SUBJECTIVELY AND OBJECTIVELY RATED MIXED AFFECTIVE STATES IN A MIXED-AGE SAMPLE OF ADULTS WITH BIPOLAR DISORDER: ASSOCIATIONS WITH AGE, SUICIDALITY, SYMPTOM SEVERITY, COGNITION AND INFLAMMATION

Introduction Mixed affective states in bipolar disorder have been associated with increased number of mood episodes, increased suicidality, higher rates of co-occurring conditions, and poorer response to treatments. In order to better understand mixed symptomatology in bipolar disorder, here we examine the prevalence and associations of subjectively reported states of simultaneously high sadness and high energy as well as objectively rated concurrently high depressive and manic symptoms. Methods We used baseline data from an ongoing longitudinal study of subjects with Bipolar Disorder (BDs) and Healthy Controls (HCs). Our mixed-age sample (mean age 48.5, SD 7.7) included 50 BDs and 91 HCs. Baseline evaluation consisted of a 2-week burst of data collection. All subjects underwent objective tests of cognitive performance, lab tests for inflammatory markers, and BDs were assessed for suicidal ideation (SI) and suicidal behavior (SB) using Columbia-Suicide Severity Rating Scale (C-SSRS) at baseline, middle and end of the 2-week period. The proportion of ratings in which SI or SB was reported (P-SI and P-SB respectively) was used as a measure of degree of SI and SB. Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Brief Psychiatric Rating Scale (BPRS), and 36-Item Short Form Health Survey (SF-36) were administered to BD subjects at baseline. Participants were given a mobile phone and affective ratings were gathered 3 times per day for 14 days at random intervals approximating morning, mid-day, and evening. Ratings were scored on a scale of 0-7 across domains such as sad/depressed, happy, energetic, etc. Short Lived Mixed Affective States (SLMAS) were defined as instances of affective ratings with simultaneously high sadness/depression (≥4) and high energy (≥4). The proportion of total reported ratings with SLMAS (P-SLMAS) were calculated for all subjects. A group with objective mixed states (group M, N=15 [30.6%]) was defined as BDs with concurrently high HAM-D and YMRS scores (HAM-D ≥ median score of 17, YMRS ≥ median score of 6). These were compared to BD patients with both HAM-D and YMRS scores lower than median (group L; N=13 [26.5%]), with high depression/low mania (group D; N=20 [20.4%]), and with high mania/low depression (group Y; N=11 [22.4%]). We examined the association of subjective mixed affect (P-SLMAS) and objective mood state group with age, suicidality, symptom severity, cognition and inflammation and to each other using correlations and ANOVAs. Results Groups were well-matched on age and sex. In terms of subjective affective ratings, while both groups had low P-SLMAS overall, BDs had significantly higher P-SLMAS compared to HCs: 9.7% (SD 13.1%) vs 3.5% (SD 7.3%), p In the BD group, P-SLMAS was significantly correlated with BPRS total score (r=0.373, p=0.012), BPRS item-3/depression score (r=0.41, p=0.004), HAM-D total score (r=0.413, r=0.004), and SF-36 mental component score (r=-0.430, p=0.011), while no significant correlation was found with YMRS total score (r=0.079, p=0.598). Significant correlations were also noted with Cognitive Failures Questionnaire-25 score (r=0.347, p=0.048) and Brief Symptom Inventory Anxiety Scale score (r=0.349, p=0.043). These significant correlations remained significant on linear regression even when proportion of ratings with high-sadness and high-energy as separate variables were taken into consideration, indicating that these significant associations with P-SLMAS were not being driven by high-sadness or high-energy individually. No correlation was found between P-SLMAS and P-SI (r=0.104, p=0.525) and P-SB (r=0.062, r=0.668). No correlation was found between age and P-SLMAS (r=0.055, p=0.520), nor were there associations of P-SLMAS with gender, race, marital status or living situation. Furthermore, no correlation was found between P-SLMAS and objective tests of cognitive performance or inflammatory markers. In terms of objectively rated mixed states, Group M had significantly higher P-SI compared to groups L, D and Y (50% vs 0%, 21% and 5% respectively, p=0.003). Group M also had higher P-SB (10% compared to 0% for all other groups), however, this did not reach statistical significance (p=0.098). No significant difference was found between groups L, D, Y and M with regards to age and other demographic variables. No differences were found with regards to CFQ-25 score, BSIAS score, objective tests of cognitive performance, or inflammatory markers. Subjectively rated mixed affect and objectively rated mixed states were not strongly associated. P-SLMAS were not significantly different across L, D, Y and M groups (p=0.103), with groups D and M showing similarly high P-SLMAS (13.4% and 14.6% respectively) and groups L and Y showing similarly low P-SLMAS (4.5% and 4.8% respectively). Conclusions SLMAS, subjectively reported short-lived states of high sadness and high energy, are reported with greater frequency in BDs compared to HCs. SLMAS appear to be a marker of depressive pathology (akin to ‘agitated depression’) and are associated with greater symptom severity. SLMAS do not show a relationship with manic symptom severity, and therefore do not show a relationship with objectively defined mixed states. While SLMAS are not associated with suicidality, objectively rated concurrently high depressive and manic symptoms are associated with greater frequency of suicidal ideation. Future work will examine relationship with psychiatric comorbidities and treatment response. This research was funded by This work was supported by NIMH grant R01 MH103318 and the Desert-Pacific Mental Illness Research, Education, and Clinical Center.