Background Individuals with autism spectrum disorder (ASD) commonly experience comorbid depression, anxiety, and impaired quality of life (QoL), significantly affecting daily functioning and social adaptation. Non-pharmacological interventions (NPIs), offering an alternative without drug-related side effects, have gained increasing attention for emotional improvement and health promotion. However, the comparative effectiveness of different NPIs remains unclear, and clinical decisions lack robust evidence. Methods This study adhered to the PRISMA-NMA guidelines. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and EBSCOhost) were systematically searched to identify randomized controlled trials (RCTs) published before March 2025. A total of 67 RCTs involving 3,604 ASD participants were included. A frequentist network meta-analysis using a multivariate random-effects model was conducted in Stata, along with pairwise meta-analyses, to compare the relative effects of mindfulness-based interventions (MBI), cognitive behavioral therapy (CBT), behavioral and functional training (BEHAVE), physical activity (PHYS), sensory therapies (SENS), technology- and family-based interventions (TAFI), and other interventions (OTH) on anxiety, depression, and QoL. Standardized mean differences (SMDs) with 95% credible intervals (CIs) were used to estimate effects, and SUCRA rankings were calculated to assess comparative efficacy. Results MBI showed the greatest improvement in anxiety symptoms (SMD = –0.84, 95% CI: –1.32 to –0.36; SUCRA = 91.4%), CBT ranked highest for depression reduction (SMD = –0.77, 95% CI: –1.25 to –0.28; SUCRA = 90.1%), and PHYS performed best for enhancing QoL (SMD = 0.59, 95% CI: 0.20 to 0.98; SUCRA = 87.5%). The analyzed population primarily consisted of high-functioning male individuals. Subgroup analyses showed stronger effects in adults and with moderate-duration interventions (9-16weeks). No significant inconsistency or publication bias was detected. Limitations Findings mainly apply to high-functioning ASD populations without intellectual disability. Heterogeneity in interventions and assessments should be considered. Conclusions Different NPIs exhibit distinct advantages in improving emotional symptoms and QoL among individuals with ASD. MBI, CBT, and PHYS demonstrate relative superiority for anxiety, depression, and QoL respectively, supporting their targeted application in clinical and rehabilitative settings. Future studies should prioritize long-term follow-up, refined intervention designs, and personalized strategies tailored to ASD subgroups to enhance clinical utility and scalability. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251021423.

Treatment resistant depression: Socio-demographic characteristics, comorbidity and treatment patterns from the All of Us Research Program.

The rationale for subtyping depression into atypical and melancholic in research and clinical settings: A narrative review.

Nomophobia, social networking site (SNS) addiction, and fear of missing out (FoMO) are increasingly recognized as interrelated digital-age phenomena that pose risks to young people's mental health. However, limited research has examined how specific symptoms across these domains interact and contribute to anxiety and depression. This study aims to make a novel contribution by applying network and flow analysis to uncover the symptom-level interconnections among nomophobia, SNS addiction, FoMO, and their links to mental health outcomes. A total of 3108 college students completed validated scales measuring SNS addiction, FoMO, nomophobia, anxiety, and depression. Gaussian graphical models and centrality indices were used to estimate symptom networks. Flow networks were constructed to identify pathways connecting symptoms to mental health outcomes. Strong intranetwork associations were found within all three domains. "FoMO on information" emerged as the most central and influential bridge symptom, connecting nomophobia and SNS addiction. Flow network analysis revealed that "FoMO on information" was also the strongest individual predictor of both anxiety and depression. Other symptoms, such as "fear of losing internet connection" and "SNS-related insomnia," also showed notable associations with mental health outcomes. These findings highlight the potential of network and flow analysis to identify transdiagnostic mechanisms across digital behavioral addictions. "FoMO on information" appears to be a key symptom linking nomophobia and SNS addiction and may represent a promising target for interventions aimed at reducing comorbid anxiety and depression among adolescents.

