Homochirality in an early peptide world

A recently proposed model of non-autocatalytic reactions in dipeptide reactions leading to spontaneous symmetry breaking and homochirality is examined. The model is governed by activation, polymerization, epimerization and depolymerization of amino acids. Symmetry breaking is primarily a consequence of the fact that the rates of reactions involving homodimers and heterodimers are different, i.e., stereoselective, and on the fact that epimerization can only occur on the N-terminal residue and not on the Cterminal residue. This corresponds to an auto-inductive cyclic process that works only in one sense. It is argued that epimerization mimics both autocatalytic behavior as well as mutual antagonism - both of which were known to be crucial for producing full homochirality.Comment: 19 pages, 7 figures, 3 boxe

Association between alexithymia and substance use : A systematic review and meta-analysis

Alexithymia has been associated with substance use, but the magnitude of the association has not been evaluated and sub-group differences, if any, are unknown. The aim of this meta-analysis is to systematically review the association between alexithymia and substance use (alcohol or illicit drugs). We identified studies through a systematic review of PubMed and Web of Science and obtained a total of 52 publications using the Toronto Alexithymia Scale-20 scale. Random effects meta-analysis was used to evaluate the overall and sub-group associations. Of the studies, 50 were cross-sectional and two longitudinal. Alexithymia was associated with any substance use (Cohen's d = 0.62, 95% confidence interval [CI] 0.49-0.76), with little difference between estimates for use of alcohol or illicit drugs. A stronger association was observed for the alexithymia dimension "Difficulty in Identifying Feelings" (d = 0.64, 95% CI = 0.47-0.81) and "Difficulty in Describing Feelings" (d = 0.44, 95% CI = 0.32-0.55) than for "Externally Oriented Thinking" (d = 0.19, 95% CI = 0.09-0.28). The association was stronger in studies with clinical patient populations (d = 0.83, 95% CI = 0.62-1.05) than in those investigating general or student populations, and in studies with a majority of male rather than female participants. These findings suggest a strong overall association between alexithymia and substance use and a very strong association among clinical patient populations. The association may be stronger with the emotion-related dimensions than with the cognition-related dimension of alexithymia. As nearly all the studies were cross-sectional, more longitudinal studies are needed.Peer reviewe

Early maladaptive schemas in chronically depressed patients : A preliminary investigation

Background Schema therapy has been proposed as a potentially effective treatment for chronic depression. However, little is known about early maladaptive schemas (EMSs), a key concept in schema therapy, in relation to chronic depression or chronic depression with comorbid personality pathology. The aim of the present study was to compare EMSs between currently chronically depressed patients with comorbid cluster C personality disorder (CDCPD), currently chronically depressed patients (CD), and patients remitted from chronic depression (CDR). Methods Based on data from a naturalistic follow-up study on psychiatric outpatients with major depressive disorder, three groups were formed according to Diagnostic and Statistical Manual of Mental Disorders-IV: CDCPD (n = 15), CD (n = 23), and CDR (n = 13). Groups were compared in terms of background information and measurements for depression (Beck Depression Inventory) and EMSs (Young Schema Questionnaire). Results Patients with CDCPD and CD did not differ in terms of background variables or the severity of depressive symptoms, but patients with CDCPD were more maladaptive with respect to the majority of EMSs. Patients with CDR were less depressed than CDCPD or CD patients, but did not differ in terms of EMSs compared with CD patients. Conclusions Comorbid cluster C personality disorder appears to be associated with more severe EMS endorsement in chronically depressed patients. Remitted patients show similar cognitive vulnerability factors in terms of EMSs compared to those currently chronically depressed. The findings suggest that EMSs may contribute to vulnerability to chronic depression. Focusing on EMSs may be beneficial in the treatment of chronic depression.Peer reviewe

Purine metabolism is dysregulated in patients with major depressive disorder

Peer reviewe

Biological and other health related correlates of long-term life dissatisfaction burden

