Dissociative Bipolar At-Risk Phenotype: Traumatic Burden and Subthreshold Affective Psychopathology in a Help-Seeking Youth Sample
Highlights
- Bipolar at-risk (BAR) status and clinically significant dissociation were highly prevalent and frequently co-occurred in this clinically enriched, second-level outpatient sample of help-seeking youths. Within the BAR subgroup, youths with dissociative symptoms reported greater traumatic burden, more severe depressive symptoms, and higher anxious temperament scores.
- Attentional impulsivity did not mediate the relationship between dissociation and affective vulnerability, suggesting a direct link between dissociative symptoms and bipolar-spectrum risk.
- Integrating systematic assessment of dissociation into early-intervention pathways may improve risk stratification for adolescents and young adults presenting with affective instability.
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Study Procedures
2.3. Study Population
2.4. Assessment Instruments
2.5. Measures and Operational Definitions
2.6. Statistical Analysis
3. Results
3.1. Sample Description
3.2. Clinical Correlates of BAR Status
3.2.1. BAR+ vs. BAR−
3.2.2. DES+ Patients Among BAR+
3.2.3. Binary Logistic Regression
3.2.4. Mediation Analysis
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- McGorry, P.; Gunasiri, H.; Mei, C.; Rice, S.; Gao, C. The youth mental health crisis: Analysis and solutions. Front. Psychiatry 2025, 15, 1517533. [Google Scholar] [CrossRef]
- Blackwell, C.K.; Wu, G.; Chandran, A.; Arizaga, J.; Enlow, M.B.; Brennan, P.A.; Burton, P.; Bush, N.R.; Cella, D.; Cummins, C.; et al. Longitudinal changes in youth mental health from before to during the COVID-19 pandemic. JAMA Netw. Open 2024, 7, e2430198. [Google Scholar] [CrossRef]
- Colic, L.; Sankar, A.; Goldman, D.A.; Kim, J.A.; Blumberg, H.P. Towards a neurodevelopmental model of bipolar disorder. Mol. Psychiatry 2025, 30, 1089–1101. [Google Scholar] [CrossRef]
- Grelle, K.; Shrestha, N.; Ximenes, M.; Perrotte, J.; Cordaro, M.; Deason, R.G.; Howard, K. The Generation Gap Revisited: Generational Differences in Mental Health, Maladaptive Coping Behaviors, and Pandemic-Related Concerns During the Initial COVID-19 Pandemic. J. Adult Dev. 2023, 30, 381–392. [Google Scholar] [CrossRef]
- Wilson, M.; Lee, H.; Dall’Aglio, L.; Li, X.; Kumar, A.; Colvin, M.K.; Smoller, J.W.; Beardslee, W.R.; Choi, K.W. Time trends in adolescent diagnoses of major depressive disorder and co-occurring psychiatric conditions in electronic health records. Res. Square 2024, preprint. [Google Scholar] [CrossRef]
- Zhong, Y.; Chen, Y.; Su, X.; Wang, M.; Li, Q.; Shao, Z.; Sun, L. Global, regional and national burdens of bipolar disorders in adolescents and young adults: A trend analysis from 1990 to 2019. Gen. Psychiatry 2024, 37, e101255. [Google Scholar] [CrossRef]
- Dagani, J.; Signorini, G.; Nielssen, O.; Bani, M.; Pastore, A.; Girolamo, G.; Large, M. Meta-analysis of the interval between onset and management of bipolar disorder. Can. J. Psychiatry 2017, 62, 247–258. [Google Scholar] [CrossRef] [PubMed]
- Macellaro, M.; Bucca, C.; Balla, I.; Galimberti, C.; Dell’Osso, B. Duration of untreated illness in bipolar disorder. Psychiatry Res. Commun. 2025, 5, 100223. [Google Scholar] [CrossRef]
- Keramatian, K.; Pinto, J.V.; Tsang, V.W.L.; Chakrabarty, T.; Yatham, L.N. Duration of untreated or undiagnosed bipolar disorder and clinical characteristics and outcomes: Systematic review and meta-analysis. Br. J. Psychiatry 2025, 227, 622–632. [Google Scholar] [CrossRef] [PubMed]
