Bipolar Disorder in the Era of Precision Psychiatry: Biomarkers, Digital Innovations, and Global Challenges

Authors

  • Amar Saxena Student, Department of Pharmacy, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, INDIA. https://orcid.org/0009-0006-3593-6927
  • Shrestha Saxena Student, Department of Arts, Lalit Kala Sansthan, Agra, Uttar Pradesh, INDIA
  • Yash Saxena Student, Department of Pharmacy, Anand College of Pharmacy, Agra, Uttar Pradesh, INDIA
  • Ashita Jain Assistant Professor, Faculty of Pharmacy, Sharda School of Pharmacy, Sharda University, Agra Uttar Pradesh, INDIA
  • Prabhat Goyal Assistant Professor, Faculty of Pharmacy, College of Pharmacy, Agra, Uttar Pradesh, INDIA
  • Ankit Kumar Dean & Head of Faculty of Pharmacy, Agrawan Heritage University, Agra, Uttar Pradesh, INDIA
  • Shivdeep Mishra Assistant Professor, Faculty of Pharmacy, College of Pharmacy, Agra, Uttar Pradesh, INDIA
  • Sanjeev Kumar Assistant Professor, Faculty of Pharmacy, Agrawan Heritage University, Agra, Uttar Pradesh, INDIA

DOI:

https://doi.org/10.55544/jrasb.4.5.1

Keywords:

Bipolar Disorder, Comorbidity, Biomarkers, Digital Psychiatry, Precision Medicine, Chronotherapy, Global Mental Health, Therapeutic Innovation

Abstract

Bipolar disorder (BD) is a severe, recurrent psychiatric illness characterized by episodes of mania, hypomania, and depression, with profound consequences for individuals, families, and societies. Affecting an estimated 1–2% of the global population, BD ranks among the top contributors to years lived with disability and premature mortality. High suicide risk, cognitive impairment, and substantial functional disability compound its impact, while comorbid conditions such as anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and substance use disorders amplify diagnostic challenges and worsen prognosis. Diagnostic delay—often 6–10 years from illness onset—remains a major barrier, reflecting overlapping transdiagnostic symptoms and the absence of reliable biomarkers in routine clinical use. Over the past decade, advances in neuroscience and translational psychiatry have begun to reshape the landscape of BD research and care. A growing body of evidence implicates dysregulated circadian rhythms, immune-inflammatory pathways, mitochondrial dysfunction, and polygenic liability as key drivers of illness course. These insights are now converging with precision psychiatry initiatives that aim to integrate genomic, neuroimaging, and peripheral biomarker data into individualized treatment strategies. In parallel, the rapid growth of digital psychiatry and artificial intelligence–enabled tools provides unprecedented opportunities for real-time mood monitoring, early relapse detection, and personalized intervention delivery. Importantly, these technologies may bridge long-standing gaps in access to care, although concerns around privacy, equity, and algorithmic bias must be addressed. Therapeutic innovation has also accelerated, with evidence supporting the adjunctive use of anti-inflammatory and neuroprotective agents, alongside chronotherapeutic approaches that target circadian instability. These interventions complement, rather than replace, existing pharmacological and psychotherapeutic frameworks, reflecting a shift toward multimodal and mechanism-informed treatment paradigms. At a systems level, global mental health perspectives highlight persistent disparities in diagnosis and treatment, particularly in low- and middle-income countries where the treatment gap exceeds 70%. Policy reforms, equitable digital infrastructure, and culturally tailored care models will be essential to ensure that advances in precision psychiatry and therapeutics are accessible worldwide. This review synthesizes emerging insights across biological, clinical, technological, and policy domains, highlighting both achievements and unmet needs in BD research and care. By emphasizing biomarkers, digital psychiatry, novel therapeutics, and global health imperatives, it outlines a roadmap for translating discovery into improved outcomes, ultimately moving toward individualized, equitable, and sustainable care for those living with bipolar disorder.

Downloads

Download data is not yet available.

References

A. S. Clemente et al., “Bipolar disorder prevalence: a systematic review and meta-analysis of the literature.,” Rev. Bras. Psiquiatr., vol. 37, no. 2, pp. 155–61, 2015, doi: 10.1590/1516-4446-2012-1693.

GBD 2019 Mental Disorders Collaborators, “Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.,” The lancet. Psychiatry, vol. 9, no. 2, pp. 137–150, Feb. 2022, doi: 10.1016/S2215-0366(21)00395-3.

T. B. Biazus et al., “All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis.,” Mol. Psychiatry, vol. 28, no. 6, pp. 2508–2524, Jun. 2023, doi: 10.1038/s41380-023-02109-9.

E. Brohan, D. Gauci, N. Sartorius, G. Thornicroft, and GAMIAN-Europe Study Group, “Self-stigma, empowerment and perceived discrimination among people with bipolar disorder or depression in 13 European countries: the GAMIAN-Europe study.,” J. Affect. Disord., vol. 129, no. 1–3, pp. 56–63, Mar. 2011, doi: 10.1016/j.jad.2010.09.001.

R. M. A. Hirschfeld, L. Lewis, and L. A. Vornik, “Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder.,” J. Clin. Psychiatry, vol. 64, no. 2, pp. 161–74, Feb. 2003, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/12633125

R. C. Kessler and E. J. Bromet, “The epidemiology of depression across cultures.,” Annu. Rev. Public Health, vol. 34, pp. 119–38, 2013, doi: 10.1146/annurev-publhealth-031912-114409.

