Use of antipsychotics and antidepressants in first-episode psychotic depression: A nationwide register-based study.

BACKGROUND: According to guidelines, psychotic depression should be treated with both antipsychotics and antidepressants, but current practice is largely unknown. We investigated the prevalence of antipsychotic and antidepressant use in first-episode psychotic depression and factors related to antipsychotic use after the diagnosis. METHODS: We identified individuals aged 16-65 with a first-episode diagnosis of psychotic depression (ICD-10 codes F32.3, F33.3) from nationwide data linkage of Finnish healthcare and population registers during 2000-2018. Point prevalence was measured as 2-week time windows every 3 months, investigating whether the individual had a modeled drug use period ongoing during the window or not, censoring to death and end of data linkage. RESULTS: The study population included 18,490 individuals (58.0% women; mean age 39.9 years, standard deviation 14.7). The prevalence of use for antidepressants (75.0%), antipsychotics (56.4%), and both (50.0%) were highest at 3 months after the diagnosis. The prevalence declined to 51.8%, 34.1%, and 28.7%, respectively, at 3 years after the diagnosis. In a logistic regression analysis, younger age (adjusted odds ratio < 25 vs. ≥55, 0.82 [95% confidence interval 0.73-0.91]), eating disorders (0.78 [0.66-0.92]), substance use disorders (0.80 [0.73-0.87]), and occupational inactivity (0.80 [0.73-0.87]) were associated with decreased odds of using antipsychotics at 3 months after diagnosis. Increased odds were found for diagnosis from inpatient care (1.74 [1.62-1.86]), and later year of cohort entry (2010-2014 vs. 2000-2004, 1.56 [1.42-1.70]). CONCLUSION: At most, half of the individuals with newly diagnosed psychotic depression used both antidepressants and antipsychotics. This likely has a negative impact on treatment success.

Triple-clad W-type fiber mitigates multipath artifacts in multimodal optical coherence tomography.

Multimodal endoscopic optical coherence tomography (OCT) can be implemented with double-clad fiber by using the presumed single-mode core for OCT and the higher numerical aperture cladding for a secondary modality. However, the quality of OCT in double-clad fiber (DCF) based systems is compromised by the introduction of multipath artifacts that are nt present in single-mode fiber OCT systems. Herein, the mechanisms for multipath artifacts in DCF are linked to its modal contents using a commercial software package and experimental measurement. A triple-clad W-type fiber is proposed as a method for achieving multimodal imaging with single-mode quality OCT in an endoscopic system. Simulations of the modal contents of a W-type fiber are compared to DCF and single-mode fiber. Finally, a W-Type fiber rotary catheter is used in a DCF-based endoscopic OCT and autofluorescence imaging (AFI) system to demonstrate multipath artifact free OCT and AFI of a human fingertip.

Multipath artifacts enable angular contrast in multimodal endoscopic optical coherence tomography.

Multipath artifacts are inherent to double-clad fiber based optical coherence tomography (OCT), appearing as ghost images blurred in the A-line direction. They result from the excitation of higher-order inner-cladding modes in the OCT sample arm which cross-couple into the fundamental mode at discontinuities and thus are detected in single-mode fiber-based interferometers. Historically, multipath artifacts have been regarded as a drawback in single fiber endoscopic multimodal OCT systems as they degrade OCT quality. In this work, we reveal that multipath artifacts can be projected into high-quality two-dimensional en face images which encode high angle backscattering features. Using a combination of experiment and simulation, we characterize the coupling of Mie-range scatterers into the fundamental image (LP01 mode) and higher-order image (multipath artifact). This is validated experimentally through imaging of microspheres with an endoscopic multimodal OCT system. The angular dependence of the fundamental image and higher order image generated by the multipath artifact lays the basis for multipath contrast, a ratiometric measurement of differential coupling which provides information regarding the angular diversity of a sample. Multipath contrast images can be generated from OCT data where multipath artifacts are present, meaning that a wealth of clinical data can be retrospectively examined.

Comparative effectiveness of mood stabilizers and antipsychotics in the prevention of hospitalization after lithium discontinuation in bipolar disorder.

