Cytochalasins as Modulators of Stem Cell Differentiation.

Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs).

"SO FAR AWAY" How Doctors Can Contribute to Making Endometriosis Hell on Earth. A Call for Humanistic Medicine and Empathetic Practice for Genuine Person-Centered Care. A Narrative Review.

"SO FAR AWAY" * How Doctors Can Contribute to Making Endometriosis Hell on Earth [* by Knopfler M. In Dire Straits. Brothers in Arms. Vertigo Records, U.K., 1985]. Abstract: The distance physicians may create within the relationship with their patients by not having a humanistic approach to their practice may strongly influence clinical outcomes. The purpose of this paper is to convey the well-known narrative of patient dissatisfaction into pro-action by discussing the aspects of dehumanization, which may occur in the relationship between physicians and women with endometriosis. Eight dimensions of dehumanization are examined and related to everyday scenarios occurring in endometriosis care settings and the possible downstream consequences on patients' clinical outcomes are described. Objectification, which may come across as minimization of pain, may not only increase patients' perception of pain but also lead to undertreatment of unrecognized forms of endometriosis, especially among adolescents. Passivity, that is not favoring shared decision-making nor self-management, may compromise adherence to treatment, reducing patients' trust in physicians and quality of life. The same consequences may result from homogenization, that is giving for granted that all patients have the same access to care. Both isolation, ie not practicing therapeutic empathy, and loss of meaning, ie not supporting patients in the re-definition of their life plans, may affect women's psychological wellbeing and further increase pain perception. Ignoring women's personal journey by not providing clear information on the consequences endometriosis may have on their lives may favor women's self-silencing. Not promoting an un-biased communication and not setting aside scientific polarization are the main features of dislocation, which may jeopardize patient empowerment. Lastly, having a reductionist approach to the body may contribute to chronicization of pain, thus compromising quality of life. This considered, taking time to listen to women with endometriosis and tailoring decisions on the basis of their individual needs should be fostered as a moral duty. Physicians should always keep in mind that they are not only deliverers of treatment; they are a form of treatment themselves.

The neglected emotional drawbacks of the prioritization of embryos to transfer.

In recent years, increasing efforts have been made to develop advanced techniques that could predict the potential of implantation of each single embryo and prioritize the transfer of those at higher chance. The most promising include non-invasive preimplantation genetic testing for aneuploidy and artificial intelligence-based algorithms using time lapse images. The psychological effect of these add-ons is neglected. One could speculate that embarking on another transfer after one or more failures with the prospect of receiving an embryo of lower potential may be distressing for the couple. In addition, the symbolic and mental representation of an embryo with 'lower capacity to implant' is currently unknown but could affect couples' choices and wellbeing. These emotional responses may also undermine adherence to the programme and, ultimately, its real effectiveness. Future trials aimed at evaluating the validity of prioritization procedures must also consider the emotional burden on the couples.

"The sound of silence" Giving voice to endometriosis-related positional dyspareunia.

Deep dyspareunia is one of the main symptoms of endometriosis. It appears to be submerged by a two-way disconnection between patients and their physicians. The aim of our review is to provide clear, ready-to-use advice on how to manage deep dyspareunia overcoming the gap in communication. Sexual history should always be taken as part of routine health care in these regards, using a patient-centered approach. An educational pelvic examination, which actively includes patients in the identification of painful areas, may prove useful to improve patients' understanding of their condition. Correlating painful pelvic areas with sexual positions and inviting patients to adopt alternative positions may represent a simple but extremely effective coping strategy to mitigate pain. Revealing and explaining to partners the nature of the pain is essential to allow them to take part in shared research of coping mechanisms, empowering the couple to make choices and changes. Couples who do not feel comfortable talking about intimacy by themselves may find that including a psychotherapist or a sexual therapist, may be a good way to start communication. Investigating and managing dyspareunia during medical encounters is a medical and ethical duty all healthcare practitioners should pursue.

Central Sensitization in Vulvodynia and Endometriosis: What Have We Been Overlooking So Far?

