Search Results (46)

Background: White matter hyperintensities (WMHs) have been implicated in late-onset psychiatric disorders, but their contribution to this clinical phenotype remains insufficiently understood. Methods: We conducted a cross-sectional transdiagnostic study of 90 consecutively admitted acute patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) meeting the predefined inclusion criteria. Patients with a late onset were compared to earlier onset (EO) psychiatric patients. Late onset was defined as the median age of the disorder onset of the sample (≥40 years). Multidimensional clinical, cognitive, psychomotor, metabolic, and neuroimaging data were evaluated (WHM burden and cerebral atrophy), and a cognitive-psychopathologic composite index was derived. Correlations and sensitivity analysis were performed. A multivariable linear regression was performed to assess the independent effects of age, vascular risk factors, and WMH severity on cognitive performance and psychiatric symptoms. Results: In patients with LO psychiatric disorders, greater WMH burden was significantly associated with poorer global cognition and specific cognitive domains, lower delusional symptoms severity, and greater suicidal thoughts/behavior intensity. These associations were markedly weaker or not present in EO patients. The regression model explained 36.5% of the variance in the cognitive-psychopathologic composite index. After adjusting for age and cumulative risk factors, Fazekas was the only significant independent predictor (β = −0.495, p = 0.001). Conclusions: WMH burden was associated with differences in clinical characteristics in LO psychiatric disorders, including cognitive and neuropsychiatric symptoms. Our findings support a possible vascular-neuropsychiatric interaction in LO phenotypes. Full article

This narrative review integrates longitudinal cohort studies, neuroimaging and biomarker research, and major clinical trials to examine how depression and cognitive decline interact across the dementia continuum. Depression and cognitive impairment frequently co-occur in late life and exhibit substantial clinical and biological overlap. Meta-analytic and large population-based cohort studies consistently show that late-life depression increases the risk of mild cognitive impairment and dementia, with stronger associations observed for vascular dementia than for Alzheimer’s disease. Neurobiological studies implicate cerebrovascular pathology, neuroinflammation, hypothalamic–pituitary–adrenal axis dysregulation, and fronto-subcortical circuit dysfunction as key mechanisms linking depressive symptoms to later cognitive decline. In a subset of older adults, new-onset depression—particularly when accompanied by executive dysfunction, subjective cognitive decline, or high white-matter hyperintensity burden—are associated with an increased likelihood of near-term cognitive decline and dementia, although evidence for a definitive prodromal state remains limited. Depression is also highly prevalent as part of the behavioral and psychological symptoms of dementia, occurring in 30–50% of individuals with Alzheimer’s disease and even higher proportions in dementia with Lewy bodies or frontotemporal dementia. Comorbid depression in dementia accelerates cognitive and functional decline, increases neuropsychiatric burden, and worsens quality of life for patients and caregivers. Therapeutically, antidepressant treatment may confer modest benefits on mood and selected cognitive domains (e.g., processing speed and executive function) in non-demented older adults, whereas in established dementia, antidepressant efficacy is limited. In contrast, cholinesterase inhibitors, memantine, and multimodal non-pharmacological interventions yield small but measurable improvements in depressive or apathy-related symptoms. Emerging disease-modifying therapies for Alzheimer’s disease have demonstrated cognitive benefits, but current trial data provide insufficient evidence regarding effects on depressive symptoms, highlighting an important gap for future research. These findings underscore the need for stage-specific, integrative strategies to address the intertwined trajectories of mood and cognition in aging. Full article

