Improvement of Work Ability After Weight Loss Surgery: Results of a Longitudinal Study of Patients Suffering from Extreme Obesity Before and 4 Years After Bariatric Surgery.

PURPOSE: Body mass index (BMI) is directly associated with employment status. Our longitudinal prospective study is aimed at ascertaining whether work ability index (WAI) 4 years after surgery remains improved, such as 1 year after surgery, or changes and whether socio-demographic or psycho-social factors influence changes in work ability. MATERIALS AND METHODS: 197 bariatric surgery candidates were recruited. Data on demographic and psycho-social characteristics were collected prior to surgery (t1) and at 6 (t2), 12 (t3), and 48 months (t4). Change effects over time in the WAI and BMI were investigated using a repeated-measures analysis of variance (ANOVA). A hierarchical multiple regression analysis was calculated to predict socio-demographic and psychosocial characteristics at t1 on WAI at t4. RESULTS: Not only a significant increase in WAI was observed between t1 and t2 and between t3 and t4 but also a significant decrease between t2 and t4. BMI reduction was significant between t1 and t2 and t3 and t4, respectively. There was no significant interaction effect of BMI reduction 4 years after surgery on decreased work ability from t2 to t4. The hierarchical multiple regression analysis revealed an association of WAI scores at t1 on WAI scores at t4 only. CONCLUSIONS: Work ability 4 years after surgery remained significantly improved compared to the values at t1-t3 assessment. Since work ability was the only predictor at t1, findings might indicate the use of psycho-social measures post bariatric surgery to increase work ability. There was no association between work ability and other socio-demographic or psycho-social factors.

Changes in Work Ability after Weight-Loss Surgery: Results of a Longitudinal Study of Persons with Morbid Obesity before and after Bariatric Surgery.

INTRODUCTION: Bariatric surgery is a life-changing treatment, but knowledge of its influence on changes in work ability is still limited. We hypothesized that self-reported work ability improves in response to surgery-induced weight loss and sociodemographical variables (e.g., age, sex, and marital status), and that psychosocial characteristics (e.g., depressive symptoms and dysfunctional eating) may have predictive value as to patients' work ability. METHODS: A total of 200 participants scheduled for bariatric surgery were recruited between September 2015 and June 2018. They completed several self-report measures at the preoperative examination (t1) and at 6- (t2) and 12 months (t3) after bariatric surgery. A repeated-measures analysis of variance was calculated to detect any changes in the work ability and body mass index (BMI) among the 3 time points. Further, a hierarchical multiple regression analysis was used to determine whether any demographical and psychosocial characteristics at (t1) would predict work ability at (t3). RESULTS: Participants (82% of whom were women) were middle-aged and showed a BMI of nearly 46 at the preoperative medical examination. Excess weight loss at (t2) and at (t3) was 49 and 66%, respectively. Work ability increased toward a moderate level after weight-loss surgery. Work ability and dysfunctional eating at (t1) showed significant predictive value with respect to work ability at (t3). DISCUSSION: The results suggest that weight-loss surgery has a positive impact on work ability, and indicate a predictive value for the extent of weight loss and dysfunctional eating behavior. Against our hypothesis and in contrast to former research, a predictive value for depressive symptoms and age was not revealed. Further research must show how interventions can support and maintain improvements in work ability after bariatric surgery, in order to reduce sick leave and unemployment in patients with preoperative morbid obesity.

Primary Sleeve Gastrectomy and Leaks: The Impact of Fundus-Wall Thickness and Staple Heights on Leakage-An Observational Study of 500 Patients.