Importance: Women experience more frequent and greater pain than men, although they receive less adequate treatment and are perceived as more anxious than males. Recent clinical research has lead to hypothesize a common etiology for overlapping chronic pain conditions and mood disorders, namely, central sensitization, which originates from an alteration of pain processing pathways in the central nervous system. Objective: The aim of this review was to collect all available evidence regarding the potential role of central sensitization in vulvodynia and endometriosis. Evidence Acquisition: A systematic literature search was performed between July and August 2022 using the electronic database PubMed. The extracted data were summarized using a narrative approach. Results: Ten articles were chosen for the review. Participants' mean age was 39.2 years (SD = 5.1). Among serum markers of central sensitization, nitric oxide levels were greater in women with endometriosis than in controls, whereas brain-derived neurotrophic factor and S100B levels differed among pain conditions with structural anomalies and those without. Functional magnetic resonance imaging showed different resting state networks between patients with endometriosis and controls. In neurophysiology studies, cases had reduced pain thresholds, compared with healthy controls. Lastly, self-reported questionnaires suggested a central component of pain in women with endometriosis-related dyspareunia and associated bladder/pelvic floor tenderness. Conclusions and Relevance: The management of vulvodynia and endometriosis may benefit from a new perspective, which considers their possible central etiology. It is compelling that treatment of pain starts to be considered a therapeutic goal in its own right.

TLDc Domain-Containing Genes in Autism Spectrum Disorder: New Players in the Oxidative Stress Response.

Oxidative stress (OS) plays a key role in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by deficits in social communication, restricted interests, and repetitive behaviors. Recent evidence suggests that the TLDc [Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic] domain is a highly conserved motif present in proteins that are important players in the OS response and in neuroprotection. Human proteins sharing the TLDc domain include OXR1, TLDC1, NCOA7, TBC1D24, and C20ORF118. This study was aimed at understanding whether TLDc domain-containing mRNAs together with specific microRNAs (200b-3p and 32-5p) and long noncoding RNAs (TUG1), known to target TLDc proteins, contributed to regulate the OS response in ASD. Data showed a significant increase in the levels of OXR1 and TLDC1 mRNAs in peripheral blood mononuclear cells (PBMCs) of ASD children compared to their neurotypically developing (NTD) counterparts, along with an increase in TUG1 mRNA expression levels, suggesting its possible role in the regulation of TLDc proteins. A positive correlation between the expression of some TLDc mRNAs and the Childhood Autism Rating Scale (CARS) global score as well as inflammatory gene expression was found. In conclusion, our data suggest a novel biological pathway in the OS response of ASD subjects that deserves further exploration.

Oxytocin Modulates Osteogenic Commitment in Human Adipose-Derived Stem Cells.

Human adipose-derived stem cells (hASCs) are commonly harvested in minimally invasive contexts with few ethical concerns, and exhibit self-renewal, multi-lineage differentiation, and trophic signaling that make them attractive candidates for cell therapy approaches. The identification of natural molecules that can modulate their biological properties is a challenge for many researchers. Oxytocin (OXT) is a neurohypophyseal hormone that plays a pivotal role in the regulation of mammalian behavior, and is involved in health and well-being processes. Here, we investigated the role of OXT on hASC proliferation, migratory ability, senescence, and autophagy after a treatment of 72 h; OXT did not affect hASC proliferation and migratory ability. Moreover, we observed an increase in SA-ß-galactosidase activity, probably related to the promotion of the autophagic process. In addition, the effects of OXT were evaluated on the hASC differentiation ability; OXT promoted osteogenic differentiation in a dose-dependent manner, as demonstrated by Alizarin red staining and gene/protein expression analysis, while it did not affect or reduce adipogenic differentiation. We also observed an increase in the expression of autophagy marker genes at the beginning of the osteogenic process in OXT-treated hASCs, leading us to hypothesize that OXT could promote osteogenesis in hASCs by modulating the autophagic process.

Cytochalasin B Influences Cytoskeletal Organization and Osteogenic Potential of Human Wharton's Jelly Mesenchymal Stem Cells.