I. Grande, M. Berk, B. Birmaher, and E. Vieta, “Bipolar disorder.,” Lancet (London, England), vol. 387, no. 10027, pp. 1561–1572, Apr. 2016, doi: 10.1016/S0140-6736(15)00241-X.

S. Tian, N. Sinclair, and S. Shah, “A Case Report of Intravascular Hemolysis and Heme Pigment-Induced Nephropathy Following AngioJet Thrombectomy for Thrombosed DIPS Shunt.,” Can. J. kidney Heal. Dis., vol. 7, p. 2054358120979233, 2020, doi: 10.1177/2054358120979233.

A. A. Nierenberg et al., “Diagnosis and Treatment of Bipolar Disorder: A Review.,” JAMA, vol. 330, no. 14, pp. 1370–1380, Oct. 2023, doi: 10.1001/jama.2023.18588.

P. Kumar, A. Satyam, D. Cigognini, A. Pandit, and D. I. Zeugolis, “Low oxygen tension and macromolecular crowding accelerate extracellular matrix deposition in human corneal fibroblast culture.,” J. Tissue Eng. Regen. Med., vol. 12, no. 1, pp. 6–18, Jan. 2018, doi: 10.1002/term.2283.

R. Segal, D. M. Angaran, F. T. Odedina, M. L. Zeigler, and J. L. Wallace, “Opportunities and responsibilities for pharmacists to improve their effectiveness in addressing medication adherence through culturally sensitive collaborations with community health workers.,” J. Am. Pharm. Assoc. (2003)., vol. 60, no. 4, pp. e25–e30, 2020, doi: 10.1016/j.japh.2020.02.023.

L. A. Short and M. C. Wagler, “Social Categories Alone Are Insufficient to Elicit an In-Group Advantage in Perceptions of Within-Person Variability.,” Perception, vol. 46, no. 8, pp. 929–940, Aug. 2017, doi: 10.1177/0301006617699226.

J. Wei et al., “Low-cost and efficient confocal imaging method for arabidopsis flower.,” Dev. Biol., vol. 466, no. 1–2, pp. 73–76, Oct. 2020, doi: 10.1016/j.ydbio.2020.07.012.

V. Nagendrababu, S. J. Pulikkotil, O. S. Sultan, J. Jayaraman, and O. A. Peters, “Methodological and Reporting Quality of Systematic Reviews and Meta-analyses in Endodontics.,” J. Endod., vol. 44, no. 6, pp. 903–913, Jun. 2018, doi: 10.1016/j.joen.2018.02.013.

S. W. Choo et al., “A collective statement in support of saving pangolins.,” Sci. Total Environ., vol. 824, p. 153666, Jun. 2022, doi: 10.1016/j.scitotenv.2022.153666.

J.-D. Karam, N. Noel, A.-L. Voisin, E. Lanoy, J.-M. Michot, and O. Lambotte, “Infectious complications in patients treated with immune checkpoint inhibitors.,” Eur. J. Cancer, vol. 141, pp. 137–142, Dec. 2020, doi: 10.1016/j.ejca.2020.09.025.

N. El Jurdi et al., “Gastrointestinal Microbiome and Mycobiome Changes during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study.,” Biol. Blood Marrow Transplant., vol. 25, no. 8, pp. 1511–1519, Aug. 2019, doi: 10.1016/j.bbmt.2019.04.007.

A. Overwater et al., “Extension of early esophageal squamous cell neoplasia into ducts and submucosal glands and the role of endoscopic ablation therapy.,” Gastrointest. Endosc., vol. 94, no. 4, pp. 832-842.e2, Oct. 2021, doi: 10.1016/j.gie.2021.04.028.

H.-Y. Li, Y.-B. Wang, X.-Y. Ren, J. Wang, H.-S. Wang, and Y.-H. Jin, “Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis.,” Pharmacology, vol. 108, no. 2, pp. 111–126, 2023, doi: 10.1159/000527668.

D. S. Freedman, A. B. Goodman, R. J. King, and C. Daymont, “The Longitudinal Relation of Childhood Height to Subsequent Obesity in a Large Electronic Health Record Database.,” Obesity (Silver Spring)., vol. 28, no. 9, pp. 1742–1749, Sep. 2020, doi: 10.1002/oby.22901.

L. Athlani, M.-C. Sapa, Y.-K. De Almeida, M. Braun, and G. Dautel, “A new capsulotomy-based dorsal approach to the wrist: A cadaver study.,” Hand Surg. Rehabil., vol. 40, no. 2, pp. 134–138, Apr. 2021, doi: 10.1016/j.hansur.2020.10.015.

T. Tayri-Wilk et al., “Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins.,” Nat. Commun., vol. 11, no. 1, p. 3128, Jun. 2020, doi: 10.1038/s41467-020-16935-w.

H. Zuo et al., “[Genetic analysis of a Chinese pedigree affected with Mucopolysaccharidosis type ⅢA].,” Zhonghua Yi Xue Yi Chuan Xue Za Zhi, vol. 40, no. 4, pp. 452–457, Apr. 2023, doi: 10.3760/cma.j.cn511374-20221107-00766.

M. Apiyo et al., “Clinical Characteristics and Outcomes of Patients Hospitalized with COVID-19 at Case Hospital, Uganda.,” Interdiscip. Perspect. Infect. Dis., vol. 2022, p. 5477790, 2022, doi: 10.1155/2022/5477790.

