This systematic review explores the role of the endocannabinoid system (ECS) in prodromal psychosis and its potential as a therapeutic target. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 22 studies published between 2000 and 2025 were analyzed, comprising preclinical research, genetic studies, neuroimaging investigations, and clinical trials. Converging evidence suggests that ECS alterations precede and potentially contribute to the development of psychotic symptoms, with CB1 receptor modifications and endocannabinoid levels correlating with symptom severity and transition risk to full-blown psychosis. Neuroimaging studies revealed reduced CB1 receptor availability in key brain regions in high-risk subjects, and intervention studies, particularly with cannabidiol-though its therapeutic mechanisms likely extend beyond ECS modulation to include dopaminergic and other neurotransmitter pathways-have shown promising results. Proposed mechanisms of action include stress response attenuation, neuroinflammatory modulation, neurodevelopmental stabilization, and normalization of the dopamine-glutamate interface. Despite limitations of existing studies, primarily small size and short duration, this review provides a solid foundation for developing ECS-targeted interventions as a promising approach to modify disease trajectory during the prodromal phase, potentially offering safer and more effective therapeutic options for individuals at clinical high risk for psychosis.

Abstract Introduction Murine ocular autoimmunity develops through 3 stages; prodrome, primary peak and secondary regulation. During the prodromal phase, leukocytes accumulate within the retina and vitreous. Methods Using the adoptive transfer of ocular antigen reactive T cells to induce experimental autoimmune uveitis, we can analyse the disease course and track the transferred cells being recruited to the ocular environment from prodrome through peak of disease to secondary regulation. Results During initiation (the prodrome) of disease ‘pathogenic’ transferred CD4+ T cells can be detected within the retina as well as an endogenous CD4+ infiltrate and as disease reaches peak, both transferred and endogenous CD4+ T cells can be found in large numbers in the retina. Active clinical disease resolves by day 21 but transferred CD4+ T cells persist within the retina when disease is in a clinically quiescent state. Concurrent transfer of RBP3 (also known as IRBP) specific and OVA specific activated cells induces a similar clinical disease phenotype and time course. Both RBP3 and OVA specific cells are recruited during active clinical disease in equal measure showing that autoantigen specific CD4+ T cells induce susceptibility for recruitment of other activated CD4+ T cells. When analysing the endogenous and transferred CD4+ T cells by RNA sequencing, differences between the two sets of gene signatures highlight genes that are also found in pathogenic T cells in other models, including upregulation of markers associated with cytokine interactions and NK cell mediated cytotoxicity. Conclusion Due to the persistence of the original transferred population throughout clinical disease, in depth analysis of this population could suggest pathways contributing to persistent ocular autoimmunity.

Background. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by an initial prodromal phase with eosinophil-driven manifestations such as asthma, nasal polyposis, and rhinitis, followed by an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic phase. Ocular involvement is possible but uncommon (approximately 15% of cases), and central retinal artery occlusion (CRAO) represents an exceedingly rare event. Although benralizumab, a monoclonal antibody targeting the IL-5 receptor, has proven effective in managing eosinophilic manifestations such as asthma and nasal polyposis, its ability to prevent vasculitic damage remains uncertain. We report a case of EGPA complicated by bilateral CRAO occurring during benralizumab therapy. Case report. A 61-year-old man with a history of adult-onset chronic rhinosinusitis and severe asthma, treated with benralizumab since 2022, presented to the emergency department in June 2024 with sudden bilateral blindness preceded by transient amaurosis episodes, without systemic symptoms or ocular pain. Ophthalmologic examination revealed markedly reduced visual acuity in both eyes (hand motion only) and a relative afferent pupillary defect. Fundus examination showed pale optic discs with central cherry-red spots. Optical coherence tomography (OCT) demonstrated inner retinal layer edema and hyperreflectivity (Figure 1a–c), while fluorescein angiography confirmed delayed retinal arteriolar filling (Figure 1d), findings consistent with CRAO. Laboratory tests revealed elevated inflammatory markers and high-titer myeloperoxidase (MPO)-ANCA positivity (134 IU/mL; positive >3 IU/mL) in the absence of peripheral eosinophilia, likely due to benralizumab therapy. Based on clinical and serological findings, a diagnosis of EGPA was established. High-dose corticosteroids and combined rituximab–cyclophosphamide therapy were initiated according to KDIGO and PEXIVAS recommendations. After an initial improvement, disease relapse occurred with increased MPO-ANCA levels, requiring steroid escalation and two additional cyclophosphamide infusions (cumulative dose: 4 g). Within six months, inflammatory markers and antibody titers normalized; however, visual loss persisted with only partial recovery (finger counting at 1 meter OD, 2/10 OS). Maintenance therapy with rituximab 500 mg every six months was started. Conclusions. This is the first reported case of EGPA complicated by bilateral CRAO occurring during benralizumab treatment. Suppression of eosinophilia did not prevent the development of a severe ANCA-mediated complication, suggesting distinct pathogenic pathways for eosinophilic and vasculitic damage. This case highlights the limitations of IL-5R inhibition in preventing systemic vasculitis and underscores the importance of early and aggressive immunosuppression to avoid irreversible outcomes.