Among perinatal stem cells of the umbilical cord, human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) are of great interest for cell-based therapy approaches in regenerative medicine, showing some advantages over other MSCs. In fact, hWJ-MSCs, placed between embryonic and adult MSCs, are not tumorigenic and are harvested with few ethical concerns. Furthermore, these cells can be easily cultured in vitro, maintaining both stem properties and a high proliferative rate for several passages, as well as trilineage capacity of differentiation. Recently, it has been demonstrated that cytoskeletal organization influences stem cell biology. Among molecules able to modulate its dynamics, Cytochalasin B (CB), a cyto-permeable mycotoxin, influences actin microfilament polymerization, thus affecting several cell properties, such as the ability of MSCs to differentiate towards a specific commitment. Here, we investigated for the first time the effects of a 24 h-treatment with CB at different concentrations (0.1-3 µM) on hWJ-MSCs. CB influenced the cytoskeletal organization in a dose-dependent manner, inducing changes in cell number, proliferation, shape, and nanomechanical properties, thus promoting the osteogenic commitment of hWJ-MSCs, as confirmed by the expression analysis of osteogenic/autophagy markers.

Plumbagin, a Natural Compound with Several Biological Effects and Anti-Inflammatory Properties.

Phytochemicals from various medicinal plants are well known for their antioxidant properties and anti-cancer effects. Many of these bioactive compounds or natural products have demonstrated effects against inflammation, while some showed a role that is only approximately described as anti-inflammatory. In particular, naphthoquinones are naturally-occurring compounds with different pharmacological activities and allow easy scaffold modification for drug design approaches. Among this class of compounds, Plumbagin, a plant-derived product, has shown interesting counteracting effects in many inflammation models. However, scientific knowledge about the beneficial effect of Plumbagin should be comprehensively reported before candidating this natural molecule into a future drug against specific human diseases. In this review, the most relevant mechanisms in which Plumbagin plays a role in the process of inflammation were summarized. Other relevant bioactive effects were reviewed to provide a complete and compact scenario of Plumbagin's potential therapeutic significance.

Non-response to first-line hormonal treatment for symptomatic endometriosis: overcoming tunnel vision. A narrative review.

One-fourth to one-third of women with endometriosis receiving first-line hormonal treatment lacks an adequate response in terms of resolution of painful symptoms. This phenomenon has been ascribed to "progesterone resistance", an entity that was theorized to explain the gap between the ubiquity of retrograde menstruation and the 10% prevalence of endometriosis among women of reproductive age.Nevertheless, the hypothesis of progesterone resistance is not free of controversies. As our understanding of endometriosis is increasing, authors are starting to set aside the traditionally accepted tunnel vision of endometriosis as a strictly pelvic disease, opening to a more comprehensive perspective of the condition. The question is: are patients not responding to first-line treatment because they have an altered signaling pathway for such treatment, or have we been overlooking a series of other pain contributors which may not be resolved by hormonal therapy?Finding an answer to this question is evermore impelling, for two reasons mainly. Firstly, because not recognizing the presence of further pain contributors adds a delay in treatment to the already existing delay in diagnosis of endometriosis. This may lead to chronicity of the untreated pain contributors as well as causing adverse consequences on quality of life and psychological health. Secondly, misinterpreting the consequences of untreated pain contributors as a non-response to standard first-line treatment may imply the adoption of second-line medical therapies or of surgery, which may entail non-negligible side effects and may not be free of physical, psychological and socioeconomic repercussions.The current narrative review aims at providing an overview of all the possible pain contributors in endometriosis, ranging from those strictly organic to those with a greater neuro-psychological component. Including these aspects in a broader psychobiological approach may provide useful suggestions for treating those patients who report persistent pain symptoms despite receiving first-line hormonal medical treatment.

Mental Health Issues as a Consequence of the Pandemic: Group Psycho-Educational Intervention to Support Patients Recovered from COVID-19 Infection.

Common psycho-physical symptoms have emerged in patients who were previously recovered for COVID-19 infection, including traumatic experience and enduring emotional disturbances. A group psycho-educational intervention of seven weekly sessions and a follow-up after three months was proposed to all Italian-speaking patients formally discharged from a public hospital in northern Italy and physically recovered from infection. Eighteen patients were recruited and divided into four age-homogenous groups, each led by two facilitators (psychologists and psychotherapists). The group sessions followed a structured format with thematic modules, including main topics, tasks, and homework assignments. Data were collected through recordings and verbatim transcripts. The objectives of the study were twofold: (1) to analyze the emerging themes and gain insight into the significant aspects of the participants' lived experience of COVID-19, and (2) to examine changes in how participants approached these themes throughout the intervention process. Semantic-pragmatic text analyses, specifically thematic analysis of elementary context and correspondence analysis, were conducted using T-LAB software. Linguistic analysis revealed a congruence between the intervention's objectives and the participants' experiences. The study highlighted an evolution in the narratives, as participants transitioned from a passive and concrete perspective on the disease to a more comprehensive cognitive and emotional elaboration of their personal illness stories. These findings hold potential relevance for healthcare services and professionals working in this field.