- McGorry, P.D.; Hartmann, J.A.; Spooner, R.; Nelson, B. Beyond the “at risk mental state” concept. World Psychiatry 2018, 17, 133–142. [Google Scholar] [CrossRef] [PubMed]
- Bechdolf, A.; Ratheesh, A.; Cotton, S.M.; Nelson, B.; Chanen, A.M.; Betts, J.; Bingmann, T.; Yung, A.R.; Berk, M.; McGorry, P.D. The predictive validity of bipolar at-risk (prodromal) criteria in help-seeking adolescents and young adults: A prospective study. Bipolar Disord. 2014, 16, 493–504. [Google Scholar] [CrossRef]
- Martini, J.; Bröckel, K.L.; Leopold, K.; Berndt, C.; Sauer, C.; Maicher, B.; Juckel, G.; Krüger-Özgürdal, S.; Fallgatter, A.J.; Lambert, M.; et al. Young people at risk for developing bipolar disorder: Two-year findings from the multicenter prospective, naturalistic Early-BipoLife study. Eur. Neuropsychopharmacol. 2024, 78, 43–53. [Google Scholar] [CrossRef] [PubMed]
- Miklowitz, D.J.; Weintraub, M.J.; Singh, M.K.; Walshaw, P.D.; Merranko, J.A.; Birmaher, B.; Chang, K.D.; Schneck, C.D. Mood instability in youth at high risk for bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry 2022, 61, 543–554. [Google Scholar] [CrossRef]
- Trinh, H.H.; Nguyen, T.T.; Nguyen, T.Q.; Ngo, N.T.; Nguyen, S.T.; Nguyen, C.V.; Mac, T.D.; Nguyen, T.H. Impacts of Adverse Childhood Experiences on Mental Health and Satisfaction With Life in First-Year College Students: Results from a Cross-Sectional Study in Vietnam. Psychiatry Investig. 2025, 22, 939–948. [Google Scholar] [CrossRef]
- Etain, B.; Lajnef, M.; Brichant-Petitjean, C.; Geoffroy, P.A.; Henry, C.; Gard, S.; Kahn, J.P.; Leboyer, M.; Young, A.H.; Bellivier, F. Childhood trauma and mixed episodes are associated with poor response to lithium in bipolar disorders. Acta Psychiatr. Scand. 2017, 135, 319–327. [Google Scholar] [CrossRef]
- Xiao, K.; Sayed, H.; Xing, J.; Zhang, X.Y.; Ai, J.; Teopiz, K.M.; Ho, R.; Rhee, T.G.; Lo, H.K.Y.; Guillen-Burgos, H.F.; et al. The prevalence, clinical impact, and therapeutic considerations of trauma in adults with bipolar disorder: A systematic review. J. Affect. Disord. 2025, 388, 119507. [Google Scholar] [CrossRef]
- Guillén-Burgos, H.F.; Gálvez-Flórez, J.F.; Moreno-López, S.; Solano, M.C.; Kwan, A.T.H.; Santamaria-Garcia, H.; Gómez-Restrepo, C.; McIntyre, R.S. The effect of childhood trauma on bipolar depression. Sci. Rep. 2025, 15, 15876. [Google Scholar] [CrossRef]
- Steardo, L.; Carbone, E.A.; Ventura, E.; De Filippis, R.; Luciano, M.; Segura-Garcìa, C.; De Fazio, P. Dissociative symptoms in bipolar disorder: Impact on clinical symptoms and treatment response. Front. Psychiatry 2021, 12, 732843. [Google Scholar] [CrossRef]
- Chen, C.-K.; Wu, L.S.-H.; Huang, M.-C.; Kuo, C.J.; Cheng, A.T. Antidepressant treatment and manic switch in bipolar I disorder: A clinical and molecular genetic study. J. Pers. Med. 2022, 12, 615. [Google Scholar] [CrossRef] [PubMed]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; Text Rev. (DSM-5-TR); APA Publishing: Washington, DC, USA, 2022. [Google Scholar]
- Spiegel, D. Recognizing traumatic dissociation. Am. J. Psychiatry 2006, 163, 566–568. [Google Scholar] [CrossRef] [PubMed]
- Cavicchioli, M.; Scalabrini, A.; Northoff, G.; Mucci, C.; Ogliari, A.; Maffei, C. Dissociation and emotion regulation strategies: A meta-analytic review. J. Psychiatr. Res. 2021, 143, 370–387. [Google Scholar] [CrossRef] [PubMed]
