Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele

Cao, Bo; Bauer, Isabelle E.; Sharma, Alok; Mwangi, Benson; Frazier, Thomas; Lavagnino, Luca; Zunta-Soares, Giovana; Walss‐Bass, Consuelo; Glahn, David C.; Kapczinski, Flávio; Nielsen, David A.; Soares, Jair C.

doi:10.1016/j.jad.2016.03.044

“…However, no other study has done a longitudinal investigation of the correlation between changes of plasma BDNF and changes of cognitive function in the subtypes of BD while considering the effects of the BDNF Val66Met polymorphism. Inconsistent results were found regarding the association between the BDNF Val66Met polymorphism and cognitive function in BD; one suggested a non-significant association 56 , one said that those with Val/Val genotypes performed better 31 , two said that those with the Met allele performed worse 57,58 , and two attribute the worse performance of BD patients with the Met allele to the smaller hippocampus volumes of patients with the Val/Val genotype 32,58 . Some researchers have reported a non-significant correlation between peripheral BDNF levels and WCST scores 59 and executive function in BP-I 60,61 .…”

Section: Discussionmentioning

confidence: 99%

The Correlation between Plasma Brain-derived Neurotrophic Factor and Cognitive Function in Bipolar Disorder is Modulated by the BDNF Val66Met Polymorphism

Lee

¹

2017

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We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners' Continuous Performance Test (CPT) were assessed at baseline and endpoint. The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r = −0.25, p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r = −0.54, p = 0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.Bipolar disorder (BD) is characterized by recurrent episodes of dysregulated moods 1,2 . With high heritability 3 , genetic factors had been regarded as an important etiology for BD. The most frequently seen subtypes of BD are bipolar I disorder (BP-I) and bipolar II disorder (BP-II). Being a chronic mental disorder, BD is increasingly regarded as a neurodegenerative disorder supported by imaging studies 4,5 . Brain-derived neurotrophic factor (BDNF) is an important protein for neuron development, growth and survival 6 . BDNF is robustly expressed

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“…However, no other study has done a longitudinal investigation of the correlation between changes of plasma BDNF and changes of cognitive function in the subtypes of BD while considering the effects of the BDNF Val66Met polymorphism. Inconsistent results were found regarding the association between the BDNF Val66Met polymorphism and cognitive function in BD; one suggested a non-significant association56, one said that those with Val/Val genotypes performed better31, two said that those with the Met allele performed worse5758, and two attribute the worse performance of BD patients with the Met allele to the smaller hippocampus volumes of patients with the Val/Val genotype3258.…”

Section: Discussionmentioning

confidence: 99%

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

Lee

¹

,

Wang

²

,

Chang

³

et al. 2016

Sci Rep

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We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners’ Continuous Performance Test (CPT) were assessed at baseline and endpoint. The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r = −0.25, p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r = −0.54, p = 0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.

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“…Indeed, verbal memory deficits of large effect size have been consistently reported in BD (Bora, Yücel, Pantelis, & Berk, 2011), in particular with regard to immediate and delayed recall (Bora et al, 2009; Martínez-Arán et al, 2004; Van Der Werf-Eldering et al, 2010; van Gorp et al, 1998). Another study showed that immediate recall was significantly impaired in BD patients with more than 3 manic episodes when compared to HC (Cao, Passos, et al, 2016). Notably, although belonging to the same age group, illness duration was considerably greater (ranging from 18.81 to 22.47 years) than that reported by our participants (approximately 9 years).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, deficits in verbal memory have been found to persist across mood phases, which may indicate that these deficits are traits markers of BD (Gualtieri & Johnson, 2006). Along with neurocognitive impairment, BD has been associated with abnormalities in a range of brain regions (Cao, Bauer, et al, 2016; Javadapour et al, 2010; Radaelli et al, 2015) including the hippocampus, a core region for declarative memory (Eldridge, Knowlton, Furmanski, Bookheimer, & Engel, 2000). …”

Section: Introductionmentioning

confidence: 99%

Effect of alcohol and illicit substance use on verbal memory among individuals with bipolar disorder

Cardoso

¹

,

Bauer

²

,

Jansen

³

et al. 2016

Psychiatry Research

Self Cite

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Background Cognitive impairment is a well-established feature of bipolar disorder (BD). Comorbid BD and substance use leads to poor psychosocial and clinical outcomes. However, knowledge on the neurocognitive functioning of individuals with dual diagnosis is limited. The aim of this study is to assess the cognitive performance of subjects with BD, BD with comorbid alcohol use disorder (AUD), and BD with comorbid illicit substance use disorders (SUD) as compared to healthy individuals. Methods We included 270 inpatients and outpatients with BD and 211 healthy controls. The diagnostic of BD and substance use disorder was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I. Demographic and clinical information were also collected. The cognitive assessment included the Wechsler Test of Adult Reading (WTAR), and a revised version of the California Verbal Learning Test (CVLT) as part of the South Texas Assessment of Neurocognition (STAN). Results The STAN was administered to 134 BD patients (100 female, M±SD: 37.37±12.74 years), 72 BD patients with AUD (40 female, M±SD: 38.42±11.82), 64 BD patients with SUD (39 female, M±SD: 34.50±10.57), and 211 healthy controls with no lifetime history of mental illness and substance use (127 female, M±SD: 34.80±12.57 years). In terms of clinical characteristics, BD+SUD showed a marginally earlier onset of illness compared to BD. Compared to HC, BD performed poorly in the immediate recall and short-delay free tests of the CVLT, while BD patients with AUD and SUD showed significant memory deficits in both the immediate recall and recognition components of the CVLT. There were no differences in memory performance between BD and BD with either AUD or SUD. Conclusions A history of substance use disorders is associated with an earlier onset of BD. BD has marked effects on processes underlying the encoding of new information, while comorbid substance use in BD impairs more specifically the recognition of previously presented information. Future longitudinal studies should evaluate the effects of AUD and SUD on illness progression and therapeutic outcomes.

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Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele

Cited by 81 publications

References 92 publications

The Correlation between Plasma Brain-derived Neurotrophic Factor and Cognitive Function in Bipolar Disorder is Modulated by the BDNF Val66Met Polymorphism

The Correlation between Plasma Brain-derived Neurotrophic Factor and Cognitive Function in Bipolar Disorder is Modulated by the BDNF Val66Met Polymorphism

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

Effect of alcohol and illicit substance use on verbal memory among individuals with bipolar disorder

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