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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 18954

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Dr. Wen Zhang

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Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL, USA
Interests: computational genetics; cancer; big data analysis; deep learning; statistical modeling; bioinformatics
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Special Issue Information

Dear Colleagues,

Psychiatric disorders represent a major challenge to global public health, with complex etiologies that involve intricate interactions between genetic, environmental, and neurological factors. This Special Issue, "Advanced Research on Psychiatric Disorders", aims to highlight cutting-edge developments in understanding, diagnosing, and treating psychiatric illnesses. We welcome contributions that explore the biological underpinnings of psychiatric disorders, particularly studies examining their correlations with neurodegenerative and neurological diseases.

In addition, this Special Issue seeks to showcase innovative applications of artificial intelligence (AI) and machine learning in psychiatric research, including predictive modeling, biomarker discovery, and personalized treatment strategies. Studies employing animal experiments to elucidate disease mechanisms, therapeutic responses, or novel intervention strategies are highly encouraged. Genetic studies that uncover risk factors, molecular mechanisms, and potential therapeutic targets are also of great interest. We especially welcome translational medicine research that bridges experimental findings to clinical applications, aiming to accelerate the development of effective treatments. Multimodal approaches integrating neuroimaging, genomics, clinical data, and computational methods will be of particular interest.

By gathering diverse methodologies and interdisciplinary perspectives, this Special Issue aims to advance our understanding of psychiatric disorders and open new avenues for early diagnosis, intervention, and personalized care. We invite researchers from psychiatry, neuroscience, bioinformatics, genetics, translational medicine, and personalized medicine to contribute original research articles, reviews, and perspectives to this timely and impactful collection.

Dr. Wen Zhang
Guest Editor

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Keywords

psychiatric disorders
artificial intelligence
predictive modeling
personalized treatment strategies
animal experiments
risk factors
multimodal approaches

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Published Papers (8 papers)

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Research

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17 pages, 1492 KB

Open AccessArticle

Antidepressant-Induced Apathy in Adolescents with a Depressive Episode While Taking Sertraline: Results of 8-Week Observational Study with Pharmacogenetic Testing for CYP2C19

by Dmitriy V. Ivashchenko, Sergey V. Grass, Vitaliy V. Sobur, Anna Y. Basova, Pavel V. Shimanov, Artem V. Shubin, Roman V. Deitch, Svetlana N. Tuchkova, Ivan N. Korsakov, Karin B. Mirzaev, Yuriy S. Shevchenko and Dmitry A. Sychev

Biomedicines 2026, 14(3), 735; https://doi.org/10.3390/biomedicines14030735 - 23 Mar 2026

Viewed by 1521

Abstract

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) scale when the antidepressant was prescribed, after one, three, and 8 weeks, taking into account other medications used. Part 3 of the ODQ scale assessed the changes that occurred after the prescription of an antidepressant. All patients were genotyped for CYP2C19*2, *3, and *17. Based on genotypes, the phenotypes of the CYP2C19 isoenzyme were determined. Results. The ODQ score at the time of enrollment was higher (65[50;79] points) compared with after 8 weeks (38.5[32.5;56.5] points). Part 3 of the ODQ-26 questionnaire remained approximately the same for 8 weeks. Patients with higher ODQ-26 values at enrollment (73[56;83] vs. 59[44;71] points) were more likely to be prescribed antipsychotics. Differences in ODQ scores remained significant up to 3 weeks after enrollment (50.5[41.5;68] vs. 45.5[36;54] points). The comparison of ODQ scores and their dynamics did not show significant differences depending on CYP2C19*2 or *17 polymorphisms, or the type of CYP2C19 metabolism. Conclusions. There was no increase in emotional blunting according to the ODQ score among adolescents with depression who took sertraline for eight weeks. No significant correlations were found between the carrier status of CYP2C19 gene variants and the development of apathy induced by antidepressants. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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16 pages, 2910 KB

Open AccessArticle

Individualized DTI-ALPS Identifies Phase-Specific Glymphatic Dysfunction in Early-Stage Bipolar Disorder

by Xiaoxi Zhao, Mingli Li, Qiang Wang, Lihong Deng, Liansheng Zhao, Hua Yu, Xiaojing Li, Wei Deng, Wanjun Guo, Tao Li and Wei Wei

Biomedicines 2026, 14(3), 699; https://doi.org/10.3390/biomedicines14030699 - 17 Mar 2026