- Fung, H.W.; Ka Ho, G.W.; Ki Lam, S.K.; Chun Chau, A.K.; Şar, V.; Ross, C.A.; Lee, K.; Chien, W.T.; Wong, J.Y. The co-occurrence of depression and dissociation: The relevance of childhood trauma. J. Psychiatr. Res. 2025, 183, 157–163. [Google Scholar] [CrossRef]
- Shim, S.; Kim, D.; Kim, E. Dissociation as a mediator of interpersonal trauma and depression. BMC Psychiatry 2024, 24, 764. [Google Scholar] [CrossRef] [PubMed]
- Chiu, C.D.; Li, D.J.; Hsieh, Y.C.; Chou, L.S.; Au, J.S.; Chen, Y.L.; Lin, C.H. Linking childhood trauma and dissociation to psychotic symptoms in major depressive disorder, bipolar disorders, and schizophrenia: A transdiagnostic examination using patient and clinician ratings. Psychol. Trauma 2024, 16, S242–S249. [Google Scholar] [CrossRef]
- Bruno, S.; Tacchino, C.; Anconetani, G.; Velotti, P. Unravelling the associations between dissociation and emotion (dys)regulation: A multidimensional meta-analytic review. J. Affect. Disord. 2025, 380, 808–824. [Google Scholar]
- Paulus, F.W.; Ohmann, S.; Möhler, E.; Plener, P.; Popus, C. Emotional dysregulation in children and adolescents with psychiatric disorders. Front. Psychiatry 2021, 12, 628252. [Google Scholar] [CrossRef]
- Şar, V. Dissociative depression is resistant to treatment-as-usual. J. Psychol. Clin. Psychiatry 2015, 3, 00128. [Google Scholar] [CrossRef]
- Boyer, S.M.; Caplan, J.E.; Edwards, L.K. Trauma-Related Dissociation and the Dissociative Disorders: Neglected Symptoms with Severe Public Health Consequences. Dela. J. Public Health 2022, 8, 78–84. [Google Scholar] [CrossRef]
- Carlson, E.B.; Putnam, F.W. Validity of the Dissociative Experiences Scale in screening for multiple personality disorder: A multicenter study. Am. J. Psychiatry 1993, 150, 1030–1036. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, J.G.; Putnam, F.W.; Carlson, E.B.; Libero, D.Z.; Smith, S.R. Development and validation of a measure of adolescent dissociation: The Adolescent Dissociative Experiences Scale. J. Nerv. Ment. Dis. 1997, 185, 491–497. [Google Scholar] [CrossRef]
- Carlson, E.B.; Putnam, F. An update on the Dissociative Experiences Scale. Dissociation 1993, 6, 16–27. [Google Scholar]
- Farrington, A.; Waller, G.; Smerden, J.; Faupel, A.W. The adolescent dissociative experiences scale: Psychometric properties and difference in scores across age groups. J. Nerv. Ment. Dis. 2001, 189, 722–727. [Google Scholar] [CrossRef] [PubMed]
- Beck, A.T.; Steer, R.A.; Ball, R.; Ranieri, W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J. Pers. Assess. 1996, 67, 588–597. [Google Scholar] [CrossRef] [PubMed]
- Hamilton, M. The assessment of anxiety states by rating. Br. J. Med. Psychol. 1959, 32, 50–55. [Google Scholar] [CrossRef]
- Montgomery, S.A.; Åsberg, M. A new depression scale designed to be sensitive to change. Br. J. Psychiatry 1979, 134, 382–389. [Google Scholar] [CrossRef] [PubMed]
- Sani, G.; Vöhringer, P.A.; Barroilhet, S.A.; Koukopoulos, A.E.; Ghaemi, S.N. The Koukopoulos Mixed Depression Rating Scale (KMDRS): An International Mood Network (IMN) validation study of a new mixed mood rating scale. J. Affect. Disord. 2018, 232, 9–16. [Google Scholar] [CrossRef]
- Spielberger, C.D. State-Trait Anxiety Inventory. In The Corsini Encyclopedia of Psychology; Weiner, I.B., Craighead, W.E., Eds.; John Wiley & Sons: Hoboken, NJ, USA, 2010. [Google Scholar]
- Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 1960, 23, 56–62. [Google Scholar] [CrossRef]
