Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.

We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample ß-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.

A comparison of symptoms of bipolar and unipolar depression in postpartum women.

BACKGROUND: Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders. METHODS: We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS). RESULTS: The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse. LIMITATIONS: Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data. CONCLUSIONS: Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.

Expanding the international conversation with fathers' mental health: toward an era of inclusion in perinatal research and practice.

Paternal mental health is beginning to be recognized as an essential part of perinatal health. Historically, fathers were not recognized as being at risk for perinatal mental illnesses or relevant to maternal and infant health outcomes. The purpose of this paper is to provide an overview of paternal perinatal mental health, leading tools to assess paternal depression and anxiety, the impact of paternal mental health on mother and child health, and future directions for the field. An international team of paternal perinatal mental health experts summarized the key findings of the field. Fathers have an elevated risk of depression and anxiety disorders during the perinatal period that is associated with maternal depression and can impact their ability to support mothers. Paternal mental health is uniquely associated with child mental health and developmental outcomes starting from infancy and continuing through the child lifespan. Tailored screening approaches for paternal mental health are essential to support fathers early in the perinatal period, which would offset health risks for the family. Recommendations on paternal mental health are provided on four key areas to support father perinatal mental health: (1) intervention research, (2) clinical training, (3) national policy, and (4) the inclusion of fathers in the focus of the International Marcé Society for Perinatal Mental Health.

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease.

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

Development and Validation of a Father Involvement in Health Measure.

Father involvement has been associated with positive child social, emotional, psychological, developmental, and health outcomes. However, tools for measuring father involvement have not kept pace with the expanding understanding of the roles of fathers, and in the area of child health, are blunt. The purpose of this study was to develop and validate a self-report measure of father involvement in preschooler's health, the Father Involvement in Health-Pre-School (FIH-PS). In phase 1 item generation, 47 items were developed based on previous qualitative work and vetted through cognitive interviews with 21 fathers of children ages 3-5 (preschool). In phase 2 psychometric validation, 560 fathers of 3-5 year olds (n=392 resident, n=168 non-resident) completed the FIH-PS item bank. Participants were predominantly white (64%), had private health insurance (53%), had a mean age of 33 years, and half were married. Item Response Theory was used to determine measurement scoring. The FIH-PS scale was reduced from a 47-item bank to a total of 20 items supporting a 4-factor scale made up of Acute Illness, General Well-being, Emotional Health, and Role Modeling. Following exploratory (n=280) and confirmatory factor (n=280) analyses, the scale followed a bifactor structure, was internally consistent (Cronbach's α=0.953), and discriminated among fathers with lower involvement. A sum-to-T-score crosswalk table was produced to standardize the scores along a normal distribution (mean=50, S=10, range 10.8-71.3). Future research and clinical applications of the FIH-PS are discussed.

Four maternal characteristics determine the 12-month course of chronic severe postpartum depressive symptoms.

BACKGROUND: Postpartum depression is a heterogeneous disorder in phenotype and etiology. Characterizing the longitudinal course of depressive symptoms over the first year after birth and identifying variables that predict distinct symptom trajectories will expedite efficient mental health treatment planning. The purpose was to determine 12-month trajectories of postpartum depressive symptoms, identify characteristics that predict the trajectories, and provide a computational algorithm that predicts trajectory membership. METHODS: A prospective cohort of women delivering at an academic medical center (2006-2011) was recruited from an urban women's hospital in Pittsburgh, PA. Women with a postpartum depressive disorder (n = 507) participated and completed symptom severity assessments at 4-8 weeks (intake), 3 months, 6 months, and 12 months. Women were predominantly Caucasian (71.8%), married (53.3%), and college educated (38.7%). Clinician interviews of depressive symptom severity, medical and psychiatric history, assessment of function, obstetric experience, and infant status were conducted. RESULTS: Analyses resulted in identification of three distinct trajectories of depressive symptoms: (1) gradual remission (50.4%), (2) partial improvement (41.8%), and (3) chronic severe (7.8%). Key predictive characteristics of the chronic severe versus gradual remission and partial improvement trajectories included parity, education, and baseline global functioning and depression severity. We were able to predict trajectory membership with 72.8% accuracy from these characteristics. CONCLUSIONS: Four maternal characteristics predicted membership in the chronic severe versus gradual remission and partial improvement trajectories with 72.8% accuracy. The trajectory groups comprise clinically relevant subgroups with the potential for tailored treatments to reduce the disease burden of postpartum depression.

Validity of the WHIPLASHED as a tool to identify bipolar disorder in women.

