Abstract
Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-β1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression.
Highlights
Of Bipolar disorder (BP), which is far wider than recognized by current diagnostic nosology[4]
DSM-5 criteria require a minimum duration of 4 days of hypomania, a growing body of evidence suggests that the DSM criteria for bipolar II disorder (BP-II) on the requisite duration of hypomania symptoms are too strict because they exclude a substantial percentage of patients with varying manifestations of bipolar syndrome[4,5,6,7,8,9]
The most recognized evidence is from family studies, some of which have reported that a family history of bipolarity in patients displaying a shorter duration of hypomania is more in line with BP-II than with unipolar depression[6,14,15]
Summary
Of BP, which is far wider than recognized by current diagnostic nosology[4]. DSM-5 criteria require a minimum duration of 4 days of hypomania, a growing body of evidence suggests that the DSM criteria for BP-II on the requisite duration of hypomania symptoms are too strict because they exclude a substantial percentage of patients with varying manifestations of bipolar syndrome[4,5,6,7,8,9]. In the BRIDGE study on a sample of 5635 patients with major depressive episodes[17], the validity of short-duration hypomania (defined by 1–3 day episodes) was examined; the study found that patients with only 1-day hypomanic episodes still differed markedly from those with unipolar depressive disorder in clinical manifestation including age of onset, illness progression, resistance to treatment, and history of suicide attempts. Their finding confirmed the existence of short-duration hypomania which has a similar validity to longer hypomanic episodes[17]. We believe our findings will serve as initial biological evidence for the classification of SBP, which might help clinicians diagnose and treat patients with SBP
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