- Hirschfeld, R.M.A.; Williams, J.B.W.; Spitzer, R.L.; Calabrese, J.R.; Flynn, L.; Keck, P.E., Jr.; Lewis, L.; McElroy, S.L.; Post, R.M.; Rapport, D.J.; et al. Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire. Am. J. Psychiatry 2000, 157, 1873–1875. [Google Scholar] [CrossRef]
- Angst, J.; Adolfsson, R.; Benazzi, F.; Gamma, A.; Hantouche, E.; Meyer, T.D.; Skeppar, P.; Vieta, E.; Scott, J. The HCL-32: Towards a self-assessment tool for hypomanic symptoms in outpatients. J. Affect. Disord. 2005, 88, 217–233. [Google Scholar] [CrossRef]
- Fico, G.; Luciano, M.; Sampogna, G.; Zinno, F.; Steardo, L., Jr.; Perugi, G.; Pompili, M.; Tortorella, A.; Volpe, U.; Fiorillo, A.; et al. Validation of the brief TEMPS-M temperament questionnaire in a clinical Italian sample of bipolar and cyclothymic patients. J. Affect. Disord. 2020, 260, 458–462. [Google Scholar] [CrossRef]
- Patton, J.H.; Stanford, M.S.; Barratt, E.S. Factor structure of the Barratt Impulsiveness Scale. J. Clin. Psychol. 1995, 51, 768–774. [Google Scholar] [CrossRef] [PubMed]
- Loewy, R.L.; Pearson, R.; Vinogradov, S.; Carrie, E.B.; Tyrone, D.C. Psychosis risk screening with the Prodromal Questionnaire–brief version (PQ-B). Schizophr. Res. 2011, 129, 42–46. [Google Scholar] [CrossRef]
- Steinberg, M.; Hall, P. The SCID-D diagnostic interview and treatment planning in dissociative disorders. Bull. Menn. Clin. 1997, 61, 108–120. [Google Scholar]
- Steinberg, M. Advances in the clinical assessment of dissociation: The SCID-D-R. Bull. Menn. Clin. 2000, 64, 146–163. [Google Scholar]
- Solmi, F.; Radua, J.; Olivola, M. Age at onset of mental disorders worldwide: Large-scale meta-analysis of 192 epidemiological studies. Mol. Psychiatry 2022, 27, 281–295. [Google Scholar] [CrossRef]
- McGrath, J.J.; Saha, S.; Al-Hamzawi, A. Age of onset and cumulative risk of mental disorders: A cross-national analysis of population surveys from 29 countries. Lancet Psychiatry 2023, 10, 192–205. [Google Scholar] [CrossRef]
- Mojtabai, R.; Olfson, M. National Trends in Mental Health Care for US Adolescents. J. Adolesc. Health 2020, 77, 703–714. [Google Scholar] [CrossRef]
- Keyes, K.M.; Platt, J. Annual Research Review: Sex, gender, and internalizing conditions among adolescents in the 21st century—Trends, causes, consequences. J. Child Psycol. Psychiatry 2024, 65, 384–407. [Google Scholar] [CrossRef] [PubMed]
- Shah, J.L.; Scott, J.; McGorry, P.D. Transdiagnostic clinical staging in youth mental health: A first international consensus statement. World Psychiatry 2022, 21, 351–365. [Google Scholar] [CrossRef] [PubMed]
- Foote, B.; Smolin, Y.; Kaplan, M.; Legatt, M.E.; Lipschitz, D. Prevalence of dissociative disorders in psychiatric outpatients. Am. J. Psychiatry 2006, 163, 623–629. [Google Scholar] [CrossRef]
- Oedegaard, K.J.; Neckelmann, D.; Benazzi, F.; Syrstad, V.E.; Akiskal, H.S.; Fasmer, O.B. Dissociative experiences differentiate bipolar-II from unipolar depressed patients: The mediating role of cyclothymia and the Type A behaviour speed and impatience subscale. J. Affect. Disord. 2008, 108, 207–216. [Google Scholar] [CrossRef]
- Şar, V. Epidemiology of dissociative disorders: An overview. Epidemiol. Res. Int. 2011, 2011, 404538. [Google Scholar] [CrossRef]
- Şar, V.; Akyüz, G.; Dogan, O. Prevalence of dissociative disorders among women in the general population. Psychiatry Res. 2007, 149, 169–176. [Google Scholar] [CrossRef] [PubMed]
