2026 ECNP Congress

PS04-4105

Clinical and neurocognitive outcomes of subthreshold bipolar phenotype in pediatric attention-deficit/hyperactivity disorder: a 3-year preliminary follow-up

Meliha Feyza Gok Cam — C. Mutlu, S. Eray Camli, V. Sahin, S. Turan · Bursa Uludag University, Child and Adolescent Psychiatry, Bursa, Türkiye

2026 ECNP Congress

Background

Subthreshold bipolar symptoms (BD-NOS, defined using modified Course and Outcome of Bipolar Youth [COBY] criteria) often overlap with ADHD in youth, complicating early differentiation [1,2]. Long-term studies show that BD-NOS does not follow a single path: some youth convert to BD-I or BD-II, others remit or shift towards depressive or anxiety disorders [3,4]. Neurocognitive deficits have been suggested as possible endophenotypes for bipolar disorder [5]. Still, the course of these subthreshold symptoms in youth first diagnosed with ADHD is less well known.

Aims

This preliminary follow-up study describes 3-year clinical and neurocognitive outcomes in children and adolescents initially diagnosed with ADHD, comparing those with persistent versus remitted subthreshold bipolar symptoms and those without baseline bipolar features.

Methods

At baseline (T1), 210 children and adolescents (10–17 years) with ADHD at Bursa Uludag University were assessed using K-SADS-PL DSM-5. Of these, 110 (52.4%) were re-assessed after a mean 3.7 years (T2; mean age 16.7±2.2 years; 75.2% male). Three groups were defined: Persistent BD-NOS (n=1), Remitted BD-NOS (n=36), and ADHD-only at baseline (n=72); one schizoaffective conversion was reported descriptively. At both timepoints, illness severity, mood symptoms and functioning were assessed with CGI-S, C-GAS, YMRS, K-SADS Mania Rating Scale, CDRS-R, and Clinician Affective Reactivity Index. The neurocognitive battery covered attention (Continuous Performance Test), executive function (Wisconsin Card Sorting Test), verbal memory (Rey AVLT), processing speed (Digit Symbol Substitution Test), semantic fluency, and social cognition (Reading the Mind in the Eyes). Group differences were analysed with Kruskal–Wallis and chi-square tests; a sensitivity analysis excluded participants on mood-related medication.

Results

Of 38 baseline BD-NOS participants, 36 (94.7%) achieved clinical remission at follow-up, 1 (2.6%) remained Persistent, and 1 (2.6%) developed schizoaffective disorder; no conversions to BD-I, BD-II, or disruptive mood dysregulation disorder (DMDD) occurred. ADHD persistence at T2 was high (88.1%) and balanced across groups (p>0.05). At T1, BDNOS-Remitted participants showed higher illness severity (CGI-S: 3.94 vs 3.03, p<0.001) and lower functioning (C-GAS: 72.5 vs 78.7, p<0.001) than ADHD-only participants, while neurocognitive performance did not differ across groups (all p>0.34). At T2, these baseline clinical differences had resolved (CGI-S, C-GAS, YMRS, K-MRS, CDRS-R, CL-ARI; all p>0.05), and neurocognitive performance was similar across groups (all p>0.05). Medication use at follow-up was comparable between Remitted and ADHD-only groups (33.3% in each); a sensitivity analysis excluding the four BDNOS-Remitted participants on mood-related medication gave similar results (all p>0.05). The single Persistent case showed high illness severity (CGI-S=5, C-GAS=55), multiple comorbidities and a positive family history of bipolar disorder.

Conclusions

In this ADHD-defined cohort, the 3.7-year course of subthreshold bipolar symptoms differed markedly from that reported in bipolar-defined samples, with 94.7% reaching clinical remission and no conversions to BD-I, BD-II, or DMDD [3,4]. BD-NOS participants were clinically more severe at baseline but did not differ neurocognitively at either timepoint, which does not support a neurocognitive trait marker for BD-NOS in this group. Comorbidity patterns will be further investigated to clarify the broader clinical significance of subthreshold bipolar phenotype in ADHD-defined youth.

References

  1. Vaudreuil, C.A.H., Faraone, S.V., Di Salvo, M., Wozniak, J.R., Wolenski, R.A., Carrellas, N.W., Biederman, J., 2019. The morbidity of subthreshold pediatric bipolar disorder: a systematic literature review and meta-analysis. Bipolar Disord. 21 (1), 16–27. https://doi.org/10.1111/bdi.12734
  2. Goldstein, B.I., Birmaher, B., Carlson, G.A., DelBello, M.P., Findling, R.L., Fristad, M., Kowatch, R.A., Miklowitz, D.J., Nery, F.G., Perez-Algorta, G., Van Meter, A., Zeni, C.P., Correll, C.U., Kim, H.-W., Wozniak, J., Chang, K.D., Hillegers, M., Youngstrom, E.A., 2017. The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: knowledge to date and directions for future research. Bipolar Disord. 19 (7), 524–543. https://doi.org/10.1111/bdi.12556
  3. Birmaher, B., Axelson, D., Goldstein, B., Strober, M., Gill, M.K., Hunt, J., Houck, P., Ha, W., Iyengar, S., Kim, E., Yen, S., Hower, H., Esposito-Smythers, C., Goldstein, T., Ryan, N., Keller, M., 2009. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am. J. Psychiatry 166 (7), 795–804. https://doi.org/10.1176/appi.ajp.2009.08101569
  4. Ribeiro-Fernández, M., Díez-Suárez, A., Chang, K.D., Soutullo, C.A., 2024. Predictors of transition from child and adolescent bipolar not otherwise specified to bipolar I disorder, a longitudinal 3.9-year study. J. Clin. Med. 13 (19), 5656. https://doi.org/10.3390/jcm13195656
  5. Meyer, S.E., Carlson, G.A., Wiggs, E.A., Martinez, P.E., Ronsaville, D.S., Klimes-Dougan, B., Gold, P.W., Radke-Yarrow, M., 2004. A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder. Dev. Psychopathol. 16 (2), 461–476. https://doi.org/10.1017/S095457940404461X