Endocannabinoids Block Headache and Anxiety Comorbidity via Two-pronged Anterior Insular Projections

Depression is a common psychiatric disorder, and increasing evidence implicates the dysregulation of extracellular ATP and hippocampal dysfunction in its pathophysiology. However, whether ATP release is involved in depression and mechanisms underlying this involvement remain unclear. Moreover, the basis for the comorbidity of depression and anxiety disorders remains unclear. In our study, we observed reduced connexin 43 (Cx43) and extracellular ATP levels in the dorsal hippocampus but not ventral hippocampus of susceptible adult male mice exposed to chronic social defeat stress. Conditional knockout of astrocytic Cx43 or its specific knockdown in dorsal hippocampal astrocytes led to depressive- and anxiety-like behaviors, whereas neuronal knockout of Cx43 had no effect on these behaviors. These deficits were accompanied by decreased extracellular ATP levels, while supplementation with exogenous ATPγS reversed these behavioral deficits. We further identified Cx43 as a critical regulator of ATP release and a modulator of astrocytic network connectivity and morphology. Notably, overexpression of Cx43 combined with the inhibition of ATP-degrading enzymes in the dorsal hippocampus restored ATP levels and ameliorated behavioral deficits. Taken together, our results demonstrate that deficiency of ATP release from dorsal hippocampal astrocytes leads to depressive- and anxiety-like behaviors, primarily through Cx43. These findings shed new light on the mechanisms by which ATP regulates depression and anxiety pathogenesis and the role of dorsal hippocampus in depression and anxiety, providing potential therapeutic targets for treating these comorbid disorders.Significance statement This study provides the first direct evidence of a causal relationship between astrocytic Cx43 in the dorsal hippocampus and depressive-like behaviors. It highlights the crucial role of ATP release in the comorbidity of depression and anxiety. Astrocyte-specific knockout or knockdown of Cx43 in the dorsal hippocampus resulted in reduced extracellular ATP levels and emotional disturbances. Conversely, restoring Cx43 expression combined with inhibition of ATP degradation rescued both ATP levels and behavioral deficits in susceptible mice. These findings underscore the central role of astrocytic Cx43-mediated ATP release in the pathophysiology of depression and highlight promising therapeutic strategies for the treatment of comorbid depression and anxiety.

To compare the efficacy of basic dermatotropic (topical and UVB 311nm) and combination therapy (with the addition of alimemazine or maritupirdine) for non-segmental vitiligo with comorbid anxiety and depressive symptoms associated with adjustment disorders caused by the stress-related effects of the dermatosis. A single-center, randomized, prospective study included 60 patients (19 men, 41 women; 29.0±7.0 years old) with unstable non-segmental vitiligo (VIDA ≥+1) and comorbid anxiety and anxiety-depressive disorders (HADS-A/D ≥11) within the framework of adaptation disorders (nosogenic reactions) (F43.2). The patients were randomly divided into three groups, with 20 patients in each group. For 8 weeks, patients in group 1 received topical therapy+UVB 311 nm; group 2 received topical therapy+UVB 311 nm+alimemazine 10-20 mg/day; and group 3 received topical therapy+UVB 311 nm+maritupiridine 20-40 mg/day. The study used the Clinical Global Impression (CGI) scale; Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Vitiligo Area and Severity Index (VASI); Visual Analog Scale of Repigmentation (G0-G4). The effectiveness of therapy was assessed by positive dynamics on the CGI scale and a decrease in the total score on the DLQI scale. By the eighth week of therapy, the median ΔVASI was 15% in group 1, 27% in group 2, and 29% in group 3 (p<0.05). Normalization of the HADS-A anxiety subscale (<8 points) was achieved in groups 1, 2, and 3, respectively: in 8/18 (44%), 16/18 (89%), and 17/19 (89%) patients; The HADS-D depressive subscale improved in 6/18 (33%), 10/18 (56%), and 15/19 (79%) patients, respectively (p<0.001). Mild adverse events, including drowsiness (4), headache (4), and dizziness (2), did not require treatment discontinuation. At the end of treatment, the average CGI-I total score was 5.1 («marked improvement»), which correlated with the changes in the DIQI scores. Comorbid anxiety and anxiety-depressive adjustment disorders caused by the stressful effects of dermatosis worsen repigmentation during standard therapy for vitiligo. Psychopharmacological correction of comorbid adjustment disorders using alimemazine or maritupirdine significantly increases the incidence of clinically significant repigmentation and effectively normalizes psychosomatic status without significant side effects in the vast majority of patients.