The majority of first episode psychosis (FEP) patients are undetected (DET-) by clinical high-risk for psychosis (CHR-P) services prior to onset and therefore do not receive preventive care for psychosis. We compared features of the psychosis prodrome (symptoms and substance use) between DET- and FEP patients detected by CHR-P services (DET+) to determine whether they share a common prodromal phase. Retrospective Reporting of Studies Conducted Using Observational Routinely Collected Health Data statement-compliant electronic health record cohort study. We extracted 65 prodromal features (symptoms and substance use before FEP onset) using natural language processing to assess the presence, duration, and first presentation of the psychosis prodrome and occurrences of features across the prodrome. Duration and feature occurrences were compared between DET+ and DET- individuals using Mann-Whitney U tests and Wilcoxon Effect Size, while presence and first presentation were compared using logistic regression. A total of 1545 FEP patients (n= 119 DET+ [mean age 28.7years; SD = 9.4; 61.6% male]) were included. There were no significant differences in the presence (DET + =85.0%, DET- = 85.6%, P= .83) or duration (DET + =18.8months, DET- = 18.4months, P= .89) of the psychosis prodrome. There were no significant differences in first presentation of psychotic symptoms between groups (Pcorr> .05). Frequency of occurrences of thought broadcasting (r= 0.07, Pcorr= .04) was higher and hostility (r= 0.08, Pcorr= .04) lower in DET+ compared to DET- across the prodrome, though effect sizes were small. DET+ and DET- individuals experience similar psychosis prodromes prior to FEP onset. DET- individuals can likely be identified earlier if detection strategies are improved.

Background: This study aims to investigate the association between the presence and severity of non-motor symptoms (constipation, REM sleep behavior disorder [RBD], hyposmia, and depression) and the severity of motor impairment in Parkinson’s disease (PD). Methods: We used data from Parkinson’s Progression Markers Initiative (PPMI), comprising patients with established PD, prodromal PD, and healthy controls. Motor disability was evaluated with the MDS-UPDRS part III. Non-motor symptoms were assessed with standardized scales for constipation (MDS-UPDRS part I sub-item), depression (15-item GDS), RBD questionnaire (RBDQ), and hyposmia (UPSIT). The relationships between non-motor symptoms and motor severity were explored using linear regression models (adjusted for age/sex). Results: Constipation was significantly more prevalent in PD and prodromal PD and independently associated with greater motor severity in both groups (p < 0.001). Constipation also correlated with increased freezing and falls. Depressive symptoms were similar across groups, but in prodromal PD, higher GDS scores were associated with worse UPDRS III scores (p = 0.02), as well as higher freezing and fall scores. Hyposmia was strongly reduced in PD and prodromal PD compared with controls but was not independently associated with motor severity. Higher RBDQ scores were associated with worse motor impairment in PD, but not in prodromal PD after adjustment. Conclusions: Constipation and REM sleep behavioral disorder were independent correlates of worse motor severity in prodromal and established PD, whereas depressive symptoms predicted more severe parkinsonism only within the prodromal phase.

