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Biomedical subjects

M O Huttunen

Publications and source records attributed to M O Huttunen.

At least 19 recordsLinked to original sources
PubMed2001

Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia.

Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.

Adult↗
PubMed2000

The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.

While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., "remembering" nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.

Adult↗
PubMed2000

Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort.

OBJECTIVE: Although case-control investigations have shown an association between obstetric complications and schizophrenia, particularly among patients with early onsets, cohort studies have mostly failed to confirm this effect. The authors examined whether a history of fetal hypoxia and other obstetric complications elevated risk for early-onset schizophrenia in a 1955 Helsinki birth cohort. METHOD: The subjects were 80 randomly selected patients with schizophrenia (36 with early and 44 with later onsets) representative of all available probands in the cohort, 61 of their nonschizophrenic siblings, and 56 demographically matched nonpsychiatric comparison subjects. Psychiatric diagnoses were obtained from structured clinical interviews, and obstetric data were taken from standardized, prospectively ascertained obstetric records. A score for hypoxia-associated obstetric complications was entered into logistic regression models, along with measures of prenatal infection and fetal growth retardation. RESULTS: Hypoxia-associated obstetric complications significantly increased the odds of early-onset schizophrenia but not of later-onset schizophrenia or unaffected sibling status, after prenatal infection and fetal growth retardation were taken into account. CONCLUSIONS: These findings support an association between obstetric complications and increased risk for early-onset schizophrenia. The authors advance a model whereby the neurotoxic effects of fetal hypoxia may lead to an early onset of schizophrenia due to premature cortical synaptic pruning.

Adult↗
PubMed1999

School performance in Finnish children and later development of schizophrenia: a population-based longitudinal study.

BACKGROUND: We examined whether children who are diagnosed as having schizophrenia in adulthood could be distinguished from their peers on performance in elementary school. METHODS: We used a case-control study design nested within a population-based birth cohort of all individuals born in Helsinki, Finland, between January 1, 1951, and December 31, 1960. Case ascertainment was from 3 national health care registers. Elementary school records were obtained for 400 children who were diagnosed as having schizophrenia in adulthood and for 408 controls. Results were analyzed for the 4 years of schooling (ages 7-11 years) that were common to all pupils. School subjects were entered into a principal components analysis and produced 3 factors: academic, nonacademic, and behavioral. These factors were compared between cases and controls after adjusting for sex and social group. Eligibility for high school and progression to high school were investigated among cases and controls. RESULTS: Cases performed significantly worse than controls only on the nonacademic factor (which loaded sports and handicrafts). There were no differences between the groups on the academic or behavioral factors, and there were no significant clinical correlates of factor scores. Cases were significantly less likely than controls to progress to high school, despite similar eligibility. CONCLUSIONS: Poor performance in sports and handicrafts during elementary school, which may indicate a motor coordination deficit, appears to be a risk factor for later schizophrenia. Poor academic performance in elementary school was not a risk factor for schizophrenia in this study. Lack of expected progression to high school among cases, despite good academic grades, provides evidence for deteriorating premorbid functional adjustment in schizophrenia.

Achievement↗
PubMed1999

Nausea during pregnancy: relation to early childhood temperament and behavior problems at twelve years.

Associations between maternal nausea during pregnancy and child behavioral outcomes were investigated in a large birth cohort. Generally, 2nd- and 3rd-trimester nausea were more predictive of child outcomes than 1st-trimester nausea. Children whose mothers reported nausea in middle or late pregnancy had lower sensory thresholds and higher levels of activity and emotional intensity in infancy and were reported to be lower in task persistence at age 5. At age 12, these children were viewed by teachers as more careless with their school work and as having more attentional and learning problems.

Age Factors↗