AimComorbid anxiety disorders and their symptoms are common in schizophrenia and may occur before a relapse. The aim of this post hoc analysis is to investigate the efficacy of lurasidone on comorbid anxiety symptoms in patients with schizophrenia.MethodsData were pooled from five Phase 3 randomized, double‐blind, placebo‐controlled 6‐week trials of lurasidone treatment of schizophrenia, focusing on the 40 and 80 mg doses compared with placebo. Subgroup analyses were performed in two subgroups: severe (baseline Positive and Negative Syndrome Scale [PANSS] G2 anxiety score ≥ 4) and non‐severe anxiety (baseline PANSS G2 score < 4).ResultsIn the severe anxiety group, both the 40 and 80 mg doses of lurasidone significantly reduced PANSS G2 score from Weeks 2 to 6 compared to placebo. In patients not receiving concomitant anxiolytics, significant improvement in the PANSS G2 score was observed at Week 6 for lurasidone 40 mg compared to placebo. In both lurasidone dose groups, PANSS total and subscale scores were significantly reduced at Week 6 compared to placebo. For baseline‐to‐Week‐6 change scores, the PANSS G2 score and PANSS positive subscale score showed a moderate correlation. There were no new AEs of concern for lurasidone in this pooled analysis.ConclusionThe results suggest treatment with 40 or 80 mg/day of lurasidone improves anxiety symptoms in schizophrenia patients with moderate to severe anxiety, at least in part, through a direct effect, and this effect was demonstrated by lurasidone monotherapy, without the use of concomitant anxiolytics.

BackgroundSchools could play a vital role in mental health care, particularly in low-income countries such as Uganda. An understanding of the prevalence and associated factors of mental health symptoms among school-going adolescents is essential for designing effective school-based interventions in Uganda This is important given Uganda’s regional disparities, where adolescents in post-conflict areas may face higher exposure to trauma and limited access to mental health care compared to those in non-conflict regions. This study aimed to investigate the prevalence rates of depressive and anxiety symptoms among school-going adolescents aged 14 to 17 years in both post-conflict and non-conflict settings. It also examines factors associated with moderate depressive and anxiety symptoms in both settings.MethodsIn total, 2845 school-going adolescents (1,273 boys; 16.3 ± 1.0 years) were screened using the Patient Health Questionnaire-9 – adolescent version, Generalized Anxiety Disorder-7, and self-report items on food insecurity, health and wealth status, history of childhood abuse and neglect and level of physical activity. Logistic regression models were applied to examine predictors of moderate to severe levels of depression and anxiety symptoms.ResultsFindings indicate that 67.5% (n = 1905) reported at least mild, 34.1% (n = 962) at least moderate, 12.7% (n = 359) at least moderate-severe and 4.9% (n = 138) severe symptoms of depression, while 65.6% (n = 1860) at least mild, 27.5% (n = 777) at least moderate and 7.8% (n = 219) severe symptoms of anxiety. In the multivariable analyses, female sex, food insecurity, poor self-reported health, co-morbid anxiety symptoms, and a history of abuse and neglect were all significantly associated with a higher odds of moderate symptoms of depression, while female sex, living in a post-conflict setting, food insecurity, poor self-reported health, co-morbid depressive symptoms, and a history of abuse were all significantly associated with a higher odds of moderate anxiety symptoms.ConclusionsA substantial proportion of school-going adolescents in Uganda report at least moderate symptoms of depression and anxiety. Government and public sector agencies should re-evaluate their strategies at both family and school levels, particularly in underserved settings. Schools can serve as platforms for screening-and-referral pathways and group-based psychosocial programs, while the health system should strengthen capacity for co-occurring conditions.