Delusional perception is a psychopathological phenomenon in which a self-referential, compulsory, obvious meaning is superimposed on the common meaning of the object or event, which is nevertheless still valid. The essay aims to an analysis of the possibility conditions of the coexistence of two different world-phenomena which share the same hyletic material. Among the variegated features of delusional perception, the essay deals mainly with temporality, as studied by Husserl and Richir, although brief analysis of spatiality and the prodromic phase of delusional perception are also provided.

Early detection of Parkinson's disease via aptamer-CRISPR platform.

Cortical functional connectivity changes in amnestic mild cognitive impairment.

ABSTRACTBackgroundThere is evidence that suggests that body dysmorphia represents a risk factor that may occur at the prodromal phase of schizophrenia, affecting ongoing developmental processes and conferring vulnerability to the disease. This study examined the psychometric properties of the Arabic Dysmorphic Concern Questionnaire (DCQ) among patients with a first‐episode schizophrenia in a Tunisian, Arabic‐speaking context.MethodA cross‐sectional study was conducted. Data collection was performed using a traditional paper‐and‐pencil approach by a single interviewer, who was one of the study's authors.ResultsOur findings showed that the unidimensional factor structure of the DCQ holds up in patients with schizophrenia from a Tunisian culture and at an early stage of their disease, and shows excellent reliability (Cronbach's α of 0.91) in this specific population. Measurement invariance was supported in terms of three levels (configural, scalar and metric). Convergent validity of the DCQ was evidenced through significant positive correlations of the scale with abnormal bodily phenomena, muscle dysmorphia and body dissatisfaction. Besides, concurrent validity was demonstrated via significant positive correlations between the DCQ and four other measures: psychological distress, disordered eating, insight and psychotic symptoms severity.ConclusionThe DCQ showed good validity and reliability for measuring dysmorphic concerns in patients with schizophrenia from a Tunisian culture and at an early stage of their disease. The sound psychometric performance of the DCQ, its short administration time, as well as easy scoring and interpretability make it an excellent instrument for use in future clinical and research endeavours.

Dynamics of sleep-wake cycles and architecture in anti-NMDAR encephalitis.

The beneficial effects of reducing the duration of untreated psychosis on longitudinal outcomes has led to implement early intervention programs during prodromal phase, especially for young people. However, little is known about psychiatric antecedents in people experiencing First Episode Psychosis (FEP). This study aimed (1) to calculate the proportion of FEP participants with previous contact with Child/Adolescent or/and Adult Mental Healthcare Services (CAMHS/AMHS) recruited within a specialized "Early Intervention in Psychosis" service, and (2) to compare sociodemographic, clinical, and treatment parameters between FEP patients with and without psychiatric antecedents across a 2-year follow-up period.At baseline, all participants (aged 12-35 years) completed the Health of the Nation Outcome Scale (HoNOS). A mixed-design ANOVA and a Kaplan-Meier survival analysis were used.The prevalence of antecedents in our FEP population was 48%. 15% had previous contact with CAMHS and only 21% of them experienced care continuity transitioning to AMHS. The most common past diagnoses in the FEP/CAMHS subgroup were conduct disorder (43.4%) and learning disorder (26.3%). Differently, the FEP/AMHS subgroup more frequently had personality disorder (50.8%) and anxious-depressive disorder (35.9%). FEP/CAMHS individuals had higher baseline HoNOS "Psychiatric symptoms" factor score and received higher total number of family psychoeducation sessions than the other subgroups.Our results suggest the importance of enhancing strategies for a better transition for adolescents. Indeed, this population appears to be at risk for higher psychiatric symptoms detected with HoNOS when developing psychosis.

Objective Clinically manifest ALS is preceded by a prodromal phase in gene mutation carriers, characterized by mild motor impairment. A well-defined prodromal phase could enable earlier diagnosis and treatment. We investigated the presence of a prodromal phase in sporadic ALS, from the perspective of patients and caregivers. Methods A survey was conducted of symptom onset in 279 ALS patients from a population-based registry and 150 caregivers. 244 patients and 123 caregivers were included in the primary qualitative analysis, followed by quantitative analysis of identified themes. A prodromal phase was defined as symptoms, in response to open-ended questions, before onset of recorded weakness, bulbar complaints or shortness of breath. Mild motor symptoms were defined as fasciculations, cramps, stiffness, atrophy, reduced sports performance, or mobility issues. Results 26.6% of patients and 17.5% of caregivers reported a prodromal phase, primarily with mild motor symptoms (patients 23.0%; caregivers 11.4%). Prodromal symptoms occurred a median of 6.0 months (IQR 2.8–11.8 months) before recorded disease onset. In closed-ended questions, 19.2% of patients and 22.2% of caregivers reported cognitive or behavioral symptoms before weakness onset, compared to only 0.6% and 1.8% in open-ended questions. Conclusions In sporadic ALS, approximately a quarter of patients report a prodromal phase characterized primarily by mild motor symptoms. However, mild motor symptoms alone are unlikely to contribute to earlier disease recognition. Cognitive or behavioral symptoms are often not recognized as part of the clinical spectrum. These findings emphasize the need for reliable biomarkers to detect ALS pathology at an early stage.

