Updated research in bipolar disorders: Subtypes, comorbidities, and novel treatment model

Ru Band Lu, Sheng Yu Lee

Research output: Contribution to journalArticlepeer-review


The two most common and severe subtypes of bipolar disorder (BP) are bipolar I (BP-I) and bipolar II disorder (BP-II) which may be two discriminating subtypes with different etiologies and characteristics during the course of illness. However, BP is commonly under-recognized even in psychiatric settings. Along with increased clinical recognition, most of the studies focusing on the differences between BP-I and BP-II only started after the years 2000 to 2003. Previous literature has documented that BP-I and BP-II might have different etiology, phenomenology, characteristics and neuropsychiatric functional impairments during the course of illness. Studies have also reported persistent cognitive impairments in patients with BP even after prolonged remission. BP is a disease with high comorbidity with-other psychiatric diseases. Among Western populations, 53-91% of bipolar patients have comorbid anxiety disorder. The lifetime prevalence of alcoholism was about 39% to 60% for BP in Western populations. The high comorbidity with alcoholism or anxiety disorder in patients with BP may produce many negative influences during the course of BP and during performance in neuropsychiatric testing. Our previous studies among the Han Chinese population in Taiwan revealed that the prevalence of comorbidity between BP and anxiety disorder is only 1/3 of BP patients, and the comorbidity of BP with alcoholism is about 10%, which is low in comparison to the high comorbidity rates in Caucasians. The relatively low comorbidity in our BP population permits us to identify subjects with only BP and no other comorbidities in order to study the influence of comorbidity on neuropsychiatric performance. We hypothesized that different subtypes of BP with or without comorbidities may have high genetic components. The genetic deficiency in BP patients may disturb neurotransmitters, neuromodulator, neuroprotective, and neurotrophic effects. Both environmental and genetic factors may induce a lot of endotoxins and exotoxins and decrease neurotrophic factors by overactivating microglial cells and inhibiting astroglia cells. Those effects may induce pre-inflammatory factors, which causes neuron damage or necrosis. This vicious cycle will allow the disease to get worse and worse. This hypothesis on the pathogenesis of neurodegeneration and inflammation of BP may be further supported by the fact that the brains of patients with BP contained fewer shrunken and withered neurons when they were treated with mood stabilizers. Studies suggested that several medications have been found to have neurotrophic and anti-inflammatory effects. Dextromethorphan (DM) has been reported to have a neuroprotective effect on monoamine neurons and to protect against endotoxicity, which is associated with the inhibition of microglia activation but not with its N-methyl-D-aspartate (NMDA) receptor antagonist property. Our research team reported that memantine hadpotent neuroprotective efficacy through two novel mechanisms: 1) increasing the release of neurotrophic factors and 2) anti-inflammatory action by inhibiting the activation of microglia. With regard to the proposed pathogenesis of BP, our research team is studying the effects of add-on DM and memantine on the treatment of BP to improve insights into the psychopathology of BP. This chapter includes updated researches on the clinical characteristics and neuropsychological performance of different subtypes of BP with or without comorbid anxiety disorders or alcoholism. We'll further review the pathogenesis of BP and via anti-inflammatory and neurotrophic effects.

Original languageEnglish
Pages (from-to)245-290
Number of pages46
JournalPsychiatry Research Journal
Issue number3-4
Publication statusPublished - 2011

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry


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