The aim of the study was to compare the real-world effectiveness of mood stabilizers and antipsychotics in the prevention of psychiatric hospitalizations and treatment failure after lithium discontinuation in a nationwide bipolar cohort. Using health-care registers, we identified everyone in Finland diagnosed with bipolar disorder during 1987-2018 who discontinued lithium after using it for at least one year (n = 4 052, median period of lithium use before discontinuation 2.7 years). The risk of psychiatric hospitalization and treatment failure (psychiatric hospitalization, death or change in medication) were investigated with within-individual Cox regression. Of mood stabilizer monotherapies, the periods of valproate use (HR = 0.83, 95% CI = 0.71 - 0.97) had lower risk of hospitalization than nonuse of mood stabilizers. Of antipsychotic monotherapies, the use of long-acting injectable (LAI) antipsychotics (HR = 0.48, 95% CI = 0.26 - 0.88) and chlorprothixene (HR = 0.62, 95% CI = 0.44 - 0.88) were associated with lower risk and the use of quetiapine (HR = 1.26, 95% CI = 1.07 - 1.48) and oral olanzapine (HR = 1.23, 95% CI = 1.01 - 1.49) with higher risk of psychiatric hospitalizations than nonuse of antipsychotics. Of mood stabilizer monotherapies, lithium use was associated with lower risk of treatment failure (HR = 0.82, 95% CI = 0.76 - 0.88) than valproate use. The results suggest that antipsychotic LAIs are especially effective in the prevention of psychiatric hospitalizations after lithium discontinuation. The need to alter used medications may be the lowest when lithium is restarted.

Trajectories of labour market marginalisation among young adults with newly diagnosed attention-deficit/hyperactivity disorder (ADHD).

AIMS: Labour market marginalisation (LMM), i.e. severe problems in finding and keeping a job, is common among young adults with attention-deficit/hyperactivity disorder (ADHD). This study aimed to disentangle the extent of LMM as well as the heterogeneity in patterns of LMM among young adults with ADHD and what characterises those belonging to these distinct trajectories of LMM. METHODS: This population-based register study investigated all 6287 young adults, aged 22-29 years, who had their first primary or secondary diagnosis of ADHD in Sweden between 2006 and 2011. Group-based trajectory (GBT) models were used to estimate trajectories of LMM, conceptualised as both unemployment and work disability, 3 years before and 5 years after the year of an incident diagnosis of ADHD. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between individual characteristics and the trajectory groups of LMM were estimated by multinomial logistic regression. RESULTS: Six distinct trajectories of LMM were found: 'increasing high' (21% belonged to this trajectory group) with high levels of LMM throughout the study period, 'rapidly increasing' (19%), 'moderately increasing' (21%), 'constant low' (12%) with low levels of LMM throughout the study period, 'moderately decreasing' (14%) and finally 'fluctuating' (13%), following a reversed u-shaped curve. Individuals with the following characteristics had an increased probability of belonging to trajectory groups of increasing LMM: low educational level (moderately increasing: OR: 1.4; CI: 1.2-1.8, rapidly increasing: OR: 1.7; CI: 1.3-2.1, increasing high: OR: 2.9; CI: 2.3-3.6), single parents (moderately increasing: OR: 1.6; CI: 1.1-2.4, rapidly increasing: OR: 2.0; CI: 1.3-3.0), those born outside the European Union/the Nordic countries (rapidly increasing: OR: 1.7; CI: 1.1-2.5, increasing high: OR: 2.1; CI: 1.4-3.1), persons living in small cities/villages (moderately increasing: OR: 2.4; CI: 1.9-3.0, rapidly increasing: OR: 2.1; CI: 1.6-2.7, increasing high: OR: 2.6; CI: 2.0-3.3) and those with comorbid mental disorders, most pronounced regarding schizophrenia/psychoses (rapidly increasing: OR: 6.7; CI: 2.9-19.5, increasing high: OR: 12.8; CI: 5.5-37.0), autism spectrum disorders (rapidly increasing: OR: 4.6; CI: 3.1-7.1, increasing high: OR: 9.6; CI: 6.5-14.6), anxiety/stress-related disorders (moderately increasing: OR: 1.3; CI: 1.1-1.7, rapidly increasing: OR: 2.0; CI: 1.6-2.5, increasing high: OR: 1.8; CI: 1.5-2.3) and depression/bipolar disorder (moderately increasing: OR: 1.3; CI: 1.0-1.6, rapidly increasing: OR: 1.7; CI: 1.4-2.2, increasing high: OR: 1.5; CI: 1.2-1.9). CONCLUSIONS: About 61% of young adults were characterised by increasing LMM after a diagnosis of ADHD. To avoid marginalisation, attention should especially be given to young adults diagnosed with ADHD with a low educational level, that are single parents and who are living outside big cities. Also, young adults with comorbid mental disorders should be monitored for LMM early in working life.

