Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts.

Alpha-synucleinopathies are featured by fibrillar inclusions in brain cells. Although α-synuclein fibrils display structural diversity, the origin of this diversity is not fully understood. We used molecular dynamics simulations to design synthetic peptides, based on the NAC 71-82 amino acid fragment of α-synuclein, that govern protofilament contacts and generation of twisted fibrillar polymorphs. Four peptides with structures based on either single or double fragments and capped or non-capped ends were selected for further analysis. We determined the fibrillar yield and the structures from these peptides found in the solution after fibrillisation using protein concentration determination assay and circular dichroism spectroscopy. In addition, we characterised secondary structures formed by individual fibrillar complexes using laser-tweezers Raman spectroscopy. Results suggest less mature fibrils, based on the lower relative ß-sheet content for double- than single-fragment peptide fibrils. We confirmed this structural difference by TEM analysis which revealed, in addition to short protofibrils, more elongated, twisted and rod-like fibril structures in non-capped and capped double-fragment peptide systems, respectively. Finally, time-correlated single-photon counting demonstrated a difference in the Thioflavin T fluorescence lifetime profiles upon fibril binding. It could be proposed that this difference originated from morphological differences in the fibril samples. Altogether, these results highlight the potential of using peptide models for the generation of fibrils that share morphological features relevant for disease, e.g., twisted and rod-like polymorphs.

A Capped Peptide of the Aggregation Prone NAC 71-82 Amino Acid Stretch of α-Synuclein Folds into Soluble ß-Sheet Oligomers at Low and Elevated Peptide Concentrations.

Although Lewy bodies and Lewy neurites are hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), misfolded α-synuclein oligomers are nowadays believed to be key for the development of these diseases. Attempts to target soluble misfolded species of the full-length protein have been limited so far, probably due to the fast aggregation kinetics and burial of aggregation prone segments in final cross-ß-sheet fibrils. A previous characterisation study of fibrils prepared from a capped peptide of the non-amyloid ß-component (NAC) 71-82 amino acid stretch of α-synuclein demonstrated an increased aggregation propensity resulting in a cross-ß-structure that is also found in prion proteins. From this, it was suggested that capped NAC 71-82 peptide oligomers would provide interesting motifs with a capacity to regulate disease development. Here, we demonstrated, from a series of circular dichroism spectroscopic measurements and molecular dynamics simulations, the molecular-environment-sensitive behaviour of the capped NAC 71-82 peptide in a solution phase and the formation of ß-sheet oligomeric structures in the supernatant of a fibrillisation mixture. These results highlighted the use of the capped NAC 71-82 peptide as a motif in the preparation of oligomeric ß-sheet structures that potentially could be used in therapeutic strategies in the fight against progressive neurodegenerative disorders, such as PD and DLB.

Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the α-Synuclein NAC 71-82 amino acid stretch contain an additional cross-ß structure also found in prion proteins.

The 71-82 fragment of the non-amyloid-ß component (NAC) region of the Parkinson's disease (PD) and dementia with Lewy bodies (DLB) related protein α-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71-82 amino acid stretch of α-Synuclein are amyloid and contain, in addition to the cross-ß structure detected in the full-length protein fibrils, a cross-ß structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71-82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of α-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71-82 peptide generated structures were stabilised by an anti-parallel and twisted ß-sheet motif. Due to its expected toxicity, this ß-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.

Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis.

Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here we show that oxidative post-translational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde adduct (MDA) modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located to three distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritis mice and RA patients. Moreover, molecular dynamic simulations revealed that these areas, here coined "hotspots", are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and provide novel leads for targeted therapeutic treatment to improve muscle function.

Author Correction: Dilution of whisky - the molecular perspective.

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Dilution of whisky - the molecular perspective.