Background: Spondyloarthritis (SpA) typically develops before 40 years of age, but increasing life expectancy has led to a growing number of cases in older adults. It is well known that age at onset may influence disease presentation, comorbidities, and patient outcomes. Objectives: To assess whether age at onset influences SpA clinical presentation. Methods: We analyzed clinical, demographic, clinimetric, and imaging data in 272 SpA patients, grouped by onset age: early (≤40, n = 119), intermediate (41–59, n = 127), and late (≥60, n = 26). All patients had a minimum follow-up duration of 12 months. Their epidemiologic, clinic, and clinimetric data were collected, as well as patient-reported outcome measures (PROs) [Patient Global Assessment (PGA), Health Assessment Questionnaire (HAQ), FACIT-Fatigue (FACIT-F), SHORT-FORM 36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment Questionnaire (WPAI), CSI (Central Sensitization Inventory), and Psoriatic Arthritis Impact of Disease (PsAID) questionnaire]. In univariate analyses, differences in categorical variables across onset groups were assessed using Fisher’s exact test; for continuous variables, between-group comparisons were performed using the Mann–Whitney U test (two-tailed) or the Kruskal–Wallis test, as appropriate, with Bonferroni correction for post hoc analyses. Multivariable regression models were subsequently fitted, adjusting for sex, diagnosis, and disease duration. For binary outcomes, multivariable logistic regression models were used, while multivariable linear regression models (ANCOVA) were applied for continuous outcomes. The overall association between onset group and each outcome was formally tested using likelihood ratio tests, comparing models including the onset variable with nested models excluding it. A p-value < 0.05 was considered statistically significant. Results: Patients’ mean age was 60.0 ± 13.7 years; 55.9% of them were males; and there were 188 cases (69.1%) of psoriatic arthritis (PsA) and 84 cases (30.9%) of ankylosing spondylitis (AS). In early-onset patients, inflammatory back pain (IBP) was more frequent, whereas late-onset patients more often presented with joint swelling. A family history of SpA and psoriasis was less common in late-onset forms. Comorbidities, including osteoporosis, osteoarthritis, hypertension, hyperuricemia, and diabetes, were more prevalent in older-onset patients, resulting in a higher overall comorbidity burden in Groups 2 and 3. Patient-reported outcomes were largely similar across age groups, although work activity limitation was more pronounced in younger patients. Conclusions: Age at onset seems to influence SpA phenotypes: early-onset could favor axial involvement, while late-onset may associate with peripheral arthritis. Late-onset forms are associated with a more severe comorbidity burden, in particular for cardiovascular risk factors. Lung involvement proved to be more prevalent with respect to the general population, so it should be checked in the routinary assessment of SpA patients. These findings suggest that rheumatologists could tailor their routine assessments based on patients’ age at disease onset. Interestingly, work productivity seems more impacted in early-onset patients. All these points highlight the importance of age at disease onset in SpA, guiding toward personalized medicine in terms of follow-up, therapy, and more holistic patient management. Full article

Background: Late-onset depression (LOD) represents a distinct clinical and biological phenotype emerging in the context of global population ageing. This study aims to synthesize current evidence on the epidemiology, risk factors, mechanistic pathways, and therapeutic approaches of LOD, integrating biological, psychological, and social dimensions. Methods: This narrative review synthesizes recent evidence across epidemiology, clinical symptomatology, neurobiology, and treatment. Where conceptually appropriate or empirically overlapping, we incorporate findings from the broader late-life depression (LLD) literature. Results: LOD emerges (as a distinct clinical and biological entity in later life) as a clinically and biologically meaningful presentation of depression in later life, representing a minority of depressive cases. It is defined by prominent apathy, psychomotor slowing, and cognitive impairment, and is closely linked to frailty, medical comorbidity, and heightened dementia risk. Pathophysiological mechanisms converge on vascular, inflammatory, oxidative, and neuroplasticity pathways, while psychosocial adversity further shapes onset and course. Treatment prioritizes efficacy and tolerability amid multiple morbidity; SSRIs and SNRIs are first-line, with pro-dopaminergic or dual-action agents addressing anhedonia and apathy, and neuromodulation or augmentation strategies reserved for resistance. Integrative approaches combining pharmacotherapy, psychotherapy, and lifestyle interventions are essential to optimize outcomes in aging populations. Conclusions: Late-onset depression (is a distinct, biologically and psychosocially driven disorder) represents a biologically and psychosocially enriched subtype in its own within the spectrum of late-life depression, requiring integrated, personalized care. Addressing neurovascular mechanisms, psychosocial adversity, and prevention through coordinated geriatric and psychiatric strategies may improve outcomes in aging populations. Full article