M. Vidailhet, A. Méneret, and E. Roze, “Dystonia: genetics, phenomenology, and pathophysiology,” Lancet Neurol., vol. 19, no. 11, pp. 881–882, Nov. 2020, doi: 10.1016/S1474-4422(20)30366-5.

M. Yan, S. R. Cantwell, M. Mason, S. Mardini, K. Bakri, and C. A. Harless, “Impact of COVID-19 on a plastic surgery residency education program: Outcomes of a survey.,” J. Plast. Reconstr. Aesthet. Surg., vol. 74, no. 3, pp. 644–710, Mar. 2021, doi: 10.1016/j.bjps.2020.10.026.

V. Domingues, “Treasure-hunting bees.,” Nat. Ecol. Evol., vol. 5, no. 12, p. 1564, Dec. 2021, doi: 10.1038/s41559-021-01585-y.

J. Li et al., “Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial.,” J. Obstet. Gynaecol. Res., vol. 47, no. 3, pp. 1145–1152, Mar. 2021, doi: 10.1111/jog.14650.

C. G. Mackworth-Young, J. K. Chan, C. C. Bunn, G. R. Hughes, and A. E. Gharavi, “Complement fixation by anti-dsDNA antibodies in SLE: measurement by radioimmunoassay and relationship with disease activity.,” Ann. Rheum. Dis., vol. 45, no. 4, pp. 314–8, Apr. 1986, doi: 10.1136/ard.45.4.314.

A. C. Viguera, L. Tondo, A. E. Koukopoulos, D. Reginaldi, B. Lepri, and R. J. Baldessarini, “Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods,” Am. J. Psychiatry, vol. 168, no. 11, pp. 1179–1185, Nov. 2011, doi: 10.1176/appi.ajp.2011.11010148.

F.-C. Zhu et al., “Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.,” Lancet (London, England), vol. 395, no. 10240, pp. 1845–1854, Jun. 2020, doi: 10.1016/S0140-6736(20)31208-3.

H. He, C. Hu, Z. Ren, L. Bai, F. Gao, and J. Lyu, “Trends in the incidence and DALYs of bipolar disorder at global, regional, and national levels: Results from the global burden of Disease Study 2017.,” J. Psychiatr. Res., vol. 125, pp. 96–105, Jun. 2020, doi: 10.1016/j.jpsychires.2020.03.015.

A. Aydogdu, C. J. Radke, S. Bezci, and E. Kirtil, “Characterization of curcumin incorporated guar gum/orange oil antimicrobial emulsion films.,” Int. J. Biol. Macromol., vol. 148, pp. 110–120, Apr. 2020, doi: 10.1016/j.ijbiomac.2019.12.255.

K. Grell et al., “The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study.,” Am. J. Epidemiol., vol. 184, no. 11, pp. 818–828, Dec. 2016, doi: 10.1093/aje/kww082.

H. Yapici Eser, A. S. Kacar, C. M. Kilciksiz, M. Yalçinay-Inan, and D. Ongur, “Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study.,” Front. psychiatry, vol. 9, p. 229, 2018, doi: 10.3389/fpsyt.2018.00229.

E. Koutroumpakis et al., “Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases.,” Am. J. Gastroenterol., vol. 110, no. 12, pp. 1707–16, Dec. 2015, doi: 10.1038/ajg.2015.370.

M. Povedano, M. Saez, J.-A. Martínez-Matos, and M. A. Barceló, “Spatial Assessment of the Association between Long-Term Exposure to Environmental Factors and the Occurrence of Amyotrophic Lateral Sclerosis in Catalonia, Spain: A Population-Based Nested Case-Control Study.,” Neuroepidemiology, vol. 51, no. 1–2, pp. 33–49, 2018, doi: 10.1159/000489664.

G. Liuzzo and C. Patrono, “COVID 19: in the eye of the cytokine storm.,” Eur. Heart J., vol. 42, no. 2, pp. 150–151, Jan. 2021, doi: 10.1093/eurheartj/ehaa1005.

M. Mukaino et al., “An Affordable, User-friendly Telerehabilitation System Assembled Using Existing Technologies for Individuals Isolated With COVID-19: Development and Feasibility Study.,” JMIR Rehabil. Assist. Technol., vol. 7, no. 2, p. e24960, Dec. 2020, doi: 10.2196/24960.

V. Spelling and M. Stefansson, “Evaluation of chromatographic parameters in supercritical fluid chromatography of amino acids as model polar analytes and extended to polypeptide separations.,” J. Chromatogr. A, vol. 1633, p. 461646, Dec. 2020, doi: 10.1016/j.chroma.2020.461646.

H. Gandomkar, H. Mahmoodzadeh, H. Tavakoli, M. Fazeli, and J. Rezaei, “Garlic-induced esophageal perforation: A case series.,” Asian J. Surg., vol. 43, no. 6, pp. 696–697, Jun. 2020, doi: 10.1016/j.asjsur.2020.01.002.

R. T. Lewinson et al., “Machine learning for prediction of cutaneous adverse events in patients receiving anti-PD-1 immunotherapy.,” J. Am. Acad. Dermatol., vol. 84, no. 1, pp. 183–185, Jan. 2021, doi: 10.1016/j.jaad.2020.04.069.

P. A. C. Wing et al., “Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter.,” J. Hepatol., vol. 75, no. 1, pp. 64–73, Jul. 2021, doi: 10.1016/j.jhep.2020.12.034.

