Keep in mind sex differences when prescribing psychotropic drugs.

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs. There are inevitable differences in efficacy, side effects and long-term treatment response between men and women. Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects. Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions, to maximize therapeutic effectiveness and to provide personalized management of care.

New pharmacotherapies to tackle the unmet needs in bipolar disorder: a focus on acute suicidality.

INTRODUCTION: Suicidal behavior is relatively frequent in patients with bipolar disorder (BD) and constitutes their most frequent cause of death. Suicide rates remain high in patients with BD despite adherence to guidelines recommending lithium as first line, and/or antidepressants, antipsychotics, psychotherapy, psychosocial interventions, and electroconvulsive therapy. Hence the need to identify more effective and rapid anti-suicide interventions. AREAS COVERED: To tackle the unmet needs of pharmacotherapy, we investigated the PubMed database on 24-25 January 2024 using strategies like ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (lithium[ti] OR clozapine[ti]), which obtained 3 results, and ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (ketamine[ti] OR esketamine[ti] OR NMDA[ti] OR glutamat*[ti]), which yielded 14 results. We explored glutamatergic abnormalities in BD and suicide and found alterations in both. The noncompetitive NMDS antagonist ketamine and its S-enantiomer esketamine reportedly decrease acute suicidality. EXPERT OPINION: Intranasal esketamine or subcutaneous ketamine, single-bolus or intravenous, and possibly other glutamate receptor modulators may improve suicidal behavior in patients with unipolar and bipolar depression. This may be achieved through prompt remodulation of glutamate activity. The correct use of glutamatergic modulators could reduce acute suicidality and mortality in patients with BD.

Is peripartum anhedonia a missing target?

The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a widely validated instrument for assessing perinatal depressive symptoms, including the dimension of anhedonia. There are studies suggesting that the neural mechanism underlying the occurrence of anhedonia in patients with major depressive disorder (MDD) and bipolar depression (BD) might be distinct. Anhedonia seems to represent a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder and is associated with significantly higher depressive symptom severity. Perinatal medicine is an important component of women's health. Treatment of anhedonia can be challenging, and the most effective treatment can be a combination of psychotherapy and medication, but the screening of anhedonia in peripartum women can prevent the development of other psychiatric disorders and maladaptive behaviors.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

Psychological factors and barriers to donating and receiving milk from human milk banks: A review.

Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child.

Unveiling the Dark Nexus: A systematic review on the interplay of mental health, substance abuse, and socio-cultural factors in femicide.

A shared definition of femicide would help to distinguish it from the murder of a woman and understand its root causes favoring prevention. We conducted a Systematic Literature Review (SLR) to assess how (and if) femicide cases were related to mental disorders. Articles papers that explicitly define or discuss femicides or articles that, albeit not expressly mention femicides, thoroughly compare generic homicides and homicides with female victims. We analyse 3546 articles were retrieved from the databases, and 75 studies fulfilled the eligibility criteria and were included in the SLR. Many forms of femicide emerge worldwide as people's values, beliefs, attitudes, and behaviours evolve (intimate partner femicide, femicide-suicide, religious femicide, honour, revolt femicide) and state of vulnerability. A tiny percentage of femicides occur at the hands of subjects with diagnosed mental disorders, and controversies exist regarding the possible link between femicide and the use of drugs and/or alcohol and other factors. The complex problem of violence against women must be addressed with a transdisciplinary approach and targeted interventions for both the victims and the perpetrators. The present SLR shows that it is not possible to link femicides to mental disorders and that socio and cultural factors appear to be more relevant. Further quantitative research is warranted to disentangle the root causes of this heinous phenomenon plaguing our times. Our studies show that using the proposed definition of feminicide would help to delimit and adequately recognise violence in courtrooms, promote the culture of equality, and identify adequate policy strategies for prevention.

Vertebral Fractures in Pediatric Suicidal Jumpers: A Retrospective Study with Epidemiological and Clinical Analysis before and after the COVID-19 Pandemic.