Detection of medications associated with Alzheimer's disease using ensemble methods and cooperative game theory.

OBJECTIVE: To study the feasibility of evaluating feature importance with Shapley Values and ensemble methods in the context of pharmacoepidemiology and medication safety. METHODS: We detected medications associated with Alzheimer's disease (AD) by examining the additive feature attribution with combined approach of Gradient Boosting and Shapley Values in the Medication use and Alzheimer's disease (MEDALZ) study, a nested case-control study of 70,719 verified AD cases in Finland. Our methodological approach is to do binary classification using Gradient boosting (an ensemble of weak classifiers) in a supervised learning manner. Then we apply Shapley Values (from cooperative game theory) to analyze how feature combinations affect the classification result. Medication use with a five to one year time-window before AD diagnosis was ascertained from Prescription register. RESULTS: Antipsychotics with low or medium dose, antidepressants with medium to high dose, and cardiovascular medications with medium to high dose were identified as the contributing features for separating cases with AD from controls. Medium to high amount of irregularity in the purchase pattern were an indicating feature for separating AD cases from controls. The similarity of medication purchases between AD cases and controls made the feature evaluation challenging. CONCLUSIONS: The combined approach of Gradient Boosting and feature evaluation with Shapley Values identified features that were consistent with findings from previous hypothesis-driven studies. Additionally, the results from the additive feature attribution identified new candidates for future studies on AD risk factors. Our approach also shows promise for studies based on observational studies, where feature identification and interactions in populations are of interest; and the applicability of using Shapley Values for evaluating feature relevance in pattern recognition tasks.

Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer's disease-nested case-control study.

We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer's disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer's disease. INTRODUCTION: To investigate the association between thiazide use and the risk of low-energy fractures (LEF), and hip fracture among community dwellers with Alzheimer's disease (AD). No prior study has evaluated the effect of thiazides on LEF risk of AD patients. METHODS: LEF cases were identified from the MEDALZ study, including all community-dwelling persons diagnosed with AD in Finland 2005-2011. During the follow-up from AD diagnoses until the end of 2015, cases with LEF (N = 10,416) and hip fracture (N = 5578) were identified. LEF cases were matched with up to three controls without LEF, according to time since AD diagnosis, age and gender. Thiazide use identified from the Prescription register data was modeled with PRE2DUP method. Current use was defined in 0-30 days' time window before the fracture/matching date, and duration of current use was assessed. The association between thiazide exposure and LEFs was assessed with conditional logistic regression. RESULTS: Current thiazide use was observed in 10.5% of LEF cases and 12.5% of controls. Current thiazide use was associated with a decreased risk of LEF (adjusted OR [aOR] 0.83, 95% CI 0.77-0.88). In terms of the duration of use, no association was observed with short-term use (< 1 year or 1-3 years), while longer use (> 3 years) was associated with a reduced risk of LEF (aOR 0.77, 95% CI 0.71-0.83) and hip fracture (aOR 0.68, 95% CI 0.60-0.78). CONCLUSIONS: Our study extends the previous knowledge of reduced fracture risk of thiazides to persons with AD, a population with significantly increased background risk of fractures.

The association between subjective maternal stress during pregnancy and offspring clinically diagnosed psychiatric disorders.

OBJECTIVE: Exposure to prenatal stress is a ubiquitous and non-specific risk factor for adverse outcomes in adulthood. In this study, we examined associations between exposure to subjective maternal stress during pregnancy and subsequent diagnosis of psychiatric disorders in offspring. METHOD: This study used the Helsinki Longitudinal Temperament Cohort, a prospective birth cohort of individuals born between 1 July 1975 and 30 June 1976 in Helsinki, Finland. The sample for this study comprised 3626 infants whose mothers had completed health and well-being assessments during pregnancy which included a measure of self-reported stress. We ran logistic regressions to assess potential associations between prenatal stress and offspring psychiatric disorder in adulthood, identified through the Finnish Hospital Discharge Register. RESULTS: Individuals whose mothers reported stress during pregnancy had significantly greater odds of developing a psychiatric disorder (OR = 1.41, 95% CI = 1.10-1.81) particularly a mood disorder (OR = 1.67, 95% CI = 1.10-2.54). These associations remained after adjusting for parental psychiatric history, and other prenatal factors. CONCLUSIONS: Individuals exposed to prenatal stress had significantly increased risk of developing psychiatric disorders later in life. This finding highlights the importance of supporting the mental health and emotional well-being of women during pregnancy.