The impact of COVID-19 perceived threat and restrictive measures on mental health in Italy, Spain, New York, and Hong Kong: An international multisite study.

In the early stages of the COVID-19 pandemic, Italy, Spain, New York, and Hong Kong stood out for the ir high rates of infections. Given this scenario, a web-based international multisite and cross-sectional study was conducted between April and May 2020 to investigate the psychological impact of the pandemic and the restrictions imposed by the governments in these countries. We expected similar patterns in European countries, and no significant differences in terms of psychological impairment between Hong Kong (with a previous experience related to SARS, but subjected to restrictions for a longer time) and the other areas. Participants were 1955 adults from the above-mentioned areas. We assessed anxiety (GAD-7), depression (PHQ-9), COVID-19-related threats, and perceived burden of restrictive measures. Two-explorative factor analyses (EFAs) with Promax rotation identified COVID-19-related factors: personal physical threat, personal economic threat, global economic threat, and restriction-related burden. ANOVAs studied locations' differences and two-separate hierarchical multiple regression analyses by location determined whether and how COVID-19-related variables were associated with anxiety and depression, adjusting for age and sex. Italy and Hong Kong showed higher anxiety than Spain (p < 0.05); Hong Kong scored higher on depression than Italy and Spain (p < 0.001), which highlighted the lowest mean-score. New York participants showed the poorest mental health conditions. Anxiety was predicted by restriction-related burden (ßNY = 0.242; ßHK = 0.116) and personal economic threat (ßNY = 0.246; ßHK = 0.145) in New York (Adj.R 2 = 0.125) and Hong Kong (Adj.R 2 = 0.079); by global economic threat (ß = 0.199) and restriction-related burden (ß = 0.124) in Italy (Adj.R 2 = 0.108); and by personal physical threat (ß = 0.144) in Spain (Adj.R 2 = 0.049). Depression was predicted by restriction-related burden (ßNY = 0.313; ßHK = 0.120) and personal economic threat (ßNY = 0.229; ßHK = 0.204) in New York (Adj.R 2 = 0.161) and Hong Kong (Adj.R 2 = 0.089); by global economic threat (ß = 0.209) in Italy (Adj.R 2 = 0.149); and no predictors emerged in Spain. Findings could contribute to understanding the specific impact of the pandemic on people's psychological health in each area, along with the factors that impacted mental health. This information may be useful to implementing prevention interventions in case of restrictions.

Women's quality of sleep and in vitro fertilization success.

Women undergoing in vitro fertilization (IVF) are emotionally challenged. Anxiety, depression, and sleep disturbances are common complaints. The impact of these symptoms on IVF outcome is however debated. In this study, we aimed at investigating whether sleep quality and psychological health can affect the chances of success of the procedure. Women undergoing IVF were recruited at the time of oocytes retrieval. Women's sleep quality and psychological health was assessed using the Pittsburgh Sleep Quality Index (PSQI), the Fertility Problem Inventory (FPI), and the Hospital Anxiety and Depression Scale (HADS). Baseline characteristics and results of the three scales were compared between women who did and did not succeed. Overall, 263 women were included, of whom 81 had a clinical pregnancy (31%). As expected, successful women were younger, and their ovarian reserve was more preserved. FPI and HADS scores did not differ. Conversely, a statistically significant difference emerged for the PSQI score, the median [interquartile range] in pregnant and non-pregnant women being 4 [3-5] and 5 [3-7], respectively (p = 0.004). The crude and adjusted OR of pregnancy in women with a PSQI > 5 (indicating impaired sleep quality) was 0.46 (95% CI 0.25-0.86, p = 0.02) and 0.50 (95% CI: 0.26-0.94, p = 0.03), respectively. In conclusion, low sleep quality is common in women scheduled for IVF and could influence the success of the procedure.

