For years, people from CEOs to novelists have taken tiny amounts of psychedelics to support well-being. New research shows that benefits for depression may be attributable to a placebo effect. Typically using psilocybin mushrooms or LSD, the archetypal microdoser sought less melting walls and open-eye kaleidoscopic visuals than boosts in mood and energy, like a gentle spring breeze blowing through the mind. Anecdotal reports pitched microdosing as a kind of psychedelic Swiss Army knife, providing everything from increased focus to a spiked libido and (perhaps most promisingly) lowered reported levels of depression. It was a miracle for many.

This study presents QuanvNeXt, an end-to-end fully quanvolutional model for EEG-based depression diagnosis. QuanvNeXt incorporates a novel Cross Residual block, which reduces feature homogeneity and strengthens cross-feature relationships while retaining parameter efficiency. We evaluated QuanvNeXt on two open-source datasets, where it achieved an average accuracy of 93.1% and an average AUC-ROC of 97.2%, outperforming state-of-the-art baselines such as InceptionTime (91.7% accuracy, 95.9% AUC-ROC). An uncertainty analysis across Gaussian noise levels demonstrated well-calibrated predictions, with ECE scores remaining low (0.0436, Dataset 1) to moderate (0.1159, Dataset 2) even at the highest perturbation (ε = 0.1). Additionally, a post-hoc explainable AI analysis confirmed that QuanvNeXt effectively identifies and learns spectrotemporal patterns that distinguish between healthy controls and major depressive disorder. Overall, QuanvNeXt establishes an efficient and reliable approach for EEG-based depression diagnosis.

Depression is a major cause of global mental illness and significantly influences suicide rates. Timely and accurate diagnosis is essential for effective intervention. Electroencephalography (EEG) provides a non-invasive and accessible method for examining cerebral activity and identifying disease-associated patterns. We propose a novel graph-based deep learning framework, named Edge-gated, axis-mixed Pooling Attention Network (ExPANet), for differentiating major depressive disorder (MDD) patients from healthy controls (HC). EEG recordings undergo preprocessing to eliminate artifacts and are segmented into short periods of activity. We extract 14 features from each segment, which include time, frequency, fractal, and complexity domains. Electrodes are represented as nodes, whereas edges are determined by the phase-locking value (PLV) to represent functional connectivity. The generated brain graphs are examined utilizing an adapted graph attention network. This architecture acquires both localized electrode characteristics and comprehensive functional connectivity patterns. The proposed framework attains superior performance relative to current EEG-based approaches across two different datasets. A fundamental advantage of our methodology is its explainability. We evaluated the significance of features, channels, and edges, in addition to intrinsic attention weights. These studies highlight features, cerebral areas, and connectivity associations that are especially relevant to MDD, many of which correspond with clinical data. Our findings demonstrate a reliable and transparent method for EEG-based screening of MDD, using deep learning with clinically relevant results.

Background: Captured between clinical appointments using mobile devices, spoken language has potential for objective, more regular assessment of symptom severity and earlier detection of relapse in major depressive disorder. However, research to date has largely been in non-clinical cross-sectional samples of written language using complex machine learning (ML) approaches with limited interpretability. Methods: We describe an initial exploratory analysis of longitudinal speech data and PHQ-8 assessments from 5,836 recordings of 586 participants in the UK, Netherlands, and Spain, collected in the RADAR-MDD study. We sought to identify interpretable lexical features associated with MDD symptom severity with linear mixed-effects modelling. Interpretable features and high-dimensional vector embeddings were also used to test the prediction performance of four regressor ML models. Results: In English data, MDD symptom severity was associated with 7 features including lexical diversity measures and absolutist language. In Dutch, associations were observed with words per sentence and positive word frequency; no associations were observed in recordings collected in Spain. The predictive power of lexical features and vector embeddings was near chance level across all languages. Limitations: Smaller samples in non-English speech and methodological choices, such as the elicitation prompt, may have also limited the effect sizes observable. A lack of NLP tools in languages other than English restricted our feature choice. Conclusion: To understand the value of lexical markers in clinical research and practice, further research is needed in larger samples across several languages using improved protocols, and ML models that account for within- and between-individual variations in language.

Major depressive disorder (MDD) is a prevalent mental health condition that negatively impacts both individual well-being and global public health. Automated detection of MDD using structural magnetic resonance imaging (sMRI) and deep learning (DL) methods holds increasing promise for improving diagnostic accuracy and enabling early intervention. Most existing methods employ either voxel-level features or handcrafted regional representations built from predefined brain atlases, limiting their ability to capture complex brain patterns. This paper develops a unified pipeline that utilizes Vision Transformers (ViTs) for extracting 3D region embeddings from sMRI data and Graph Neural Network (GNN) for classification. We explore two strategies for defining regions: (1) an atlas-based approach using predefined structural and functional brain atlases, and (2) an cube-based method by which ViTs are trained directly to identify regions from uniformly extracted 3D patches. Further, cosine similarity graphs are generated to model interregional relationships, and guide GNN-based classification. Extensive experiments were conducted using the REST-meta-MDD dataset to demonstrate the effectiveness of our model. With stratified 10-fold cross-validation, the best model obtained 81.51\% accuracy, 85.94\% sensitivity, 76.36\% specificity, 80.88\% precision, and 83.33\% F1-score. Further, atlas-based models consistently outperformed the cube-based approach, highlighting the importance of using domain-specific anatomical priors for MDD detection.