Background Mental health is interconnected with somatic health and can manifest itself in biological processes. Life dissatisfaction is an indicator of subjective well-being, but information on its biological correlates is scarce. The aim of this study was to investigate the biological correlates along with other health-related factors of long-term life dissatisfaction in a population-based sample. Methods As part of the Kuopio Depression Study, health questionnaires were sent to a randomly selected population-based sample in 1998, 1999, and 2001. In 2005, among a clinically studied sub-sample (n = 305), the 7-year long-term life dissatisfaction burden was assessed by summing life satisfaction scores from previous health questionnaires. Several sociodemographic, health, health behavior, and biological factors were investigated in respect to their associations to categorized (low and high) and continuous (linear regression) life satisfaction burden score (higher values indicating dissatisfaction). Results In the final linear regression model long-term life dissatisfaction burden was significantly associated with poor social support (B = 0.138; p < 0.001), marital status (i.e. living alone) (B = 0.049; p = 0.019), current smoking (B = 0.087; p < 0.001), poor sleep (B = 0.052; p = 0.001), use of statins (B = −0.052; p = 0.002) and lower serum adiponectin level (B = −0.001; p = 0.039) whereas association of metabolic syndrome was marginally nonsignificant (B = 0.029; p = 0.055). Conclusion Long-term life dissatisfaction is associated with adverse health, health behavioral, and social factors, as well as with a decreased anti-inflammatory buffer capacity, all indicating close relationships between subjective well-being and somatic morbidity.BioMed Central open acces

Increased Serum PAI-1 Levels in Subjects with Metabolic Syndrome and Long-Term Adverse Mental Symptoms: A Population-Based Study

Depression is an independent risk factor for cardiovascular diseases and is associated with metabolic syndrome (MetS). Levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue-type and urokinase-type plasminogen activators, are associated with MetS. To clarify the role of PAI-1 in subjects with long-term adverse mental symptomatology (LMS; including depression) and MetS, we measured circulating PAI-1 levels in controls (n = 111), in subjects with MetS and free of mental symptoms (n = 42), and in subjects with both MetS and long-term mental symptoms (n = 70). PAI-1 increased linearly across the three groups in men. In logistic regression analysis, men with PAI-1 levels above the median had a 3.4-fold increased likelihood of suffering from the comorbidity of long-term adverse mental symptoms and MetS, while no such associations were detected in women. In conclusion, our results suggest that in men high PAI-1 levels are independently associated with long-term mental symptomatology

Global arginine bioavailability ratio is decreased in patients with major depressive disorder

Background: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. Methods: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n= 33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. Results: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. Limitations: The MDD group was not medication-free. Conclusions: Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.Peer reviewe

Kuopio birth cohort - design of a Finnish joint research effort for identification of environmental and lifestyle risk factors for the wellbeing of the mother and the newborn child

Background: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. Methods: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omits; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. Discussion: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.Peer reviewe

Unemployment and ill health: a connection through inflammation?

<p>Abstract</p> <p>Background</p> <p>Unemployment is a source of acute and long-term psychosocial stress. Acute and chronic psychosocial stress can induce pronounced changes in human immune responses. In this study we tested our hypothesis that stress-induced low-grade tissue inflammation is more prevalent among the unemployed.</p> <p>Methods</p> <p>We determined the inflammatory status of 225 general population subjects below the general retirement age (65 years in Finland). Those who had levels of both interleukin-6 (≥ 0.97 pg/mL) and high-sensitivity C-reactive protein (≥ 1.49 mg/L) above the median were assessed to have an elevated inflammatory status (n = 72).</p> <p>Results</p> <p>An elevated inflammatory status was more common among the unemployed than among other study participants (59% versus 30%, p = 0.011). In the final multivariate model, those who were unemployed had over five-fold greater odds for having an elevated inflammatory status (OR 5.20, 95% CI 1.55-17.43, p = 0.008).</p> <p>Conclusion</p> <p>This preliminary finding suggests that stress-induced low-grade inflammation might be a link between unemployment and ill health.</p