BACKGROUND: The aim of this study was to investigate the validity of the WHIPLASHED clinician-administered interview, a mnemonic of questions on clinical factors and illness course used to screen for bipolar disorder, as a self-report questionnaire. METHODS: Participants (n = 82) were females recruited from an outpatient academic women's mental health clinic. Relevant symptom data were extracted from a self-report questionnaire designed to parallel the WHIPLASHED interview questions. A score of ≥5 on WHIPLASHED was defined as a positive screen for bipolar spectrum disorder by its developer. We examined the capacity of self-reported WHIPLASHED scores ≥5 to differentiate bipolar from unipolar depression in women. Diagnostic assessments were conducted with the Mini International Neuropsychiatric Interview. RESULTS: Women were diagnosed with unipolar (n = 54) and bipolar (n = 28) depression. The majority of subjects were white (67%), employed (68%) and married (57%) with a mean age of 36.8 years. The receiver operating characteristic curve demonstrated that WHIPLASHED had strong predictive ability (AUC = 0.877) in differentiating bipolar from unipolar depression. A cutoff score of ≥5 generated 96% sensitivity and 52% specificity, while raising the threshold to 6 generated 89% sensitivity and 76% specificity for a bipolar disorder diagnosis. LIMITATIONS: Our sample was small and composed of female patients at a single treatment center. CONCLUSIONS: In this sample, WHIPLASHED was a valid screening tool to differentiate bipolar from unipolar depression. While existing instruments focus on primary symptoms of bipolar disorder, the WHIPLASHED is useful in exploring subtypes of bipolar disorder in which depression dominates the clinical course.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

Are children with chronic illnesses requiring dietary therapy at risk for disordered eating or eating disorders? A systematic review.

OBJECTIVE: Pediatric chronic illnesses (CI) can affect a child's mental health. Chronic illnesses with treatment regimens that specify a therapeutic diet may place the child at increased risk for disordered eating and specific eating disorders (ED). The aim of this review is to examine the relation between diet-treated CI and disordered eating and to determine the order of onset to infer directionality. Diet-treated CI is hypothesized to precede and to be associated with disordered eating. METHOD: A comprehensive search of empirical articles that examine the relation between diet-treated CI (diabetes, cystic fibrosis, celiac disease, gastrointestinal disorders, and inflammatory bowel diseases) and disordered eating was conducted in Medline and PsycINFO using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A table of the sample's characteristics, ED measures, major pertinent findings, and the onset of CI in relation to ED were provided. RESULTS: Diet-treated CI was associated with disordered eating and ED. Diet-treated CI had onset prior to disordered eating in most studies, except for inflammatory bowel diseases. Disordered eating and unhealthy weight management practices put children at risk for poor medical outcomes. DISCUSSION: Interventions for diet-treated CI require a focus on diet and weight, but may increase the risk for disordered eating. Future research is needed to elucidate the mechanisms that transform standard treatment practices into pathological eating, including characteristics and behaviors of the child, parents/care providers, family, and treatment providers.

Paternal Mental Health: Why Is It Relevant?

Father's mental health is an emerging area of interest that is beginning to be recognized in research, and to a lesser extent in clinical practice and society. Fathers are part of a parenting dyad with 2 partners who are responsible for their children's emotional development. Similar to mothers, the risk for mental health problems increases once a male becomes a father, but there is limited research examining this issue. The purpose of this review is to present the available literature on father's mental health and its effect on child emotional health through various mechanisms. In general, father's mental health was found to be related to increased child internalizing and externalizing behaviors, but each disorder had different risk factors, and a unique effect on parenting behaviors and the child's emotional health. The most developed paternal mental health literature is focused on depression. However, key conceptual and methodological problems exist that may limit our understanding of paternal depression. Additionally, the focus on paternal depression may not accurately represent the largest risk for paternal psychopathology and the resultant child mental health outcomes because men have an increased likelihood of displaying externalizing behaviors. Implications for research, clinical practice, and policy are discussed.

Apparatus for testing gas-surface reactions for epicatalysis.

Recently, a new mode of gas-surface heterogeneous catalysis (epicatalysis) has been identified, having potential applications ranging from industrial and green chemistry to novel forms of power generation. This article describes an inexpensive, easily constructed, vacuum-compatible apparatus by which multiple candidate gas-surface combinations can be rapidly screened for epicatalytic activity. In exploratory experiments, candidate surfaces (teflon, kapton, glass, and gold) and gases (helium, argon, cyclohexane, water, methanol, formic acid, and acetic acid) were tested for epicatalytic activity. Kapton and teflon displayed small but reproducible differences in formic acid and methanol dimer desorption, thereby demonstrating the first examples of room-temperature epicatalysis. Other gas-surface combinations showed smaller or inconclusive evidence for epicatalysis.