S. Laureti, A. Gerardino, F. D’Acapito, D. Peddis, and G. Varvaro, “The role of chemical and microstructural inhomogeneities on interface magnetism.,” Nanotechnology, vol. 32, no. 20, p. 205701, May 2021, doi: 10.1088/1361-6528/abe260.

W. E. M. van Dijk, O. N. Brandwijk, K. M. J. Heitink-Polle, R. E. G. Schutgens, K. P. M. van Galen, and R. T. Urbanus, “Hemostatic changes by thrombopoietin-receptor agonists in immune thrombocytopenia patients.,” Blood Rev., vol. 47, p. 100774, May 2021, doi: 10.1016/j.blre.2020.100774.

N. Hiebert, T. Carrau, M. Bartling, A. Vilcinskas, and K.-Z. Lee, “Identification of entomopathogenic bacteria associated with the invasive pest Drosophila suzukii in infested areas of Germany.,” J. Invertebr. Pathol., vol. 173, p. 107389, Jun. 2020, doi: 10.1016/j.jip.2020.107389.

Q. Zhang, Y. Zhou, Y. Li, B. Ali, and Z. Zhu, “Functional characterization of Kid-Kis and MazF-MazE in Sf9 cells and Mythimna separata embryos.,” Pestic. Biochem. Physiol., vol. 174, p. 104814, May 2021, doi: 10.1016/j.pestbp.2021.104814.

X. Wang et al., “Photo-thermo catalytic selective oxidation of cyclohexane by In-situ prepared nonstoichiometric Molybdenum oxide and Silver-palladium alloy composite.,” J. Colloid Interface Sci., vol. 607, no. Pt 2, pp. 954–966, Feb. 2022, doi: 10.1016/j.jcis.2021.09.058.

M. Guiotto, P. G. di Summa, G. Argentino, and M. Cherubino, “The proximal ulnar perforator flap (PUPF) for hand digital reconstruction: an anatomical study.,” J. Plast. Surg. Hand Surg., vol. 55, no. 4, pp. 255–259, Aug. 2021, doi: 10.1080/2000656X.2021.1873793.

E. de Los Reyes et al., “Intracerebroventricular Cerliponase Alfa for Neuronal Ceroid Lipofuscinosis Type 2 Disease: Clinical Practice Considerations From US Clinics.,” Pediatr. Neurol., vol. 110, pp. 64–70, Sep. 2020, doi: 10.1016/j.pediatrneurol.2020.04.018.

G. Li, S. Zhao, S. Wang, Y. Sun, Y. Zhou, and X. Pan, “A 7-year surveillance of the drug resistance in Klebsiella pneumoniae from a primary health care center.,” Ann. Clin. Microbiol. Antimicrob., vol. 18, no. 1, p. 34, Nov. 2019, doi: 10.1186/s12941-019-0335-8.

J. Zhang et al., “Alterations in mitochondrial dynamics with age-related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility.,” Aging Cell, vol. 20, no. 7, p. e13419, Jul. 2021, doi: 10.1111/acel.13419.

S.-H. Lee et al., “An isotropic EPI database and analytical pipelines for rat brain resting-state fMRI.,” Neuroimage, vol. 243, p. 118541, Nov. 2021, doi: 10.1016/j.neuroimage.2021.118541.

V. Vacharathit, R. M. Walsh, J. Utech, and S. H. Asfaw, “Action in Healthcare Sustainability is a Surgical Imperative: This is a Novel Way to Do It.,” J. Surg. Educ., vol. 79, no. 2, pp. 275–278, 2022, doi: 10.1016/j.jsurg.2021.09.002.

S. J. Wu et al., “The Prevalence of Elevated Alanine Aminotransferase Levels Meeting Clinical Action Thresholds in Children with Obesity in Primary Care Practice.,” J. Pediatr., vol. 240, pp. 280–283, Jan. 2022, doi: 10.1016/j.jpeds.2021.09.033.

A. Coelho, J. Peixoto, A. Canedo, L. J. Kappelle, A. Mansilha, and G. J. de Borst, “Critical analysis of the literature and standards of reporting on stroke after carotid revascularization.,” J. Vasc. Surg., vol. 75, no. 1, pp. 363-371.e2, Jan. 2022, doi: 10.1016/j.jvs.2021.05.055.

T. M. Bateman, “Reducing Radiation While Improving the Quality and Efficiency of Nuclear Cardiology Procedures.,” JACC. Cardiovasc. Imaging, vol. 14, no. 9, pp. 1829–1831, Sep. 2021, doi: 10.1016/j.jcmg.2021.05.001.

G.-X. Ruan, E. Barry, D. Yu, M. Lukason, S. H. Cheng, and A. Scaria, “CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10.,” Mol. Ther., vol. 25, no. 2, pp. 331–341, Feb. 2017, doi: 10.1016/j.ymthe.2016.12.006.

N. D. Woodward et al., “Correlation of individual differences in schizotypal personality traits with amphetamine-induced dopamine release in striatal and extrastriatal brain regions.,” Am. J. Psychiatry, vol. 168, no. 4, pp. 418–26, Apr. 2011, doi: 10.1176/appi.ajp.2010.10020165.

X. Lu, X. Feng, X. Li, and J. Zhao, “The adsorption properties of endoglucanase to lignin and their impact on hydrolysis.,” Bioresour. Technol., vol. 267, pp. 110–116, Nov. 2018, doi: 10.1016/j.biortech.2018.06.031.