Cited by 1 | Viewed by 824

Abstract

Background: The glymphatic system, essential for brain waste clearance and neuroimmune regulation, remains underexplored in the context of bipolar disorder (BD) among young populations. Methods: Using diffusion tensor image analysis along the perivascular space (DTI-ALPS), we compared ALPS indices derived from the conventional FSL-based (cFSL) pipeline with those from the individualized ALPS (iALPS) pipeline. A cohort of young adults comprising 77 individuals with BD and 289 healthy controls was analyzed to evaluate methodological consistency and to identify disorder-specific alterations in glymphatic function. Results: The two pipelines showed only moderate agreement (Lin’s concordance correlation coefficient = 0.52–0.60), suggesting that differences in ROI placement strategies significantly affect ALPS estimation. While the cFSL pipeline detected no group differences, the iALPS pipeline identified a trend-level reduction in ALPS index in patients with BD during depressive episodes, particularly in the right hemisphere (p = 0.036, uncorrected, FDR-adjusted p = 0.071). No significant glymphatic alterations were observed in individuals with early-stage BD. Conclusions: These findings suggest that glymphatic dysfunction in psychiatric disorders may be phase-specific on illness. The use of individualized and automated analytical strategies, such as the iALPS pipeline, appears to enhance sensitivity to subtle, state-related brain changes that conventional methods may overlook. This methodological advancement provides a more biologically informed framework for future large-scale and longitudinal studies aimed at elucidating the role of glymphatic function in the pathophysiology of psychiatric disorders. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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22 pages, 4931 KB

Open AccessArticle

Magnesium Transporter SLC41A1 Links Magnesium Homeostasis to NMDA Receptor-Related Synaptic Dysfunction: A Transdiagnostic Therapeutic Target for Neuropsychiatric Disorders

by Xinru Chen, Wenhao Deng, Xinrui Chen and Yang Yu

Biomedicines 2026, 14(3), 610; https://doi.org/10.3390/biomedicines14030610 - 9 Mar 2026

Viewed by 769

Abstract

Background: Neuropsychiatric disorders such as Alzheimer’s disease (AD), bipolar disorder (BD), and depression exhibit shared glutamatergic abnormalities, although their upstream molecular mechanisms remain poorly defined. Magnesium (Mg²⁺) serves as a key regulator of N-methyl-D-aspartate (NMDA) receptor function; however, the role of Mg²⁺ transporters, particularly SLC41A1, has not been systematically investigated. As NMDA receptor dysregulation contributes to emotional and cognitive impairments, elucidating Mg²⁺-NMDA signaling may enable the development of novel therapeutic strategies. Methods: We integrated Mendelian randomization, locus colocalization, human brain transcriptomics, functional enrichment, and co-expression analyses to determine whether SLC41A1 functions as a cross-disorder molecular driver. In addition, in vitro electrophysiological experiments using field potential recordings in hippocampal Schaffer-CA1 synapses were conducted to validate its functional role in NMDA receptor-mediated synaptic transmission. Results: Genetically elevated SLC41A1 expression increased the risk of AD, BD, depression, and alcohol dependence, with strong colocalization analyses supporting shared causal variants. Transcriptomic profiling revealed SLC41A1 upregulation in AD and BD, with enrichment in magnesium transport, mitochondrial function, and synaptic signaling pathways. Co-expression networks across GTEx brain regions demonstrated strong correlations with NMDA-related genes (e.g., GRINA, CAMK2G, GRIN2C). Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. Conclusions: This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg²⁺ homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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19 pages, 2458 KB

Open AccessArticle

Maresin-1 Ameliorates Chronic Unpredictable Stress-Induced Depressive-like Behaviors Associated with Dynamic Modulation of Hippocampal Microglial Activity and TSPO PET Signals

by Anhai Zheng, Tian Qiu, Lei Shi, Lixia Wang, Zhu Xia, Zhiping Peng, Li Kuang and Jiamei Guo

Biomedicines 2026, 14(2), 335; https://doi.org/10.3390/biomedicines14020335 - 31 Jan 2026

