Employment status, mental disorders and service use in the working age population

OBJECTIVES: This study examined the association between employment status and specific DSM-IV (Diagnostic and Statistical Manual for Mental Disorders, IVth edition) depressive, anxiety and alcohol use disorders and the association between employment status and service use for these disorders. METHODS: As part of the representative population-based "Health 2000 Study" of Finns aged 30 years or over, 3440 employed, 429 unemployed, and 820 economically inactive persons of working age (30-64 years) participated in a comprehensive health examination, including the standardized Composite International Diagnostic Interview. RESULTS: The risk of mental disorders was generally higher among the unemployed and the economically inactive than among the employed. The respective odds ratios were 1.79 [95% confidence interval (95% CI) 1.26-2.54] and 1.54 (95% CI 1.06-2.25) for depressive disorders, 2.68 (95% CI 1.85-3.89) and 2.53 (95% CI 1.76-3.65) for anxiety disorders, and 2.58 (95% CI 1.82-3.65) and 1.43 (95% CI 0.91-2.22) for alcohol use disorders. Similar results were obtained for most of the specific categories of these disorders. Among the persons with anxiety disorders, the odds for treatment contact were 2.35 (95% CI 1.06-5.23) times higher for the unemployed than for the employed after control for disorder severity. For those with an alcohol use disorder, the corresponding odds ratio was 3.51 (95% CI 1.23-9.98). CONCLUSIONS: Common mental disorders are less prevalent among the employed than among unemployed and economically inactive people. Among those with anxiety or alcohol use disorders, service use is less common among the employed than among the unemployed. This difference is not explained by the severity of the clinical state.     

Effect of the Pro12Ala polymorphism of the PPARg2 gene on serum adiponectin changes

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) gene and adiponectin, a protein secreted from adipose tissue, have been associated with insulin sensitivity. The present study demonstrates that in Finnish servicemen who were on a high-caloric diet for 6 mo only subjects with the Ala 12 allele of PPARγ2 had a significant increase in adiponectin levels with weight loss induced by heavy exercise. This study demonstrates an interaction of genetic and environmental factors in the regulation of serum adiponectin concentrations. Department of Medicine, University of Kuopio, Finland.     

Speech-sound-selective auditory impairment in children with autism: they can perceive but do not attend

In autism, severe abnormalities in social behavior coexist with aberrant attention and deficient language. In the attentional domain, attention to people and socially relevant stimuli is impaired the most. Because socially meaningful stimulus events are physically complex, a deficiency in sensory processing of complex stimuli has been suggested to contribute to aberrant attention and language in autism. This study used event-related brain potentials (ERP) to examine the sensory and early attentional processing of sounds of different complexity in high-functioning children with autism. Acoustically matched simple tones, complex tones, and vowels were presented in separate oddball sequences, in which a repetitive “standard” sound was occasionally replaced by an infrequent “deviant” sound differing from the standard in frequency (by 10%). In addition to sensory responses, deviant sounds elicited an ERP index of automatic sound-change discrimination, the mismatch negativity, and an ERP index of attentional orienting, the P3a. The sensory sound processing was intact in the high-functioning children with autism and was not affected by sound complexity or “speechness.” In contrast, their involuntary orienting was affected by stimulus nature. It was normal to both simple- and complex-tone changes but was entirely abolished by vowel changes. These results demonstrate that, first, auditory orienting deficits in autism cannot be explained by sensory deficits and, second, that orienting deficit in autism might be speech–sound specific.     

Genotoxicity of short single-wall and multi-wall carbon nanotubes in human bronchial epithelial and mesothelial cells in vitro

Although some types of carbon nanotubes (CNTs) have been described to induce mesothelioma in rodents and genotoxic effects in various cell systems, there are few previous studies on the genotoxicity of CNTs in mesothelial cells. Here, we examined in vitro DNA damage induction by short multi-wall CNTs (MWCNTs; 10–30 nm × 1–2 μm) and single-wall CNTs (SWCNTs; >50% SWCNTs, ∼40% other CNTs; <2 nm × 1–5 μm) in human mesothelial (MeT-5A) cells and bronchial epithelial (BEAS 2B) cells, using the single cell gel electrophoresis (comet) assay and the immunoslot blot assay for the detection of malondialdehyde (M₁dG) DNA adducts. In BEAS 2B cells, we also studied the induction of micronuclei (MN) by the CNTs using the cytokinesis-block method. The cells were exposed to the CNTs (5–200 μg/cm², corresponding to 19–760 μg/ml) for 24 and 48 h in the comet assay and for 48 and 72 h in the MN and M₁dG assays. Transmission electron microscopy (TEM) showed more MWCNT fibres and SWCNT clusters in BEAS 2B than MeT-5A cells, but no significant differences were seen in intracellular dose expressed as area of SWCNT clusters between TEM sections of the cell lines. In MeT-5A cells, both CNTs caused a dose-dependent induction of DNA damage (% DNA in comet tail) in the 48-h treatment and SWCNTs additionally in the 24-h treatment, with a statistically significant increase at 40 μg/cm² of SWCNTs and (after 48 h) 80 μg/cm² of both CNTs. SWCNTs also elevated the level of M₁dG DNA adducts at 1, 5, 10 and 40 μg/cm² after the 48-h treatment, but both CNTs decreased M₁dG adduct level at several doses after the 72-h treatment. In BEAS 2B cells, SWCNTs induced a statistically significant increase in DNA damage at 80 and 120 μg/cm² after the 24-h treatment and in M₁dG adduct level at 5 μg/cm² after 48 h and 10 and 40 μg/cm² after 72 h; MWCNTs did not affect the level of DNA damage but produced a decrease in M₁dG adducts in the 72-h treatment. The CNTs did not affect the level of MN. In conclusion, MWCNTs and SWCNTs induced DNA damage in MeT-5A cells but showed a lower (SWCNTs) or no (MWCNTs) effect in BEAS 2B cells, suggesting that MeT-5A cells were more sensitive to the DNA-damaging effect of CNTs than BEAS 2B cells, despite the fact that more CNT fibres or clusters were seen in BEAS 2B than MeT-5A cells. M1dG DNA adducts were induced by SWCNTs but decreased after a 3-day exposure to MWCNTs and (in MeT-5A cells) SWCNTs, indicating that CNTs may lead to alterations in oxidative effects within the cells. Neither of the CNTs was able to produce chromosomal damage (MN).     