Introduction: The most feared complication of laparoscopic sleeve gastrectomy (LSG) is staple-line leakage. Staple height and fundus-wall thickness might influence such leakage, and this study examined their possible impact on leak incidence. Factors including gender, age, comorbidities, and reinforcement of the staple line were also investigated. Methods: A total of 500 patients between 17 and 71 years of age who were scheduled for LSG were selected to participate in the study. For technical reasons, 53 were excluded. The fundus-wall thickness of 447 patients after LSG was investigated. The impact of staple height, fundus-wall thickness, demographic and medical factors on leak incidence were investigated. Most of our patients (309) were female (69%), while 138 were male (31%). Results: The mean thickness of the proximal fundus wall was 2,904 µm, 3,172 µm in men and 2,784 µm in women. The leak rate was 4.9%. Age, fundus-wall thickness, and BMI showed a strong influence on leak risk, but this effect was significant only for age (p = 0.01). Patient gender and staple size showed no significant influence on the correlation between fundus-wall thickness and leak risk. Gender displayed a small effect of influence on this correlation, with η2 = 0.05. Discussion: Because older age had a significant effect on increasing the risk of staple-line leakage, there is a need for a more specific focus on these patients. Thinner fundus wall and female gender might predispose patients to staple-line leaks, but a significant value could not be reached. Therefore, staple size should remain the surgeon's choice based on clinical experience.

Changes in Patients' Relationship Satisfaction After Weight Loss Surgery: Results of a Study of Persons with Morbid Obesity and Their Relationship Satisfaction Before and 1 Year After Bariatric Surgery.

OBJECTIVE: Bariatric surgery is a life-changing treatment, but knowledge of its influence on changes in relationship satisfaction (RS) is still limited. The present study examines whether a patient's RS changes after having bariatric surgery, in response to the surgery-induced weight loss. The predictive value of further variables such as age and sex are also investigated. METHODS: A total of 145 participants scheduled for bariatric surgery were recruited between September 2015 and June 2018. RS was assessed with a reliable and valid short form of a standardized self-report measure, which was completed before, 6 months and 12 months after surgery. RESULTS: Loss of excess weight at 6 and 12 months post-surgery was 49% and 66.3%, respectively. The repeated measures ANOVA for the factor "PFB-K" revealed a statistically significant effect, with F (2, 288) = 7.40, p = .001, and η2 = .05, and for the factor "BMI" with F (2, 288) = 505.99, p < .001, and η2 = .78. The highest mean RS score was observed 6 months post-surgery. Sex showed a statistical trend of influence on RS: F (1, 143) = 3.24, p = .074, and η2 = .022. At all three measurement points, men showed higher mean RS scores than women. CONCLUSION: Bariatric surgery leads to significant weight loss and indicates an increase in RS. While a correlation with the amount of weight lost remains unclear, a trend was seen towards higher RS in subjects with higher weight loss. Men in particular reported higher RS.

Psychosocial Predictors of Work Ability in Morbidly Obese Patients: Results of a Cross-Sectional Study in the Context of Bariatric Surgery.

BACKGROUND: Obesity is associated with a higher risk of work disability and premature early retirement. OBJECTIVE: The aim of this study was to examine psychosocial predictors for work ability prior to surgery. METHODS: Based on a sample of 197 surgery-seeking obese patients (preoperative body mass index [BMI] above 35 kg/m2) from a German bariatric surgery unit, the present cross-sectional study examined based on standardized self-rating measures whether depressive symptoms, dysfunctional eating behaviors, relationship satisfaction, and life satisfaction have a predictive value for work ability. RESULTS: Considerable impairment of work ability was found in 51.8% of morbidly obese participants (n = 102). Multiple regression analyses revealed that older age, greater depressive symptoms, and lower life satisfaction were significant predictors of preoperative work ability. BMI, gender, relationship satisfaction, and dysfunctional eating behaviors did not predict work ability. CONCLUSIONS: Our findings might indicate the use of further psychosocial measures following bariatric surgery to increase work ability.

Relationships of growth factors, proinflammatory cytokines, and anti-inflammatory cytokines with long-term clinical results of autologous bone marrow mononuclear cell transplantation in STEMI.

