Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder.

OBJECTIVE: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. METHODS: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. RESULTS: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. CONCLUSION: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.

OBJETIVO: A ciclagem para mania associada ao antidepressivo tem sido relacionada à aceleração do ciclo e pior evolução, mas há poucos estudos na literatura sobre este assunto. O objetivo deste estudo foi comparar prospectivamente a evolução de pacientes com mania associada a antidepressivo com pacientes com mania espontânea, em relação a tempo para recaída e polaridade do novo episódio. MÉTODO: Vinte e quatro pacientes com transtorno bipolar, de acordo com os critérios diagnósticos do DSM-IV, foram seguidos por 12 meses: 12 pacientes com mania associada a antidepressivo e 12 pacientes com mania espontânea. Os pacientes foram avaliados semanalmente com a Escala para Mania de Young e a Escala para Depressão de Hamilton até remissão do episódio inicial e, mensalmente, até completar o período de seguimento de 12 meses. RESULTADOS: Onze pacientes com mania associada ao antidepressivo tiveram uma recorrência no seguimento, sendo todos os episódios depressivos. No grupo de mania espontânea, seis pacientes apresentaram recorrência, sendo dois episódios depressivos, e quatro episódios de mania (p = 0,069 para novo episódio e p = 0,006 para polaridade do episódio). Pacientes com mania associada a antidepressivo recaíram em um menor período de tempo que os pacientes com mania espontânea (p = 0,016). CONCLUSÕES: Neste estudo prospectivo, os pacientes com mania associada a antidepressivo apresentaram maior risco de recorrência, especialmente episódios depressivos, e com menor duração de remissão quando comparados aos pacientes com mania espontânea.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome.

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.