Substance Use Disorder (SUD) represents one of the most frequent conditions worldwide which commonly coexists with major depressive disorder (MDD). This comorbidity (SUD + MDD) is one of the most prevalent with patients showing certain social and clinical characteristics that could lead to a worsening of their cognitive performance. However, despite these particularities, only a few studies have addressed the possible differences in cognitive performance between patients with SUD + MDD compared with those with SUD-only patients. Therefore, the aim of this study is to examine the clinical and cognitive profile of patients with SUD + MDD vs. SUD-only who are in early remission phase. For this purpose, 271 male patients underwent a clinical and neuropsychological assessment (SUD + MDD group: N = 101; SUD-only group: N = 170). Results indicated that SUD + MDD patients showed worse cognitive performance than SUD in visuospatial reasoning, verbal memory and learning, recognition, and processing speed even after a 3-month period of abstinence. Furthermore, these patients exhibited more self-reported prefrontal symptoms, as well as worse social and clinical conditions. This study indicates that the neurocognitive and clinical profile of patients with SUD + MDD could represent a risk since their characteristics have been associated with poorer recovery and prognosis. Our results could be helpful in clinical practice highlighting the need for cognitive remediation strategies in these populations, providing information that would allow the implementation of more appropriate treatments and preventive strategies.

Major depressive disorder (MDD) patients commonly encounter multiple types of functional disabilities, such as social, physical, and role functioning. MDD is related to an accreted risk of brain atrophy, aging-associated brain diseases, and mortality. Based on recently available studies, there are correlations between notable biological brain aging and MDD in adulthood. Despite several clinical and epidemiological studies that associate MDD with aging phenotypes, the underlying mechanisms in the brain remain unknown. The key areas in the study of biological brain aging in MDD are structural brain aging, impairment in functional connectivity, and the impact on cognitive function and age-related disorders. Various measurements have been used to determine the severity of brain aging, such as the brain age gap estimate (BrainAGE) or brain-predicted age difference (BrainPAD). This review summarized the current results of brain imaging data on the similarities between the manifestation of brain structural changes and the age-associated processes in MDD. This review also provided recent evidence of BrainPAD or BrainAGE scores in MDD, brain structural abnormalities, and functional connectivity, which are commonly observed between MDD and age-associated processes. It serves as a basis of current reference for future research on the potential areas of investigation for diagnostic, preventive, and potentially therapeutic purposes for brain aging in MDD.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer\'s disease, Parkinson\'s disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of \"MCCA+jICA\" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the \"MCCA+jICA\" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from \"MCCA+jICA\" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.

Depression is an eminently treatable disorder that responds to psychotherapy or medications; the efficacy of each has been established in hundreds of controlled trials. Nonetheless, the prevalence of depression has increased in recent years despite the existence of efficacious treatments-a phenomenon known as the treatment-prevalence paradox. We consider several possible explanations for this paradox, which range from a misunderstanding of the very nature of depression, inflated efficacy of the established treatments, and a lack of access to efficacious delivery of treatments. We find support for each of these possible explanations but especially the notion that large segments of the population lack access to efficacious treatments that are implemented as intended. We conclude by describing the potential of using lay therapists and digital technologies to overcome this lack of access and to reach historically underserved populations and simultaneously guarantee the quality of the interventions delivered.

Major mood disorder (i.e. major depressive disorder [MDD] and bipolar disorders [BPDs]) are among the most prevalent and disabling mental illnesses. Several, frequently intertwining theories (such as the monoamine, neuroinflammatory and neurotrophic theories) exist to explain the etiopathogenic background of mood disorders. A lesser-known hypothesis addresses the role of oxidative stress (OS; i.e. the overproduction and accumulation of free radicals) in the pathogenesis of these mental disorders. Free radicals are capable of damaging phospholipids, polyunsaturated fatty acids, proteins and nucleic acids. In the brain, OS impairs inter alia synaptic signalling and neuroplasticity. In the current paper, in addition to a brief description of the aforementioned pathophysiological processes involved in mood disorders (with a special focus on OS), we discuss in detail the results of studies on changes in non-enzymatic antioxidant uric acid (UA) levels in major mood disorders. Findings to date indicate that UA - a routinely measured laboratory parameter - may be a candidate biomarker to distinguish between MDD and BPD. Since the diagnostic criteria are identical for major depressive episodes regardless of whether the episode occurs in the context of MDD or BPD and also bearing in mind that the treatment for those two disorders is different, we may conclude that the identification of biomarkers to enable MDD to be distinguished from BPD would be of great clinical relevance.