AIM: The aim of the study was to test the hypothesis suggesting that the pre-intervention levels of proinflammatory cytokines, anti-inflammatory cytokines, and angiogenic growth factors predict the long-term clinical results of autologous bone marrow-derived mononuclear cell (ABMMC) transplantation in patients with primary ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: From 2003 to 2006, a total of 62 patients with primary STEMI were enrolled in an open randomized study registered under the title ESTABOMA. Patients were randomized into two groups: group 1 included patients treated with percutaneous coronary intervention (PCI) and ABMMC transplantation (n = 28); group 2 comprised patients treated only with PCI (n = 34). Follow-up study was performed 7.96 ± 0.96 years after STEMI and involved physical examination, six-minute walk test, echocardiography, and determination of brain natriuretic peptide (BNP) levels. The total and cardiovascular mortality rates were higher in group 1 compared with group 2: 36% (n = 10) vs. 12% (n = 4) (p = 0.02) and 29% (n = 8) vs. 6% (n = 2) (p = 0.03), respectively. Lower levels of proinflammatory cytokines were observed in group 1 after PCI and ABMMC transplantation. Serum levels of FGF, VEGF, and IL-10, determined before PCI and ABMMC transplantation were prognostically significant long-term indicators of unfavorable course of CAD after STEMI.

Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity.

G72 (syn. DAOA, D-amino acid oxidase activator) is a susceptibility gene for both schizophrenia and bipolar disorder. Diffusion tensor imaging studies hint at changes in fiber tract integrity in both disorders. We aimed to investigate whether a G72 susceptibility haplotype causes changes in fiber tract integrity in young healthy subjects. We compared fractional anisotropy in 47 subjects that were either homozygous for the M23/M24 risk haplotype (n = 20) or homozygous for M23(rs3918342)/M24(rs1421292) wild type (n = 27) using diffusion tensor imaging with 3 T. Tract-based spatial statistics, a method especially developed for diffusion data analysis, was used to delineate the major fiber tracts. We found clusters of increased FA values in homozygous risk haplotype carriers in the right periinsular region and in the right inferior parietal lobe (IPL). We did not find clusters indicating decreased FA values. The insula and the IPL have been implicated in both schizophrenia and bipolar pathophysiology. Increased FA values might reflect changes in dendritic morphology as previously described by in vitro studies. These findings further corroborate the hypothesis that a shared gene pool between schizophrenia and bipolar disorder might lead to neuroanatomic changes that confer an unspecific vulnerability for both disorders.

A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects.

BACKGROUND: Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis. METHODS: We compared fractional anisotropy in 54 subjects that were either homozygous for the risk C allele carriers (n = 31) for rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for diffusion data analysis, was used to improve white matter registration and to focus the statistical analysis to major fiber tracts. RESULTS: Statistical analysis showed that homozygous risk C allele carriers featured elevated fractional anisotropy (FA) in the right perihippocampal region and the white matter proximate to the left area 4p as well as the right hemisphere of the cerebellum. We found three clusters of reduced FA values in homozygous C allele carriers: in the left superior parietal region, the right prefrontal white matter and in the deep white matter of the left frontal lobe. CONCLUSION: Our results highlight the importance of Neuregulin-1 for structural connectivity of the right medial temporal lobe. This finding is in line with well known neuropathological findings in this region in patients with schizophrenia.

The impact of a Dysbindin schizophrenia susceptibility variant on fiber tract integrity in healthy individuals: a TBSS-based diffusion tensor imaging study.

Schizophrenia is a severe neuropsychiatric disorder with high heritability, though its exact etiopathogenesis is yet unknown. An increasing number of studies point to the importance of white matter anomalies in the pathophysiology of schizophrenia. While several studies have identified the impact of schizophrenia susceptibility gene variants on gray matter anatomy in both schizophrenia patients and healthy risk variant carriers, studies dealing with the impact of these gene variants on white matter integrity are still scarce. We here present a study on the effects of a Dysbindin schizophrenia susceptibility gene variant on fiber tract integrity in healthy young subjects. 101 subjects genotyped for Dysbindin-gene variant rs1018381, though without personal or first degree relative history of psychiatric disorders underwent diffusion tensor imaging (DTI), 83 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) analysis to delineate the major fiber tracts. Carriers of the minor allele T of the rs1018381 in the Dysbindin gene showed two clusters of reduced fractional anisotropy (FA) values in the perihippocampal region of the right temporal lobe compared to homozygote carriers of the major allele C. Clusters of increased FA values in T-allele carriers were found in the left prefrontal white matter, the right fornix, the right midbrain area, the left callosal body, the left cerebellum and in proximity of the right superior medial gyrus. Dysbindin has been implicated in neurite outgrowth and morphology. Impairments in anatomic connectivity as found associated with the minor Dysbindin allele in our study may result in increased risk for schizophrenia due to altered fiber tracts.

