Childhood trauma is a significant environmental stressor linked to mood disorder. It can affect not only the individuals directly involved but also the next generation through the intergenerational transmission of trauma. This study aimed to investigate, for the first time, the co-occurrence of childhood trauma in youths with mood disorders and their parents. We assessed 443 individuals, 100 youths with DSM-5 mood disorders, 100 youths healthy controls (HCs), 92 s' parents and 161 adult HCs. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). The distribution patterns of childhood trauma subtypes was estimated through a multivariate model. Intraclass correlations (ICC) were calculated to account for the familial clustering of the sample. We found significantly higher scores for Patients as compared to Young-HC in all the subtypes of childhood trauma (p < 0.05). Considering Parents and Adult-HC groups, Physical abuse (p = 0.001) and Emotional neglect showed higher scores in Parents (p < 0.001). Regarding the familial clustering of the sample, emotional (p < 0.001) and sexual abuse (p = 0.001), and emotional (p = 0.3) and physical neglect (p = 0.003) showed statistical significance, but only emotional abuse reveled a medium level ICC (0.25). Our study highlights the effect of intergenerational transmission of childhood trauma on the diagnosis of mood disorders in youths. Our findings underscore the significance of systematically assessing childhood trauma, in particular emotional abuse, in youths with mood disorders and their parents. Additionally, there is urgent need for evidence-based preventive measures aimed at promoting positive parenting strategies and emotionally supportive environments for children.

Objective: Pain is among the most common and debilitating symptoms experienced by oncology patients and has been associated with adverse mental health outcomes, including depression and suicide. Nevertheless, the relationship between pain and suicide in oncology populations remains insufficiently characterized. A clearer understanding of this interplay is essential to guide personalized approaches aimed at reducing cancer-related burden and improving quality of life. Methods: We searched PubMed and PsycInfo without imposing limits regarding publication date using pain* AND (suicid* OR “self-harm” OR “self-injurious behavior” OR “self-inflicted injury” or “self-killing”) AND (cancer* OR oncolog* OR tumor* OR neoplasm* OR metasta*). A total of 832 articles were identified, and 15 of them were included in our review. Results: Inadequately managed pain in cancer patients is associated with a significantly elevated risk of suicidal ideation. This association is further exacerbated in individuals presenting with depressive symptoms, advanced-stage disease, or limited access to timely psychological support. These factors may interact synergistically, intensifying the emotional and cognitive burden of pain, thereby increasing vulnerability in cancer patients. Conclusions: Cancer-related pain should be conceptualized as a highly variable indicator of psychological vulnerability. Factors influencing this variability include cancer type and severity, as well as the presence of past psychopathology. These findings support the need for a personalized medicine approach, whereby pain management and psychosocial interventions are tailored to patient-specific factors such as disease stage, psychological comorbidity, and access to supportive care.

Background/Objectives: Lithium is the gold standard for treating Bipolar Disorder (BD), but its effectiveness varies widely. While clinical and environmental factors may influence response, it remains unclear if screening tools can reliably predict lithium response outcomes. This study explores this potential using two widely used screening instruments for BD. Methods: A total of 146 patients with BD were evaluated. Lithium response was assessed using the Alda Scale, while hypomanic and manic symptoms were characterized through the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ). Group differences in HCL-32 and MDQ scores were analyzed using ANOVA, and a multivariate model was employed to identify predictors of lithium response. Results: Of the total sample, 46 (31.5%) patients were identified as lithium responders based on the Alda Scale. Responders exhibited significantly higher HCL-32 scores compared to non-responders (p = 0.023), while no differences were observed in MDQ scores or other sociodemographic characteristics. Linear regression analysis revealed that HCL-32 scores were a significant predictor of Alda Scale scores, with no associations found for age, gender, or MDQ scores. Conclusions: Our study underscores the importance of considering hypomanic symptoms when estimating lithium response in BD, particularly by utilizing the HCL-32 during screening.

Background/Objectives: P-glycoprotein (P-gp, ABCB1/MDR1) is a key ATP-binding cassette transporter involved in multidrug resistance in cancer, limiting intracellular accumulation of various chemotherapeutic (CT) agents. Several antidepressants (ADs) have been shown to modulate P-gp function. This dual pharmacological profile raises the possibility of repurposing ADs as chemosensitizers to enhance anticancer drug efficacy. The objective of this review was to summarize the available evidence on the combined use of ADs and chemotherapeutics to overcome P-gp-mediated resistance. Methods: A systematic search was performed in PubMed, Scopus, and PsycInfo/PsycArticles databases using a comprehensive search string combining terms for P-gp, ADs, chemotherapy, and drug resistance. Inclusion criteria were preclinical or clinical studies investigating the effect of ADs in combination with chemotherapeutics on P-gp-mediated resistance in cancer models. Eleven relevant studies were identified and qualitatively analyzed. Results: Across diverse cancer models, including colon, breast, and multidrug-resistant cell lines, several ADs significantly enhanced the cytotoxicity of many chemotherapeutic agents. The proposed mechanisms involved downregulation of P-gp expression, inhibition of efflux activity, and increased intracellular drug accumulation. Conclusions: The combination of ADs with CT agents shows promising potential in overcoming P-gp-mediated multidrug resistance, enhancing antitumor efficacy in preclinical models. Further translational and clinical research is needed to validate these findings, optimize dosing strategies, and assess the risk–benefit profile in cancer patients, particularly those with comorbid depressive disorders.

Central nervous system (CNS) tumors account for nearly one third of pediatric cancers and remain the leading cause of cancer-related mortality in children. Cranial radiotherapy is a cornerstone of treatment for many high-grade and embryonal brain tumors, often in combination with surgery and chemotherapy. However, improved survival has been accompanied by a growing burden of late neurocognitive, emotional, social, and endocrine sequelae. Damage to hippocampal neural stem and progenitor cells partly drives radiation-induced cognitive decline, which leads to reduced neurogenesis and increased gliogenesis. Lithium has emerged as a promising strategy to protect or repair the irradiated brain through its neuroprotective, anti-inflammatory, anti-apoptotic, and pro-neurogenic effects. Preclinical evidence supports its potential to mitigate radiation-induced brain injury. In cellular models, lithium appears to protect neural progenitors and hippocampal neurons from irradiation-related damage but does not confer comparable protection to tumor cells. In juvenile rodent models, lithium administration before, during, or after cranial irradiation has been associated with reduced apoptosis in hippocampal neurogenic regions, preservation or restoration of neurogenesis, attenuation of neuroinflammation, and improvement of cognitive and behavioral outcomes. Importantly, delayed lithium treatment has also shown restorative effects, indicating a potential role as a neuroregenerative strategy for survivors with late effects. Mechanistically, these benefits appear to arise from modulation of apoptotic pathways, GSK-3β-related signaling, neurogenic cell fate, and epigenetic programs that promote neuronal differentiation over gliogenesis. These data have provided the rationale for early clinical translation and ongoing trials now assessing whether lithium can improve neurocognitive outcomes after cranial radiotherapy in pediatric brain tumor patients. This narrative review summarizes the preclinical basis and emerging clinical evidence for lithium as a potential adjunct to radiotherapy while discussing key unresolved issues, including optimal timing, treatment duration, tumor safety, and patient selection.