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G Fraser,
R Breuer,
E Vassos,
N Durmishi,
T Silagadze,
M C O'Donovan,
U Thorsteinsdottir,
B Etain,
I Melle,
J B Vincent, [......],
M Arrojo,
M Raleva,
V Kaleda,
J Powell,
B Riley,
K Paketchieva,
N Craddock,
J Sanjuán,
M J Owen,
I Giegling
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ABSTRACT: BACKGROUND: Both low birthweight and high birthweight have been associated with an increased risk for schizophrenia and cognitive impairments in the general population. We assessed the association between birthweight and cognitive performance in persons with schizophrenia and their unaffected first-degree relatives. Method We investigated a population-based family sample comprising persons with schizophrenia (n = 142) and their unaffected first-degree relatives (n = 277). Both patients and relatives were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) and a comprehensive neuropsychological test battery was administered. Information on birthweight was obtained from obstetric records. We used generalized estimating equation (GEE) models to investigate the effect of birthweight, as a continuous variable, on cognitive functioning, adjusting for within-family correlation and relevant covariates. RESULTS: Both low birthweight and high birthweight were associated with lower performance in visuospatial reasoning, processing speed, set-shifting and verbal and visual working memory among persons with schizophrenia and their unaffected first-degree relatives compared to individuals with birthweight in the intermediate range. The group × birthweight interactions were non-significant. CONCLUSIONS: Both low birthweight and high birthweight are associated with deficits in cognition later in life. Schizophrenia does not seem to modify the relationship between birthweight and cognition in families with schizophrenia.
Psychological Medicine 01/2013; · 6.16 Impact Factor
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S Steinberg,
S de Jong,
M Mattheisen,
J Costas,
D Demontis,
S Jamain,
O P H Pietiläinen,
K Lin,
S Papiol,
J Huttenlocher, [......],
M Rietschel,
S Cichon,
M Ruggeri,
S Tosato,
A Palotie,
D St Clair,
D Rujescu,
D A Collier,
H Stefansson,
K Stefansson
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ABSTRACT: Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).Molecular Psychiatry advance online publication, 20 November 2012; doi:10.1038/mp.2012.157.
Molecular psychiatry 11/2012; · 15.05 Impact Factor
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ABSTRACT: Cognitive functioning in anxiety disorders has received little investigation, particularly among young adults and in non-clinical samples. The present study examined cognitive functioning in a population-based sample of young adults with anxiety disorders in comparison to healthy peers.
A population-based sample of 21-35-year-olds with a lifetime history of anxiety disorders (n=75) and a random sample of healthy controls (n=71) derived from the same population were compared in terms of performance in neuropsychological tests measuring verbal and visual short-term memory, verbal long-term memory, attention, psychomotor processing speed, and executive functioning.
In general, young adults with anxiety disorders did not have major cognitive impairments when compared to healthy peers. When participants with anxiety disorder in remission were excluded, persons with current anxiety disorder scored lower in visual working memory tests. Current psychotropic medication use and low current psychosocial functioning associated with deficits in executive functioning, psychomotor processing speed, and visual short-term memory.
Lifetime history of anxiety disorders is not associated with cognitive impairment among young adults in the general population. However, among persons with anxiety disorders, current psychotropic medication use and low psychosocial functioning, indicating more severe symptoms, may associate with cognitive impairments.
European Psychiatry 09/2011; 26(6):346-53. · 2.77 Impact Factor
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ABSTRACT: The determinants of everyday functioning in persons with psychotic disorder have not been widely studied in community dwelling samples. Our aim was to investigate limitations in everyday functioning among subjects with psychotic disorders in a population-based study.
Everyday functioning was assessed in a nationally representative sample of 7112 persons aged 30+ using interviewer observations and self-reports, while verbal fluency and memory were also measured. Diagnostic assessment of DSM-IV psychotic disorders was based on SCID interview and case-note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia (n=61), other non-affective psychotic disorders (ONAP) (n=79) and affective psychoses (n=45).
Non-affective psychotic disorder was significantly associated with limitations in everyday functioning, as well as with deficits in verbal fluency and memory. Negative symptoms, depression, age, gender, verbal memory deficits, and reduced visual acuity were predictors of limitations in everyday functioning even after controlling for sociodemographic factors and chronic medical conditions, and difficulties in social functioning were also related to expressive speech problems.