- Mychailyszyn, M.P.; Brand, B.L.; Webermann, A.R.; Şar, V.; Draijer, N. Differentiating Dissociative from Non-Dissociative Disorders: A Meta-Analysis of the Structured Clinical Interview for DSM Dissociative Disorders (SCID-D). J. Trauma Dissociation 2021, 22, 19–34. [Google Scholar] [CrossRef] [PubMed]
- Černis, E.; Loe, B.S.; Lofthouse, K.; Waite, P.; Molodynski, A.; Ehlers, A.; Freeman, D. Measuring dissociation across adolescence and adulthood: Developing the short-form Černis Felt Sense of Anomaly scale (ČEFSA-14). Behav. Cogn. Psychother. 2024, 52, 163–177. [Google Scholar] [CrossRef]
- Foote, B.; Smolin, Y.; Neft, D.I.; Lipschitz, D. Dissociative disorders and suicidality in psychiatric outpatients. J. Nerv. Ment. Disord. 2008, 196, 29–36. [Google Scholar] [CrossRef]
- Černis, E.; Chan, C.; Cooper, M. What is the relationship between dissociation and self-harming behaviour in adolescents? Clin. Psychol. Psychother. 2019, 26, 328–338. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, R.; Ando, S.; Kiyono, T.; Minami, R.; Endo, K.; Miyashita, M.; Yamasaki, S.; Kanata, S.; Fujikawa, S.; Hiraiwa-Hasegawa, M.; et al. The longitudinal relationship between dissociative symptoms and self-harm in adolescents: A population-based cohort study. Eur. Child. Adolesc. Psychiatry 2024, 33, 561–568. [Google Scholar] [CrossRef]
- McGuinness, M.; McCarthy, A.; Wu, X.; Almandi, M.; Bhangu, D.; Collinson, L.; Shang, X.; Černis, E. Identifying Preliminary Risk Profiles for Dissociation in 16- to 25-Year-Olds Using Machine Learning. Early Interv. Psychiatry 2025, 19, e70015. [Google Scholar] [CrossRef]
- Campbell, M.C.; Smakowski, A.; Rojas-Aguiluz, M.; Goldstein, L.H.; Cardeña, E.; Nicholson, T.R.; Reinders, A.A.T.S.; Pick, S. Dissociation and its biological and clinical associations in functional neurological disorder: Systematic review and meta-analysis. BJPsych Open 2022, 9, e2. [Google Scholar] [CrossRef]
- Bechdolf, A.; Nelson, B.; Cotton, S.M.; Chanen, A.; Thompson, A.; Kettle, J.; Conus, P.; Amminger, G.P.; Yung, A.R.; Berk, M.; et al. A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults. Br. J. Psychiatry 2010, 127, 316–320. [Google Scholar] [CrossRef] [PubMed]
- Fusar-Poli, P.; Rutigliano, G.; Stahl, D.; Davies, C.; Bonoldi, I.; Reilly, T.; McGuire, P. Development and Validation of a Clinically Based Risk Calculator for the Transdiagnostic Prediction of Psychosis. JAMA Psychiatry 2017, 74, 493–500. [Google Scholar] [CrossRef]
- Stefanelli, R.; Estradé, A.; Azis, M.; Stefana, A.; Bonoldi, I.; Damiani, S.; De Micheli, A.; Floris, V.; Provenzani, U.; Ballan, L.; et al. The semi-structured interview for bipolar at-risk states (SIBARS): Psychometric properties and validation. J. Affect. Disord. 2025, 3871, 19529. [Google Scholar] [CrossRef]
- Ratheesh, A.; Hammond, D.; Watson, M.; Betts, J.; Siegel, E.; McGorry, P.; Berk, M.; Cotton, S.; Chanen, A.; Nelson, B.; et al. Bipolar At-Risk Criteria and Risk of Bipolar Disorder Over 10 or More Years. JAMA Netw. Open 2023, 6, e2334078. [Google Scholar] [CrossRef] [PubMed]
- Rajkumar, R.P. Dissociative Symptoms and Disorders in Patients With Bipolar Disorders: A Scoping Review. Front. Psychiatry 2022, 13, 925983. [Google Scholar] [CrossRef]
- Janiri, D.; Simonetti, A.; Moccia, L.; Hirsch, D.; Montanari, S.; Mazza, M.; Di Nicola, M.; Kotzalidis, G.D.; Sani, G. What Came First, Mania or Depression? Polarity at Onset in Bipolar I and II: Temperament and Clinical Course. Brain Sci. 2023, 14, 17. [Google Scholar] [CrossRef]
