling biases. Our aim was to report clinical and social outcomes of schizophrenia in the longitudinal, unselected, population-based Northern Finland 1966 Birth Cohort, and describe associated factors.
Subjects with DSM-III-R schizophrenia (N=109) were followed prospectively from mid-pregnancy up to age 35 years. Used outcome measures were positive and negative symptoms, global clinical impression, use of antipsychotics, psychiatric hospitalisations, social and occupational functioning. Several definitions of good and poor outcomes were explored, and predictors of outcomes were analysed.
In a subsample of 59 cases with complete information of outcomes, good clinical outcome varied from 10% to 59%, and good social outcome 15-46%, depending on definition of outcomes. Poor clinical outcome varied 41-77% and poor social 37-54%. Two subjects recovered fully using the most stringent definition of outcome. Lack of friends in childhood, father's high social class, lower school performance and earlier age of illness onset predicted poor outcomes. When the whole sample was considered, early infant development around the age of 1 year was associated with worse course of illness.
Outcomes were heterogeneous and relatively poor in this sample of relatively young schizophrenia subjects. The results were influenced by the definitions and measurements of outcomes. Persons having a sub-optimal developmental trajectory with poor social contacts, poor school performance, and early age of illness onset seem to have the worst outcome.
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.
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.
Several instruments have been developed to detect subjects who are at risk for mental disorders.
We aimed to address the predictive validity of several personality, schizotypal and mania scales for psychiatric hospitalisations.
As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort, Temperament and Character Inventory (TCI, temperament part), Physical Anhedonia Scale, Social Anhedonia Scale (SAS), Perceptual Aberration Scale, Hypomanic Personality Scale (HPS), Bipolar II scale (BIP2) and Schizoidia scale were filled in by 4,857 subjects. We dichotomized scores in the scales (highest 10% by gender vs. others). Also subscales of TCI and BIP2 were used as predictors. In a longitudinal study setting using hospital discharge register we followed those without previous hospitalisation (N=4,727; 2,092 males and 2,635 females) from 31 years for eight years and recorded hospitalisations due to psychotic, substance use, anxiety, mood and personality disorders.
In total 78 (1.7%) of subjects were hospitalized due to psychiatric disorder during the follow-up. Most of the instruments predicted several disorders. Mood lability subscale of BIP2 predicted (p<0.05) all diagnostic groups. Most specific predictors were SAS (Odds Ratio 3.84; 95% CI 1.44-10.28) and HPS (4.01; 1.52-10.60) for psychosis and novelty seeking subscale of TCI (3.00; 1.41-6.36) and energy/activity (2.68; 1.26-5.68) and social anxiety (3.90; 1.84-8.28) subscales of BIP2 for substance use disorders.
Scales measuring schizotypal or manic symptoms were good predictors for different psychiatric hospitalisations. Many of the scales predicted several disorders, only few scales predicted only one specific disorder.
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.
Social withdrawal is among the first signs of the prodromal state of psychosis seen in clinical samples. The aim of this prospective study was to find out whether difficulty in making contact with others and social withdrawal precede first episode psychosis in the young general population.
The members of the Northern Finland Birth Cohort 1986 (n = 6274) completed the PROD-screen questionnaire in 2001–2002. The Finnish Hospital Discharge Register was used to detect both new psychotic and non-psychotic disorders requiring hospitalisation during 2003–2008.
Twenty-three subjects developed psychosis and 89 developed a non-psychotic mental disorder requiring hospitalisation during the follow-up. Of those who developed psychosis, 35% had reported difficulty or uncertainty in making contact with others and 30% social withdrawal in adolescence. In hospitalised non-psychotic disorder, the corresponding precentages were 10 and 13% and in the control group without hospital-treated mental disorder 9 and 11%. The differences between psychotic and non-psychotic hospitalised subjects (P < 0.01) as well as controls (P < 0.001) were statistically significant regarding difficulty or uncertainty in making contact with others.
In this general population-based sample self-reported difficulty or uncertainty in making contact with others in adolescence preceded psychosis specifically compared to hospitalised non-psychotic mental disorders and controls.
To analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample.
The sample was the Northern Finland 1966 Birth Cohort. In 1999–2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates.
After controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness.
This study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.
In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness.
Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools.
Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d = –0.51, P = 0.078). Time without antipsychotic medication associated with increased TGM (P = 0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry.
Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.
Since the outcome in schizophrenia is heterogeneous and often poor, identification of specific predictors of outcome would be useful in clinical practice.
Subjects with schizophrenic psychoses (n = 103) included in the Northern Finland 1966 Birth Cohort (n = 12,058), representing the general population, were followed-up for an average of 16.4 years. Predictor and outcome data were collected from the nationwide Finnish Hospital Discharge Register, hospital records and interviews.
Insidious onset of illness predicted a rehospitalization due to psychosis in the 2 years after the initial discharge. Being single, having an early onset, insidious onset, suicidal ideations upon the first admission, a rehospitalization and a high number of treatment days due to psychosis in the early stages of the illness all predicted a poorer clinical outcome in the longer term, after a minimum follow-up of 10 years.
This population-based study indicates that clinical and sociodemographic factors around the onset of illness have significance for the long-term outcome in schizophrenia. These prognostic factors should be taken into account in clinical practice.
The participation rates in epidemiologic studies have declined in recent decades. Missing data reduce sample size, statistical power, and scientific quality.
To study use of home interviews in recruiting individuals with a psychosis.
To evaluate effect of home-recruitment on non-response bias.
In the Northern Finland 1966 Birth Cohort, field surveys on psychosis were conducted in 1999-2001 and 2008-2010. In order to increase participation in the follow-up sample, cases were offered to be interviewed at home. We studied symptoms, illness severity, functioning, cognition, antipsychotics use, and grey matter (GM) volume between home-recruited and regular participants (RP), and non-participants (NP). Effect sizes (d) were calculated to compare the differences.
Altogether 18 (33%) out of the follow-up sample (n=54) were home-recruited, 27 did not participate. Home-recruited had more symptoms, lower functioning, cognition and GM volume, and they had used more antipsychotics compared to RP and NP in baseline. NP did not differ from RP. The same differences occurred when home-recruited were compared with RP in the follow-up study.
[Selected information from baseline study]
CVLT, total recall
Grey matter volume
Owing to the home-recruitment we were able to collect data that may be reasonably non-biased in terms of nonresponse bias, which will yield valid estimates in our future studies on change over time in brain and cognitive ability, prevalence and severity of psychotic illnesses, outcome, medication use, and other issues of interest.
Recently many studies have suggested more brain morphometric changes occurring in people with schizophrenia who use antipsychotic medication compared to those who do not.
We will study the brain morphology of subjects with schizophrenia spectrum disorder with and without antipsychotic medication.
Our aim was to compare the brain morphology of subjects with schizophrenia spectrum disorder with and without antipsychotic medication after in average ten years of illness, and analyse the association between cumulative dose of lifetime antipsychotic medication and brain morphology.
Data of 66 subjects with schizophrenia spectrum disorder (mean duration of illness 10.4 years) from the Northern Finland 1966 Birth Cohort were gathered by interview and from hospital records. Structural MRI data at age 34 years were acquired from all participants on a GE Signa system operating at 1.5T.
Of the subjects 16 (24%) had taken no antipsychotics during the previous year. We found no significant differences on total grey matter volumes (TGM) between subjects with and without antipsychotic medication. In the voxel-based analyses subjects with medication had lower volume in left parahippocampal gurys (p = 0.003), when adjusted for sex, onset age, TGM and remission status. There were no associations between lifetime antipsychotic dose and brain morphology.
We were able to study effects of antipsychotic medication in population-based sample. Brain morphology in medicated and non-medicated persons were similar and the cumulative lifetime medication had no effect on brain morphology, which suggests that possible medication effect in cross-sectional measures of brain morphology is small.
