No effect of obstetric complications on basal ganglia volumes in schizophrenia

Haukvik, Unn K.; McNeil, Thomas F.; Nesvåg, Ragnar; Söderman, Erik; Jönsson, Erik G.; Agartz, Ingrid

doi:10.1016/j.pnpbp.2010.02.024

Cited by 11 publications

(7 citation statements)

References 212 publications

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“…42 Although obstetric complications were correlated with changes in hippocampal volume in that study, 42 no correlations were found for cortical thickness 119 or volume of basal ganglia. 120 Thus, issues of selective vulnerability to early insults need to be understood in more detail before genetic variation can be related to the risk of schizophrenia. A recent study compiled 12 candidate endophenotypes and tested associations with n = 94 candidate genes.…”

Section: Endophenotypes For Matched Genesmentioning

confidence: 99%

An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

et al. 2012

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Investigating and understanding gene-environment interaction (G Â E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia-hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes (n = 42 genes) met the criteria for a link to ischemia-hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia-hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G Â E interactions in clinical genetic and translational neuroscience studies.

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Section: Endophenotypes For Matched Genesmentioning

confidence: 99%

An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

et al. 2012

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“…Bilateral hippocampal atrophy has been detected in adolescents with a history of perinatal asphyxia diagnosed as hypoxic-ischemic encephalopathy, along with worse verbal long-term memory (Maneru et al, 2003). In schizophrenia, patients with obstetric complications have shown reduced hippocampal volumes (McNeil et al, 2000; Van Erp et al, 2002; Schulze et al, 2003; Ebner et al, 2008), while no effects have been observed in volumes of basal ganglia (Haukvik et al, 2010). However, effects of antipsychotic medication have to be taken into consideration when investigating brain regions (Lieberman et al, 2005).…”

Section: Birth and Obstetric Complicationsmentioning

confidence: 99%

The impact of environmental factors in severe psychiatric disorders

Schmitt¹,

Malchow²,

Hasan³

et al. 2014

Front. Neurosci.

261

164

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During the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis. Apart from the influence of risk genes in severe psychiatric disorders, environmental factors may also impact brain development during the perinatal period. Several environmental factors such as antenatal maternal virus infections, obstetric complications entailing hypoxia as common factor or stress during neurodevelopment have been identified to play a role in schizophrenia and bipolar disorder, possibly contributing to smaller hippocampal volumes. In major depression, psychosocial stress during the perinatal period or in adulthood is an important trigger. In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders. Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders.

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“…In the present study, the number of OCs with severity scores of o3 was calculated for each individual subject to form one continuous variable. Scores <3 are considered not to be harmful to the foetus (McNeil & Sjostrom, 1995 ;Haukvik et al 2010). Obstetric characteristics are presented in Table 1.…”

Section: Assessment Of Ocsmentioning

confidence: 99%

Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls

et al. 2011

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Background. The increased occurrence of obstetric complications (OCs) in patients with schizophrenia suggests that alterations in neurodevelopment may be of importance to the aetiology of the illness. Abnormal cortical folding may reflect subtle deviation from normal neurodevelopment during the foetal or neonatal period. In the present study, we hypothesized that OCs would be related to cortical folding abnormalities in schizophrenia patients corresponding to areas where patients with schizophrenia display altered cortical folding when compared with healthy controls.Method. In total, 54 schizophrenia patients and 54 healthy control subjects underwent clinical examination and magnetic resonance image scanning on a 1.5 T scanner. Information on OCs was collected from original birth records. An automated algorithm was used to calculate a three-dimensional local gyrification index (lGI) at numerous points across the cortical mantle.Results. In both schizophrenia patients and healthy controls, an increasing number of OCs was significantly related to lower lGI in the left pars triangularis (p<0.0005) in Broca's area. For five other anatomical cortical parcellations in the left hemisphere, a similar trend was demonstrated. No significant relationships between OCs and lGI were found in the right hemisphere and there were no significant case-control differences in lGI.Conclusions. The reduced cortical folding in the left pars triangularis, associated with OCs in both patients and control subjects suggests that the cortical effect of OCs is caused by factors shared by schizophrenia patients and healthy controls rather than factors related to schizophrenia alone.

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No effect of obstetric complications on basal ganglia volumes in schizophrenia

Abstract: The present results do not support the hypothesis that OCs are related to alterations in basal ganglia volume in chronic schizophrenia.

Cited by 11 publications

References 212 publications

An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

The impact of environmental factors in severe psychiatric disorders

Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls

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