Showing papers by "L. Trevor Young published in 2016"
United States Department of Health and Human Services1, University of Göttingen2, Ludwig Maximilian University of Munich3, University of Bonn4, Charité5, Dokkyo Medical University6, University of Barcelona7, Karolinska University Hospital8, State University of Campinas9, Medical University of Graz10, University of California, San Diego11, Mayo Clinic12, Paris Diderot University13, McGill University Health Centre14, University of Queensland15, National Taiwan University16, University Hospital of Basel17, University of Adelaide18, Newcastle University19, Douglas Mental Health University Institute20, Poznan University of Medical Sciences21, Geneva College22, French Institute of Health and Medical Research23, Neuroscience Research Australia24, University of New South Wales25, Dalhousie University26, Johns Hopkins University27, Osaka University28, University of Lorraine29, Goethe University Frankfurt30, Hokkaido University31, University of Gothenburg32, Karolinska Institutet33, Veterans Health Administration34, University of Antioquia35, University of Calgary36, University of Cagliari37, Aarhus University38, University of Cincinnati39, University of Naples Federico II40, University of Salerno41, Nagoya University42, Harvard University43, Dresden University of Technology44, Montreal Neurological Institute and Hospital45, United States Department of Veterans Affairs46, National Institutes of Health47, University of Iowa48, Roy J. and Lucille A. Carver College of Medicine49, Heidelberg University50, University of Toronto51, RIKEN Brain Science Institute52
TL;DR: A genome-wide association study of lithium response in 2,563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen); the largest attempted so far finds a single locus of four linked SNPs on chromosome 21 met genome- wide significance criteria for association with lithium response.
258 citations
TL;DR: The findings suggest that immune-activation in the frontal cortex may occur both in patients with BD and schizophrenia, while complex I dysfunction and NLRP3-inflammasome activation may be more specific to BD.
96 citations
TL;DR: It is suggested that lower BDNF levels, mitochondrial dysfunction, oxidative stress, inflammation and excitotoxicity may be contributing to neuronal and glial cell death in MDD, leading to decreased brain volume and cognitive dysfunction with multiple recurrent episodes.
Abstract: Major depression (MDD) is a chronic psychiatric condition in which patients often show increasing cognitive impairment with recurring episodes. Neurodegeneration may play an important component in the pathogenesis of MDD associated with cognitive complaints. In agreement with this, patients with MDD show decreased brain volumes in areas implicated in emotional regulation and cognition, neuronal and glial cell death as well as activation of various pathways that can contribute to cell death. Therefore, the aim of this review is to provide an integrative overview of potential contributing factors to neurodegeneration in MDD. Studies have reported increased neuronal and glial cell death in the frontal cortex, amygdala, and hippocampus of patients with MDD. This may be due to decreased neurogenesis from lower levels of brain-derived neurotrophic factor (BDNF), excitotoxicity from increased glutamate signaling, and lower levels of gamma-aminobutyric acid (GABA) signaling. In addition, mitochondrial dysfunction and oxidative stress are found in similar brain areas where evidence of excitotoxicity has been reported. Also, levels of antioxidant enzymes were reported to be increased in patients with MDD. Inflammation may also be a contributing factor, as levels of inflammatory cytokines were reported to be increased in the prefrontal cortex of patients with MDD. While preliminary, studies have also reported neuropathological alterations in patients with MDD. Together, these studies suggest that lower BDNF levels, mitochondrial dysfunction, oxidative stress, inflammation and excitotoxicity may be contributing to neuronal and glial cell death in MDD, leading to decreased brain volume and cognitive dysfunction with multiple recurrent episodes. This highlights the need to identify specific pathways involved in neurodegeneration in MDD, which may elucidate targets that can be treated to ameliorate the effects of disease progression in this disorder.
89 citations
TL;DR: The results suggest that elevated BMI is a significant contributor to inflammation in BD, more so even than recent mood illness severity, and point to inflammation as an important predictor of illness course, particularly depressive relapse.
36 citations
TL;DR: Lower levels of brain derived neurotrophic factor (BDNF) are found in patients with bipolar disorder than in healthy comparators, and these effects appear to be specific to patients with BD type I.
Abstract: Objectives Decreased levels of brain derived neurotrophic factor (BDNF) have been found in adult patients with bipolar disorder (BD) compared with a comparison group, yet there are no data specifically examining this in geriatric patients. The objective of this study was to examine whether euthymic late-life BD patients have lower BDNF levels than healthy comparators. Design Cross-sectional study. Setting Clinics at the University of Pittsburgh and the Centre for Addiction and Mental Health (Toronto). Participants Older patients with BD (age ≥ 50 years, N = 118) and similarly aged healthy comparators (N = 76). There were both BD type I (N = 91) and type II (N = 27) patients. Measurements Serum BDNF levels were assessed in BD patients and healthy comparators. Results We found lower levels of BDNF in patients with BD than in healthy comparators (9.0 ± 6.2 versus 12.3 ± 8.9 pg/µg, t (192) = −3.01, p = 0.002), which remained even after controlling for age, sex, lithium use, and site (F (1,176) = 4.32, p = 0.039). This decrease was found specifically in patients with BD type I (8.0 ± 5.5 versus 12.3 ± 8.9 pg/µg, t (165) = 3.7, Bonferroni p 0.001), but not type II (12.0 ± 7.5 versus 12.3 ± 8.9 pg/µg, t (101) = 0.14, Bonferroni p = 1.0). Conclusions Older patients with BD have lower serum levels of BDNF compared with similarly aged comparators. These effects appear to be specific to patients with BD type I. Future studies are needed to investigate the impact of reduced BDNF levels on cognition, mood, and other aspects of BD throughout the life course.
18 citations
TL;DR: Dentate gyrus–cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder and healthy controls is examined and whether BD‐II is associated with elevated peripheral levels of oxidative stress is investigated.
Abstract: Objectives Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. Methods We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). Results First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. Conclusions These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders.
16 citations
TL;DR: The results suggest thatDJ-1 is not significantly altered in BD subjects, however further studies are needed to examine DJ-1 expression levels in a cohort of older patients with BD.
Abstract: Phenomenologically, bipolar disorder (BD) is characterized by biphasic increases and decreases in energy. As this is a state-related phenomenon, identifying regulators responsible for this phasic dysregulation has the potential to uncover key elements in the pathophysiology of BD. Given the evidence suggesting mitochondrial complex I dysfunction in BD, we aimed to identify the main regulators of complex I in BD by reviewing the literature and using the published microarray data to examine their gene expression profiles. We also validated protein expression levels of the main complex I regulators by immunohistochemistry. Upon reviewing the literature, we found PARK-7, STAT-3, SIRT-3 and IMP-2 play an important role in regulating complex I activity. Published microarray studies however revealed no significant direction of regulation of STAT-3, SIRT-3, and IMP-2, but a trend towards downregulation of PARK-7 was observed in BD. Immunocontent of DJ-1 (PARK-7-encoded protein) were not elevated in post mortem prefrontal cortex from patients with BD. We also found a trend towards upregulation of DJ-1 expression with age. Our results suggest that DJ-1 is not significantly altered in BD subjects, however further studies are needed to examine DJ-1 expression levels in a cohort of older patients with BD.
11 citations