A. Singh, J. Bajpai, A. Tiwari, and A. K. Bajpai, “Designing casein-coated iron oxide nanostructures (CCIONPs) as superparamagnetic core-shell carriers for magnetic drug targeting.,” Prog. Biomater., vol. 4, no. 1, pp. 39–53, Mar. 2015, doi: 10.1007/s40204-014-0035-6.

M.-M. Zhang, Y.-H. Ma, P. Li, Y. Jia, and K.-L. Han, “Detection of atherosclerosis-related hypochlorous acid produced in foam cells with a localized endoplasmic reticulum probe.,” Chem. Commun. (Camb)., vol. 56, no. 17, pp. 2610–2613, Feb. 2020, doi: 10.1039/d0cc00090f.

C. Cuerva, J. A. Campo, P. Ovejero, M. R. Torres, and M. Cano, “Polycatenar pyrazole and pyrazolate ligands as building blocks of new columnar Pd(II) metallomesogens.,” Dalton Trans., vol. 43, no. 23, pp. 8849–60, Jun. 2014, doi: 10.1039/c4dt00369a.

I. L. Holster, V. E. Valkhoff, and E. T. T. L. Tjwa, “Reply: To PMID 23470618.,” Gastroenterology, vol. 145, no. 5, p. 1164, Nov. 2013, doi: 10.1053/j.gastro.2013.09.042.

A. C. Tonon, A. Nexha, M. Mendonça da Silva, F. A. Gomes, M. P. Hidalgo, and B. N. Frey, “Sleep and circadian disruption in bipolar disorders: From psychopathology to digital phenotyping in clinical practice.,” Psychiatry Clin. Neurosci., vol. 78, no. 11, pp. 654–666, Nov. 2024, doi: 10.1111/pcn.13729.

Y. Takaesu, “Circadian rhythm in bipolar disorder: A review of the literature.,” Psychiatry Clin. Neurosci., vol. 72, no. 9, pp. 673–682, Sep. 2018, doi: 10.1111/pcn.12688.

M. Ribeiro, A. Lourenço, M. Lemos, J. Bastos, and J. M. Pereira, “A review: Circadian Rhythm Dysfunction and Bipolar Disorder,” Eur. Psychiatry, vol. 65, no. S1, pp. S408–S408, Jun. 2022, doi: 10.1192/j.eurpsy.2022.1035.

L. B. Alloy, T. H. Ng, M. K. Titone, and E. M. Boland, “Circadian Rhythm Dysregulation in Bipolar Spectrum Disorders,” Curr. Psychiatry Rep., vol. 19, no. 4, p. 21, Apr. 2017, doi: 10.1007/s11920-017-0772-z.

T. Roloff, I. Haussleiter, K. Meister, and G. Juckel, “Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder,” Int. J. Bipolar Disord., vol. 10, no. 1, p. 6, Dec. 2022, doi: 10.1186/s40345-022-00254-8.

A. Buchmann et al., “Associations between heart rate variability, peripheral inflammatory markers and major depressive disorder,” J. Affect. Disord., vol. 304, pp. 93–101, May 2022, doi: 10.1016/j.jad.2022.02.017.

M. J. McCarthy et al., “Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi‐disciplinary literature review and agenda for future research from the ISBD task force on chronobiology,” Bipolar Disord., vol. 24, no. 3, pp. 232–263, May 2022, doi: 10.1111/bdi.13165.

P. A. Sommers, “What physicians should know about consumer satisfaction.,” Am. J. Med. Sci., vol. 295, no. 5, pp. 415–7, May 1988, doi: 10.1097/00000441-198805000-00001.

A. L. Whittock, A. M. Cowden, M. Wills, and V. G. Stavros, “Examining the substituent effect on mycosporine-inspired ultraviolet filters.,” Phys. Chem. Chem. Phys., vol. 25, no. 10, pp. 7401–7406, Mar. 2023, doi: 10.1039/d2cp05934g.

S. Jiménez-Fernández, M. Gurpegui, D. Garrote-Rojas, L. Gutiérrez-Rojas, M. D. Carretero, and C. U. Correll, “Oxidative stress parameters and antioxidants in adults with unipolar or bipolar depression versus healthy controls: Systematic review and meta-analysis.,” J. Affect. Disord., vol. 314, pp. 211–221, Oct. 2022, doi: 10.1016/j.jad.2022.07.015.

R. T. de Sousa et al., “Oxidative stress in early stage Bipolar Disorder and the association with response to lithium.,” J. Psychiatr. Res., vol. 50, pp. 36–41, Mar. 2014, doi: 10.1016/j.jpsychires.2013.11.011.

A. Zongo, S. Simpson, J. A. Johnson, and D. T. Eurich, “Effect of a pharmacy comprehensive chronic diseases care plan on use of lipid-lowering drugs among patients with hypertension.,” J. Manag. care Spec. Pharm., vol. 27, no. 4, pp. 426–434, Apr. 2021, doi: 10.18553/jmcp.2021.27.4.426.

M. Pahuja and D. Burkhoff, “Right Ventricular Afterload Sensitivity Has Been on My Mind.,” Circ. Heart Fail., vol. 12, no. 9, p. e006345, Sep. 2019, doi: 10.1161/CIRCHEARTFAILURE.119.006345.

A. R. Van Meter, E. A. Youngstrom, and R. L. Findling, “Cyclothymic disorder: a critical review.,” Clin. Psychol. Rev., vol. 32, no. 4, pp. 229–43, Jun. 2012, doi: 10.1016/j.cpr.2012.02.001.

