Testing the Hypothesis of Accelerated Cerebral White Matter Aging in Schizophrenia and Major Depression

Kochunov, Peter; Glahn, David C.; Rowland, Laura M.; Olvera, Rene L.; Winkler, Anderson M.; Yang, Ying; Sampath, Hemalatha; Carpenter, W.; Duggirala, Ravindranath; Curran, Joanne E.; Blangero, John; Hong, L. Elliot

doi:10.1016/j.biopsych.2012.10.002

Cited by 112 publications

(115 citation statements)

References 58 publications

(75 reference statements)

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“…One study found that those with schizophrenia exhibit accelerated decline of whole brain fractional anisotropy, an index of white matter integrity measured using diffusion-weighted MRI. 40 Other studies have reported that individuals with bipolar disorder exhibit accelerated grey matter reduction with age 41 and rapid decline of levels of brain-derived neurotrophic factor, an index of neuronal survival and integrity that is associated with aging effects in the brain. 42 Given that aberrant reward processing has also been reported in individuals with schizophrenia and bipolar disorder, [43][44][45][46] researchers might profitably take a transdiagnostic approach to identifying potential protective factors and treatment targets of accelerated cellular aging across psychiatric disorders.…”

Section: J Psychiatry Neurosci 2017;42(3)mentioning

confidence: 99%

Accelerated aging of the putamen in patients with major depressive disorder

Sacchet

Camacho

Livermore

et al. 2017

JPN

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IntroductionMajor depressive disorder (MDD) is primarily characterized by depressed mood and a blunted experience of pleasure (i.e., anhedonia). 1 The disorder is prevalent and chronic and represents a substantial personal, social and economic burden. [2][3][4] Neuroscience promises to elucidate mechanisms under lying depressive pathophysiology, leading to more effective approaches to the prevention and treatment of this debilitating disorder.Considerable evidence indicates that reward processing is dysfunctional in individuals with MDD. 5,6 The basal ganglia (BG) are a set of subcortical structures, including the striatum (caudate and putamen), nucleus accumbens and pallidum, that are critically involved in these reward processing steps. 7Previously research has indicated that depressed individuals have decreased activation in the striatum, 5,6 and some investigators have hypothesized that this abnormal activity affects decision-making. 5 Research in both animals and humans suggests that the dorsal striatum is involved in action selection and initiation and in encoding and integrating sensorimotor, cognitive and motivational/emotional information.8 Current evidence is mixed regarding specific roles of the putamen and caudate in reward processing. The results of several studies using fMRI suggest that whereas the putamen specifi cally encodes reward-related feedback, the caudate encodes both reward and punishment feedback.9,10 Finally, researchers have reported that the putamen is activated most strongly during anticipation of reward, whereas the caudate is activated most strongly during the receipt of reward. 8,10,11 A growing body of research indicates that adults with MDD have smaller volumes of the caudate 12-15 and putamen 13,14,16,17 than healthy controls. Postmortem studies have also reported smaller putamen volumes in depressed than in nondepressed adults. 18 It is important to note that these studies typically include adult samples with a mean age older than 40 years. Depression-associated differences in BG volumes are less consistent in samples of both younger adults 19,20 and adolescents. 21 It appears, therefore, that this discrepancy is associated with age differences in the study Background: Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants. Methods: We obtained whole-brain T 1 -weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests. Results: We included 232 individuals (116 patients with MDD) in our analy...

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Section: J Psychiatry Neurosci 2017;42(3)mentioning

confidence: 99%

Accelerated aging of the putamen in patients with major depressive disorder

Sacchet

Camacho

Livermore

et al. 2017

JPN

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“…This has led to a suggestion that schizophrenia is associated with accelerated biological aging (Anthes, 2014;Dawes et al, 2011;Kirkpatrick et al, 2008;Kochunov et al, 2013;Koutsouleris et al, 2014;Lindqvist et al, 2015;Okusaga, 2014;Schnack et al, 2016;Shivakumar et al, 2014). Whereas men have overall higher death rates than women, mortality ratios in schizophrenia (standardized to the general population with respect to age, race/ethnicity and geographic region) are higher in women than in men with schizophrenia, with cardiovascular disease being a leading cause of premature death in both genders (Olfson et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Leukocyte telomere length: Effects of schizophrenia, age, and gender

Wolkowitz

Jeste

Martin

et al. 2017

Journal of Psychiatric Research

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a b s t r a c tBackground: Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age. Methods: We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years. Results: Overall, LTL was inversely associated with age (t(249) ¼ -6.2, p < 0.001), and a gender effect on the rate of LTL decrease with age was found (t(249) ¼ 2.20, p ¼ 0.029), with men declining more rapidly than women. No significant overall effect of diagnosis on the rate of decline was detected. However, at the average sample age (48 years), there was a significant gender effect in both schizophrenia and HC groups (t(249) ¼ 2.48, p ¼ 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) ¼ 2.43, p ¼ 0.016) -at the average sample age, women with schizophrenia had shorter LTL than HC women. Discussion: Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women.Published by Elsevier Ltd.

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“…Rodríguez-Sánchez et al (2007) reported that when processing speed was removed from a multivariate model, the cognitive deficits observed in patients with schizophrenia were no longer significant compared with healthy controls. Furthermore, schizophrenia patients show an accelerated ageing decline in cerebral white matter linked to an accelerated decay in processing speed when compared to healthy participants in cross-sectional and longitudinal studies (Karbasforoushan et al, 2015;Kochunov et al, 2013;Liu et al, 2013;Ritchie et al, 2015). Thus, deficits in speed of information processing represent an important cognitive marker of risk (Gur et al, 2014;Seidman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia

Alloza

Cox

Duff

et al. 2016

Psychiatry Research: Neuroimaging

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Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing.

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Testing the Hypothesis of Accelerated Cerebral White Matter Aging in Schizophrenia and Major Depression

Cited by 112 publications

References 58 publications

Accelerated aging of the putamen in patients with major depressive disorder

Accelerated aging of the putamen in patients with major depressive disorder

Leukocyte telomere length: Effects of schizophrenia, age, and gender

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia

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