Late pregnancy represents a critical period for the onset of eating disorder symptoms, particularly in the presence of psychological and relational vulnerabilities. Among these, the quality of the romantic relationship has received limited empirical attention, despite its potential role in shaping women’s psychological adjustment, influencing both mood and body image. The present study examined the association between romantic relationship quality and eating disorder symptoms during the third trimester of pregnancy, considering the mediating roles of depressive symptoms and body dissatisfaction. A sample of 231 Italian pregnant women (Mage = 32.3 years) completed four self-report measures: the Dyadic Adjustment Scale-7, the Edinburgh Postnatal Depression Scale, the Body Image in Pregnancy Scale, and the Eating Disorder Examination Questionnaire-Short. A serial mediation model was tested, including pre-pregnancy body mass index as a covariate. Results indicated that lower romantic relationship quality was associated with greater eating disorder symptoms through higher depressive symptoms and body dissatisfaction, which acted both independently and sequentially. These findings highlight the complex interplay between relational and psychological factors in the development of disordered eating during pregnancy, emphasizing the need for early screening and integrated interventions addressing both interpersonal and intrapersonal domains. Full article

Background/Objectives: Major depressive disorder (MDD), including late-onset forms, is a prevalent and disabling condition. Despite multiple pharmacological treatment options, over half of patients fail to achieve full remission. This systematic review aims to assess current evidence on the influence of pharmacogenetic factors on antidepressant response and safety, with a focus on patients with major and late-life depression. Methods: We conducted a systematic review following PRISMA guidelines (PROSPERO: CRD42020212345). Studies published in the past five years involving adult patients with MDD or late-onset depression and pharmacogenetic data were included. Results: From 793 abstracts screened, 29 studies with 39,975 participants were included. CYP2C19 and CYP2D6 were the most frequently analyzed genes (41% and 17% of studies, respectively). Poor metabolizers for CYP2C19 showed higher plasma levels of SSRIs, leading to increased adverse effects. In contrast, ultrarapid metabolizers had significantly lower response rates. Variants in SLC6A4 and other genes (e.g., HTR2A, ABCB1) were also associated with treatment outcomes. Combinatorial pharmacogenetic testing showed superior predictive value compared to single-gene approaches. Conclusions: Genetic variants in CYP2C19, CYP2D6, and SLC6A4 may affect the efficacy and tolerability of antidepressant therapy. Integrating this information into clinical practice may allow more personalized prescribing and improved outcomes. Full article

Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer’s disease and related dementias (AD/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD/ADRD in women. Women have unique risk factors for late onset of AD/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women’s vulnerability to AD/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD/ADRD in women for developing preventive measures. Full article

Background: Late-onset depression (LOD) has been increasingly recognized as a risk factor for dementia, yet the temporal and causal nature of this relationship remains unclear. Objective: The purpose of this review is to investigate the temporal association between LOD and dementia. Methods: A comprehensive search for studies examining the temporal relationship between LOD and dementia was conducted using MEDLINE via Ovid. The end date of the search was 9 September 2024. A total of 3450 studies were identified, of which 27 met the inclusion criteria. This review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and an article quality assessment was completed. Results: The review demonstrated a significant temporal association between LOD and the risk of dementia, with the highest risk observed within the first decade following depression onset. LOD was consistently associated with an increased likelihood of developing dementia, particularly Alzheimer’s disease, compared to depression at earlier life stages. Conclusions: This systematic review highlights the significant association between LOD and dementia risk, emphasizing the need for early recognition and intervention. Future research should investigate the age at which LOD becomes a risk factor for dementia, the relationship between depression severity, family history of dementia, and dementia risk, as well as the efficacy of preventative treatments. Full article