Factors associated with onset timing, symptoms, and severity of depression identified in the postpartum period.

BACKGROUND: Unipolar and bipolar depression identified in the postpartum period have a heterogeneous etiology. The objectives of this study are to examine the risk factors that distinguish the timing of onset for unipolar and bipolar depression and the associations between depression onset by diagnosis, and general and atypical depressive symptoms. METHODS: Symptoms of depression were assessed at 4- to 6-weeks postpartum by the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms in an obstetrical sample of 727 women. Data were analyzed using ANOVA, Chi-square, and linear regression. RESULTS: Mothers with postpartum onset of depression were more likely to be older, Caucasian, educated, married/cohabitating, have one or no previous child, and have private insurance in contrast to mothers with pre-pregnancy and prenatal onset of depression. Mothers with bipolar depression were more likely to have a pre-pregnancy onset. Three general and two atypical depressive symptoms distinguished pre-pregnancy, during pregnancy, and postpartum depression onset, and the presence of agitation distinguished between unipolar and bipolar depression. LIMITATIONS: The sample was urban, which may not be generalizable to other populations. The study was cross-sectional, which excludes potential late onset of depression (after 4-6 weeks) in the first postpartum year. CONCLUSIONS: A collective set of factors predicted the onset of depression identified in the postpartum for mothers distinguished by episodes of unipolar versus bipolar depression, which can inform clinical interventions. Future research on the onset of major depressive episodes could inform prophylactic and early psychiatric interventions.

Adapting, piloting and evaluating complex public health interventions: lessons learned from the Nurse-Family Partnership in Canadian public health settings.

INTRODUCTION: The Nurse-Family Partnership (NFP) is a home-visit program for young and first-time, socially and economically disadvantaged mothers. Evidence from three United States randomized controlled trials (RCTs) on the effectiveness of this intervention at improving pregnancy outcomes, improving child health and development, and increasing maternal economic self-sufficiency is robust. However, the effectiveness of the NFP in Canada, with its different health and social care context, needs to be determined. The purpose of this article is to describe the complex process for moving the NFP from the research arena to full implementation in Canada. METHODS: This process of evaluation in Canada includes (1) adapting the intervention; (2) piloting the intervention in small-scale feasibility and acceptability studies; and (3) conducting an RCT and process evaluation through a study called the British Columbia Healthy Connections Project (BCHCP). This large-scale evaluation also creates an opportunity to expand the NFP evidence base by conducting an additional study to examine potential biological mechanisms linking intervention and behavioural outcomes in children. RESULTS: Adaptation of the NFP home-visit materials is a continuous process. A pilot project determined that it was feasible to enrol eligible women into the NFP. This pilot also determined that, in Canada, it was most appropriate for public health agencies to implement the NFP and for public health nurses to deliver the intervention. Finally, the pilot showed that this intensive home-visit program was acceptable to clients, their family members and health care providers. Through the BCHCP, the next steps - the RCT and process evaluation - are currently underway. The BCHCP will also set the foundation for long-term evaluation of key public health outcomes in a highly vulnerable population of families.

TITRE: Adaptation, mise à l'épreuve et évaluation d'interventions complexes en santé publique : leçons tirées du Nurse-Family Partnership dans le secteur de la santé publique au Canada. INTRODUCTION: Le Nurse-Family Partnership (NFP) est un programme de visites à domicile destiné aux nouvelles jeunes mères défavorisées sur le plan socioéconomique. Les données issues de trois essais contrôlés randomisés (ECR) américains ont solidement démontré l'efficacité des interventions quant à l'amélioration de l'issue de la grossesse, de la santé et du développement des enfants ainsi que de l'autonomie économique des mères. Cependant, l'efficacité du NFP dans le contexte canadien des services de santé et des services sociaux, qui diffère de celui des États-Unis, reste à déterminer. Cet article vise à décrire le processus complexe suivi pour adapter la recherche sur le NFP et mettre ainsi en oeuvre ce programme au Canada. MÉTHODOLOGIE: L'évaluation menée au Canada se divise en trois étapes : 1) adaptation de l'intervention, 2) mise à l'épreuve de l'intervention dans des études de faisabilité et d'acceptabilité à petite échelle et 3) réalisation d'un ECR et d'une évaluation du processus dans le cadre de l'étude intitulée British Columbia Healthy Connections Project (BCHCP). Cette évaluation à grande échelle permettra d'enrichir la base de données probantes du NFP par la tenue d'une étude supplémentaire sur les mécanismes biologiques susceptibles de témoigner de la relation entre l'intervention et les effets sur le comportement des enfants. RÉSULTATS: L'adaptation de la documentation du NFP pour les visites à domicile est un processus continu. Un projet pilote a montré la faisabilité du recrutement des femmes admissibles au NFP. Il a aussi révélé qu'il était préférable au Canada que le NFP soit mis en oeuvre par les organismes de santé publique et que les infirmières et infirmiers en santé publique (ISP) s'occupent des interventions. Enfin, il a montré que ce programme intensif de visites à domicile a bénéficié d'une réception positive de la part des clientes, des membres de leur famille et des fournisseurs de soins de santé. Les prochaines étapes ­ à savoir l'ECR et l'évaluation du processus ­ ont été entamées dans le cadre du BCHCP. Ce projet jettera les bases d'une évaluation à long terme des principaux résultats en matière de santé publique concernant des familles hautement vulnérables.