Freezing of gait is a debilitating motor symptom in Parkinson's disease that significantly increases fall risk and impairs quality of life. The poorly understood pathophysiology of freezing of gait presents challenges for early prediction and therapeutic intervention. This prospective study investigated whether eye movement abnormalities, specifically in the anti-saccade paradigm, could predict freezing of gait onset in Parkinson's disease patients over a two-year follow-up period. We analysed longitudinal data from the Ontario Neurodegenerative Disease Research Initiative, focusing on Parkinson's disease patients without freezing of gait at baseline who underwent comprehensive clinical evaluations and eye movement recordings. Anti-saccade reaction time and error ratio, combined with clinical measures including right upper extremity rigidity, demonstrated significant predictive value for freezing of gait development within two years. These findings suggest that eye movement deficits and upper limb rigidity emerge years before freezing of gait onset, indicating a prodromal phase in freezing of gait pathogenesis. The predictive relationship between these measures supports the hypothesis of shared neural substrates, potentially involving the mesencephalic locomotor region, in the development of both oculomotor dysfunction and gait freezing episodes.

Background: Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) are major global health challenges characterized by progressive neuronal loss. Their early diagnosis remains difficult due to overlapping clinical features and the absence of definitive biochemical markers in the prodromal phase. Imaging techniques have transformed diagnostic neurology by providing non-invasive visualization of structural, functional, and molecular changes in the brain, thereby complementing clinical and biochemical assessments. Objective: This review aims to synthesize current evidence on the role of neuroimaging modalities in diagnosing neurodegenerative diseases, emphasizing their diagnostic value, emerging biomarkers, and potential for integration with biochemical and genetic data. Methods: A narrative review approach was adopted. Peer-reviewed studies published between 2010 and 2024 were identified through PubMed, Scopus, and Google Scholar using the keywords neurodegenerative diseases, MRI, PET, SPECT, biomarkers, and diagnostic imaging. Studies focusing on imaging-based diagnosis, disease differentiation, and biomarker validation in AD, PD, FTD, and ALS were included. Findings were synthesized thematically to describe diagnostic principles, clinical applications, and comparative strengths of each modality. Results: Magnetic resonance imaging (MRI) remains the cornerstone of structural assessment, identifying hallmark patterns such as hippocampal atrophy in AD and midbrain degeneration in PD. Functional imaging modalities—functional MRI (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT)—enable detection of altered cerebral activity, hypometabolism, and perfusion abnormalities before overt atrophy occurs. Emerging techniques such as diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and hybrid PET/MRI systems enhance early detection by providing microstructural and molecular insights. Quantitative imaging biomarkers, including hippocampal volume, dopamine transporter activity, and cortical metabolic indices, demonstrate high diagnostic accuracy and facilitate longitudinal disease monitoring. Integrating imaging with CSF and genetic biomarkers further improves diagnostic specificity and enables precision stratification. Conclusion: Imaging serves as a cornerstone in the early and differential diagnosis of neurodegenerative diseases, bridging the gap between molecular pathology and clinical presentation. Despite challenges of cost, accessibility, and standardization, advancements in multimodal imaging, artificial intelligence, and quantitative biomarker analysis are transforming diagnostic neurology into a precision-based discipline. Continued technological integration promises earlier detection, individualized disease profiling, and optimized therapeutic interventions.