Melatonin finely tunes proliferation and senescence in hematopoietic stem cells.

Human hematopoietic stem/progenitor cells (HSPCs) are pluripotent cells that gradually lose their self-renewal and regenerative potential, to give rise to mature cells of the hematopoietic system by differentiation. HSPC infusion is used to restore hematopoietic function in patients with a variety of onco-hematologic and immune-mediated disorders. The functionality of these cells is therefore of great importance to ensure the homeostasis of the hematopoietic system. Melatonin plays an important role as immunomodulatory and oncostatic hormone. In the present manuscript, we aimed at evaluating the activity of melatonin in modulating HSPC senescence, in the attempt to improve their hemopoietic regenerative potential. We exposed HSPCs to melatonin, in different conditions, and then analyzed the expression of genes regulating cell cycle and cell senescence. Moreover, we assessed cell senescence by ß-galactosidase and telomerase activity. Our results showed the ability of melatonin to counteract HSPC senescence, thus paving the way for enhanced efficiency in their clinical application.

Cytochalasin B Modulates Nanomechanical Patterning and Fate in Human Adipose-Derived Stem Cells.

Cytoskeletal proteins provide architectural and signaling cues within cells. They are able to reorganize themselves in response to mechanical forces, converting the stimuli received into specific cellular responses. Thus, the cytoskeleton influences cell shape, proliferation, and even differentiation. In particular, the cytoskeleton affects the fate of mesenchymal stem cells (MSCs), which are highly attractive candidates for cell therapy approaches due to their capacity for self-renewal and multi-lineage differentiation. Cytochalasin B (CB), a cyto-permeable mycotoxin, is able to inhibit the formation of actin microfilaments, resulting in direct effects on cell biological properties. Here, we investigated for the first time the effects of different concentrations of CB (0.1-10 µM) on human adipose-derived stem cells (hASCs) both after 24 h (h) of CB treatment and 24 h after CB wash-out. CB influenced the metabolism, proliferation, and morphology of hASCs in a dose-dependent manner, in association with progressive disorganization of actin microfilaments. Furthermore, the removal of CB highlighted the ability of cells to restore their cytoskeletal organization. Finally, atomic force microscopy (AFM) revealed that cytoskeletal changes induced by CB modulated the viscoelastic properties of hASCs, influencing their stiffness and viscosity, thereby affecting adipogenic fate.

Intimate Partner Violence in the COVID-19 Era: A Health, Psychological, Forensic and Legal Perspective.

This commentary aims to provide a multidisciplinary framework on intimate partner violence (IPV) during the COVID-19 pandemic (with a specific focus on the most predominant form of gender-based violence, i.e., male violence towards women), commenting on the multiple negative consequences of the pandemic on gender violence and providing elements of effective practice. We searched literature for reports/studies on the issue of IPV during the COVID-19 pandemic, focusing on health, psychological, forensic, and legal aspects. The combined effects of lockdowns, isolation at home with abusive partners, quarantine, and economic worries/loss of a job could significantly facilitate violence against women and, at the same time, diminish women's chances to seek for help, with a strong negative impact on their life. The continued offer of clinical, psychological, forensic, and legal services for survivors of violence, despite the modifications to the provision of these services due to the new needs related to the COVID-19 pandemic, appears of utmost importance. All actions to support survivors of IPV are expected to be multidisciplinary, including the involvement of social and/or legal services and health systems, and woman-centred. Implementing these measures in the COVID-19 era appears challenging but is of primary importance.

Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue.

Opioids are considered the oldest drugs known by humans and have been used for sedation and pain relief for several centuries. Nowadays, endogenous opioid peptides are divided into four families: enkephalins, dynorphins, endorphins, and nociceptin/orphanin FQ. They exert their action through the opioid receptors (ORs), transmembrane proteins belonging to the super-family of G-protein-coupled receptors, and are expressed throughout the body; the receptors are the δ opioid receptor (DOR), µ opioid receptor (MOR), κ opioid receptor (KOR), and nociceptin/orphanin FQ receptor (NOP). Endogenous opioids are mainly studied in the central nervous system (CNS), but their role has been investigated in other organs, both in physiological and in pathological conditions. Here, we revise their role in stem cell (SC) biology, since these cells are a subject of great scientific interest due to their peculiar features and their involvement in cell-based therapies in regenerative medicine. In particular, we focus on endogenous opioids' ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia-reperfusion), and differentiation towards different lineages, such as neurogenesis, vasculogenesis, and cardiogenesis.

