Abstract:
:It has become increasingly appreciated that the long-term treatment of complex neuropsychiatric disorders like bipolar disorder (BD) involves the strategic regulation of signaling pathways and gene expression in critical neuronal circuits. Accumulating evidence from our laboratories and others has identified the family of protein kinase C (PKC) isozymes as a shared target in the brain for the long-term action of both lithium and valproate (VPA) in the treatment of BD. In rats chronically treated with lithium at therapeutic levels, there is a reduction in the levels of frontal cortical and hippocampal membrane-associated PKC alpha and PKC epsilon. Using in vivO microdialysis, we have investigated the effects of chronic lithium on the intracellular cross-talk between PKC and the cyclic AMP (cAMP) generating system in vivo. We have found that activation of PKC produces an increase in dialysate cAMP levels in both prefrontal cortex and hippocampus, effects which are attenuated by chronic lithium administration. Lithium also regulates the activity of another major signaling pathway the c-Jun N-terminal kinase pathway--in a PKC-dependent manner. Both Li and VPA, at therapeutically relevant concentrations, increase the DNA binding of activator protein 1 (AP-1) family of transcription factors in cultured cells in vitro, and in rat brain ex vivo. Furthermore, both agents increase the expression of an AP-1 driven reporter gene, as well as the expression of several endogenous genes known to be regulated by AP-1. Together, these results suggest that the PKC signaling pathway and PKC-mediated gene expression may be important mediators of lithium's long-term therapeutic effects in a disorder as complex as BD.
journal_name
Bipolar Disordjournal_title
Bipolar disordersauthors
Chen G,Masana MI,Manji HKdoi
10.1034/j.1399-5618.2000.20303.xkeywords:
subject
Has Abstractpub_date
2000-09-01 00:00:00pages
217-36issue
3 Pt 2eissn
1398-5647issn
1399-5618journal_volume
2pub_type
杂志文章,评审abstract:OBJECTIVE:To review research findings on clinical effects of discontinuing lithium maintenance treatment. METHODS:Data from studies reported since 1970 plus our recent findings were updated. RESULTS:Discontinuing lithium maintenance treatment led to marked increases of early affective morbidity and suicidal risk. Gra...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1034/j.1399-5618.1999.10106.x
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:To investigate the diagnostic profile of women referred for postpartum depression. METHODS:Fifty-six women seen consecutively with the referral diagnosis of postpartum depression were administered structured instruments to gather information about their DSM-IV Axis I diagnoses. RESULTS:In terms of frequency...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2008.00606.x
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVES:Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. METHODS:In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm...
journal_title:Bipolar disorders
pub_type: 杂志文章,随机对照试验
doi:10.1111/bdi.12594
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVES:We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD). METHODS:We acquired whole-brain fMRI data in 21 patients with BD an...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12241
更新日期:2014-12-01 00:00:00
abstract:OBJECTIVES:To compare the quality of life (QOL) of patients having dual diagnosis of bipolar affective disorder and substance dependence with those having either diagnosis alone and with healthy controls. METHODS:Cross-sectional assessment of the four groups of subjects was made. Euthymic bipolar patients and those su...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2004.00173.x
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVES:The present study examined the 5-year longitudinal course of cognitive functioning in a large sample of well-characterized patients with bipolar disorder (BP), compared to healthy controls (HCs), and the influence of cognitive reserve factors (e.g., education and IQ) on cognitive change over time. METHODS:P...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12470
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVES:Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium-induced encephalopathy depends on the poisoning pattern has not be...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12482
更新日期:2017-03-01 00:00:00
abstract:OBJECTIVES:The study was designed to test an audit-based quality improvement programme (QIP) addressing lithium prescribing and monitoring in UK mental health services. METHODS:A baseline clinical audit was conducted against the following standards: (i) measurement of renal and thyroid function before initiating treat...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12128
更新日期:2013-12-01 00:00:00
abstract:OBJECTIVES:As part of a cost-effectiveness analysis for Department of Veterans Affairs Cooperative Studies Program #430, 'Reducing the Efficacy-Effectiveness Gap in Bipolar Disorder,' we conducted a time and motion study to quantify the time psychiatric clinical nurse specialist (CNS) care managers spent providing care...