Whisky is distilled to around 70% alcohol by volume (vol-%) then diluted to about 40 vol-%, and often drunk after further slight dilution to enhance its taste. The taste of whisky is primarily associated with amphipathic molecules, such as guaiacol, but why and how dilution enhances the taste is not well understood. We carried out computer simulations of water-ethanol mixtures in the presence of guaiacol, providing atomistic details on the structure of the liquid mixture. We found that guaiacol is preferentially associated with ethanol, and, therefore, primarily found at the liquid-air interface in mixtures that contain up to 45 vol-% of ethanol. At ethanol concentrations of 59 vol-% or higher, guaiacol is increasingly surrounded by ethanol molecules and is driven to the bulk. This indicates that the taste of guaiacol in the whisky would be enhanced upon dilution prior to bottling. Our findings may apply to other flavour-giving amphipathic molecules and could contribute to optimising the production of spirits for desired tastes. Furthermore, it sheds light on the molecular structure of water-alcohol mixtures that contain small solutes, and reveals that interactions with the water may be negligible already at 89 vol-% of ethanol.

Prevalence of depression: Comparisons of different depression definitions in population-based samples of older adults.

BACKGROUND: Depression prevalence in older adults varies largely across studies, which probably reflects methodological rather than true differences. This study aims to explore whether and to what extent the prevalence of depression varies when using different diagnostic criteria and rating scales, and various samples of older adults. METHODS: A population-based sample of 3353 individuals aged 60-104 years from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were examined in 2001-2004. Point prevalence of depression was estimated by: 1) diagnostic criteria, ICD-10 and DSM-IV-TR/DSM-5; 2) rating scales, MADRS and GDS-15; and 3) self-report. Depression prevalence in sub-samples by dementia status, living place, and socio-demographics were compared. RESULTS: The prevalence of any depression (including all severity grades) was 4.2% (moderate/severe: 1.6%) for ICD-10 and 9.3% (major: 2.1%) for DSM-IV-TR; 10.6% for MADRS and 9.2% for GDS-15; and 9.1% for self-report. Depression prevalence was lower in the dementia-free sample as compared to the total population. Furthermore, having poor physical function, or not having a partner were independently associated with higher depression prevalence, across most of the depression definitions. LIMITATIONS: The response rate was 73.3% and this may have resulted in an underestimation of depression. CONCLUSION: Depression prevalence was similar across all depression definitions except for ICD-10, showing much lower figures. However, independent of the definition used, depression prevalence varies greatly by dementia status, physical functioning, and marital status. These findings may be useful for clinicians when assessing depression in older adults and for researchers when exploring and comparing depression prevalence across studies.

Key Residues and Phosphate Release Routes in the Saccharomyces cerevisiae Pho84 Transceptor: THE ROLE OF TYR179 IN FUNCTIONAL REGULATION.

Pho84, a major facilitator superfamily (MFS) protein, is the main high-affinity Pi transceptor in Saccharomyces cerevisiae Although transport mechanisms have been suggested for other MFS members, the key residues and molecular events driving transport by Pi:H+ symporters are unclear. The current Pho84 transport model is based on the inward-facing occluded crystal structure of the Pho84 homologue PiPT in the fungus Piriformospora indica However, this model is limited by the lack of experimental data on the regulatory residues for each stage of the transport cycle. In this study, an open, inward-facing conformation of Pho84 was used to study the release of Pi A comparison of this conformation with the model for Pi release in PiPT revealed that Tyr179 in Pho84 (Tyr150 in PiPT) is not part of the Pi binding site. This difference may be due to a lack of detailed information on the Pi release step in PiPT. Molecular dynamics simulations of Pho84 in which a residue adjacent to Tyr179, Asp178, is protonated revealed a conformational change in Pho84 from an open, inward-facing state to an occluded state. Tyr179 then became part of the binding site as was observed in the PiPT crystal structure. The importance of Tyr179 in regulating Pi release was supported by site-directed mutagenesis and transport assays. Using trehalase activity measurements, we demonstrated that the release of Pi is a critical step for transceptor signaling. Our results add to previous studies on PiPT, creating a more complete picture of the proton-coupled Pi transport cycle of a transceptor.

DSM-IV and DSM-5 Prevalence of Social Anxiety Disorder in a Population Sample of Older People.