BACKGROUND: From the beginning of the COVID-19 pandemic, reports in the literature confirm a significant increase in suicide attempts in children and adolescents. At the Bambino Gesù Pediatric Hospital Emergency Department (Rome, Italy), there was a dramatic increase in suicidal jumpers. Many of these presented vertebral fractures. METHODS: This retrospective study includes all suicidal jumpers with vertebral fractures treated from April 2017 to March 2023. We collected and compared data from three years before to three years after the pandemic, analyzing vertebral fractures. RESULTS: From April 2019 to March 2020, 141 cases of suicide attempt arrived at the emergency department. Five of these were suicidal jumpers without vertebral fractures. From April 2020 to March 2023, 362 cases of suicide were hospitalized and 19 were suicidal jumpers; 12 reported vertebral fractures (mean age 14 years). Seven patients were treated by percutaneous pedicle fixation. Three patients needed an open spinal surgery by posterior approach. One case with cervical fractures was treated by Halo-Vest. CONCLUSIONS: This is the first report that shows a sharp increase in vertebral body fractures due to suicide jumping attempts in children and adolescents. This could be a new epidemiological phenomenon persisting or even increasing over time in the pediatric population as a consequence of the COVID-19 pandemic.

Gut microbiota in women: The secret of psychological and physical well-being.

The gut microbiota works in unison with the host, promoting its health. In particular, it has been shown to exert protective, metabolic and structural functions. Recent evidence has revealed the influence of the gut microbiota on other organs such as the central nervous system, cardiovascular and the endocrine-metabolic systems and the digestive system. The study of the gut microbiota is outlining new and broader frontiers every day and holds enormous innovation potential for the medical and pharmaceutical fields. Prevention and treatment of specific women's diseases involves the need to deepen the function of the gut as a junction organ where certain positive bacteria can be very beneficial to health. The gut microbiota is unique and dynamic at the same time, subject to external factors that can change it, and is capable of modulating itself at different stages of a woman's life, playing an important role that arises from the intertwining of biological mechanisms between the microbiota and the female genital system. The gut microbiota could play a key role in personalized medicine.

Alexithymia, Burnout, and Hopelessness in a Large Sample of Healthcare Workers during the Third Wave of COVID-19 in Italy.

In the present study, we aimed to assess the frequency of and the relationships between alexithymia, burnout, and hopelessness in a large sample of healthcare workers (HCWs) during the third wave of COVID-19 in Italy. Alexithymia was evaluated by the Italian version of the 20-item Toronto Alexithymia Scale (TAS-20) and its subscales Difficulty in Identifying Feelings (DIF), Difficulty in Describing Feelings (DDF), and Externally Oriented Thinking (EOT), burnout was measured with the scales emotional exhaustion (EE), depersonalisation (DP), and personal accomplishment (PA) of the Maslach Burnout Test (MBI), hopelessness was measured using the Beck Hopelessness Scale (BHS), and irritability (IRR), depression (DEP), and anxiety (ANX) were evaluated with the Italian version of the Irritability' Depression' Anxiety Scale (IDA). This cross-sectional study recruited a sample of 1445 HCWs from a large urban healthcare facility in Italy from 1 May to 31 June 2021. The comparison between individuals that were positive (n = 214, 14.8%) or not for alexithymia (n = 1231, 85.2%), controlling for age, gender, and working seniority, revealed that positive subjects showed higher scores on BHS, EE, DP IRR, DEP, ANX, DIF, DDF, and EOT and lower on PA than the not positive ones (p < 0.001). In the linear regression model, higher working seniority as well as higher EE, IRR, DEP, ANX, and DDF scores and lower PA were associated with higher hopelessness. In conclusion, increased hopelessness was associated with higher burnout and alexithymia. Comprehensive strategies should be implemented to support HCWs' mental health and mitigate the negative consequences of alexithymia, burnout, and hopelessness.

MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the "breakthrough therapy" designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

Migrants' mental health recovery in Italian reception facilities.