Binding symbols and sounds: evidence from event-related oscillatory gamma-band activity

The present study intended to examine the neural basis of audiovisual integration, hypothetically achieved by synchronized gamma-band oscillations (30-80 Hz) that have been suggested to integrate stimulus features and top-down information. To that end, we studied the impact of visual symbolic information on early auditory sensory processing of upcoming sounds. In particular, we used a symbol-to-sound-matching paradigm in which simple score-like patterns predict corresponding sound patterns. Occasionally, a single sound is incongruent with the corresponding element of the visual pattern. In response to expected sounds congruent with the corresponding visual symbol, a power increase of phase-locked (evoked) activity in the 40-Hz band was observed peaking 42-ms poststimulus onset. Thus, for the first time, we demonstrated that the comparison process between a neural model, the expectation, and the current sensory input is implemented at very early levels of auditory processing. Subsequently, expected congruent sounds elicited a broadband power increase of non-phase-locked (induced) activity peaking 152-ms poststimulus onset, which might reflect the formation of a unitary event representation including both visual and auditory aspects of the stimulation. Gamma-band responses were not present for unexpected incongruent sounds. A model explaining the anticipatory activation of cortical auditory representations and the match of experience against expectation is presented.     

Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families

OBJECTIVE: Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples. METHODS: We performed a combined analysis of the primary genome scan data of the Autism Genetic Resource Exchange (AGRE) and Finnish autism samples to reveal susceptibility loci potentially shared by these study samples. RESULTS: In the initial combined data analysis, the best loci (p < 0.05) were observed at 1p12-q25, 3p24-26, 4q21-31, 5p15-q12, 6q14-21, 7q33-36, 8q22-24, 17p12-q21, and 19p13-q13. The combined analysis of Finnish and AGRE families showed the most promising shared locus on 3p24-26 with nonparametric logarithm of odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide increased linkage evidence for the earlier identified loci on 3q25-27 or 17p12-q21. However, the 17p12-q21 locus remained promising also in the combined sample (NPL(all) =2.38, p = 0.0076). INTERPRETATION: Our study of 314 autism families highlights the importance of further analyses on 3p24-26 locus involving comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a positional and functional candidate gene for autism.     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.     

Occupational burnout and medically certified sickness absence: a population-based study of Finnish employees

OBJECTIVE: Occupational burnout is a common problem in working populations, but its association with sickness absence is poorly understood. The contribution of occupational burnout to medically certified sickness absence was examined in a population-based sample of employees. METHODS: A representative sample of 3151 Finnish employees aged 30-60 years participated in a comprehensive health study in 2000-2001, including an assessment of physician-diagnosed physical illnesses and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders based on the Composite International Diagnostic Interview. Burnout was measured with the Maslach Burnout Inventory-General Survey. Sickness absences longer than 9 days in 2000-2001 were extracted from a register of the Social Insurance Institution of Finland. RESULTS: The occurrence of medically certified sickness absence was more prevalent among employees with burnout than among those without burnout. After adjusting for sociodemographic factors and mental and physical disorders, the odds ratio of sickness absence for severe burnout was 6.9 [95% confidence interval (95% CI)=2.7-17.8] for men and 2.1 (95% CI=1.1-4.0) for women. Among employees with mental or physical disorders, severe burnout was associated with a 7.7-fold risk of sickness absence among men and with a 2.6-fold risk among women. The duration of absence was related to burnout among men with absences, for whom severe burnout accounted for 52 excess sickness absence days during the 2-year period after adjusting for sociodemographic factors, mental disorders, and physical illnesses. CONCLUSIONS: Severe burnout is associated with a substantial excess risk of medically certified sickness absence among both men and women. This association is independent of prevalent mental disorders and physical illnesses.