journal_title:Bipolar disorders
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1399-5618.2004.00159.x
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVES:The aim of the current study was to inform ongoing attempts to identify clinically meaningful subcategories of auditory verbal hallucination (AVH), and to evaluate evidence that might pertain to the suitability of current psychological interventions for people with bipolar disorder (BD) who experience psycho...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/bdi.12520
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Data from several studies suggest that medications, such as ketoconazole, which lower cortisol levels, may be effective for major depressive disorder (MDD). As with MDD, the manic, depressive, and mixed phases of bipolar disorder are frequently associated with elevated cortisol levels. The literature on the ...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1034/j.1399-5618.2001.030103.x
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVES:Hypomania in bipolar disorders is characterized by disinhibited, fearless and reward-seeking behavior. This behavioral pattern suggests that early and automatic responding to socio-emotional cues such as facial expressions might be aberrant in hypomania. The present study tested the predictions that particip...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2007.00425.x
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Acute mania can be modeled in animals using D-amphetamine (AMPH). Acute AMPH injections are associated with monoamine depletion, loss of neurofilaments and neurite degeneration. However, the precise mechanisms underlying AMPH-induced neurotoxicity are still unclear. Several studies have demonstrated that oxi...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2006.00318.x
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVES:Suicide is a leading cause of death in the USA. Although factors elevating long-term risk for suicide are known and include bipolar disorder, signs of imminent suicide risk are difficult to study and not well specified. Acute risk determinations must be made to determine the appropriate level of care to safe...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12092
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVES:Pediatric bipolar disorder is currently diagnosed based on signs and symptoms, and without objective diagnostic biomarkers. In the present study, we investigated the utility of structural neuroanatomical signatures of the amygdala to objectively differentiate individual subjects with pediatric bipolar disord...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12222
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:Recent theories regarding the neuropathology of bipolar disorder suggest that both neurodevelopmental and neurodegenerative processes may play a role. While magnetic resonance imaging has provided significant insight into the structural, functional, and connectivity abnormalities associated with bipolar disor...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/j.1399-5618.2012.01024.x
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Neurocognitive deficits are prevalent, persistent, and implicated as mediators of functional impairment in adults with bipolar disorder. Notwithstanding progress in the development of pharmacological treatments for various phases of bipolar disorder, no available treatment has been proven to be reliably effi...
journal_title:Bipolar disorders
pub_type: 杂志文章,随机对照试验
doi:10.1111/bdi.12006
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVES:The purpose of the present study has been to examine differences in the laterality of pain in patients with migraine and comorbid unipolar depressive (UP) and bipolar II (BP II) disorders. METHODS:Semi-structured interviews of 102 patients with major affective disorders were conducted, using DSM-IV criteria...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1034/j.1399-5618.2002.01226.x
更新日期:2002-10-01 00:00:00
abstract:OBJECTIVES:A high prevalence rate of bipolar disorder (BP) comorbid with alcohol dependence (AD) (BP+AD) in Western patients with BP has been reported, but whether this is true for Han Chinese with BP is uncertain. We explored the prevalence of BP+AD in a Han Chinese population with BP, and investigated the effect of a...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12313
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVES:In this study, we aimed to determine the role of genetic variations within the zinc finger protein 804A (ZNF804A) gene, a candidate for a psychosis risk-conferring gene, in the development of schizophrenia (SZ) and bipolar disorder (BP) in the Korean population. METHODS:A total of 921 patients with SZ, bipo...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12493
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVE:Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot s...
journal_title:Bipolar disorders
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1034/j.1399-5618.2000.020107.x
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVES:Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/bdi.12595
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVES:A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400-800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Youn...
journal_title:Bipolar disorders
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1399-5618.2008.00614.x
更新日期:2008-09-01 00:00:00
abstract::Lithium, the major drug used to treat manic depressive illness, robustly protects cultured rat brain neurons from glutamate excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors. The lithium neuroprotection against glutamate excitotoxiciy is long-lasting, requires long-term pretreatment and occurs at therap...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1034/j.1399-5618.2002.01179.x
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVES:The use of olanzapine (OLZ) in the prevention of postpartum psychosis (PP) and mood episodes in women with bipolar disorder was investigated in a naturalistic, prospective study. METHODS:Eleven women received OLZ alone or in combination with an antidepressant or mood stabilizer, and 14 women received either...
journal_title:Bipolar disorders
pub_type: 临床试验,杂志文章
doi:10.1111/j.1399-5618.2006.00335.x
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:This study examined health care resource utilization and direct health care costs among patients diagnosed with bipolar I disorder in a privately insured population. METHODS:Health care claims data for 2883 patients with a primary diagnosis of bipolar disorder were compared over a 1-year period (1997) with c...
journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1034/j.1399-5618.2002.01148.x
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Neurovascular abnormalities are relevant to the pathophysiology of bipolar disorder (BD), which can be assessed using cerebral blood flow (CBF) imaging. CBF alterations have been identified in BD, but studies to date have been small and inconclusive. We aimed to determine cortical gray matter CBF (GM-CBF) di...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/bdi.12966
更新日期:2020-06-24 00:00:00
abstract:OBJECTIVES:Cognitive dysfunction affects a significant proportion of people with bipolar disorder (BD), but the cause, trajectory and correlates of such dysfunction remains unclear. Increased understanding of these factors is required to progress treatment development for this symptom dimension. METHODS:This paper pro...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/bdi.12821
更新日期:2020-02-01 00:00:00
abstract:INTRODUCTION:Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative th...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/bdi.12622
更新日期:2018-06-01 00:00:00
abstract::Calcium channel antagonists (CCAs) have many clinical applications, including their possible use in the treatment of bipolar disorder. Two justifications for this last application are some overlap in physiological activities of CCAs with those of lithium, and a possible association between bipolar disorder and calcium...
journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1034/j.1399-5618.2000.020204.x
更新日期:2000-06-01 00:00:00