Table 1 Definition of subphenotypes in BD.

Inter-episode remission

Collected at the SWEBIC telephone interview. The question was first introduced as follows: “Bipolar disorder is said to be an episodic illness. One can have depressive, hypomanic, manic, or mixed episodes. Have you had depressions or episodes with elated mood?” Provided that the respondent answered yes, the follow-up question read: “How have you been between these episodes?” (if the patient reported more than one episode) or “How have you been since your last episode?” (if the patient had only had one mood episode). The response alternatives were: (i) “Completely recovered, back to normal, became well, working or studying, I am doing well now”, (ii) “Never fully recovered to the functioning prior to illness debut, have remaining difficulties such as need to work part time, (iii) “Not recovered, chronically functionally impaired, not able to work, being on long term sickness leave or receiving disability pension”, (iv) “Don’t know”, (v) “Don’t want to answer”. This variable is unavailable in familial coaggregation analysis.

The inter-episode remission was evaluated by interview and case-note review with OPCRIT item number 90 (i.e., course of disorder) categorized as: (i) Good remission, (ii) Partial remission, (iii) No remission, and (iv) Unknown. [52] To generate more balanced subgroups, we merged partial and no remission because only 12 individuals reported ‘no remission’.

Global assessment of functioning (GAF)

GAF (1–100) was collected from BipoläR where treating physicians rates the GAF-symptom and GAF-function dimensions. [25] We used the mean GAF during the follow-up.

GAF-function was rated by selecting the lowest range that best described the functioning during the last week before interview as assessed by the interviewer.

Psychotic symptom during mood episodes

History of psychotic symptoms during mood episodes was collected from the SWEBIC telephone interview. The question read: “Have you ever lost touch with reality and had psychotic symptoms, i.e., heard or seen things that other people did not see or hear, experienced things that you later on realized were not real?” The raters were asked to weigh in their clinical judgement and instructed to code an uncertain response, or response that the rater did not consider psychotic (i.e., depersonalization/ derealization experiences) as ‘no’. In familial coaggregation analysis, this phenotype was identified in the National Patient Registry, with ICD-10 codes displayed in supplementary Table S1.

The lifetime history of any psychosis during mood episodes was recoded as Yes or No using data from the interview and case-note review.

Comorbid anxiety disorders

Anxiety disorders were identified in the National Patient Registry, with ICD codes displayed in supplementary Table S1.

The lifetime presence of known anxiety disorder was defined as the presence of a doctor diagnosis of any anxiety disorder recorded in the medical case-notes or reported at interview, or significantly impairing anxiety episodes ascertained during the SCAN interview.