Persons with schizophrenia and ONAP have significantly more problems in everyday functioning than the general population. One significant predictor of problems was reduced visual acuity, which at least in some situations could be easily corrected.
European Psychiatry 03/2011; 27(6):409-15. · 2.77 Impact Factor
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ABSTRACT: Cognitive deficits in alcohol dependence (AD) have been observed, poorer verbal ability being among the most consistent findings. Genetic factors influence both cognitive ability and AD, but whether these influences overlap is not known.
A subset of 602 monozygotic (MZ) and dizygotic (DZ) twins from FinnTwin16, a population-based study of Finnish twins, was used to study the associations of verbal ability with DSM-III-R diagnosis and symptoms of AD, the maximum number of drinks consumed in a 24-h period, and the Rutgers Alcohol Problem Index (RAPI) scores. These twins, most of them selected for within-pair discordance or concordance for their RAPI scores at age 18.5 years, were studied with neuropsychological tests and interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) in young adulthood (mean age 26.2 years, range 23-30 years).
All alcohol problem measures were associated with lower scores on the Vocabulary subtest of the Wechsler Adult Intelligence Scale - Revised (WAIS-R), a measure of verbal ability. In bivariate genetic models, Vocabulary and the alcohol problem measures had moderate heritabilities (0.54-0.72), and their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31).
Poorer verbal ability and AD have partly overlapping biological etiology. The genetic and environmental influences on the development of cognitive abilities, alcohol problems and risk factors for AD should be studied further with prospective longitudinal designs.
Psychological Medicine 03/2011; 41(3):641-51. · 6.16 Impact Factor
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S Steinberg,
O Mors,
A D Børglum,
O Gustafsson,
T Werge,
P B Mortensen,
O A Andreassen,
E Sigurdsson,
T E Thorgeirsson,
Y Böttcher, [......],
I Agartz,
H Petursson,
M M Nöthen,
M Rietschel,
L Peltonen,
D Rujescu,
D A Collier,
H Stefansson,
D St Clair,
K Stefansson
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ABSTRACT: A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).
Molecular psychiatry 01/2011; 16(1):59-66. · 15.05 Impact Factor
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P Soronen,
H M Ollila,
M Antila,
K Silander,
O M Palo,
T Kieseppä,
J Lönnqvist,
L Peltonen, A Tuulio-Henriksson,
T Partonen,
T Paunio
Molecular psychiatry 01/2010; 15(1):4-6. · 15.05 Impact Factor
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A Ingason,
D Rujescu,
S Cichon,
E Sigurdsson,
T Sigmundsson,
O P H Pietiläinen,
J E Buizer-Voskamp,
E Strengman,
C Francks,
P Muglia, [......],
T Werge,
R A Ophoff,
M Rietschel,
M M Nöthen,
H Petursson,
H Stefansson,
L Peltonen,
D Collier,
K Stefansson,
D M St Clair
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ABSTRACT: Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.
Molecular psychiatry 09/2009; 16(1):17-25. · 15.05 Impact Factor
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ABSTRACT: Mental health risk factors in adolescence were examined as predictors of mental distress in early adulthood. A cohort of 709 Finnish adolescents was studied in 1990 (mean age 16.8) and in 1995. Trait anxiety, defence styles, life events, self-esteem and somatic symptoms were evaluated as predictors of high scores in the General Health Questionnaire in adulthood. Females (36%) were more likely to be distressed than males (23%). High trait anxiety and somatic symptom scores among adolescent females, and high immature defence style scores among males predicted mental distress. Males with low trait anxiety in adolescence had less distress. The results indicate trait anxiety as an important predictor of mental distress. Gender differences in other predictors suggest gender differences in coping.
07/2009; 56(2):121-125.
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ABSTRACT: Psychiatric co-morbidity is often inadequately controlled for in studies on cognitive functioning in depression. Our recent study established no major deficits in cognition among young adults with a history of pure unipolar depression. The present study extends our previous work by examining the effects of psychiatric co-morbidity and other disorder characteristics on depression-related cognitive functioning.
Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample aged 21-35 years with a lifetime history of unipolar depressive disorders (n=126) and a random sample of healthy controls derived from the same population (n=71). Cognitive functioning was also compared between the subgroups of pure (n=69) and co-morbid (n=57) depression.