BACKGROUND: Forced migration leaves deep marks on the psychological well-being of migrants, with post-traumatic stress disorder (PTSD) and other psychological conditions being prevalent among them. While research has clarified the extent to which pre-migration trauma is a predictor of mental health outcomes, the role of post-migration stressors in the settlement environment are yet to be fully characterized. METHODS: We monitored mental health of a cohort of 100 asylum-seekers during their 14-day COVID-19-related quarantine in reception facilities in Rome, Italy, through the administration of six questionnaires (a demographic survey, the WHO-5 well-being index, the Primary Care PTSD Screen for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5), the Harvard Trauma Questionnaire, the Trauma and Loss Spectrum-Self Report, and the LiMEs-Italian version). Through the combination of statistical analysis and supervised learning, we studied the impact of the first contact with the reception system on asylum-seekers' mental health and sought for possible risk and shielding factors for PTSD. RESULTS: We find that sheltering in refugee centers has a positive impact on migrants' mental health; asylum-seekers with PTSD reported more traumatic events and personality characteristics related to loss and trauma; life events are predictors of PTSD in asylum-seekers. CONCLUSIONS: We identify past traumatic experiences as predictors of PTSD, and establish the positive role the immediate post-migration environment can play on migrants' psychological well-being. We recommend for host countries to implement reception models that provide effective protection and integration of asylum-seekers, similar to those in the Italian system.

Traumatic experiences before and during migration can impact the psychological well-being of migrants. This can result in post-traumatic stress disorder (PTSD), a disorder in which prior experience of traumatic events can lead to severe anxiety. We asked migrants to fill in questionnaires about their well-being during a 14-day quarantine in reception facilities in Rome, Italy. We evaluated whether the migrants had symptoms of PTSD and the impact of the quarantine on their mental health. We found that migrants who had experienced past traumatic events were more likely to have PTSD, and that staying in a safe and welcoming place in Italy helped improve their mental wellbeing. These findings underline the importance of designing suitable policies to support migrants' mental health when they arrive in host countries.

The Patient's Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression.

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients' perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients' view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith-Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients' and clinicians' perspectives, although with some differential effects on specific symptoms at given time-points. Including patients' viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.

Prevalence of anxiety and depression risk during the prepartum period in the different groups of women and responses from the Italian National Health Service.

BACKGROUND: Specific screening for anxiety and depression in pregnant women is important to identify those at risk and to provide timely intervention. The aims of the study were: 1) to compare the risk of anxiety and depression in four groups of pregnant women belonging to four types of healthcare centers distinguished by the level of risk: at low-risk; at high-risk for an obstetric reason; at high-risk for fetal anomalies; at high-risk for psychiatric conditions and 2) to identify the response that the National Health Service offers to women positively screened for anxiety and depression. METHODS: A cross-sectional study was conducted on 2801 pregnant women, cared for by National Health Service, divided into four groups: 1) low-risk pregnancy (N.=1970); 2) high-risk pregnancy for an obstetric reason (N.=218); 3) high-risk for fetal anomalies (N.=505); and 4) high-risk for psychiatric conditions (N.=108). Participants were screened using the Edinburgh Postnatal Depression Scale, the General Anxiety Disorder, and sociodemographic, anamnestic, and clinic questionnaires. RESULTS: 28.9% of participants obtained an EPDS Score ≥9 and 17.1% a GAD-7 Score ≥8. The group at high-risk for fetal anomalies presented the highest prevalence of anxiety (29.3%) and depression (49.1%) while the group at low risk presented the lowest prevalence of anxiety (13%) and depression (24.6%). The groups at risk for obstetric reasons presented an intermediate prevalence. Psychiatric conditions constituted a higher risk for anxiety than depression. Counselling is recommended for about 70% of women at risk for anxiety and depression. Moreover, about 15% of women positive for screening were initiated into psychotherapy and about 1.5% into pharmacotherapy. 15% of women positive for screening were referred to other specialists. CONCLUSIONS: This study underlined the relevance of a prompt response by the National Health Service to mental health needs, especially in the risk conditions related to obstetric and/or fetal anomalies and psychopathology.