Genetic variation in G72 correlates with brain activation in the right middle temporal gyrus in a verbal fluency task in healthy individuals.

The D-amino acid oxidase activator gene (G72) has been found associated with several psychiatric disorders such as schizophrenia, major depression, and bipolar disorder. Impaired performance in verbal fluency tasks is an often replicated finding in the mentioned disorders. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and lateral temporal areas and could possibly constitute an endophenotype. Therefore, it is of interest whether genes associated with the disorders, such as G72, modulate verbal fluency performance and its neural correlates. Ninety-six healthy individuals performed a semantic verbal fluency task while brain activation was measured with functional MRI. All subjects were genotyped for two single nucleotide polymorphisms (SNP) in the G72 gene, M23 (rs3918342) and M24 (rs1421292), that have previously shown association with the above-mentioned disorders. The effect of genotype on brain activation was assessed with fMRI during a semantic verbal fluency task. Although there were no differences in performance, brain activation in the right middle temporal gyrus (BA 39) and the right precuneus (BA 7) was positively correlated with the number of M24 risk alleles in the G72 gene. G72 genotype does modulate brain activation during language production on a semantic level in key language areas. These findings are in line with structural and functional imaging studies in schizophrenia, which showed alterations in the right middle temporal gyrus.

The effects of a DTNBP1 gene variant on attention networks: an fMRI study.

BACKGROUND: Attention deficits belong to the main cognitive symptoms of schizophrenia and come along with altered neural activity in previously described cerebral networks. Given the high heritability of schizophrenia the question arises if impaired function of these networks is modulated by susceptibility genes and detectable in healthy risk allele carriers. METHODS: The present event-related fMRI study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 of the DTNBP1 (dystrobrevin-binding protein 1) gene on brain activity in 80 subjects while performing the attention network test (ANT). In this reaction time task three domains of attention are probed simultaneously: alerting, orienting and executive control of attention. RESULTS: Risk allele carriers showed impaired performance in the executive control condition associated with reduced neural activity in the left superior frontal gyrus [Brodmann area (BA) 9]. Risk allele carriers did not show alterations in the alerting and orienting networks. CONCLUSIONS: BA 9 is a key region of schizophrenia pathology and belongs to a network that has been shown previously to be involved in impaired executive control mechanisms in schizophrenia. Our results identified the impact of DTNBP1 on the development of a specific attention deficit via modulation of a left prefrontal network.

COMT genotype and its role on hippocampal-prefrontal regions in declarative memory.

INTRODUCTION: Memory dysfunction is a prominent feature in schizophrenia. Impairments of declarative memory have been consistently linked to alterations especially within hippocampal-prefrontal regions. Due to the high heritability of schizophrenia, susceptibility genes and their modulatory impact on the neural correlates on memory are of major relevance. In the present study the influence of the COMT val(158)met status on the neural correlates of declarative memory was investigated in healthy subjects. METHODS: From an initial behavioural sample of 522 healthy individuals (Sheldrick et al., 2008), 84 subjects underwent fMRI scanning while performing a memory encoding and a retrieval task. The COMT val(158)met status was determined for the whole sample and correlated with cortical activation within the group of n=84 individuals. RESULTS: There were no effects of COMT status on behavioural performance. For declarative memory processing the number of met alleles predicted circumscribed bilateral insula and anterior hippocampus activations during memory encoding as well as less deactivations within the bilateral posterior parahippocampal gyri during memory retrieval. DISCUSSION: Although declarative memory performance was unaffected, the neural correlates within hippocampal-prefrontal regions demonstrate a link between COMT val(158)met carrier status and brain areas associated with declarative memory processing. The study contributes to a better understanding of the role that susceptibility genes might play in the aetiology of schizophrenia.

Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals.