The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case-control study.

OBJECTIVE: To assess the association between benzodiazepine and related drug (BZDR) use and risk of Alzheimer's disease (AD) with cumulative consumption and duration of use based models. METHOD: A nationwide nested case-control study of all Finnish community-dwelling persons who received clinically verified AD diagnosis in 2005-2011 (N = 70 719) and their matched controls (N = 282 862). AD diagnosis was based on DSM-IV and NINCDS-ADRDA criteria. BZDR purchases were extracted from the Prescription Register since 1995. The association between BZDR use and AD was assessed using conditional logistic regression with 5-year lag time between exposure and outcome. RESULTS: Benzodiazepine and related drug use was associated with modestly increased risk of AD (adjusted OR 1.06, 95% CI 1.04-1.08). A dose-response relationship was observed with both cumulative consumption and duration. Adjustment for other psychotropics removed the cumulative dose-response relationship by attenuating the ORs in the highest dose category. CONCLUSION: Benzodiazepine and related drug use in general was associated with modestly increased risk of AD. No major differences were observed between different subcategories of BZDRs (i.e. benzodiazepines, Z drugs, short-/medium-acting or long-acting BZDRs). As dose-response relationship abolished after adjustment for other psychotropics, it is possible that the association may partially be due to antidepressants and/or antipsychotics, or concomitant use of these medications.

Mortality in schizophrenia: 30-year nationwide follow-up study.

OBJECTIVE: Recent reports suggest that the mortality gap between persons with schizophrenia and the general population is increasing. We investigated the mortality, age at death, and causes of death among persons diagnosed with schizophrenia and the general population in Finland during 1984-2014. METHODS: All persons with schizophrenia in Finland were identified from hospital discharge register, and compared with the Finnish population aged 16 years and older during 1984-2014, based on data from Statistics Finland. Age at death and standardized mortality ratio (SMR) were calculated for each follow-up year. RESULTS: Mean age at death increased from 57.6 years in 1984 to 70.1 years in 2014 in persons with schizophrenia, and from 70.9 to 77.5 years in the general population. All-cause SMR remained stable during the follow-up (2.6 in 1984 and 2.7 in 2014). A major change was observed in SMR for suicides which decreased from 11.0 in 1984 to 6.6 in 2014 (-40%). The SMRs for cardiovascular and cancer deaths showed increasing trends. CONCLUSION: The longevity of persons with schizophrenia is improving at approximately the same rate as the general population but suicide rates have declined substantially. However, there is still a major disparity in mortality compared with general population.

Iron-Terephthalate Coordination Network Thin Films Through In-Situ Atomic/Molecular Layer Deposition.

Iron terephthalate coordination network thin films can be fabricated using the state-of-the-art gas-phase atomic/molecular layer deposition (ALD/MLD) technique in a highly controlled manner. Iron is an Earth-abundant and nonhazardous transition metal, and with its rich variety of potential applications an interesting metal constituent for the inorganic-organic coordination network films. Our work underlines the role of the metal precursor used when aiming at in-situ ALD/MLD growth of crystalline inorganic-organic thin films. We obtain crystalline iron terephthalate films when FeCl3 is employed as the iron source whereas depositions based on the bulkier Fe(acac)3 precursor yield amorphous films. The chemical composition and structure of the films are investigated with GIXRD, XRR, FTIR and XPS.

Proton pump inhibitor use and risk of hip fractures among community-dwelling persons with Alzheimer's disease-a nested case-control study.