J. Kasckow et al., “Trajectories of suicidal ideation in depressed older adults undergoing antidepressant treatment,” J. Psychiatr. Res., vol. 73, pp. 96–101, Feb. 2016, doi: 10.1016/j.jpsychires.2015.11.004.

A. Muneer, “Mixed States in Bipolar Disorder: Etiology, Pathogenesis and Treatment.,” Chonnam Med. J., vol. 53, no. 1, pp. 1–13, Jan. 2017, doi: 10.4068/cmj.2017.53.1.1.

A. Fagiolini et al., “Diagnosis, Epidemiology and Management of Mixed States in Bipolar Disorder.,” CNS Drugs, vol. 29, no. 9, pp. 725–40, Sep. 2015, doi: 10.1007/s40263-015-0275-6.

M. Hassan, R. Elzehery, Y. M. Mosaad, M. Mostafa, I. H. R. Elkalla, and M. Elwasify, “Clinical characteristics of bipolar 1 disorder in relation to interleukin-6: a cross-sectional study among Egyptian patients,” Middle East Curr. Psychiatry, vol. 30, no. 1, p. 21, Mar. 2023, doi: 10.1186/s43045-023-00297-2.

M. Thoresen, “Combining two good treatments makes it worse,” Brain. Behav. Immun., vol. 71, pp. 7–8, Jul. 2018, doi: 10.1016/j.bbi.2018.04.008.

H. E. A. Çeli̇k, G. Tuna, D. Ceylan, and S. Küçükgöncü, “A comparative meta-analysis of peripheral 8-hydroxy-2′-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder,” Psychoneuroendocrinology, vol. 151, p. 106078, May 2023, doi: 10.1016/j.psyneuen.2023.106078.

A. Azzi, “Tocopherols, tocotrienols and tocomonoenols: Many similar molecules but only one vitamin E,” Redox Biol., vol. 26, p. 101259, Sep. 2019, doi: 10.1016/j.redox.2019.101259.

K. Coello et al., “Oxidation of DNA and RNA in young patients with newly diagnosed bipolar disorder and relatives,” Transl. Psychiatry, vol. 14, no. 1, p. 81, Feb. 2024, doi: 10.1038/s41398-024-02772-8.

D. S. Palmer et al., “Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia,” Nat. Genet., vol. 54, no. 5, pp. 541–547, May 2022, doi: 10.1038/s41588-022-01034-x.

E. A. Stahl et al., “Genome-wide association study identifies 30 loci associated with bipolar disorder,” Nat. Genet., vol. 51, no. 5, pp. 793–803, May 2019, doi: 10.1038/s41588-019-0397-8.

A. Lotan et al., “Alterations in the expression of a neurodevelopmental gene exert long-lasting effects on cognitive-emotional phenotypes and functional brain networks: translational evidence from the stress-resilient Ahi1 knockout mouse,” Mol. Psychiatry, vol. 22, no. 6, pp. 884–899, Jun. 2017, doi: 10.1038/mp.2016.29.

B. Pavlova, R. H. Perlis, M. Alda, and R. Uher, “Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis.,” The lancet. Psychiatry, vol. 2, no. 8, pp. 710–717, Aug. 2015, doi: 10.1016/S2215-0366(15)00112-1.

C. Schiweck et al., “Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis.,” Neurosci. Biobehav. Rev., vol. 124, pp. 100–123, May 2021, doi: 10.1016/j.neubiorev.2021.01.017.

H. Grunze, M. Schaefer, H. Scherk, C. Born, and U. W. Preuss, “Comorbid Bipolar and Alcohol Use Disorder—A Therapeutic Challenge,” Front. Psychiatry, vol. 12, Mar. 2021, doi: 10.3389/fpsyt.2021.660432.

T. Honjo et al., “ApoB-100-related peptide vaccine protects against angiotensin II-induced aortic aneurysm formation and rupture.,” J. Am. Coll. Cardiol., vol. 65, no. 6, pp. 546–56, Feb. 2015, doi: 10.1016/j.jacc.2014.11.054.

G. M. Slavich, “Stressnology: The primitive (and problematic) study of life stress exposure and pressing need for better measurement.,” Brain. Behav. Immun., vol. 75, pp. 3–5, Jan. 2019, doi: 10.1016/j.bbi.2018.08.011.

B. Li et al., “Sequence motifs and prediction model of GBE editing outcomes based on target library analysis and machine learning.,” J. Genet. Genomics, vol. 49, no. 3, pp. 254–257, Mar. 2022, doi: 10.1016/j.jgg.2021.11.007.

L. Hou et al., “Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.,” Hum. Mol. Genet., vol. 25, no. 15, pp. 3383–3394, Aug. 2016, doi: 10.1093/hmg/ddw181.

S. A. Viczek, K. B. Jensen, and K. A. Francesconi, “Arsenic-Containing Phosphatidylcholines: A New Group of Arsenolipids Discovered in Herring Caviar.,” Angew. Chem. Int. Ed. Engl., vol. 55, no. 17, pp. 5259–62, Apr. 2016, doi: 10.1002/anie.201512031.

I. Arrazola, J. S. Pedernales, L. Lamata, and E. Solano, “Digital-Analog Quantum Simulation of Spin Models in Trapped Ions.,” Sci. Rep., vol. 6, p. 30534, Jul. 2016, doi: 10.1038/srep30534.