Metacognitive therapy and work-focus for patients with depression, anxiety or comorbid depression and anxiety on sick leave: a single-centre, open-label randomised controlled trial

Functional movement disorders (FMDs) manifest as involuntary motor symptoms incongruent with known neuroanatomy. Once attributed to psychological factors, FMDs are now recognized as neurobiological conditions involving disrupted brain networks. They account for 2-20% of movement disorder referrals globally. While multidisciplinary rehabilitation benefits 60-70% of patients, 30-40% remain treatment-refractory, highlighting the need for biologically targeted therapies. This review synthesizes evidence on neuromodulation for FMDs, aiming to: (1) identify modifiable neural circuits, (2) evaluate clinical efficacy across phenotypes, (3) distinguish neurobiological from placebo-mediated effects, and (4) identify biomarkers for precision medicine. We conducted a narrative review (PubMed, Embase, 2000-2025), assessing risk-of-bias using RoB-2 and MINORS tools. FMD pathophysiology involves cortical hyperexcitability, limbic-motor decoupling, and predictive coding deficits. TMS reveals reduced intracortical inhibition and shortened cortical silent periods in M1; fMRI shows altered emotional-motor connectivity. rTMS demonstrates therapeutic potential, though placebo responses are prominent. Anodal tDCS over the left DLPFC shows promise in functional dystonia, especially with comorbid anxiety. FMDs reflect circuit-level dysfunction, supporting neuromodulation as a rational intervention. High-frequency rTMS over M1 and anodal tDCS over DLPFC yield modest clinical benefits, but placebo effects remain a confounder. Future progress requires addressing methodological gaps, validating biomarkers, and integrating neuromodulation within personalized, multidisciplinary frameworks that account for socioeconomic and psychosocial contexts to meaningfully reduce disability.

Introduction and Importance: Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) commonly prescribed for major depressive disorder and smoking cessation. It is preferred for its minimal serotonergic activity and favorable side effect profile. However, rare adverse events such as tinnitus—the perception of sound without an external source—have been occasionally reported. Case Presentation: We report a 45-year-old male treated for depression with bupropion 150 mg/day, who developed bilateral low-pitched humming tinnitus after the dose was increased to 300 mg/day. He had no history of ear disease, noise trauma, or ototoxic medication use. Physical examination, audiometry, and brain MRI were unremarkable. Following dose reduction, the tinnitus partially improved, and it completely resolved after stopping the drug. Discussion: The temporal correlation between dose escalation and tinnitus onset, along with symptom resolution after drug cessation and lack of alternative causes, suggests a probable adverse drug reaction. The exact mechanism remains uncertain but may involve altered dopaminergic or noradrenergic signaling within the auditory system. Only a few cases of bupropion-induced tinnitus have been documented, making this report a relevant addition to the limited literature. Conclusion: This case underscores the rarity, bilateral nature, and reversibility of bupropion-induced tinnitus. It highlights the importance of clinician vigilance, structured patient education during dose escalation, and timely intervention to prevent unnecessary morbidity. As this is a single case report, broader clinical studies are warranted to substantiate causality and incidence. This case underscores the importance of clinician awareness regarding bupropion-induced tinnitus, particularly at higher doses. The rarity and reversibility highlight the need for vigilance, patient education during dose escalation, and timely dose adjustment or discontinuation. Limitations include the single-case design and possible confounders such as comorbid anxiety.

Relevance. Parkinson's disease is a neurodegenerative disease of the nervous system and one of the most topical problems in neurology. Motor fluctuations are a common complication of long-term levodopa treatment in patients with Parkinson's disease. Рurpose of the study. To study the effect of motor fluctuations on the psychoemotional state and quality of life of patients with Parkinson's disease. Materials and methods of the study. The study included 120 patients with various clinical forms of Parkinson's disease. To compare the parameters during the study, the patients were divided into 2 groups: patients with motor fluctuations (55 people) and patients without motor fluctuations (65 people). All patients underwent clinical neurological and neuropsychological examinations. Research results. In the group with motor fluctuations, the comorbid form of affective disorders, that is, depression + anxiety, was significantly higher: in the group with fluctuations - 54.5% (30/55 patients), in the group without fluctuations - 24.6% (16/65 patients). When assessing the significance of this difference using the χ² test, the obtained value was p&lt;0.01. Thus, it can be noted that motor fluctuations are strongly associated with more severe and comorbid forms of mental disorders (depression and anxiety). The results obtained based on the PDQ-39 scale domains show that psychoemotional disorders have varying degrees of negative impact on virtually all areas of life. Conclusion. When assessing quality of life using the PDQ-39 questionnaire, patients with anxiety and depression showed a significant decrease in indicators such as mobility, daily activities, emotional state, cognitive function, and social support. The greatest negative impact was observed in the group with comorbid depression and anxiety.