- Hafeman, D.M.; Merranko, J.; Axelson, D.; Goldstein, B.I.; Goldstein, T.; Monk, K.; Hickey, M.B.; Sakolsky, D.; Diler, R.; Iyengar, S.; et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am. J. Psychiatry 2016, 173, 695–704. [Google Scholar] [CrossRef]
- Cho, M.; Lee, H.; Park, C.H.K. Latent profiles of affective temperaments can support differentiation of bipolar I disorder, bipolar II disorder, and major depressive disorder. J. Psychiatr. Res. 2026, 194, 79–84. [Google Scholar] [CrossRef]
- Sala, R.; Axelson, D.A.; Castro-Fornieles, J.; Goldstein, T.R.; Ha, W.; Liao, F.; Gill, M.K.; Iyengar, S.; Strober, M.A.; Goldstein, B.I.; et al. Comorbid anxiety in children and adolescents with bipolar spectrum disorders: Prevalence and clinical correlates. J. Clin. Psychiatry 2010, 71, 1344–1350. [Google Scholar] [CrossRef] [PubMed]
- van Meter, A.R.; Burke, C.; Youngstrom, E.A.; Faedda, G.L.; Correll, C.U. The bipolar prodrome: Meta-analysis of symptom prevalence prior to initial or recurrent mood episodes. J. Amer. Academ. Child Adolesc. Psychiatry 2016, 77, e142–e151. [Google Scholar] [CrossRef] [PubMed]
- Martini, J.; Leopold, K.; Pfeiffer, S.; Berndt, C.; Boehme, A.; Roessner, V.; Fusar-Poli, P.; Young, A.H.; Correll, C.U.; Bauer, M.; et al. Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden. Int. J. Bipolar. Disord. 2021, 9, 23. [Google Scholar] [CrossRef]
- Freeman, K.; Zwicker, A.; Fullerton, J.M.; Hafeman, D.M.; van Haren, N.E.M.; Merranko, J.; Goldstein, B.I.; Stapp, E.K.; de la Serna, E.; Moreno, D.; et al. Polygenic Scores and Mood Disorder Onsets in the Context of Family History and Early Psychopathology. JAMA Netw. Open 2025, 8, e255331. [Google Scholar] [CrossRef]
- Apicella, M.; Pontillo, M.; Maglio, G.; Di Vincenzo, C.; Della Santa, G.; Andracchio, E.; Vicari, S. Non-suicidal self-injury in adolescents: A clinician’s guide to understanding the phenomenon, diagnostic challenges, and evidence-based treatments. Front. Psychiatry 2025, 16, 1605508. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.C.; Chen, M.H.; Bai, Y.M.; Chen, T.J.; Su, T.P. Resistance to antidepressant treatment among patients with major depressive disorder: A nationwide study. Int. Clin. Psychopharmacol. 2025, 40, 333–338. [Google Scholar] [CrossRef]
- Li, C.T.; Bai, Y.M.; Huang, Y.L.; Su, T.P. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: Cohort study. Br. J. Psychiatry 2012, 200, 45–51. [Google Scholar] [CrossRef] [PubMed]
- Barbuti, M.; Pacchiarotti, I.; Vieta, E.; Azorin, J.-M.; Angst, J.; Bowden, C.L.; Mosolov, S.; Young, A.H.; Perugi, G.; BRIDGE-II-Mix Study Group. Antidepressant-induced hypomania/mania in patients with major depression: Evidence from the BRIDGE-II-MIX study. J. Affect. Disord. 2017, 219, 187–192. [Google Scholar] [CrossRef]
- Swann, A.C.; Lijffijt, M.; Lane, S.D.; Steinberg, J.L.; Moeller, F.G. Increased trait-like impulsivity and course of illness in bipolar disorder. Bipolar Disord. 2009, 11, 280–288. [Google Scholar] [CrossRef]
- Luciano, M.; Sampogna, G.; Mancuso, E.; Simonetti, A.; De Fazio, P.; Di Nicola, M.; Di Lorenzo, G.; Pepe, M.; Sambataro, F.; Signorelli, M.S.; et al. Trait-Related Impulsivity, Affective Temperaments and Mood Disorders: Results from a Real-World Multicentric Study. Brain Sci. 2022, 12, 1554. [Google Scholar] [CrossRef] [PubMed]