OBJECTIVES: To examine the prevalence of social anxiety disorders (SAD) with (DSM-IV) and without (DSM-5) the person's own assessment that the fear was unreasonable, in a population sample of older adults. Further, to determine whether clinical and sociodemographic correlates of SAD differ depending on the criteria applied. DESIGN: Cross-sectional. SETTING: General population in Gothenburg, Sweden. PARTICIPANTS: A random population-based sample of 75- and 85-year olds (N = 1200) without dementia. MEASUREMENTS: Psychiatric research nurses carried out a semi-structured psychiatric examination including the Comprehensive Psychopathological Rating Scale. DSM-IV SAD was diagnosed with the Mini International Neuropsychiatric Interview. SAD was diagnosed according to DSM-IV and DSM-5 criteria. The 6-month duration criterion in DSM-5 was not applied because of lack of information. Other assessments included the Global Assessment of Functioning (GAF), the Brief Scale for Anxiety (BSA), and the Montgomery Åsberg Depression Rating Scale (MADRS). RESULTS: The 1-month prevalence of SAD was 2.5% (N = 30) when the unreasonable fear criterion was defined in accordance with DSM-IV and 5.1% (N = 61) when the DSM-5 criterion was applied. Clinical correlates (GAF, MADRS, and BSA) were worse in SAD cases identified by either procedure compared with all others, and ratings for those reporting unreasonable fear suggested greater (albeit nonsignificant) overall psychopathology. CONCLUSIONS: Shifting the judgment of how reasonable the fear was, from the individual to the clinician, doubled the prevalence of SAD. This indicates that the DSM-5 version might increase prevalence rates of SAD in the general population. Further studies strictly applying all DSM-5 criteria are needed in order to confirm these findings.

Depression and Depression Treatment in a Population-Based Study of Individuals Over 60 Years Old Without Dementia.

OBJECTIVE: To estimate the prevalence of depression in a population-based sample of older adults, and to identify the individual profile of people who received depression treatment. DESIGN: Cross-sectional. SETTING: Central area (Kungsholmen) in Stockholm, Sweden. PARTICIPANTS: A randomized population-based sample of individuals aged 60 years and older (N = 3,084) without dementia from the Swedish National Study of Aging and Care in Kungsholmen examined between 2001 and 2004. MEASUREMENTS: Experienced physicians carried out a semi-structured psychiatric examination including the Comprehensive Psychopathological Rating Scale. Depression was diagnosed according to DSM-IV-TR and DSM-5 criteria. Information regarding drug treatment and psychotherapy was collected during the examination and is based on self-report. RESULTS: The prevalence of depression was 5.9% (major depression: 0.8%, minor depression: 5.1%). In the total sample, 8.3% were prescribed an antidepressant and 0.9% were treated with psychotherapy. Among individuals with depression, fewer than one-third received treatment with psychotherapy or antidepressants, but almost half were prescribed anxiolytic or hypnotic drugs. Individuals with self-reported depression and anxiety were more likely to receive depression treatment whereas individuals with depression who reported insomnia were less likely to receive depression treatment. CONCLUSIONS: Our findings indicate that even in a central urban area of a country with an advanced healthcare system depression in old age is often unrecognized and untreated. In addition, almost half of those with depression received potentially inappropriate drug treatment with anxiolytics or hypnotics.

In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies.

All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.

The Analysis Portal and the Swedish LifeWatch e-infrastructure for biodiversity research.

BACKGROUND: During the last years, more and more online portals were generated and are now available for ecologists to run advanced models with extensive data sets. Some examples are the Biodiversity Virtual e-Laboratory (BioVel) Portal (https://portal.biovel.eu) for ecological niche modelling and the Mobyle SNAP Workbench (https://snap.hpc.ncsu.edu) for evolutionary and population genetics analysis. Such portals have the main goal to facilitate the run of advanced models, through access to large-capacity computers or servers. In this study, we present the Analysis Portal (www.analysisportal.se), which is a part of the Swedish LifeWatch e-infrastructure for biodiversity research that combines a variety of Swedish web services to perform different kinds of dataprocessing. NEW INFORMATION: For the first time, the Swedish Analysis Portal for integrated analysis of species occurrence data is described in detail. It was launched in 2013 and today, over 60 Million Swedish species observation records can be assessed, visualized and analyzed via the portal. Datasets can be assembled using sophisticated filtering tools, and combined with environmental and climatic data from a wide range of providers. Different validation tools, for example the official Swedish taxon concept database Dyntaxa, ensure high data quality. Results can be downloaded in different formats as maps, tables, diagrams and reports.