BackgroundSchizophrenia (Sz), once seen solely as a brain disorder, is now recognised as a systemic illness involving immune and metabolic dysregulation. The intestinal barrier has emerged as a key player in gut–brain–immune interactions. However, studies in early, antipsychotic free stages remain scarce and often neglect confounding factors such as smoking and metabolic syndrome.MethodsWe measured two complementary markers: lipopolysaccharide-binding protein (LBP), reflecting endotoxin exposure and systemic immune activation, and intestinal fatty acid-binding protein (I-FABP), indicating gut epithelial damage and permeability changes, in blood from 96 acutely ill, antipsychotic-free Sz patients (61 first-episode, 35 relapsed) and 96 matched controls. Associations with innate immunity, metabolic parameters, smoking, and clinical features were assessed using nonparametric statistics and random forest regression. Group differences were tested using covariate adjustment, as well as in a separate analysis of non-smokers (Sz: n = 42; controls: n = 84).ResultsMedian LBP was higher in Sz (21.96 µg/mL) vs. controls (18.10 µg/mL; FDR-adjusted p = 0.021, δ = 0.209) but became non-significant after adjusting for smoking (FDR-adjusted p = 0.199). In contrast, I-FABP was lower in Sz (218.2 pg/mL) than controls (315.0 pg/mL; FDR-adjusted p = 0.021, δ = –0.195) and remained robust across smoking-adjusted analyses. No differences were found between first-episode and relapsed patients for either marker.LBP correlated strongly with CRP (r = 0.557, p < 0.001) and neutrophils (r = 0.468, p < 0.001) and was moderately predicted by immune models (pseudo-R2 = 0.354 overall; 0.273 Sz; 0.449 controls). Links to waist circumference and blood pressure were weaker (pseudo-R2: 0.048–0.104). I-FABP showed fewer immune associations and was not correlated with LBP (r = –0.017, FDR-adjusted p = 0.819), suggesting distinct mechanisms.ConclusionsOur findings suggest separable gut‑related processes in antipsychotic-free Sz. The apparent LBP elevation was not schizophrenia‑specific; its strong correlations with CRP and neutrophils point to smoking related inflammation rather than a schizophrenia specific effect. Accordingly, prior findings of LBP elevations in Sz likely reflect unaccounted smoking. In contrast, reduced I-FABP, independent of smoking, may indicate epithelial injury. The absent correlation between LBP and I-FABP highlights distinct pathophysiological dimensions of gut dysfunction. Longitudinal studies, ideally spanning prodromal phases and integrating microbiome, dietary, smoking, and permeability assessments, are needed to clarify temporal dynamics and guide stratified treatments.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12974-025-03584-3.

The Family Violence Death Review Committee (FVDRC) have historically classified those deaths that do not apparently fit within a pattern of violence as ‘aberrant’. The article aims to determine if the FVDRC classification system has been incorrectly identifying deaths as aberrant when there is the potential to prevent such deaths. Within this investigation, we reviewed the classification of apparently aberrant deaths within the Aotearoa New Zealand Family Violence Death Review system. We also reviewed the literature that describes the nexus between mental disorder and family violence homicide to inform future classifications. Most homicides, including those associated with mental disorder, do not occur ‘out of the blue’ and are, as such, incorrectly classified as aberrant. Some of those incorrectly classified describe non-compliance with medication in combination with drug/alcohol abuse and/or a history of violence or trauma in the family. Engagement with the psychiatric community will increase awareness of psycho-bio-social risks across the life course of families and individuals and allow preventative interventions and solutions to be identified. This provides hope for families who are supporting people with severe mental disorders, highlighting the importance of effective, comprehensive support in the community. There are a small number of cases that are truly aberrant. In these, the homicide occurred during the sudden onset of an acute first episode psychosis after a very short prodromal phase, often identified in retrospect and atypical in the life of the offender.