A. Cieza, K. Causey, K. Kamenov, S. W. Hanson, S. Chatterji, and T. Vos, “Global estimates of the need for rehabilitation based on the Global Burden of Disease study 2019: a systematic analysis for the Global Burden of Disease Study 2019.,” Lancet (London, England), vol. 396, no. 10267, pp. 2006–2017, Dec. 2021, doi: 10.1016/S0140-6736(20)32340-0.

E. Salagre et al., “Toward Precision Psychiatry in Bipolar Disorder: Staging 2.0,” Front. Psychiatry, vol. 9, Nov. 2018, doi: 10.3389/fpsyt.2018.00641.

V. Oliva, G. Fico, M. De Prisco, X. Gonda, A. R. Rosa, and E. Vieta, “Bipolar disorders: an update on critical aspects,” Lancet Reg. Heal. - Eur., vol. 48, p. 101135, Jan. 2025, doi: 10.1016/j.lanepe.2024.101135.

D. Janiri and S. Frangou, “Precision neuroimaging biomarkers for bipolar disorder,” Int. Rev. Psychiatry, vol. 34, no. 7–8, pp. 727–735, Nov. 2022, doi: 10.1080/09540261.2022.2106121.

B. S. Fernandes et al., “Precision psychiatry with immunological and cognitive biomarkers: a multi-domain prediction for the diagnosis of bipolar disorder or schizophrenia using machine learning,” Transl. Psychiatry, vol. 10, no. 1, p. 162, May 2020, doi: 10.1038/s41398-020-0836-4.

O. B. Smeland, C. Busch, O. A. Andreassen, and M. Manchia, “Novel Multimodal Precision Medicine Approaches and the Relevance of Developmental Trajectories in Bipolar Disorder,” Biol. Psychiatry, vol. 98, no. 4, pp. 343–353, Aug. 2025, doi: 10.1016/j.biopsych.2025.03.010.

L. F. Saccaro, G. Amatori, A. Cappelli, R. Mazziotti, L. Dell’Osso, and G. Rutigliano, “Portable technologies for digital phenotyping of bipolar disorder: A systematic review.,” J. Affect. Disord., vol. 295, pp. 323–338, Dec. 2021, doi: 10.1016/j.jad.2021.08.052.

L. Orsolini, M. Fiorani, and U. Volpe, “Digital Phenotyping in Bipolar Disorder: Which Integration with Clinical Endophenotypes and Biomarkers?,” Int. J. Mol. Sci., vol. 21, no. 20, Oct. 2020, doi: 10.3390/ijms21207684.

C. Langholm et al., “Classifying and clustering mood disorder patients using smartphone data from a feasibility study,” npj Digit. Med., vol. 6, no. 1, p. 238, Dec. 2023, doi: 10.1038/s41746-023-00977-7.

R. Zhong, X. Wu, J. Chen, and Y. Fang, “Using Digital Phenotyping to Discriminate Unipolar Depression and Bipolar Disorder: Systematic Review,” J. Med. Internet Res., vol. 27, p. e72229, May 2025, doi: 10.2196/72229.

Y. Zhang et al., “The comprehensive clinical benefits of digital phenotyping: from broad adoption to full impact,” npj Digit. Med., vol. 8, no. 1, p. 196, Apr. 2025, doi: 10.1038/s41746-025-01602-5.

J. Torous et al., “The evolving field of digital mental health: current evidence and implementation issues for smartphone apps, generative artificial intelligence, and virtual reality,” World Psychiatry, vol. 24, no. 2, pp. 156–174, Jun. 2025, doi: 10.1002/wps.21299.

T. de Azevedo Cardoso, S. Kochhar, J. Torous, and E. Morton, “Digital Tools to Facilitate the Detection and Treatment of Bipolar Disorder: Key Developments and Future Directions.,” JMIR Ment. Heal., vol. 11, p. e58631, Apr. 2024, doi: 10.2196/58631.

J. D. Rosenblat et al., “Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis.,” Bipolar Disord., vol. 18, no. 2, pp. 89–101, Mar. 2016, doi: 10.1111/bdi.12373.

Y. Du et al., “Efficacy and acceptability of anti-inflammatory agents in major depressive disorder: a systematic review and meta-analysis,” Front. Psychiatry, vol. 15, May 2024, doi: 10.3389/fpsyt.2024.1407529.

H. Gong et al., “Anti-inflammatory interventions for the treatment and prevention of depression among older adults: a systematic review and meta-analysis,” Transl. Psychiatry, vol. 15, no. 1, p. 114, Apr. 2025, doi: 10.1038/s41398-025-03317-3.

J. F. Gottlieb et al., “The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology,” Bipolar Disord., vol. 21, no. 8, pp. 741–773, Dec. 2019, doi: 10.1111/bdi.12847.

J. F. Gottlieb et al., “The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology.,” Bipolar Disord., vol. 21, no. 8, pp. 741–773, Dec. 2019, doi: 10.1111/bdi.12847.

S. Wang, Z. Zhang, L. Yao, N. Ding, L. Jiang, and Y. Wu, “Bright light therapy in the treatment of patients with bipolar disorder: A systematic review and meta-analysis,” PLoS One, vol. 15, no. 5, p. e0232798, May 2020, doi: 10.1371/journal.pone.0232798.