BACKGROUND: Hip fractures are a major health concern among older persons with Alzheimer's disease, who usually use many concomitant drugs for several diseases. Evidence of the association between proton pump inhibitor use and risk of hip fracture is contradictory. AIM: To investigate whether the long-term use of proton pump inhibitor is associated with risk of hip fractures among community-dwelling persons with Alzheimer's disease. METHODS: In this nested case-control study, the nationwide MEDALZ data were utilised. Community-dwelling persons with Alzheimer's disease who encountered incident hip fracture (N = 4818; mean age 84.1) were included as cases. Four controls were matched for each case at the date of hip fracture (N = 19 235; mean age 84.0). The association between hip fracture and duration of current PPI use (ongoing use during 0-30 days before the index date), and cumulative duration of use during 10 years before was investigated with conditional logistic regression. RESULTS: Long-term or cumulative proton pump inhibitor use was not associated with an increased risk of hip fracture. Current proton pump inhibitor use was associated with an increased risk of hip fracture (adjusted OR 1.12, 95% CI 1.03-1.22). The risk was increased in short-term current use (<1 year) (adjusted OR 1.23, 95% CI 1.10-1.37). CONCLUSIONS: The increased risk of hip fracture was evident only in short-term proton pump inhibitor use, but no association was found for long-term or cumulative use. Thus, our findings do not support previous assumptions that long-term proton pump inhibitor use would be associated with an increased risk of hip fractures.

Differences in analgesic use in community-dwelling persons with and without Alzheimer's disease.

BACKGROUND: There are conflicting findings about analgesic use among persons with cognitive impairment compared to cognitively intact older persons. The objective of our study was to investigate the prevalence of analgesic use in community-dwelling persons with and without Alzheimer's disease (AD), within six months after AD diagnosis and to find out factors associated with the use of analgesics and specific analgesic groups. METHOD: We utilized data from register based MEDALZ (Medication use and Alzheimer's disease) cohort consisting of all community-dwelling persons diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Altogether, 67,215 persons with AD and one comparison person for each case were included. Drug use data were collected from the Prescription Register and comorbidities from Special Reimbursement and Hospital Discharge Registers. RESULTS: Statistically significant (p < 0.001) yet mostly small differences were found for analgesics use: analgesics were used by 34.9% and 33.5% of persons with and without AD, respectively. Paracetamol was the most frequently used analgesic both among persons with (25.0%) and without AD (19.1%). Persons with AD used less frequently NSAIDs (Nonsteroidal Anti-inflammatory Drugs) (13.2% vs. 17.3%) and mild opioids (5.0% vs. 7.1%), while the use of strong opioids was more common in comparison to persons without AD (1.3% vs. 1.1%, respectively). Analgesic users were more likely women, aged ≥80 years, had asthma/COPD, cardiovascular disease, diabetes, cancer, hip fracture, osteoporosis, rheumatoid arthritis, and lower socioeconomic position. CONCLUSION: Further studies are needed to evaluate the adequateness of pain relief in older persons with and without AD. SIGNIFICANCE: Persons with Alzheimer's disease (AD) used more frequently paracetamol and less frequently NSAIDs and mild opioids. A decreasing trend of NSAID use was observed among persons with AD during the study period.

Iron-based inorganic-organic hybrid and superlattice thin films by ALD/MLD.

Here we present novel layer-by-layer deposition processes for the fabrication of inorganic-organic hybrid thin films of the (-Fe-O-C6H4-O-)n type and also superlattices where thicker iron oxide layers alternate with monomolecular-thin organic layers. The processes are based on a combination of atomic layer deposition (ALD) and molecular layer deposition (MLD) techniques where the cyclopentadienyl iron dicarbonyl dimer (Cp2Fe2(CO)4) is used as the iron source and hydroquinone (HQ) as the organic precursor. For the (-Fe-O-C6H4-O-)n hybrid films a growth rate value as high as 3.7 Å per cycle was achieved at 180 °C. Superlattices where thin crystalline iron oxide layers of the magnetite structure alternate with single organic layers consisting of benzene rings were moreover successfully fabricated from the same precursors at 160 °C using water as the source of oxygen in the ALD cycles for the magnetite layers. We foresee that our new ALD/MLD processes offer a valuable novel tool to modify the properties of magnetite thin films and even more widely possess the potential to boost the ALD/MLD research frontier on functional transition metal oxide based thin films.

Infant brain responses associated with reading-related skills before school and at school age.