This study aims to examine whether objectively measured sleep disturbances occur in the prodromal phase of mood episodes in patients with bipolar disorder. Thirteen patients with bipolar disorder were studied using a replicated single-case time-series design for 180 days with continuous actigraphy and a daily Ecological Momentary Assessment of mood symptoms. Eight patients were suitable for analysis. Sleep variables (sleep onset, sleep offset, sleep efficiency, sleep duration, sleep onset latency, minutes awake after start of sleep, composite phase deviation) were estimated using actigraphy. Mean shifts and extreme values in the data were assessed using change point analysis and statistical process control. Mean shifts and extreme values in sleep were studied in the two weeks preceding depressive episodes and manic episodes. Changes in sleep were observed in the two weeks preceding mood episodes in two out of three individuals with a manic episode and in four out of five individuals with a depressive episode. There were individual differences in the type of sleep variables that showed change. However, these changes did not occur at a higher rate than during phases in which patients were stable. The order of change in sleep and EMA assessed mood could not be disentangled. The current study illustrates the heterogeneity of the type of sleep disturbances as assessed with actigraphy in the weeks before mood episodes.

Integrating molecular imaging with near-infrared theranostics to improve early detection and therapy of Alzheimer's disease.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a parasomnia characterized by dream-enacting behaviors caused by the loss of muscle atonia during REM sleep. It is widely recognized as a prodromal phase of α-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies. Longitudinal cohort and pathological studies have demonstrated that approximately 70% of patients with iRBD develop defined neurodegenerative disorders within 10 years. Recent advances have identified several promising biomarkers to predict phenoconversion, including dopamine transporter imaging (DaT SPECT), cerebrospinal fluid α-synuclein detected via RT-QuIC, decreased CSF Aβ42, and elevated CSF/serum albumin ratio indicating blood-brain barrier dysfunction. Moreover, functional magnetic resonance imaging studies have revealed altered connectivity in the frontostriatal and posterior cortical networks in patients with iRBD, which correlates with cognitive and motor symptoms. These multimodal markers have significant potential for stratifying phenoconversion risks and guiding early therapeutic interventions. Future efforts should focus on standardizing biomarker assays and validating them through multicenter longitudinal studies to enhance diagnostic precision and support disease-modifying clinical trials in the prodromal phase of Lewy body diseases.

BackgroundDepression is a prevalent psychiatric disorder that is commonly associated with a high risk of recurrence and suicide. One of its core symptoms is cognitive impairment, which can occur during the prodromal, acute (76.9 – 94.0%), and remission phases (32.4 – 44.0%). This impairment substantially contributes to both health and socioeconomic burdens. Recent evidence suggests the therapeutic potential of electroacupuncture; however, its adjunctive efficacy compared with that of standard pharmacotherapy remains ambiguous. This study aimed to assess the effectiveness and safety of using conventional antidepressants alone versus in combination with electroacupuncture.MethodsThis multicenter, prospective, open-label randomized controlled trial enrolled 120 patients diagnosed with depression. The patients were randomly assigned at a 1:1 ratio to receive either conventional pharmacotherapy alone or pharmacotherapy combined with electroacupuncture. The intervention lasted for four weeks, followed by a post-treatment observation period. The Perceived Deficits Questionnaire for Depression (PDQ-D) was the primary outcome measured. The 17-item Hamilton Depression Rating Scale (HAMD-17), N-back task, Stroop Color-Word Test (SCWT), Trail Making Test-Part B (TMT-B), and functional near-infrared spectroscopy (fNIRS) indicators, such as the concentration of oxyhemoglobin (oxy-Hb), integral values, and centroid values, were the secondary outcomes assessed. R 4.5.0 was used to conduct the analyses.ResultsA total of 103 of the 120 participants completed the study. Significant main effects of time and time ×group interactions across most outcomes (P < 0.05) were revealed using linear mixed-effects modeling. The electroacupuncture group demonstrated significantly lower PDQ-D scores (P < 0.05) post-treatment, indicating greater cognitive improvement. This group also demonstrated superior performance in HAMD-17, N-back, SCWT, TMT-B, and fNIRS metrics. Most group main effects were non-significant (P > 0.05); however, the interaction effects indicated a stronger response to the combined intervention.ConclusionCompared with pharmacotherapy alone, the combination of pharmacotherapy with electroacupuncture improved cognitive symptoms, mood, and executive function more effectively in patients with depression over a short period. In addition, this combination was associated with enhanced cortical activation on fNIRS. The combined treatment was found to be safe and effective, suggesting promising implications for clinical practice and future research.Clinical trial registrationhttps://www.chictr.org.cn/hvshowproject.html?id=250167&v=1.0, identifier ChiCTR2400082987