Aberrations in non-verbal social cognition have been reported to coincide with major depressive disorder. Yet little is known about the role of the eyes. To fill this gap, the present study explores whether and, if so, how reading language of the eyes is altered in depression. For this purpose, patients and person-by-person matched typically developing individuals were administered the Emotions in Masked Faces task and Reading the Mind in the Eyes Test, modified, both of which contained a comparable amount of visual information available. For achieving group homogeneity, we set a focus on females as major depressive disorder displays a gender-specific profile. The findings show that facial masks selectively affect inferring emotions: recognition of sadness and anger are more heavily compromised in major depressive disorder as compared with typically developing controls, whereas the recognition of fear, happiness, and neutral expressions remains unhindered. Disgust, the forgotten emotion of psychiatry, is the least recognizable emotion in both groups. On the Reading the Mind in the Eyes Test patients exhibit lower accuracy on positive expressions than their typically developing peers, but do not differ on negative items. In both depressive and typically developing individuals, the ability to recognize emotions behind a mask and performance on the Reading the Mind in the Eyes Test are linked to each other in processing speed, but not recognition accuracy. The outcome provides a blueprint for understanding the complexities of reading language of the eyes within and beyond the COVID-19 pandemic.

Mental health has deteriorated globally due to COVID-19, climate crisis, economic policies, and regional conflicts, requiring immediate attention. This study aims to comprehend the relationship between economic uncertainty and the prevalence of anxiety disorders, major depressive disorder, and eating disorders across various demographics and countries. Using robust fixed-effect models, we analyzed the relationship between economic uncertainty and mental disorders in 110 countries from 1991 to 2019. Our analysis also explored whether this association varies across genders and age groups. Our analysis indicates that economic uncertainty is associated with higher prevalence rates of anxiety and major depressive disorders, though no similar association is observed for eating disorders. In the subgroup analyses, while females have a significant association exclusively with anxiety disorders, males have associations with anxiety and major depressive disorders. The age-specific analyses show that economic uncertainty is associated with anxiety disorders for almost all age groups above 15 years, except for ages between 40 and 54. For major depressive disorders, this association becomes significant after the 40-44 age group. However, we see no significant association among age groups for eating disorders.

BACKGROUND: Considering the high comorbidity, shared risk factors, and genetic pathways between irritable bowel syndrome (IBS) and major depressive disorder (MDD), we hypothesized that there would be both shared and disorder-specific alterations in brain function.
METHODS: A total of 39 IBS patients, 39 MDD patients, and 40 healthy controls (HCs) were enrolled and matched for sex, age, and educational level. All subjects underwent resting-state functional MRI. The clinical variables of anxiety, depression, gastrointestinal symptoms and alexithymia were recorded. The 12 subregions of the striatum were employed as seeds to assess their functional connectivity (FC) with every voxel throughout the whole brain.
RESULTS: Compared to HC, IBS and MDD patients exhibited aberrant frontal-striatal circuitry. We observed a common decrease in FC between the dorsal striatum and regions of the hippocampus, sensorimotor cortex, and prefrontal cortex (PFC) in both IBS and MDD patients. Patients with IBS exhibited disorder-specific decreases in FC within the striatum, along with reduced connectivity between the ventral striatum and sensorimotor cortex. In contrast, MDD patients showed disorder-specific hyperconnectivity in the medial PFC-limbic system. Receiver operating characteristic curve analysis showed that frontal-striatal FC values could serve as transdiagnostic markers of IBS and MDD. Within the IBS group, striatal connectivity was not only negatively associated with weekly abdominal pain days but also negatively correlated with the levels of anxiety and alexithymia.
CONCLUSIONS: This exploratory analysis indicated that patients with IBS and MDD exhibited both shared and disorder-specific frontal-striatal circuit impairments, potentially explaining both comorbidity and distinct phenotypes.

UNASSIGNED: Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.
UNASSIGNED: We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode.
UNASSIGNED: Univariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736-1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004-1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073-1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk.
UNASSIGNED: We provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.