Resilience and Attachment in Patients with Major Depressive Disorder and Bipolar Disorder.

BACKGROUND: Resilience represents one of the fundamental elements of attachment and has often been investigated in mood disorders. This study aims to investigate possible correlations between attachment and resilience in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: 106 patients (51 MDD, 55 BD) and 60 healthy controls (HCs) were administered the 21-item Hamilton Depression Rating Scale (HAM-D-21), the Hamilton Anxiety Rating Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Barratt Impulsiveness Scale-11 (BIS-11), the Toronto Alexithymia Scale (TAS), the Connor-Davidson Resilience Scale (CD-RISC), and Experiences in Close Relationship (ECR). RESULTS: MDD and BD patients did not significantly differ from each other according to the HAM-D-21, HAM-A, YMRS, SHAPS, and TAS, while they scored higher than HCs on all these scales. Patients in the clinical group scored significantly lower on CD-RISC resilience than HCs (p < 0.01). A lower proportion of secure attachment was found among patients with MDD (27.4%) and BD (18.2%) compared to HCs (90%). In both clinical groups, fearful attachment prevailed (39.2% patients with MDD; 60% BD). CONCLUSIONS: Our results highlight the central role played by early life experiences and attachment in participants with mood disorders. Our study confirms the data from previous research showing a significant positive correlation between the quality of attachment and the development of resilience capacity, and supports the hypothesis that attachment constitutes a fundamental aspect of resilience capacity.

COVID-19 pandemic in the intensive care unit: Psychological implications and interventions, a systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic produced changes in intensive care units (ICUs) in patient care and health organizations. The pandemic event increased patients' risk of developing psychological symptoms during and after hospitalisation. These consequences also affected those family members who could not access the hospital. In addition, the initial lack of knowledge about the virus and its management, the climate of fear and uncertainty, the increased workload and the risk of becoming infected and being contagious, had a strong impact on healthcare staff and organizations. This highlighted the importance of interventions aimed at providing psychological support to ICUs, involving patients, their relatives, and the staff; this might involve the reorganisation of the daily routine and rearrangement of ICU staff duties. AIM: To conduct a systematic review of psychological issues in ICUs during the COVID-19 pandemic involving patients, their relatives, and ICU staff. METHODS: We investigated the PubMed and the ClinicalTrials.gov databases and found 65 eligible articles, upon which we commented. RESULTS: Our results point to increased perceived stress and psychological distress in staff, patients and their relatives and increased worry for being infected with severe acute respiratory syndrome coronavirus-2 in patients and relatives. Furthermore, promising results were obtained for some psychological programmes aiming at improving psychological measures in all ICU categories. CONCLUSION: As the pandemic limited direct inter-individual interactions, the role of interventions using digital tools and virtual reality is becoming increasingly important. All considered, our results indicate an essential role for psychologists in ICUs.

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR "mood disord*"[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR "eating disorder*"[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR "attention-deficit"[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2-HO-1, BDNF-TrkB, and cyclic AMP-CREB pathways, could protect from depression, while glycogen synthase kinase-3ß and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.

Neuroanatomical Correlates of the Late Positive Potential in Youth with Pediatric Bipolar Disorder.

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified. OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD. METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. Linear regressions tested the relationship between LPP amplitude and cortical thickness/deep gray matter volumes. RESULTS: PBD had a more pronounced LPP amplitude for happy faces and a thinner cortex in prefrontal areas than HC. While considering both groups, a higher LPP amplitude was associated with a thicker cortex across occipital and frontal lobes, and with a smaller right globus pallidus volume. In addition, a higher LPP amplitude for happy faces was associated with smaller left caudate and left globus pallidus volumes across both groups. Finally, the LPP amplitude correlated negatively with right precentral gyrus thickness across youth with PBD, but positively across HC. CONCLUSION: Neural correlates of LPP in youth included fronto-occipital areas that have been associated also with emotion processing and control. The opposite relationship between BPD and HC of LPP amplitude and right precentral gyrus thickness might explain the inefficacy of the emotional control system in PBD.