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Abstract

Background/Objectives: Maresin-1 (MaR1), a specialized pro-resolving mediator (SPM) derived from omega-3 fatty acids, has demonstrated potent anti-inflammatory and pro-resolving properties. However, its effects on depression-like behaviors and the associated dynamics of neuroinflammation, particularly in the context of chronic stress, are not yet fully understood. This study aimed to investigate the therapeutic potential of MaR1 in a chronic unpredictable stress (CUS) model and to monitor its dynamic effects on neuroimmune activity using longitudinal in vivo imaging. Methods: Adolescent male C57BL/6J mice were subjected to a 5-week CUS protocol. Mice exhibiting stable anhedonia were randomized to receive intraperitoneal injections of either MaR1 (5 µg/kg) or vehicle every other day for 4 weeks. During this period, CUS procedures were maintained. Depression-like behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and open field test (OFT). Dynamic changes in neuroinflammation were monitored via longitudinal [18F]DPA-714 positron emission tomography (PET) scans at baseline and after 2 and 4 weeks of treatment. Ex vivo analyses included immunofluorescence quantification of hippocampal microglia (ionized calcium-binding adaptor molecule 1, Iba1), astrocytes (glial fibrillary acidic protein, GFAP), and 18 kDa translocator protein (TSPO) co-expression, alongside quantitative polymerase chain reaction (qPCR) and Western blotting for inflammatory markers (IL-1β, IL-4, TSPO). Results: MaR1 treatment selectively alleviated depression-like behaviors, significantly reversing CUS-induced anhedonia in the SPT and improving locomotor activity, while its effect on despair-like behavior (TST) was not statistically significant. Longitudinal PET imaging revealed a biphasic neuroimmune response, characterized by an initial increase in [18F]DPA-714 standardized uptake value (SUV) at 2 weeks, followed by a return toward baseline at 4 weeks. Histologically, MaR1 reversed CUS-induced hippocampal microglial loss, resulting in a rebound of microglial numbers, and normalized astrocytic activation. At the molecular level, MaR1 dynamically modulated cytokine expression, culminating in a significant upregulation of the pro-resolving marker IL-4 and TSPO at 4 weeks. Conclusions: These findings indicate that Maresin-1 treatment is associated with behavioral improvement and dynamic modulation of glial activity and TSPO PET signals in the hippocampus. This study highlights the value of TSPO PET imaging for monitoring dynamic glial changes during therapeutic intervention and provides supportive evidence for targeting neuroimmune pathways in depression. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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12 pages, 24620 KB

Open AccessArticle

Impact of Post-Traumatic Stress Disorder Management Through Reconsolidation Therapy on Fibromyalgia Syndrome: A Pilot Study

by Ghina Harika Germaneau, Delphine Rannou, Elodie Charrier, Yassir El Fairouqi, Alain Brunet, Damien Doolub, Nicolas Langbour, Isabelle Raviart, Issa Wassouf and Nemat Jaafari

Biomedicines 2026, 14(1), 190; https://doi.org/10.3390/biomedicines14010190 - 15 Jan 2026

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Abstract

Background: Fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD) may co-occur and are associated with increased symptom burden, functional impairment, and reduced quality of life. Accumulating evidence suggests shared neurobiological mechanisms. Trauma-focused interventions targeting maladaptive memory processes may therefore represent a relevant therapeutic approach in this population. Objective: To evaluate the feasibility, tolerability, and preliminary clinical associations of a brief reconsolidation-based therapy in women with comorbid FMS and PTSD. Methods: This multicenter pilot study included adult women diagnosed with FMS and PTSD who underwent six sessions of reconsolidation therapy combining traumatic memory reactivation with propranolol administration. Clinical outcomes were assessed at baseline and at 3-month follow-up using the Fibromyalgia Impact Questionnaire (FIQ), the Impact of Event Scale–Revised (IES-R), the Montgomery–Åsberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI), the Rosenberg Self-Esteem Scale (RSES), and the SF-36. Changes over time were analyzed using paired statistical tests and linear mixed-effects models. Results: Fourteen participants completed the intervention and follow-up assessments. The intervention was feasible and well tolerated. Changes over time were observed in fibromyalgia-related quality of life (FIQ scores), PTSD symptom severity (IES-R), and depressive symptoms (MADRS, BDI), as well as in selected SF-36 domains, including vitality, social functioning, and mental health. A progressive decrease in IES-R scores was observed across treatment sessions. Conclusions: This pilot study suggests that reconsolidation-based therapy is feasible in women with comorbid FMS and PTSD and was associated with changes in PTSD symptoms and fibromyalgia-related functional impact. Given the exploratory design and absence of a control group, these findings should be interpreted cautiously and warrant confirmation in larger, controlled trials. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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13 pages, 1540 KB

Open AccessArticle

Nonlinear Adaptive Control of Bipolar Mood Disorder: A New Approach for Quenching the Mood Swing

by Ugur Hasirci

Biomedicines 2025, 13(12), 3090; https://doi.org/10.3390/biomedicines13123090 - 15 Dec 2025