NINE-YEAR FOLLOW-UP OF SPECIFIC PHOBIA IN A POPULATION SAMPLE OF OLDER PEOPLE.

BACKGROUND: Little is known about the long-term course of specific phobia (SP) in the general population. We examined the prevalence and course of SP and subthreshold fears in an older population followed over 9 years. METHOD: A psychiatric examination was performed in a population-based sample of 558 70-year-olds, among whom 303 dementia-free survivors were followed up at both ages 75 and 79. Fears were rated with respect to level of anxiety and social or other consequences. DSM-IV SP was diagnosed when fears were associated with prominent anxiety and had social or other consequences. All other fears were labeled subthreshold fears. RESULTS: The prevalence of SP declined from 9.9% at age 70 to 4.0% at age 79. The reason was that the prevalence of fears associated with prominent anxiety (mandatory in the diagnosis) decreased whereas the prevalence of fears that gave social or other consequences remained stable. A total of 14.5% of the population had SP at least once during the study. Among these, 11.4% had SP and 65.9% had specific fear at all three examinations. CONCLUSION: The prevalence of fears associated with prominent anxiety decreased with age, resulting in an overall decline in the prevalence of SP. SP seems to be a fluctuating disorder, and in most cases an exacerbation of chronic subthreshold fears.

Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance.

The development of in silico strategies for the study of the molecular imprinting process and the properties of molecularly imprinted materials has been driven by a growing awareness of the inherent complexity of these systems and even by an increased awareness of the potential of these materials for use in a range of application areas. Here we highlight the development of theoretical and computational strategies that are contributing to an improved understanding of the mechanisms underlying molecularly imprinted material synthesis and performance, and even their rational design.

A functional monomer is not enough: principal component analysis of the influence of template complexation in pre-polymerization mixtures on imprinted polymer recognition and morphology.

In this report, principal component analysis (PCA) has been used to explore the influence of template complexation in the pre-polymerization phase on template molecularly imprinted polymer (MIP) recognition and polymer morphology. A series of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)-crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate (MMA) as the functional monomer, and the stoichiometry between template, functional monomer and crosslinker was varied. The polymers were characterized using radioligand equilibrium binding experiments, gas sorption measurements, swelling studies and data extracted from molecular dynamics (MD) simulations of all-component pre-polymerization mixtures. The molar fraction of the functional monomer in the MAA-polymers contributed to describing both the binding, surface area and pore volume. Interestingly, weak positive correlations between the swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed. Polymers prepared with MMA as a functional monomer and a polymer prepared with only EGDMA were found to share the same characteristics, such as poor rebinding capacities, as well as similar surface area and pore volume, independent of the molar fraction MMA used in synthesis. The use of PCA for interpreting relationships between MD-derived descriptions of events in the pre-polymerization mixture, recognition properties and morphologies of the corresponding polymers illustrates the potential of PCA as a tool for better understanding these complex materials and for their rational design.

Towards global QSAR model building for acute toxicity: Munro database case study.

A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

On the influence of crosslinker on template complexation in molecularly imprinted polymers: a computational study of prepolymerization mixture events with correlations to template-polymer recognition behavior and NMR spectroscopic studies.

Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contribution of crosslinker to determining the nature of molecularly imprinted polymer-template selectivity.

Prevalence of obsessive-compulsive disorder in relation to depression and cognition in an elderly population.