Antidepressant nonadherence is pervasive, driving relapse, hospitalization, suicide risk, and billions in avoidable costs. Clinicians need tools that detect adherence lapses promptly, yet current methods are either invasive (serum assays, neuroimaging) or proxy-based and inaccurate (pill counts, pharmacy refills). We present the first noninvasive biomarker that detects antidepressant intake from a single night of sleep. A transformer-based model analyzes sleep data from a consumer wearable or contactless wireless sensor to infer antidepressant intake, enabling remote, effortless, daily adherence assessment at home. Across six datasets comprising 62,000 nights from >20,000 participants (1,800 antidepressant users), the biomarker achieved AUROC = 0.84, generalized across drug classes, scaled with dose, and remained robust to concomitant psychotropics. Longitudinal monitoring captured real-world initiation, tapering, and lapses. This approach offers objective, scalable adherence surveillance with potential to improve depression care and outcomes.

Background Major depressive disorder (MDD) is a leading cause of global disability, yet current diagnostic approaches often rely on subjective assessments and lack the ability to integrate multimodal clinical information. Large language models (LLMs) hold promise for enhancing diagnostic accuracy through advanced reasoning but face challenges in interpretability, hallucination, and reliance on synthetic data. Methods We developed MDD-Thinker, an LLM-based diagnostic framework that integrates supervised fine-tuning (SFT) with reinforcement learning (RL) to strengthen reasoning ability and interpretability. Using the UK Biobank dataset, we generated 40,000 reasoning samples, supplemented with 10,000 samples from publicly available mental health datasets. The model was fine-tuned on these reasoning corpora, and its diagnostic and reasoning performance was evaluated against machine learning, deep learning, and state-of-the-art LLM baselines. Findings MDD-Thinker achieved an accuracy of 0.8268 and F1-score of 0.8081, significantly outperforming traditional baselines such as SVM and MLP, as well as general-purpose LLMs. Incorporating both SFT and RL yielded the greatest improvements, with relative gains of 29.0% in accuracy, 38.1% in F1-score, and 34.8% in AUC. Moreover, the model demonstrated comparable reasoning performance compared to much larger LLMs, while maintaining computational efficiency. Interpretation This study presents the first reasoning-enhanced LLM framework for MDD diagnosis trained on large-scale real-world clinical data. By integrating SFT and RL, MDD-Thinker balances accuracy, interpretability, and efficiency, offering a scalable approach for intelligent psychiatric diagnostics. These findings suggest that reasoning-oriented LLMs can provide clinically reliable support for MDD detection and may inform broader applications in mental health care.

This study integrates causal inference, graph analysis, temporal complexity measures, and machine learning to examine whether individual symptom trajectories can reveal meaningful diagnostic patterns. Testing on a longitudinal dataset of N=45 individuals affected by General Anxiety Disorder (GAD) and/or Major Depressive Disorder (MDD) derived from Fisher et al. 2017, we propose a novel pipeline for the analysis of the temporal dynamics of psychopathological symptoms. First, we employ the PCMCI+ algorithm with nonparametric independence test to determine the causal network of nonlinear dependencies between symptoms in individuals with different mental disorders. We found that the PCMCI+ effectively highlights the individual peculiarities of each symptom network, which could be leveraged towards personalized therapies. At the same time, aggregating the networks by diagnosis sheds light to disorder-specific causal mechanisms, in agreement with previous psychopathological literature. Then, we enrich the dataset by computing complexity-based measures (e.g. entropy, fractal dimension, recurrence) from the symptom time series, and feed it to a suitably selected machine learning algorithm to aid the diagnosis of each individual. The new dataset yields 91% accuracy in the classification of the symptom dynamics, proving to be an effective diagnostic support tool. Overall, these findings highlight how integrating causal modeling and temporal complexity can enhance diagnostic differentiation, offering a principled, data-driven foundation for both personalized assessment in clinical psychology and structural advances in psychological research.

Depression is a common mental illness across current human society. Traditional depression assessment relying on inventories and interviews with psychologists frequently suffer from subjective diagnosis results, slow and expensive diagnosis process as well as lack of human resources. Since there is a solid evidence that depression is reflected by various human internal brain activities and external expressive behaviours, early traditional machine learning (ML) and advanced deep learning (DL) models have been widely explored for human behaviour-based automatic depression assessment (ADA) since 2012. However, recent ADA surveys typically only focus on a limited number of human behaviour modalities. Despite being used as a theoretical basis for developing ADA approaches, existing ADA surveys lack a comprehensive review and summary of multi-modal depression-related human behaviours. To bridge this gap, this paper specifically summarises depression-related human behaviours across a range of modalities (e.g. the human brain, verbal language and non-verbal audio/facial/body behaviours). We focus on conducting an up-to-date and comprehensive survey of ML-based ADA approaches for learning depression cues from these behaviours as well as discussing and comparing their distinctive features and limitations. In addition, we also review existing ADA competitions and datasets, identify and discuss the main challenges and opportunities to provide further research directions for future ADA researchers.

Depression is one of the most prevalent mental health disorders worldwide, with estimates indicating that around 5% of the worlds' adult population [1, 2] suffers from this condition. The primary methods for screening and monitoring depression rely on self-reported questionnaires, such as the Patient Health Questionnaire (PHQ-9) [3], Beck's Depression Inventory (BDI) [4] and Hamilton Depression Ratings Scale (HDRS) [5]. While these questionnaires are effective to varying degrees at screening patients for depression, they provide only limited information about the affected underlying neuro-cognitive processes in individuals, limiting the ability to personalize treatments. Given the heterogeneity of depressive symptomatology across patient populations [6, 7], it is crucial to elucidate the underlying neurophysiological mechanisms to support the development of more effective and individualized procedures for screening, monitoring, and treatment. Prior functional imaging studies have identified increased activity in anterior cin-gulate cortex (especially the subgenual anterior cingulate) during presentation of emotional stimuli, altered connectivity in prefrontal cortical areas, and default mode network as potential differentiating markers in depressed participants [8-13].