The subgroups of pure and co-morbid depression did not differ in any of the cognitive measures assessed. Only mildly compromised verbal learning was found among depressed young adults in total, but no other cognitive deficits occurred. Received treatment was associated with more impaired verbal memory and executive functioning, and younger age at first disorder onset with more impaired executive functioning.
Psychiatric co-morbidity may not aggravate cognitive functioning among depressed young adults. Regardless of co-morbidity, treatment seeking is associated with cognitive deficits, suggesting that these deficits relate to more distress.
Psychological Medicine 06/2009; 40(1):29-39. · 6.16 Impact Factor
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J Wedenoja,
A Loukola, A Tuulio-Henriksson,
T Paunio,
J Ekelund,
K Silander,
T Varilo,
K Heikkilä,
J Suvisaari,
T Partonen,
J Lönnqvist,
L Peltonen
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ABSTRACT: Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.
Molecular psychiatry 08/2008; 13(7):673-84. · 15.05 Impact Factor
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J Suvisaari,
T Aalto-Setälä, A Tuulio-Henriksson,
T Härkänen,
S I Saarni,
J Perälä,
M Schreck,
A Castaneda,
J Hintikka,
L Kestilä,
S Lähteenmäki,
A Latvala,
S Koskinen,
M Marttunen,
H Aro,
J Lönnqvist
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ABSTRACT: The effect of mental disorders may be particularly detrimental in early adulthood, and information on mental disorders and their correlates in this age group is important.
A questionnaire focusing on mental health was sent to a nationally representative two-stage cluster sample of 1863 Finns aged 19 to 34 years. Based on a mental health screen, all screen-positives and a random sample of screen-negatives were asked to participate in a mental health assessment, consisting of the Structured Clinical Interview for DSM-IV (SCID-I) interview and neuropsychological assessment. We also obtained case-notes from all lifetime mental health treatments. This paper presents prevalences, sociodemographic associations and treatment contacts for current and lifetime mental disorders.
Forty percent of these young Finnish adults had at least one lifetime DSM-IV Axis I disorder, and 15% had a current disorder. The most common lifetime disorders were depressive disorders (17.7%) followed by substance abuse or dependence (14.2%) and anxiety disorders (12.6%). Of persons with any lifetime Axis I disorder, 59.2% had more than one disorder. Lower education and unemployment were strongly associated with current and lifetime disorders, particularly involving substance use. Although 58.3% of persons with a current Axis I disorder had received treatment at some point, only 24.2% had current treatment contact. However, 77.1% of persons with a current Axis I disorder who felt in need of treatment for mental health problems had current treatment contact.
Mental disorders in young adulthood are common and often co-morbid, and they may be particularly harmful for education and employment in this age group.
Psychological Medicine 06/2008; 39(2):287-99. · 6.16 Impact Factor
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ABSTRACT: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset.
Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70).
Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning.
The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected.
The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction.
Journal of Affective Disorders 03/2008; 110(1-2):36-45. · 3.52 Impact Factor
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ABSTRACT: We have previously reported evidence of linkage and association between markers on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish nuclear families, leading to the recent identification of four significantly associated haplotypes that specifically implicate the Translin-Associated Factor X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the genetic etiology of schizophrenia. Previously, the DISC genes were found to be disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with schizophrenia and related disorders in a large Scottish pedigree. Interestingly, we also reported earlier suggestive linkage between endophenotypic quantitative traits of visual and verbal memory and microsatellite markers in close proximity to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of TRAX/DISC would be associated with visual and/or verbal memory function impairments that are known to aggregate with schizophrenia in families. One haplotype of DISC1, HEP3, displayed association with poorer performance on tests assessing short-term visual memory and attention. Analysis of affected and unaffected offspring separately revealed that both samples contribute to the observed association to visual working memory. These results provide genetic support to the view that the DISC1 gene contributes to sensitivity to schizophrenia and associated disturbances and affects short-term visual memory functions. This finding should stimulate studies aiming at the molecular characterization of how the specific alleles of DISC1 affect the visual memory functions and eventually participates in the development of schizophrenia.