INTRODUCTION: In Jyväskylä Longitudinal Study of Dyslexia, we have investigated neurocognitive processes related to phonology and other risk factors of later reading problems. Here we review studies in which we have investigated whether dyslexic children with familial risk background would show atypical auditory/speech processing at birth, at six months and later before school and at school age as measured by brain event-related potentials (ERPs), and how infant ERPs are related to later pre-reading cognitive skills and literacy outcome. PATIENTS AND METHODS: One half of the children came from families with at least one dyslexic parent (the at-risk group), while the other half belonged to the control group without any familial background of dyslexia. RESULTS: Early ERPs were correlated to kindergarten age phonological processing and letter-naming skills as well as phoneme duration perception, reading and writing skills at school age. The correlations were, in general, more consistent among at-risk children. Those at-risk children who became poor readers also differed from typical readers in the infant ERP measures at the group level. ERPs measured before school and at the 3rd grade also differed between dyslexic and typical readers. Further, speech perception at behavioural level differed between dyslexic and typical readers, but not in all dyslexic readers. CONCLUSIONS: These findings suggest persisting developmental differences in the organization of the neural networks sub-serving auditory and speech perception, with cascading effects on later reading related skills, in children with familial background for dyslexia. However, atypical auditory/speech processing is not likely a sufficient reason by itself for dyslexia but rather one endophenotype or risk factor.

A simplified local control model of calcium-induced calcium release in cardiac ventricular myocytes.

Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.

Life events are important in the course of hopelessness-a 2-year follow-up study in a general population.

BACKGROUND: The association between life events and hopelessness in a general population is unknown. AIM: The aim of this study was to examine the course of hopelessness and how positive and negative life events are associated with it. METHOD: This was a 2- year follow-up study among general population adults, excluding any with a mental disorder. The impact of 15 occasional life events during the follow-up was assessed and the course of hopelessness measured with the Beck Hopelessness Scale (HS). RESULTS: Four percent of the study subjects with no hopelessness at baseline and 56% of those with hopelessness at baseline reported hopelessness on follow-up. In multiple logistic regression analyses, a notable worsening of the subjective financial situation was revealed as the most important life event, both in becoming hopeless during the follow-up (OR 5.07; 95% CI 2.20-11.7) and in continued hopelessness (OR 7.51, 95% CI 2.19-25.8). Moreover, considerable interpersonal conflicts at work (OR 3.29, 95% CI 1.17-9.27) were associated with becoming hopeless. However, a notable positive change in common living conditions (OR 0.16, 95% CI 0.04-0.74) was found to be a protective factor against becoming hopeless. All these variables remained significant even when adjusted for change in depression scores (BDI). CONCLUSION: Hopelessness may be persistent in a general population. The impact of life events, especially a notable worsening of the subjective financial situation, is important in becoming or remaining hopeless.

Gender differences in the association of adult hopelessness with adverse childhood experiences.

BACKGROUND: The impact of childhood traumatic events on long-term psychological development has been widely studied. Nevertheless, little research has been carried out on possible associations between adverse childhood experiences (ACEs) and hopelessness in adulthood, and whether any gender differences exist. AIM: The aim of this study was to examine the association between ACEs (poor relationship between parents, unhappiness of childhood home, hard parenting, physical punishment, domestic violence, alcohol abuse in primary family) and current hopelessness without any mental disorder in a general population sample. METHOD: 1598 adults (43 % were men), aged 25-64 years, completed self-report measures to assess ACEs and hopelessness by means of the Beck Hopelessness Scale (HS). Logistic regression was used to adjust for the effects of sociodemographic factors on the association between the cumulative number of ACEs and hopelessness. RESULTS: Whereas several bivariate associations were found between ACEs and hopelessness, none of them remained significant in multivariate analysis. However, men who reported three or more ACEs were 2.79 times (95 % CI 1.17-6.63) and women 2.19 times (95 % CI 1.04-4.65) more likely to be hopeless compared with those without any ACEs. In women (OR 2.25, 95 % CI 1.01-5.00), but not in men, this relationship remained significant after adjusting for several current covariates. CONCLUSION: Clustering of ACEs may have long-lasting effects by increasing the risk of hopelessness in adulthood, especially in women. Increased awareness of the frequency of ACEs and their subsequent consequences, such as hopelessness, may encourage health care professionals to undertake preventive work in primary and mental health care.