Viewed by 674

Abstract

Background/Objectives: Mood disorders are described by marked disruptions in emotions. Generally speaking, mood disorders are classified into two main categories: unipolar mood disorder, also known as unipolar depression, and bipolar mood disorder, also called manic-depressive illness. It is estimated that 40 million people live with bipolar disorder worldwide. Mathematical modeling of the dynamics of bipolar disorder may help to both better understand and treat the illness. This is especially important for bipolar disorder since, unlike unipolar disorder, there is an oscillation to be quenched between hypomanic and depressive episodes. Methods: By using a nonlinear dynamical model of bipolar disorder, this study offers two different control (treatment) approaches for the disorder. The first one is a nonlinear exact model knowledge controller assuming that all the parameters of the patient model are known. The second one is a nonlinear adaptive controller assuming that all the parameters are unknown. Results: Both controllers aim to drive both emotional mood and the change rate to a stable state. The Backstepping Technique is utilized as a nonlinear controller design tool. For both controllers, Lyapunov-type arguments are used to design the controller and to prove the stability of the designed controllers. Numerical simulation results are also provided to show the performance and feasibility of the proposed controllers. Conclusions: It has been shown that a nonlinear controller is capable of driving the emotional mood to its equilibrium point, zero, by quenching the mood swing. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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Review

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37 pages, 1592 KB

Open AccessReview

Microbiome-Informed Precision Electroconvulsive Therapy: Oral–Gut–Immune Signatures and Seizure Biology as Candidate Predictors of Response—A Narrative Review

by Bernard Rybczynski, Maciej Maslyk, Michal Pruc, Monika Janeczko, Iwona Niewiadomska and Lukasz Szarpak

Biomedicines 2026, 14(7), 1467; https://doi.org/10.3390/biomedicines14071467 - 28 Jun 2026

Viewed by 225

Abstract

Background/Objectives: Electroconvulsive therapy (ECT) is among the most effective treatments for severe major depression, treatment-resistant depression, psychotic and bipolar depression, catatonia, and selected psychotic disorders. Yet response, remission, seizure adequacy, and cognitive tolerability remain difficult to predict for an individual patient. This review examines whether oral and gut microbial signatures can inform precision ECT as contextual biological markers, rather than as standalone explanations of ECT efficacy. Methods: A structured narrative PubMed/MEDLINE search was conducted on 1 May 2026 and supplemented by targeted manual searches of Crossref, Google Scholar, journal websites, and reference lists updated through 17 May 2026. Evidence was grouped as direct human ECT–microbiome studies, indirect human ECT biomarker studies, preclinical electroconvulsive shock (ECS) studies, and mechanistic microbiome–gut–brain literature. Results: Direct human ECT–microbiome evidence remains very limited and currently consists of two small prospective cohorts with sufficient microbiome data, totaling approximately 25 patients across studies, plus one single-patient case report. In severe or treatment-resistant depression, a pilot oral microbiome study with sufficient microbiological data from 14 patients reported higher pre-treatment oral alpha diversity in responders than in non-responders, without a consistent global oral microbiome shift after ECT. In schizophrenia, a small stool microbiome cohort of 11 patients suggested that baseline Bifidobacterium and Lactobacillus proportions may relate to symptom improvement, although sample size and confounding preclude firm inference. Conclusions: Microbiome-informed precision ECT remains a biologically plausible research direction, but current human evidence supports only cautious evaluation of baseline microbial context as a candidate predictor, not clinical microbiome-guided ECT, mediation, or microbiome-modifying intervention. The strongest current biological bridge comes from inflammatory markers, particularly baseline CRP and IL-6. Preclinical ECS studies support gut inflammatory, motility and vagal mechanisms, but they cannot substitute for human validation. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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Other

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9 pages, 1171 KB

Open AccessPerspective

Is Cerebrolysin Useful in Psychiatry Disorders?

by Szymon Florek, Patryk Główczyński, Karina Badura-Brzoza and Robert Pudlo

Biomedicines 2025, 13(7), 1661; https://doi.org/10.3390/biomedicines13071661 - 8 Jul 2025

Viewed by 11579

Abstract

Background/Objectives: Cerebrolysin is a well-known mixture of peptides that has been used for many years, primarily in patients with neurological disorders. Thanks to its unique properties, this substance supports endogenous repair mechanisms and protects the brain from damaging factors. Cerebrolysin is most widely used in Eastern European countries. However, data on the potential use of cerebrolysin in mental disorders are difficult to find in the literature. This review focuses on the potential use of cerebrolysin in psychiatry, and two independent researchers searched three full-text medical article databases to compile it. Methods: To conduct this scoping review, two independent researchers searched three full-text article databases, Embase, Scopus, and Web of Science, by entering the following phrases: “cerebrolysin psychiatry”, “cerebrolysin depression”, “cerebrolysin mood”, “cerebrolysin bipolar”, “cerebrolysin schizophrenia”, and “cerebrolysin addiction”. Results: The results show that this specific substance could have a relatively small application in psychiatry. Conclusions: The limited amount of available research on the use of cerebrolysin suggests that it may have some significance in supporting the treatment of depression and autism spectrum disorders and alleviating adverse effects during treatment with neuroleptics. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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