Molecular Psychiatry 01/2006; 10(12):1097-103. · 13.67 Impact Factor
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ABSTRACT: We aimed to evaluate the diagnostic accuracy of a highly structured diagnostic interview in relation to a semi-structured diagnostic procedure. We compared the World Health Organization Composite International Diagnostic Interview Short Form (CIDI-SF) in diagnosing major depressive episode (MDE) to consensus diagnoses based on the SCAN interview (Schedules for Clinical Assessment in Neuropsychiatry).
Subjects comprised a follow-up sample of 239 20-24-year-old former high-school students who were administered the SCAN and immediately thereafter the CIDI-SF. Concordance was estimated for 12-month MDE, using different cut-points of the CIDI-SF and for any affective disorders.
Correspondence between instruments was moderate for MDE (kappa = 0.43, sensitivity 0.71, specificity 0.82), but better for any affective disorder (kappa = 0.60, sensitivity 0.70, specificity 0.90). Most false negatives suffered from their depression as much as those correctly identified by the CIDI-SF. False negativity was mainly due to not endorsing the stem questions of the CIDI-SF. Of the false positives almost half had an affective disorder other than MDE.
The CIDI-SF seems to function best in identifying a broader category of affective disorders. It could be useful in large-scale community surveys where more extensive psychiatric interviews are not feasible.
Psychological Medicine 11/2002; 32(7):1309-14. · 6.16 Impact Factor
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ABSTRACT: We aimed to provide prevalence data on depression and other current mental disorders, impairment, need of psychiatric care and use of mental health services among young adults.
Based on a semi-structured clinical interview, current DSM-IV disorders, impairment, need of psychiatric care and use of mental health services were evaluated in a sample of 20-24-year-old young urban adults (N = 245), mean age 21.8, screened from a baseline population of 706. One-month prevalence estimates for disorders were calculated by the double sampling method, using various additional criteria to identify cases.
One in four young adults (23.8%) suffered from a current mental disorder, the most prevalent being depressive (10.8%), anxiety (6.9%), substance use (6.2%) and personality disorders (6.0%). Prevalence estimates varied substantially according to the use of additional diagnostic criteria. Impairment (GAF < 61) together with DSM-IV symptom criteria produced an overall disorder prevalence of 10.3%, and 5.5% for depression. Prevalences were higher for females than males, except for alcohol abuse and personality disorders. Current co-morbidity was found in 39% of subjects with any disorder, and in more than half of those with depression. One-third of subjects with a current disorder reported an associated contact with psychiatric services and 16% had an ongoing contact.
Our findings support the use of additional criteria to produce clinically relevant prevalence data. Co-morbidity should receive special attention due to its amplification of both need for psychiatric care and severity of impairment. Finally, our results show disturbed young adults to be severely undertreated.
Psychological Medicine 08/2001; 31(5):791-801. · 6.16 Impact Factor
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ABSTRACT: Background. We aimed to provide prevalence data on depression and other current mental disorders, impairment, need of psychiatric care and use of mental health services among young adults.
Psychological Medicine 06/2001; 31(05):791 - 801. · 6.16 Impact Factor
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ABSTRACT: Initiation to cannabis is often the first step in the use of illicit drugs. We studied the correlates of initiation in a 5-year follow-up study. A total of 21.4% of the subjects reported using cannabis at some time. Of the 139 users, 89.2% had tried cannabis not more than once or a few times. This initiation to cannabis was related to male gender, absence of mother, frequent lack of interest and early age at first sexual intercourse in logistic regression analysis. These factors seem to be useful in predicting initiation to cannabis.
Drug and Alcohol Dependence 06/2001; 62(3):175-80. · 3.38 Impact Factor
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ABSTRACT: Somatisation is common among adolescents.
To study factors predicting somatisation later in adulthood.
Self report questionnaires were administered at baseline examination in 1990 to students (mean age 16.8 years) in schools, and by mail five years later. Results are based on the 615 subjects with no serious disease or injury at baseline.
Regression analyses showed that in men the level of somatic symptoms in 1995 was significantly predicted by the respective level in 1990 and by relief smoking. In women, the level of somatic symptoms in 1995 was significantly predicted by the respective level in 1990, self esteem, and the number of negative life events in 1990. After exclusion of cases with a long standing disease in 1995, the multivariate results remained materially similar except that self esteem was no longer significant among women.
These findings may help in early identification of adolescents with somatisation persisting into early adulthood.
Archives of Disease in Childhood 12/2000; 83(5):388-92. · 2.88 Impact Factor