Recent studies have shown that cannabis use acts as a specific risk factor provoking the onset of psychosis in vulnerable individuals. Association of adolescent cannabis use and psychosis risk was studied after adjustment with prodromal symptoms.
To assess possible causality between cannabis use and the risk of psychosis.
To examine associations between cannabis use and the risk of psychosis in 10 years follow-up while taking into account the prodromal symptoms of psychosis in a prospective general population sample.
The sample (N=6258) composed of a prospective Northern Finland Birth Cohort 1986. Questionnaire on prodromal symptoms for psychosis (PROD-screen) and on drug use was conducted when the cohort members were 15-16 years old. The participants were asked if they had tried cannabis: never, once, 2-4 times, 5 times or more. Information on psychoses was gathered from registers until age 27 years.
In total 102 new psychoses emerged. The proportion of psychoses in the groups 'never”, 'once”, '2-4 times”, '5 times or more” were 1.5%, 2.8%, 3.6%, and 8.5%, respectively. The hazard ratio (HR) for risk of psychosis in subjects who had tried cannabis 5 times or more was 5.9 (95% CI 2.4-14.4) when compared to non-users. The association remained statistically significant when adjusted for prodromal symptoms and parental psychosis (HR 2.6, 1.0-6.6). When gender and smoking was taken into account association was no longer significant (HR 2.3, 0.9-6.0).
Adolescent cannabis use associates with increased risk of first-episode psychosis even after controlling for baseline prodromal symptoms.
Relatively little is known on longitudinal effects of antipsychotic medication on brain morphometry in schizophrenia after the illness onset. There are inconsistent findings on medication effects on brain structures.
We will study the effect of antipsychotic medication on brain volumes in schizophrenia.
The aim of the current study was to systematically review previous literature on longitudinal MRI studies of antipsychotic effects on brain morphometric changes in schizophrenia and related psychoses.
Studies were systematically collected using four different databases. A study was included if subjects were scanned twice, the average scanning interval was at least two years and antipsychotic medication data was used to predict morphometric changes. The studies focused on several different brain areas; we categorized these into eleven larger areas.
In total 22 studies fulfilled our inclusion criteria. The main finding of our study was that most of the reported correlations were statistically non-significant. The significant associations between antipsychotic use and brain changes were reported from various areas. In the studies with significant findings, use of antipsychotics more often associated with decrease than increase of brain volumes, even in the very few studies taking into account illness severity.
Antipsychotic medication should be adjusted to lowest possible dose for reducing psychotic symptoms and prescribed with caution especially to people not suffering from psychosis. More studies in different kind of patient populations are needed to clarify the possible adverse effect antipsychotic medication may have on brain structure.
We analyzed longitudinal course of illness in schizophrenia until age 43 years, and its correlates to antipsychotic medication and cognition.
Northern Finland 1966 Birth Cohort Study has been followed serially since mid-pregnancy. Structural and functional MRI, cognitive, and clinical examinations were performed at ages 34 (73 schizophrenic psychoses, 104 controls) and 43 (63 schizophrenic psychoses, 192 controls); 40 cases and 75 controls participated in both surveys. Psychiatric outcomes have been ascertained through data linkage to a national case registers, hospital charts and clinical evaluations.
Prognosis of schizophrenia is heterogeneous: minority of individuals experience recovery, some achieve remission, but many are on disability pension, and excess mortality (especially suicides) is common. Long duration of untreated psychosis, early age of illness onset and presence of suicidal ideation associated with poorer long-term outcome. Both cases and non-psychotic controls show a small decline in verbal learning and memory, but the difference in decline is not significantly more pronounced in cases. Higher doses of antipsychotics at age 43-years associated to lower education and poorer clinical and functional outcomes, and high cumulative life-time use of antipsychotics associated to decrease of verbal learning and memory in 9-year follow-up.
Based on this naturalistic sample, midlife progression of schizophrenia may follow a variety of different trajectories. Poor clinical course is common but not necessary outcome. Compared to controls, more pronounced cognitive decline was not seen in schizophrenia cases. However, high doses of antipsychotics may relate to a decrease of verbal learning and memory.