BACKGROUND: Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be overrepresented in patients suffering from bipolar disorder, schizophrenia or major depression. While the functions underlying the pathophysiology of these psychiatric disorders are yet unknown, impaired performance in verbal fluency tasks is an often replicated finding. We investigated the influence of the rs1006737 single nucleotide polymorphism (SNP) on verbal fluency and its neural correlates. METHODS: Brain activation was measured with functional magnetic resonance imaging (fMRI) during a semantic verbal fluency task in 63 healthy male individuals. They additionally performed more demanding verbal fluency tasks outside the scanner. All subjects were genotyped for CACNA1C rs1006737. RESULTS: For the behavioral measures outside the scanner, rs1006737genotype had an effect on semantic but not on lexical verbal fluency with decreased performance in risk-allele carriers. In the fMRI experiment, while there were no differences in behavioural performance, increased activation in the left inferior frontal gyrus as well as the left precuneus was found in risk-allele carriers in the semantic verbal fluency task. CONCLUSIONS: The rs1006737 variant does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in bipolar disorder, schizophrenia and major depression and may explain some of the cognitive and brain activation variation found in these disorders.

The impact of dystrobrevin-binding protein 1 (DTNBP1) on neural correlates of episodic memory encoding and retrieval.

Episodic memory impairment is a frequently reported symptom in schizophrenia. It has been shown to be associated with reduced neural activity of the hippocampus and prefrontal cortex. Given the high heritability of schizophrenia the question arises if alterations in brain activity are modulated by susceptibility genes and might be detectable in healthy risk allele carriers. The present study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 (P1578) of the dystrobrevin-binding protein 1 (DTNBP1) on brain activity in 84 healthy subjects assessed by functional magnetic resonance imaging (fMRI) while they performed an episodic memory task comprising encoding and retrieval of faces. During encoding, the group of risk allele carriers (n = 29) showed enhanced neural activity in the left middle frontal gyrus (BA 11) and bilaterally in the cuneus (BA 17, 7) when compared with the nonrisk carrier group (n = 55). During retrieval, the risk group (compared to the non risk group) showed increased right hemispheric neural activity comprising the medial frontal gyrus (BA 9), inferior frontal gyrus (BA 9), and inferior parietal lobule (BA 40). Since there were no behavioral performance differences, increased neural activity of the risk group might be interpreted as a correlate of higher effort or differing cognitive strategies in order to compensate for a genetically determined slight cognitive deficit. Interestingly, the laterality of increased prefrontal activity is in accordance with the well known hemispheric encoding/retrieval asymmetry (HERA) model of episodic memory.

The effect of G72 genotype on neural correlates of memory encoding and retrieval.

Polymorphisms in the G72 (also named d-amino acid oxidase activator, DAOA) gene increase the vulnerability for schizophrenia and affective psychosis. Three recent genetic neuroimaging studies showed that variation in G72 influences the brain activity in the medial temporal lobe (MTL), supporting the hypothesis that G72 might play a modulatory role on brain activity in MTL structures. In the present study we therefore investigated the effect of G72 on the neural correlates of long-term memory encoding and retrieval in a large sample of healthy subjects (n=83) using functional magnetic resonance imaging. A face encoding and a face retrieval memory task were chosen because on the one hand they specifically activate MTL structures and on the other hand they tap into memory processes that are compromised in patients with schizophrenia and affective disorder. Despite a strong a-priori hypothesis of genotype group activation differences in the MTL along with a large sample size we did neither find an effect of G72 genotype status on brain activity in the MTL nor in any other brain regions. The present data therefore do not support the view of a general modulatory role of G72 on MTL brain activity, at least not in the domain of long-term memory encoding and retrieval. Our results highlight the importance of replication studies in genetic neuroimaging.

The effect of Neuregulin 1 on neural correlates of episodic memory encoding and retrieval.