Cell Responsiveness to Physical Energies: Paving the Way to Decipher a Morphogenetic Code.

We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of physical forces in cellular decisions, stressing the intriguing similarities in early morphogenesis, tissue regeneration, and oncogenic drift. Compelling evidence is presented, showing that biological patterns are strongly embedded in the vibrational nature of the physical energies that permeate the entire universe. We describe biological dynamics as informational processes at which physics and chemistry converge, with nanomechanical motions, and electromagnetic waves, including light, forming an ensemble of vibrations, acting as a sort of control software for molecular patterning. Biomolecular recognition is approached within the establishment of coherent synchronizations among signaling players, whose physical nature can be equated to oscillators tending to the coherent synchronization of their vibrational modes. Cytoskeletal elements are now emerging as senders and receivers of physical signals, "shaping" biological identity from the cellular to the tissue/organ levels. We finally discuss the perspective of exploiting the diffusive features of physical energies to afford in situ stem/somatic cell reprogramming, and tissue regeneration, without stem cell transplantation.

A Tailored Lipid Supplement Restored Membrane Fatty Acid Composition and Ameliorates In Vitro Biological Features of Human Amniotic Epithelial Cells.

Cell culture conditions influence several biological and biochemical features of stem cells (SCs), including the membrane lipid profile, thus limiting the use of SCs for cell therapy approaches. The present study aims to investigate whether the in vitro culture may alter the membrane fatty acid signature of human Amniotic Epithelial Cells (hAECs). The analysis of the membrane fatty acid composition of hAECs cultured in basal medium showed a loss in polyunsaturated fatty acids (PUFA), in particular in omega-6 (ω-6) content, compared to freshly isolated hAECs. The addition to the basal culture medium of a chemically defined and animal-free tailored lipid supplement, namely Refeed®, partially restored the membrane fatty acid signature of hAECs. Although the amelioration of the membrane composition did not prolong hAECs culture lifespan, Refeed® influenced cell morphology, counteracted the onset of senescence, and increased the migratory capacity as well as the ability of hAECs to inhibit Peripheral Blood Mononuclear Cell (PBMC) proliferation. This study provides new information on hAEC features during culture passages and demonstrates that the maintenance of the membrane fatty acid signature preserved higher cell quality during in vitro expansion, suggesting the use of lipid supplementation for SC expansion in cell-based therapies.

Predictors of Postpartum Depression among Italian Women: A Longitudinal Study.

INTRODUCTION: Postpartum depression is commonly experienced by mothers worldwide and is associated with anxiety disorders, parenting stress, and other forms of distress, which may lead to a complex illness condition. Several studies have investigated the risk factors for this disorder, including biological and socio-demographic variables, medical and obstetric factors, and psychological and relational dimensions. The present study aimed to describe the psychological status of mothers up to 12 months postpartum, and to investigate the predictors of depressive symptoms at 12 months postpartum, considering obstetric factors along with psychological and relational variables. METHODS: A sample of 137 women completed a questionnaire composed of a sheet on anamnestic and obstetric information and the following scales: Wijma Delivery Experience Questionnaire; State-Trait Anxiety Inventory; Edinburgh Postnatal Depression Scale; Parenting Stress Index (Short Form); Dyadic Adjustment Scale; and Multidimensional Scale of Perceived Social Support. Data were collected at four assessment times: 2-3 days, 3 months, 6 months, and 12 months postpartum. RESULTS: Findings showed that the highest percentage of women with clinically significant symptoms of anxiety (state and trait) and depression was found at 12 months postpartum, which indicated that this was the most critical time. The quality of childbirth experience and trait anxiety at three months postpartum emerged as significant predictors of postpartum depression at 12 months. CONCLUSION: Our findings highlight the importance of providing stable programs (such as educational programs) to mothers in the first year postpartum. Furthermore, because the quality of the childbirth experience is one of the most important predictors of PPD at 12 months postpartum, effort should be made by healthcare professionals to guarantee a positive experience to all women to reduce possible negative long-term consequences of this experience.