- De Filippis, R.; Carbone, E.A.; D’Angelo, M.; Liuzza, M.T.; De Fazio, P.; Steardo, L., Jr. The mediation role of impulsivity between childhood trauma and dissociative symptomatology in bipolar disorder. Riv. Psichiatr. 2023, 58, 84–92. [Google Scholar] [CrossRef]
- Richard-Lepouriel, H.; Kung, A.-L.; Hasler, R.; Bellivier, F.; Prada, P.; Gard, S.; Ardu, S.; Kahn, J.-P.; Dayer, A.; Henry, C.; et al. Impulsivity and its association with childhood trauma experiences across bipolar disorder, attention deficit hyperactivity disorder and borderline personality disorder. J. Affect. Disord. 2019, 244, 33–41. [Google Scholar] [CrossRef]
- Etain, B.; Aas, M. Childhood Maltreatment in Bipolar Disorders. Curr. Top. Behav. Neurosci. 2021, 48, 277–301. [Google Scholar] [PubMed]



| Variable (Yes Listed) | BAR− (%) | BAR+ (%) | p | OR (95% CI) |
|---|---|---|---|---|
| Sociodemographic | ||||
| Age < 18 years | 52.4 | 52.9 | 1.000 | 1.02 (0.41–2.53) |
| Female gender | 50.0 | 67.6 | 0.266 | - |
| Italian nationality | 100 | 97.6 | 1.000 | 1.83 (1.49–2.85) |
| Support teacher | 11.9 | 5.9 | 0.614 | 0.46 (0.08–2.55) |
| School refusal | 17.1 | 21.9 | 0.828 | 1.46 (0.42–4.37) |
| Working | 7.1 | 14.7 | 0.489 | 2.24 (0.49–10.14) |
| NEET status | 16.7 | 23.5 | 0.647 | 1.54 (0.49–4.78) |
| Living with family of origin | 85.7 | 76.5 | 0.462 | 0.54 (0.17–1.75) |
| Clinical | ||||
| Loneliness | 21.4 | 48.5 | 0.026 | 3.45 (1.26–9.42) |
| Social isolation | 31.0 | 52.9 | 0.088 | 2.51 (0.98–6.42) |
| Hyperconnectedness | 23.5 | 16.7 | 0.933 | 0.65 (0.12–3.46) |
| History of trauma (any) | 35.7 | 50.0 | 0.307 | 1.80 (0.72–4.53) |
| Current environmental conflict | 45.2 | 55.9 | 0.489 | 1.53 (0.62–3.81) |
| First contact with psychiatric services | 11.9 | 11.8 | 1.000 | 0.99 (0.24–4.00) |
| Psychiatric familiar history | 72.5 | 78.1 | 0.784 | 1.35 (0.46–4.02) |
| Familiar history of affective disorders | 36.8 | 65.6 | 0.031 | 3.27 (1.22–8.75) |
| Parental history of affective disorders | 37.5 | 68.8 | 0.016 | 3.67 (1.37–9.81) |
| Lifetime anxiety disorders | 54.8 | 79.4 | 0.045 | 3.19 (1.14–8.92) |
| Lifetime eating disorders | 28.6 | 26.5 | 1.000 | 0.90 (0.33–2.48) |
| Lifetime neurodevelopmental disorders | 11.9 | 23.5 | 0.302 | 2.28 (0.67–7.75) |
| Lifetime suicide attempts | 7.1 | 17.6 | 0.293 | 2.79 (0.64–12.10) |
| Lifetime NSSI | 31.0 | 73.5 | <0.001 | 6.20 (2.27–16.91) |
| Lifetime substance abuse | 29.3 | 32.4 | 0.971 | 1.16 (0.43–3.09) |
| Lifetime alcohol abuse | 12.2 | 14.7 | 1.000 | 1.24 (0.33–4.71) |
| Lifetime legal involvement | 0.0 | 2.9 | 0.447 | 0.44 (0.34–0.57) |
| Lifetime antidepressant treatment | 9.5 | 29.4 | 0.037 | 3.96 (1.11–14.05) |
| Lifetime mood stabilizer treatment | 17.1 | 17.6 | 1.000 | 1.04 (0.31–3.45) |
| Lifetime antipsychotic treatment | 26.2 | 44.1 | 0.163 | 2.22 (0.85–5.84) |
| Lifetime BDZ treatment | 34.1 | 32.4 | 1.000 | 0.92 (0.35–2.42) |
| BAR− (mean, SD) | BAR+ (mean, SD) | p-value | Cohen’s d | |
| Age at onset | 12.55 (3.72) | 12.15 (4.91) | 0.687 | 0.09 |
| Age at first psychiatric treatment | 15.55 (3.57) | 14.82 (4.99) | 0.527 | 0.17 |
| Psychopathological (test scoring) | ||||
| BDI-II | 18.60 (13.83) | 25.38 (14.10) | 0.082 | 0.49 |
| MADRS | 11.13 (7.58) | 17.60 (8.90) | 0.005 | 0.79 |
| KMDRS | 10 (5.45) | 15.44 (8.45) | 0.126 | 0.03 |
| STAI-Y1 | 52.60 (14.92) | 53.18 (10.65) | 0.930 | 0.02 |
| briefTEMPS cyclothymic | 15.87 (5.62) | 25.75 (5.72) | <0.001 | 1.73 |
| briefTEMPS irritable | 12.80 (4.99) | 20.37 (7.21) | 0.001 | 1.23 |
| briefTEMPS anxious | 17.13 (5.62) | 23.11 (5.91) | 0.004 | 1.02 |