OBJECTIVES: We examined the 1-month prevalence of obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) not fulfilling OCD criteria in relation to sex, age, social and mental function, comorbid depression, and cognitive functioning in an elderly nondemented population. SETTINGS AND PARTICIPANTS: Population-based sample (N = 900), stratified into two age groups: 70-year-olds (335 women and 224 men) and those aged 78 and above (341 women). MEASUREMENTS: Semi-structured interviews. Psychiatric symptoms were assessed with the Comprehensive Psychopathological Rating Scale and Mini-International Neuropsychiatric Interview, mental and social function with the GAF-scale, memory function with the Word Recall Task and general cognition with MMSE. OCD and Depression were diagnosed according to DSM-IV. RESULTS: The one-month prevalence of OCD was 2.9%; a further 21% had OCS. Among 70-year-olds, the prevalence of OCD was 1.3% in men and 4.5% in women. Depression was more common among those with OCD (34.6%) than among those with (12.7%) and without (8.0%) OCS. GAF-score was lower among those with OCD (74.8) and OCS (82.9) compared with individuals without obsessions and compulsions (88.2). The association between OCD and GAF-score remained after adjustment for age, sex, and depression. The OCD subgroup with checking behavior had more memory and concentration problems and did worse on Word Recall Task than other groups in our sample. CONCLUSIONS: We found that OCD and OCS are common among the elderly. Both conditions are related to depression and poorer mental and social functioning. Physicians who meet elderly patients need to be aware of OCD as it is potentially treatable.

Molecular dynamics approaches to the design and synthesis of PCB targeting molecularly imprinted polymers: interference to monomer-template interactions in imprinting of 1,2,3-trichlorobenzene.

The interactions between each component of the pre-polymerisation mixtures used in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5-pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four molecular dynamics simulations. These simulations revealed that the relative frequency of functional monomer-template (FM-T) interactions was consistent with results obtained by the synthesis and evaluation of the actual MIPs. The higher frequency of 1 interaction with trimethylstyrene (TMS; 54.7%) than 1 interaction with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%) also correlated well with the observed differences in IF (3.7) of 2 MIPs imprinted using PFS as the FM than the IF (2.8) of 2 MIPs imprinted using TMS as the FM. The TMS-1 interaction dominated the molecular simulation due to high interaction energies, but the weaker TMS-2 resulted in low interaction maintenance, and thus lower IF values. Examination of the other pre-polymerisation mixture components revealed that the low levels of TMS-2 interaction was, in part, due to interference caused by the cross linker (CL) ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason was, however, attributed to MeOH interactions with TMS in both a hydrogen bond and perpendicular configuration. This positioned a MeOH directly above the π-orbital of all TMS for an average of 63.8% of MD2 creating significant interference to π-π stacking interactions between 2 and TMS. These findings are consistent with the deviation from the 'normal' molecularly imprinted polymer synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29 observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations correctly predicted the high level of interference from other MIP synthesis components. The effect on PFS-1 interaction by MeOH was significantly lower and thus this system was not adversely affected.

Welfare state regimes, gender, and depression: a multilevel analysis of middle and high income countries.

Using the 2002 World Health Survey, we examine the association between welfare state regimes, gender and mental health among 26 countries classified into seven distinct regimes: Conservative, Southeast Asian, Eastern European, Latin American, Liberal, Southern/Ex-dictatorship, and Social Democratic. A two-level hierarchical model found that the odds of experiencing a brief depressive episode in the last 12 months was significantly higher for Southern/Ex- dictatorship countries than for Southeast Asian (odds ratio (OR) = 0.12, 95% confidence interval (CI) 0.05-0.27) and Eastern European (OR = 0.36, 95% CI 0.22-0.58) regimes after controlling for gender, age, education, marital status, and economic development. In adjusted interaction models, compared to Southern/Ex-dictatorship males (reference category), the odds ratios of depression were significantly lower among Southeast Asian males (OR = 0.16, 95% CI 0.08-0.34) and females (OR = 0.23, 95% CI 0.10-0.53) and Eastern European males (OR = 0.41, 95% CI 0.26-0.63) and significantly higher among females in Liberal (OR = 2.00, 95% CI 1.14-3.49) and Southern (OR = 2.42, 95% CI 1.86-3.15) regimes. Our results highlight the importance of incorporating middle-income countries into comparative welfare regime research and testing for interactions between welfare regimes and gender on mental health.