BackgroundNo study has simultaneously investigated the associations of anxiety comorbidities, persistent depressive disorder (PDD), depression, anxiety, and somatic symptoms at baseline with the total and longest durations of paid employment (DPE) as well as the total number of reasons for occupational impairment (OI) over a 10-year period among patients with major depressive disorder (MDD). The study aimed to investigate these issues.MethodsAt baseline, 290 subjects with MDD were enrolled. MDD and anxiety comorbidities were confirmed using the Structured Clinical Interview for DSM-IV-TR. The Depression and Somatic Symptoms Scale and the Hospital Anxiety and Depression Scale were employed. At the 10-year follow-up point, 113 subjects were investigated. The total and longest DPE were clarified and recorded. A 28-item list was used to investigate the subjective reasons for OI. Multiple linear regression models were used for statistical analysis.ResultsFor the total and longest DPE, 14.2% and 40.7% of the subjects were less than five years, respectively. An increase of one anxiety comorbidity in subjects was associated with a decrease of 4.6 months in the total DPE compared to those without. Subjects with greater somatic symptoms, PDD, and the female gender at baseline reported more reasons for OI. Fatigue, somatic discomfort, decreased motivation, and sensitivity to comments were common reasons for OI.ConclusionsIn the treatment of depression, clinicians should pay more attention to the above treatable factors, including anxiety comorbidities, PDD, fatigue, decreased motivation, and somatic symptoms, to improve OI.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-025-07504-w.

BackgroundThe co-occurrence of depression and anxiety in adolescents is associated with a greater risk than the presence of depressive symptoms alone. Predicting anxiety disorders among depressed adolescents is critical for interventions and therapeutic tools.MethodsWe recruited 2316 depressed adolescents through the Chinese Adolescent Depression Cohort (CADC) and collected 34 predictive factors for model construction. The Light Gradient Boosting Machine (LightGBM) prediction model and Shapley Additive Explanations (SHAP) algorithm were implemented for in-depth interpretation of the predictive importance of different factors. Furthermore, chi-square automatic interaction detection (CHAID) and ordinal logistic regression were used to explore the factor interactions and validate the importance of the SHAP value-based factors, respectively.ResultsNine key risk factors were identified. In addition to depressive severity, rumination, perceived stress, sleep quality, alexithymia, peer victimization, academic stress level, emotion-focused coping, and parental overprotect were recognized as key risk factors for the onset of anxiety. Resilience was recognized as a protective factor. Interaction analysis captured critical interactions between depression and six other risk factors in relation to different levels of anxiety risks. Interactions between the protective effect of resilience and four risk factors were also analyzed. High-risk subgroups and low-risk groups for different levels of anxiety were identified through the CHAID decision tree. The high-risk subgroups for severe anxiety include (1) adolescents with severe depression symptoms, (2) with moderate depression symptoms and high rumination, and (3) with severe depression symptoms and high alexithymia. The low-risk subgroups are (1) adolescents with low depression and rumination, (2) with low depression, low alexithymia, and more parental care, (3) with low depression, moderate rumination, and moderate academic stress.ConclusionsUtilizing an explainable machine learning approach enables us to identify the risk and protective factors for anxiety disorders among depressed adolescents. The SHAP analysis results suggest that depression severity was the most important predictor for co-morbid anxiety. CHAID decision tree further identified risk subgroups. These findings suggest that clinical workers take into consideration the above risk and protective factors as well as their interactions to develop appropriate therapies for the prevention of comorbid anxiety with depression.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12911-025-03225-y.

Efficacy of applet-based acceptance and commitment therapy focused on repetitive negative thinking for adults with comorbid anxiety and depression: A randomized controlled trial with mediation analysis.

Is emotional neglect the first psychological threat? Differentiating ICD-11 PTSD and complex PTSD with comorbid anxiety and depression.

Relationships among sleep quality, anxiety, and depression among Chinese nurses: A network analysis.

Psychiatric symptoms and alzheimer's disease: Depression-anxiety comorbidity effects and their neurobiological mediating mechanisms.

Association Between Financial Hardship, Resilience and Comorbid Depression and Anxiety Symptomatology in Youth From Bogota, Buenos Aires, and Lima