Neuregulin 1 (NRG1) has been found to be associated with schizophrenia. Impaired performance in episodic memory tasks is an often replicated finding in this disorder. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and medial temporal areas. Therefore, it is of interest whether genes associated with the disorder, such as NRG1, modulate episodic memory performance and its neural correlates. Ninety-four healthy individuals performed an episodic memory encoding and a retrieval task while brain activation was measured with functional MRI. All subjects were genotyped for the single nucleotide polymorphism (SNP) rs35753505 in the NRG1 gene. The effect of genotype on brain activation was assessed with fMRI during the two tasks. While there were no differences in performance, brain activation in the cingulate gyrus (BA 24), the left middle frontal gyrus (BA 9), the bilateral fusiform gyrus and the left middle occipital gyrus (BA 19) was positively correlated with the number of risk alleles in NRG1 during encoding. During retrieval brain activation was positively correlated with the number of risk alleles in the left middle occipital gyrus (BA 19). NRG1 genotype does modulate brain activation during episodic memory processing in key areas for memory encoding and retrieval. The results suggest that subjects with risk alleles show hyperactivations in areas associated with elaborate encoding strategies.

Impact of schizophrenia-risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals.

Working memory (WM) dysfunction is a hallmark feature of schizophrenia. Functional imaging studies using WM tasks have documented both prefrontal hypo- and hyperactivation in schizophrenia. Schizophrenia is highly heritable, and it is unclear which susceptibility genes modulate WM and its neural correlates. A strong linkage between genetic variants in the dysbindin 1 gene and schizophrenia has been demonstrated. The aim of this study was to investigate the influence of the DTNBP1 schizophrenia susceptibility gene on WM and its neural correlates in healthy individuals. Fifty-seven right-handed, healthy male volunteers genotyped for DTNBP1 SNP rs1018381 status were divided in heterozygous risk-allele carriers (T/C) and homozygous noncarriers (C/C). WM was assessed by a 2-back vs. 0-back version of the Continuous Performance Test (CPT), while brain activation was measured with fMRI. DTNBP1 SNP rs1018381 carrier status was determined and correlated with WM performance and brain activation. Despite any differences in behavioral performance, risk-allele carriers exhibited significantly increased activation of the bilateral middle frontal gyrus (BA 9), a part of the dorsolateral prefrontal cortex (DLPFC), compared to noncarriers. This difference did not correlate with WM performance. The fMRI data provide evidence for an influence of genetic variation in DTNBP1 gene region tagged by SNP rs1018381 on bilateral middle frontal gyrus activation during a WM task. The increased activation in these brain areas may be a consequence of "inefficient" or compensatory DLPFC cognitive control functions.

Effect of the G72 (DAOA) putative risk haplotype on cognitive functions in healthy subjects.

BACKGROUND: In the last years, several susceptibility genes for psychiatric disorders have been identified, among others G72 (also named D-amino acid oxidase activator, DAOA). Typically, the high-risk variant of a vulnerability gene is associated with decreased cognitive functions already in healthy individuals. In a recent study however, a positive effect of the high-risk variant of G72 on verbal working memory was reported. In the present study, we therefore examined the relationship between G72 genotype status and a broad range of cognitive functions in 423 healthy individuals. METHODS: The G72 carrier status was assessed by the two single nucleotide polymorphisms (SNPs) M23 and M24. Subjects were divided into three risk groups (low, intermediate and high risk). RESULTS: G72 status influenced a number of cognitive functions, such as verbal working memory, attention, and, at a trend level, spatial working memory and executive functions. Interestingly, the high-risk allele carriers scored better than one or even both other groups. CONCLUSION: Our data show that the putative high-risk haplotype (i.e. homozygote C/C-allele carriers in SNP M23 and homozygote T/T-allele carriers in SNP M24) is in healthy individuals not necessarily associated with worse performance in cognitive functions, but even with better performance in some domains. Further work is required to identify the mechanisms of G72 on brain functions.

Subclinical hypothyroidism after radioiodine exposure: Ukrainian-American cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident (1998-2000).

BACKGROUND: Hypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent. OBJECTIVE: This study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident. METHODS: This is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals < 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum. RESULTS: Mean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH > 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between (131)I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO < or = 60 U/mL compared with individuals with ATPO > 60 U/mL (p < 0.001). CONCLUSIONS: This is the first study to find a significant relationship between prevalence of hypothyroidism and individual (131)I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies.

Genetic variation in the schizophrenia-risk gene neuregulin 1 correlates with brain activation and impaired speech production in a verbal fluency task in healthy individuals.

Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty-nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRG1 (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk-alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk-alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities.