Päivikki Tanskanen

Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33–35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between fronto-cerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.

Morphometric Brain Abnormalities in Schizophrenia in a Population-Based Sample: Relationship to Duration of Illness

Biased recruitment and sample selection may cause variability in neuroimaging studies. Epidemiologically principled population-based magnetic resonance imaging (MRI) studies of schizophrenia are very rare. We gathered structural MRI data on 154 subjects from the Northern Finland 1966 Birth Cohort, aged 33-35 (100 controls, 54 schizophrenia patients). Regional differences in density of gray matter, white matter, and cerebrospinal fluid (CSF) were identified between groups using nonparametric statistical analysis, and the relationship of the regional differences to duration of illness was explored. Gray matter reductions were found bilaterally in the cerebellum, thalamus, basal ganglia, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, cuneus, and lingual gyrus; in the left posterior cingulate, superior frontal gyrus, transverse temporal gyrus, and precuneus; and in the right postcentral gyrus. Gray matter excesses were observed bilaterally in the basal ganglia, anterior cingulate, and medial orbitofrontal cortices. There were white matter deficits in an extensive network including inter- and intrahemispheric tracts bilaterally in the frontal, temporal, parietal, and occipital lobes, subcortical structures, cerebellum, and brain stem. CSF excesses were found bilaterally in the lateral ventricles, third ventricle, interhemispheric, and left Sylvian fissure. We replicated the previous findings of structural brain abnormalities in schizophrenia on a general population level. Gray and white matter deficits were associated with duration of illness suggesting either that developmental brain deficits relate to an earlier age of onset or that brain abnormalities in schizophrenia are progressive in nature.

Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999-2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.

The brain structural disposition to social interaction.

Social reward dependence (RD) in humans is a stable pattern of attitudes and behaviour hypothesized to represent a favourable disposition towards social relationships and attachment as a personality dimension. It has been theorized that this long‐term disposition to openness is linked to the capacity to process primary reward. Using brain structure measures from magnetic resonance imaging, and a measure of RD from Cloninger’s temperament and character inventory, a self‐reported questionnaire, in 41 male subjects sampled from a general population birth cohort, we investigated the neuro‐anatomical basis of social RD. We found that higher social RD in men was significantly associated with increased gray matter density in the orbitofrontal cortex, basal ganglia and temporal lobes, regions that have been previously shown to be involved in processing of primary rewards. These findings provide evidence for a brain structural disposition to social interaction, and that sensitivity to social reward shares a common neural basis with systems for processing primary reward information.

Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Cardiovascular Regulation and Hippocampal Sclerosis

Summary:  Purpose: Cardiovascular dysregulation has been detected in patients with temporal lobe epilepsy (TLE) by using cardiovascular reflex tests and analysis of heart rate variability (HRV). The two methods have not previously been used in the same study to compare them in the assessment of cardioregulatory function. Magnetic resonance imaging (MRI) is considered the best method to reveal structural changes such as hippocampal sclerosis associated with TLE. It is not known whether these structural changes modify cardioregulatory function in patients with TLE.

Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort

BACKGROUND Duration of untreated psychosis (DUP) has been linked with poor prognosis and changes in the brain structure in schizophrenia at least at the beginning of the disease, but it is still unknown whether DUP relates to brain morphometry in the longer term. Our aim was to analyze the relation between DUP and the brain structure in schizophrenia in the general population, after several years of illness. METHODS Brains of subjects with psychosis from the Northern Finland 1966 Birth Cohort (NFBC 1966) were scanned with MRI during 1999-2001 after an 11-year follow-up. DUP was assessed from medical records and regressed against global and local tissue density measurements. The brain morphometric and the DUP information were available for 46 subjects with DSM-III-R schizophrenia. RESULTS The DUP did not correlate with volumes of the total gray or white matter or the cerebrospinal fluid. The length of DUP associated positively with reduced densities of the right limbic area and the right hippocampus. CONCLUSIONS Long DUP was slightly associated with reductions of gray matter densities in the limbic area and especially the hippocampus after several years follow-up, supporting the hypothesis that, compared to short DUP, long DUP might be a marker of different disease trajectories including subtle morphometric changes.

Neuregulin-1 genotype is associated with structural differences in the normal human brain

The human neuregulin-1 (NRG-1) gene is highly expressed in the brain, is implicated in numerous functions associated with neuronal development, and is a leading candidate gene for schizophrenia. The T allele of SNP8NRG243177, part of a risk haplotype for schizophrenia, has been previously associated with decreases in white matter in the right anterior internal capsule and the left anterior thalamic radiation. To our knowledge no studies have described the effects of SNP8NRG243177 on grey matter volume at a voxelwise level. We assessed associations between this SNP and brain structure in 79 general population volunteers from the Northern Finland 1966 Birth Cohort (NFBC 1966). We show, for the first time, that genetic variation in SNP8NRG243177 is associated with variation in frontal brain structure in both grey and white matter. T allele carriers showed decreased grey matter volume in several frontal gyri, including inferior, middle and superior frontal gyri and the anterior cingulate gyrus, as well as decreased white matter volume in the regions of the genu and body of the corpus callosum, anterior and superior corona radiata, anterior limb of the internal capsule and external capsule regions traversed by major white matter tracts of the anterior thalamic radiation, and the inferior fronto-occipital fasciculus. These results suggest that this genetic variant may mediate risk for schizophrenia, in part, through its effect on brain structure in these regions.

Is Prematurity Associated With Adult Cognitive Outcome and Brain Structure

Previous studies have indicated that preterm birth and low birth weight are associated with structural brain abnormalities and neurocognitive deficits in childhood and adolescence, although very few studies have included follow-up in adulthood. Here we assessed the effect of preterm delivery (524 subjects; mean 34.6 weeks, S.D. = 1.7) or low birth weight (366 subjects; mean 2159 g, S.D. = 303) on educational and occupational outcomes at age 31 years in the Northern Finland 1966 Birth Cohort, along with 10,132 term, normal birth weight control subjects. Cognitive tests and brain morphology using magnetic resonance imaging were assessed at age 33-35 years in a subset of the cohort (9 subjects; 95 controls). The preterm or low birth weight subjects had slightly lower school ratings and lower educational levels in adulthood, and they performed worse in verbal learning. The low birth weight subjects were less likely to be employed. There were no mean differences in the magnetic resonance imaging tissue segmentation analysis of the brain. In conclusion, although there were no overall changes in brain morphology in the preterm or low birth weight group, there was evidence for slightly poorer educational and occupational careers and cognitive capacity, which may reflect functional disruption not evident in structure.

Volumes of brain, grey and white matter and cerebrospinal fluid in schizophrenia in the Northern Finland 1966 Birth Cohort: an epidemiological approach to analysis.

Magnetic resonance imaging (MRI) studies in schizophrenia have seldom involved a general population birth cohort or other epidemiological samples. We studied the Northern Finland 1966 Birth Cohort and identified all people with psychotic disorders. Along with an unaffected age-matched control sample (n = 100) from the cohort, 54 subjects with schizophrenia underwent MRI brain scan at age 33-35 years from which we defined volumes of whole brain, grey and white matter and intracranial cerebrospinal fluid (CSF). Whole brain, grey and white matter volumes were 2-3% smaller in the schizophrenia subjects, who showed a 7% increase in CSF volume. These volume changes were independent of the effects of gender, family history of psychosis, perinatal risks or age at onset of illness. Moreover, there was no evidence that the effects were due to particular subgroups of cases having very low or high values. Rather, there were linear trends in the associations between whole brain and grey matter volume measures and schizophrenia. Our study replicates the previous findings of brain volume differences in schizophrenia on a general population level.