D. Sikkens, R. F. Riemersma-Van der Lek, Y. Meesters, R. A. Schoevers, and B. C. M. Haarman, “Combined sleep deprivation and light therapy: Clinical treatment outcomes in patients with complex unipolar and bipolar depression.,” J. Affect. Disord., vol. 246, pp. 727–730, Mar. 2019, doi: 10.1016/j.jad.2018.12.117.

J. B. Savitz et al., “Treatment of bipolar depression with minocycline and/or aspirin: an adaptive, 2×2 double-blind, randomized, placebo-controlled, phase IIA clinical trial,” Transl. Psychiatry, vol. 8, no. 1, p. 27, Jan. 2018, doi: 10.1038/s41398-017-0073-7.

J. Coelho, F. Pécune, J.-A. Micoulaud-Franchi, B. Bioulac, and P. Philip, “Promoting mental health in the age of new digital tools: balancing challenges and opportunities of social media, chatbots, and wearables,” Front. Digit. Heal., vol. 7, Mar. 2025, doi: 10.3389/fdgth.2025.1560580.

N. Titov, B. F. Dear, L. Staples, A. Fisher, H. D. Hadjistavropoulos, and O. Nielssen, “Key questions to ask before implementing a Digital Mental Health Service (DMHS): A primer for policy makers,” Internet Interv., vol. 41, p. 100857, Sep. 2025, doi: 10.1016/j.invent.2025.100857.

M. Fornaro, A. Miola, D. De Berardis, A. Squassina, M. Manchia, and M. Solmi, “Perspectives on Precision Psychiatry Using Antipsychotics in the Management of Bipolar Disorder,” Brain Sci., vol. 15, no. 5, p. 430, Apr. 2025, doi: 10.3390/brainsci15050430.

E. Sackey, A. Ofori-Atta, S. Ohene, K. Obeng, and D. Ben-Zeev, “mHealth and Digital Innovations as Catalysts for Transforming Mental Health Care in Ghana,” Glob. Heal. Sci. Pract., vol. 12, no. 6, p. e2400062, Dec. 2024, doi: 10.9745/GHSP-D-24-00062.

R. Robillard et al., “Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study,” Front. Psychiatry, vol. 9, Dec. 2018, doi: 10.3389/fpsyt.2018.00624.

V. S. Efimova, L. V Isaeva, P. S. Orekhov, M. E. Bozdaganyan, M. A. Rubtsov, and L. A. Novikova, “Using a viral 2A peptide-based strategy to reconstruct the bovine P450scc steroidogenic system in S. cerevisiae: Bovine P450scc system expression using 2A peptides.,” J. Biotechnol., vol. 325, pp. 186–195, Jan. 2021, doi: 10.1016/j.jbiotec.2020.10.028.

L. F. Saccaro, G. Amatori, A. Cappelli, R. Mazziotti, L. Dell’Osso, and G. Rutigliano, “Portable technologies for digital phenotyping of bipolar disorder: A systematic review,” J. Affect. Disord., vol. 295, pp. 323–338, Dec. 2021, doi: 10.1016/j.jad.2021.08.052.

Y.-W. Lin et al., “Novel HDGF/HIF-1α/VEGF axis in oral cancer impacts disease prognosis.,” BMC Cancer, vol. 19, no. 1, p. 1083, Nov. 2019, doi: 10.1186/s12885-019-6229-5.

J. Looijestijn et al., “Draining the pond and catching the fish: Uncovering the ecosystem of auditory verbal hallucinations.,” NeuroImage. Clin., vol. 20, pp. 830–843, 2018, doi: 10.1016/j.nicl.2018.09.016.

V. Pereira-Sanchez et al., “COVID-19 effect on mental health: patients and workforce.,” The lancet. Psychiatry, vol. 7, no. 6, pp. e29–e30, Jun. 2020, doi: 10.1016/S2215-0366(20)30153-X.

P. E. Head et al., “DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining.,” Nucleic Acids Res., vol. 51, no. 15, pp. 7972–7987, Aug. 2023, doi: 10.1093/nar/gkad549.

A. B. Niculescu and H. Le-Niculescu, “Precision medicine in psychiatry: biomarkers to the forefront,” Neuropsychopharmacology, vol. 47, no. 1, pp. 422–423, Jan. 2022, doi: 10.1038/s41386-021-01183-3.

J. Morzinski, D. Simposon, K. Marcdante, L. A. Meurer, M. A. Gilligan, and T. Chandler, “Evaluating the Career Impact of Faculty Development Using Matched Controls.,” Fam. Med., vol. 51, no. 10, pp. 841–844, Nov. 2019, doi: 10.22454/FamMed.2019.195240.

S. Chávez-López, J. de Jesús Lugo-Trampe, M. Ibarra-Ramírez, G. Calvo-Anguiano, L. E. Martínez-de-Villarreal, and L. D. Campos-Acevedo, “A case series of infants with increased VAMP7 gene dosage at birth and virilization defects.,” J. Pediatr. Urol., vol. 16, no. 4, pp. 423.e1-423.e6, Aug. 2020, doi: 10.1016/j.jpurol.2019.11.001.

Downloads

Published

2025-10-04

How to Cite

Saxena, A., Saxena, S., Saxena, Y., Jain, A., Goyal, P., Kumar, A., … Kumar, S. (2025). Bipolar Disorder in the Era of Precision Psychiatry: Biomarkers, Digital Innovations, and Global Challenges. Journal for Research in Applied Sciences and Biotechnology, 4(5), 1–18. https://doi.org/10.55544/jrasb.4.5.1

Similar Articles

1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)