Alterations in the Atlantic cod (Gadus morhua) hepatic thiol-proteome after methylmercury exposure.

Proteomic studies in general have demonstrated that the most effective and thorough analysis of biological samples requires subfractionation and/or enrichment prior to downstream processing. In the present study, Atlantic cod (Gadus morhua) liver samples were fractionated using activated thiol sepharose to isolate hepatic proteins containing free/reactive cysteines. This subset of proteins is of special interest when studying the physiological effects attributed to methylmercury (MeHg) exposure. Methylmercury is a persistent environmental contaminant that has a potent affinity toward thiol groups, and can directly bind proteins via available cysteine residues. Further, alterations in the cod thiol-proteome following MeHg exposure (2 mg/kg body weight) were explored with two-dimensional gel electrophoresis combined with downstream mass spectrometry analyses for protein identifications. Thirty-five protein spots were found to respond to MeHg exposure, and 13 of these were identified when searching cod-specific databases with acquired mass spectrometry data. Among the identified thiol-containing proteins, some are known to respond to MeHg treatment, including constituents of the cytoskeleton, and proteins involved in oxidative stress responses, protein synthesis, protein folding, and energy metabolism. Methylmercury also appeared to affect cod heme metabolism/turnover, producing significantly altered levels of hemoglobin and hemopexin in liver following metal exposure. The latter finding suggests that MeHg may also affect the hematological system in Atlantic cod.

The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines.

Copy number variation (CNV) at the 15q11.2 region has been identified as a significant risk locus for neurological and neuropsychiatric conditions such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the individual roles for genes at this locus in nervous system development, function and connectivity remain poorly understood. Haploinsufficiency of one gene in this region, Cyfip1, may provide a model for 15q11.2 CNV-associated neuropsychiatric phenotypes. Here we show that altering CYFIP1 expression levels in neurons both in vitro and in vivo influences dendritic complexity, spine morphology, spine actin dynamics and synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor lateral diffusion. CYFIP1 is highly enriched at synapses and its overexpression in vitro leads to increased dendritic complexity. Neurons derived from Cyfip1 heterozygous animals on the other hand, possess reduced dendritic complexity, increased mobile F-actin and enhanced GluA2-containing AMPA receptor mobility at synapses. Interestingly, Cyfip1 overexpression or haploinsufficiency increased immature spine number, whereas activity-dependent changes in spine volume were occluded in Cyfip1 haploinsufficient neurons. In vivo, Cyfip1 heterozygous animals exhibited deficits in dendritic complexity as well as an altered ratio of immature-to-mature spines in hippocampal CA1 neurons. In summary, we provide evidence that dysregulation of CYFIP1 expression levels leads to pathological changes in CNS maturation and neuronal connectivity, both of which may contribute to the development of the neurological symptoms seen in ASD and SCZ.

Effects of permethrin on biomarkers in Mediterranean clams (Ruditapes decussatus).

The present study was focused on the assessment of Catalase (CAT) and Acetylcholinesterase (AChE) activities in Mediterranean clams (Ruditapes decussatus) exposed to 50, 100 and 150 µg/L of Permethrin for 5, 10, 15, 20 and 25 days. In water, the measured concentrations of Permethrin in the treated aquariums were respectively 16.66, 38.24 and 55.61 µg/L. Results showed that CAT activity was increased after 5 days of exposure to high concentration reaching maximum value of 10.14 µmol/min/mg proteins after 25 days. However, no significant changes in AChE activity after 5 days of exposure were detected in all treated groups. AChE activity was significantly inhibited after 10 days with 100 and 150 µg/L and still depending on concentration and time. Maximum inhibition of AChE activity was reached after 25 days with the highest concentration of Permethrin. Our data indicated that exposure to Permethrin modifies biomarker profiles inducing oxidative stress and reducing AChE activity in Mediterranean clams.