| BIS-11 total | 16.84 (12.36) | 71.82 (10.14) | 0.031 | 0.52 |
| BIS-11 attentional | 18.16 (4.73) | 20.67 (3.56) | 0.014 | 0.59 |
| BIS-11 motor | 20.57 (5.91) | 21.85 (5.67) | 0.359 | 0.22 |
| BIS-11 non-planning | 27.22 (3.92) | 29.70 (5.38) | 0.030 | 0.54 |
| BAR− (median, IQR) | BAR+ (median, IQR) | p-value | r | |
| HAM-D | 7.00 (8) | 11.00 (11) | 0.073 | 0.21 |
| HAM-A | 13.50 (13) | 17.00 (17) | 0.305 | 0.12 |
| STAI-Y2 | 54.50 (28) | 58.00 (16) | 0.973 | 0.003 |
| briefTEMPS-M depressive | 20.00 (10) | 27.00 (10) | 0.038 | 0.35 |
| briefTEMPS-M hyperthymic | 15.00 (9) | 17.00 (8) | 0.595 | 0.09 |
| PQ-B symptom total score | 4.50 (9) | 10.00 (12) | 0.015 | 0.37 |
| Variable | BAR+/DES− (Mean, SD) | BAR+/DES+ (Mean, SD) | p-Value | Cohen’s d |
|---|---|---|---|---|
| BDI-II | 16.67 (12.33) | 30.60 (12.72) | 0.015 | 1.09 |
| MADRS | 14.43 (6.87) | 21.64 (9.84) | 0.042 | 0.88 |
| HAM-D | 13.13 (5.79) | 11.00 (6.16) | 0.426 | 0.35 |
| KMDRS | 12.00 (7.78) | 18.20 (8.11) | 0.120 | 0.78 |
| STAI-Y1 | 52.31 (10.74) | 53.75 (10.88) | 0.711 | 0.13 |
| BIS-11 attentional | 19.15 (3.53) | 21.65 (3.30) | 0.047 | 0.73 |
| BIS-11 motor | 21.15 (5.15) | 22.30 (6.07) | 0.579 | 0.20 |
| BIS-11 non-planning | 28.23 (6.19) | 30.65 (4.69) | 0.212 | 0.45 |
| BIS-11 total | 67.77 (10.17) | 74.45 (9.45) | 0.063 | 0.69 |
| briefTEMPS-M depressive | 23.13 (6.69) | 26.20 (4.92) | 0.277 | 0.53 |
| briefTEMPS-M cyclothymic | 23.00 (6.39) | 27.58 (4.62) | 0.078 | 0.86 |
| briefTEMPS-M irritable | 19.56 (6.80) | 21.10 (7.84) | 0.654 | 0.21 |
| briefTEMPS-M anxious | 19.44 (5.34) | 26.40 (4.35) | 0.006 | 1.43 |
| BAR+/DES− (median, IQR) | BAR+/DES+ (median, IQR) | p-value | r | |
| HAM-A | 16 (24) | 17 (20) | 0.424 | 0.14 |
| STAI-Y2 | 57 (42) | 58.5 (16) | 0.083 | 0.30 |
| briefTEMPS-M hyperthymic | 18.5 (11) | 13 (8) | 0.884 | 0.04 |
| PQ-B symptom total score | 11 (15) | 9.5 (11) | 0.631 | 0.10 |
| Variables in Equation | Wald | p-Value | OR (95% CI) |
|---|---|---|---|
| Female gender | 2.353 | 0.125 | 2.293 (1.081–6.739) |
| Age | 0.567 | 0.452 | 1.065 (0.794–6.624) |
| Loneliness | 4.919 | 0.027 | 3.397 (0.153–10.012) |
| Dissociation | 4.677 | 0.031 | 3.165 (1.114–8.991) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Share and Cite
Scopetta, F.; Barbi, M.; Cinesi, G.; De Giorgi, F.; Tortorella, A.; Menculini, G. Dissociative Bipolar At-Risk Phenotype: Traumatic Burden and Subthreshold Affective Psychopathology in a Help-Seeking Youth Sample. Brain Sci. 2026, 16, 349. https://doi.org/10.3390/brainsci16040349
Scopetta F, Barbi M, Cinesi G, De Giorgi F, Tortorella A, Menculini G. Dissociative Bipolar At-Risk Phenotype: Traumatic Burden and Subthreshold Affective Psychopathology in a Help-Seeking Youth Sample. Brain Sciences. 2026; 16(4):349. https://doi.org/10.3390/brainsci16040349
Chicago/Turabian StyleScopetta, Francesca, Marta Barbi, Gianmarco Cinesi, Filippo De Giorgi, Alfonso Tortorella, and Giulia Menculini. 2026. "Dissociative Bipolar At-Risk Phenotype: Traumatic Burden and Subthreshold Affective Psychopathology in a Help-Seeking Youth Sample" Brain Sciences 16, no. 4: 349. https://doi.org/10.3390/brainsci16040349
APA StyleScopetta, F., Barbi, M., Cinesi, G., De Giorgi, F., Tortorella, A., & Menculini, G. (2026). Dissociative Bipolar At-Risk Phenotype: Traumatic Burden and Subthreshold Affective Psychopathology in a Help-Seeking Youth Sample. Brain Sciences, 16(4), 349. https://doi.org/10.3390/brainsci16040349