Background: An increased risk of cognitive decline has been reported in patients with older age bipolar disorder (OABD); however, the underlying factors contributing to this association remain unclear. This cross-sectional study aims to identify the clinical features associated with cognitive impairment in OABD. Methods: A total of 152 participants, aged at least 50 years and diagnosed with bipolar disorder (BD) and related disorders in agreement with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria, were included in the study and divided into two subgroups based on the presence/absence of cognitive impairment, defined as a diagnosis of Mild Neurocognitive Disorder or Major Neurocognitive Disorder. Univariate comparisons and multivariate logistic regression models were performed to investigate the associations between clinical variables and cognitive impairment. Results: Cognitively impaired patients had a higher prevalence of otherwise specified BD/cyclothymic disorder, while BD type 2 was more common in the cognitively unimpaired group. Additionally, the cognitively impaired group had a later onset of major mood episodes (p < 0.05), fewer lifetime depressive episodes (p = 0.006), a higher prevalence of vascular leukoencephalopathy (p = 0.022) and dyslipidemia (p = 0.043), a lower prevalence of agoraphobia (p = 0.040), worse global functioning (p < 0.001), and higher psychopathology severity (p < 0.001). Late onset, vascular leukoencephalopathy, and dyslipidemia were all independently associated with cognitive impairment. Conclusions: Atypical BD, late onset of mood episodes, and somatic comorbidities like vascular leukoencephalopathy and dyslipidemia are associated with a higher risk of developing cognitive impairment and neurodegenerative disorders in OABD patients. Full article

The Junggar Basin basement comprises microcontinental blocks amalgamated through successive paleo-oceanic accretion events. Stratigraphic and provenance studies within the basin are crucial for reconstructing its evolution and understanding the closure of paleo-oceanic systems. This study presents an integrated petrographic and geochemical analysis of the Lower Jurassic Badaowan Formation sandstones in the Dongdaohaizi Depression, located in the eastern Junggar Basin. The results reveal a progressive decrease in lithic fragment content and an increase in quartz content from older to younger strata within the Badaowan Formation, indicating an increase in compositional maturity. Provenance analysis indicates that the sandstones are predominantly derived from tuffaceous rocks, granites, basalts, and minor metamorphic rocks. Heavy mineral assemblages, including zircon, chromian spinel, tourmaline, and garnet, suggest parent rocks consisting primarily of intermediate to acidic igneous rocks, mafic igneous rocks, and metamorphic rocks. Integrated petrographic and geochemical data from the surrounding areas of the Dongdaohaizi Depression confirm that the Badaowan Formation sandstones are primarily sourced from the eastern Kelameili Mountain. The continued uplift and migration of the Kelameili Mountain during the Early Jurassic played a dominant role in shaping the sedimentary provenance. LA-ICP-MS analyses reveal that the rare earth element (REE) concentrations in the Lower Jurassic sandstones are slightly lower than the average REE content of the upper continental crust. The sandstones exhibit weak differentiation between light and heavy REEs, reflecting a depositional environment characterized by anoxic reducing conditions. Geochemical results indicate a tectonic setting dominated by a passive continental margin and continental island arc in the source area. Synthesizing these findings with related studies, we propose that the Kelameili Ocean, as part of the Paleo-Asian Ocean, underwent a complex evolution involving multiple oceanic basins and microcontinental subduction–collision systems. From the Middle Ordovician to Late Silurian, the Kelameili region evolved as a passive continental margin. With the onset of subduction during the Middle Devonian to Early Carboniferous, the eastern Junggar Basin transitioned into a continental island arc system. This tectonic transition was likely driven by episodic or bidirectional subduction of the Kelameili Ocean. Full article

Background and Objectives: Growing evidence suggested that abnormal lipid metabolism (ALM) was associated with an increased severity of depressive symptoms, but no previous studies have examined the differences in comorbid ALM in major depressive disorder (MDD) patients of different ages of onset. We aim to compare the differences in the prevalence and clinical correlates of ALM between early-onset and late-onset patients with first-episode and drug-naive (FEDN) MDD patients. Methods: Using a cross-sectional design, we recruited a total of 1718 FEDN MDD outpatients in this study. We used the 17-item Hamilton Rating Scale for Depression (HAMD-17), The Hamilton Anxiety Rating Scale (HAMA), the Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity Scale (CGI-S) to assess their depression, anxiety, and psychotic symptoms and clinical severity, respectively. Results: There were 349 patients (20.3%) in the early-onset subgroup and 1369 (79.7%) in the late-onset subgroup. In this study, 65.1% (1188/1718) of patients were diagnosed with ALM. The prevalence of ALM in the late-onset group (81.5%, 1116/1369) was significantly higher than that in the early-onset group (20.6%, 72/349) (p = 0.36, OR = 1.147, 95%CI = 0.855–1.537). The HAMD total score (OR = 1.34, 95% CI = 1.18–1.53, p < 0.001) was the only risk factor for ALM in early-onset MDD patients. In late-onset MDD patients, the HAMD total score (OR = 1.19, 95% CI = 1.11–1.28, p < 0.001), TSH (OR = 1.25, 95% CI = 1.16–1.36, p < 0.001), CGI (OR = 1.7, 95% CI = 1.31–2.19, p < 0.001), and anxiety (OR = 2.22, 95% CI = 1.23–4.02, p = 0.008) were risk factors for ALM. Conclusion and Scientific Significance: Our results suggest that there are significant differences in the prevalence and clinical factors of comorbid ALM between early-onset and late-onset FEND MDD patients. Full article

Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA_A receptors (EC₅₀ 42–194 µM) and persistent neuronal Na⁺ currents (IC₅₀ 59 µM). Side effects include QT_c interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.5 (I_Na), hCav1.2 (α1c + β2 + α2δ1) (I_CaL), hKv7.1 + minK (I_Ks), and hKv11.1 (hERG) (I_Kr). We found IC50 of 87.6 µM (peak I_Na), 46.5 µM (late I_Na), and 509.75 µM (I_CaL). In experiments on Ncyte^® ventricular cardiomyocytes, APD90 was reduced with 28.6 ± 13.5% (mean ± SD) by cenobamate 200 µM. Cenobamate’s marked inhibition of I_Na raises the theoretical possibility of cardiac arrhythmia induction at therapeutic concentrations in the context of preexisting myocardial pathology, in the presence of action potential conduction and repolarization heterogeneity. This hypothetical mechanism is consistent with the known effects of class Ib antiarrhythmics. In simulations with a linear strand of 50 cardiomyocytes with variable inter-myocyte conductance based on a modified O’Hara–Rudy model, we found a negligible cenobamate-induced conduction delay in normal tissue, but a marked delay and also a block when gap junction conduction was already depressed. Full article

The comorbidity between late-life depression and neurocognitive disorders (NCDs) in the elderly is a subject of increasing interest within the scientific and medical community. We conducted a narrative review of clinical studies focused on depression and NCDs, primarily covering articles published over the past 25 years. Compared with younger adults, depression in the elderly is often characterized by difficulties in expressing sadness, more pronounced somatic, anxiety, and psychotic symptoms, as well as a heightened risk of suicide and cognitive impairment. Depressive symptoms in the elderly may mimic NCDs, act as prodromal signs of future NCDs, or represent a clinical dimension of dementia. NCDs and late-life depression share specific clinical similarities, particularly at illness onset, emphasizing the importance of early differential diagnosis to guide the development of precise, integrated, and tailored interventions. Full article

Early life stress (ELS) increases predisposition to major depressive disorder (MDD), with neuroinflammation playing a crucial role. This study investigated the long-term effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on ELS-induced depressive-like behavior and messenger RNA (mRNA) of pro-inflammatory cytokines in the medial prefrontal cortex (mPFC) and CA1 regions. We also assessed whether these gene expression alterations were present at the onset of URB597 treatment during late adolescence. ELS induced a depressive-like phenotype in adult male and female rats, which was reversed by URB597. In the mPFC, ELS downregulated nuclear factor kappa B1 (nfκb1) in both sexes, while URB597 normalized this expression exclusively in males. In females, ELS downregulated interleukin (il) 6 and tumor necrosis factor alpha (tnfα) but upregulated il1β and corticotropin-releasing factor (crf); URB597 normalized il6, il1β, and crf. In the CA1, ELS downregulated il1β and tnfα in males and upregulated il1β expression in females, which was reversed by URB597. Some of these effects began in late adolescence, including mPFC-nfκb1 expression in both sexes, mPFC-il6 and mPFC-il1β in females, CA1-il1β and CA1-tnfα in males, and CA1-il1β in females. These findings highlight URB597 as a therapeutic approach for reversing ELS-induced depressive-like behavior by associating with changes in the gene expression of neuroinflammatory cytokines, with notable sex differences. Full article

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico–limbic–striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico–striatal–cerebellar network in the neurophysiopathology of LLD. Full article