Prefrontal brain morphology and executive function in healthy and depressed elderly
Semel Institute for Neuroscience and Human Behavior, Geriatric Division, UCLA, Los Angeles, CA 90024-1759, USA. International Journal of Geriatric Psychiatry
(Impact Factor: 2.87).
05/2009; 24(5):459-68. DOI: 10.1002/gps.2137
Late-life depression is known to correlate independently with decreased brain volumes in anterior cingulate, gyrus rectus and orbitofrontal cortex and with executive dysfunction, but the relationship between morphometry of reduced volume regions and executive dysfunction has not been well defined.
Nondepressed and depressed elders completed five executive tests, a standard panel of laboratory tests and magnetic resonance imaging. Images of the prefrontal cortex were manually masked and automatically segmented and regional brain volumes were calculated. Executive scores and error rates were regressed on bilateral white and gray matter volumes of anterior cingulate, gyrus rectus and orbitofrontal.
Gyrus rectus was associated positively with scores on sequencing and nonverbal abstract reasoning, and negatively with two fluency error scores. Four positive interactions indicated that performance of controls was more closely associated with increased volume than that of depressed patients. Anterior cingulate was associated positively with two nonverbal reasoning tasks and with three positive interactions. Orbitofrontal volumes were negatively associated with correct responses and errors on two fluency tasks. One interaction showed controls' performance decreased more than depressed patients with increased volume.
Individual executive tasks correlate positively with volumes of anterior cingulate and gyrus rectus regions and negatively with orbitofrontal region. The orbitofrontal relationship suggests a loss of inhibitory control with decreased volume because both correct and incorrect answers on fluency tasks increased per unit decrease in volume.
Available from: Johanna C Badcock
- "The brain circuitry supporting adult levels of inhibitory control centers on the prefrontal cortex (PFC), within which the ventral prefrontal cortex (VPFC) is proposed to play a primary role. Imaging studies of frontal gray matter volume reveal distinctly non-linear changes during development, with peak volume arising around 11–12 years of age (being somewhat earlier in females), followed by a rapid decline during adolescence (Gogtay and Thompson, 2010) and further decreases in volume in older adulthood (Elderkin-Thompson et al., 2009). In conjunction with these changes, recent evidence indicates that inhibitory processing in different subdivisions of PFC exhibits different operating characteristics before and after the onset of puberty (Luna et al., 2010). "
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ABSTRACT: The National Institute of Mental Health initiative called the Research Domain Criteria (RDoC) project aims to provide a new approach to understanding mental illness grounded in the fundamental domains of human behavior and psychological functioning. To this end the RDoC framework encourages researchers and clinicians to think outside the [diagnostic] box, by studying symptoms, behaviors or biomarkers that cut across traditional mental illness categories. In this article we examine and discuss how the RDoC framework can improve our understanding of psychopathology by zeroing in on hallucinations- now widely recognized as a symptom that occurs in a range of clinical and non-clinical groups. We focus on a single domain of functioning-namely cognitive [inhibitory] control-and assimilate key findings structured around the basic RDoC "units of analysis," which span the range from observable behavior to molecular genetics. Our synthesis and critique of the literature provides a deeper understanding of the mechanisms involved in the emergence of auditory hallucinations, linked to the individual dynamics of inhibitory development before and after puberty; favors separate developmental trajectories for clinical and non-clinical hallucinations; yields new insights into co-occurring emotional and behavioral problems; and suggests some novel avenues for treatment.
Frontiers in Human Neuroscience 03/2014; 8:180. DOI:10.3389/fnhum.2014.00180 · 3.63 Impact Factor
Available from: Christopher F Murphy
- "Furthermore, our findings complement reports that semantic clustering indices differentiate depressed elderly patients from controls, and that patients' executive functioning mediates episodic memory performance on list learning tasks (Elderkin-Thompson et al. 2007). Deficient strategy utilization may occur through ineffective inhibition of automatic actions, and mobilization of other goal-directed, strategic behavior (Deckersbach et al. 2005; Elderkin-Thompson et al. 2008; Nobre et al. 1999; Schoenbaum et al. 1998). "
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ABSTRACT: This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression.
Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates.
Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001).
Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.
International Journal of Geriatric Psychiatry 05/2012; 27(5):506-12. DOI:10.1002/gps.2743 · 2.87 Impact Factor
Available from: Jen-Chuen Hsieh
- "Executive dysfunction has been the most replicated cognitive function deficit in MDD, and it has been found to correlate with social disability (Kiosses et al., 2000), poor antidepressant response (Kalayam and Alexopoulos, 1999; Dunkin et al., 2000), and a higher probability of relapse (Alexopoulos et al., 2000). Early studies linked executive dysfunction with prefrontal cortical deficits (Rogers et al., 2004; Vasic et al., 2007; Elderkin-Thompson et al., 2009), though limbic structures were found to produce the same correlations. In an ROI-based study, Frodl et al. (2006) found significantly lower hippocampal volumes in MDD patients, which were correlated with poorer performance in executive function, as measured by the Wisconsin Card Sorting Test (WCST). "
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ABSTRACT: This study uses surfaced-based morphometry to investigate cortical thinning and its functional correlates in patients with major depressive disorder (MDD). Subjects with MDD (N=36) and healthy control subjects (N=36) were enrolled in the study. Each subject received T1 structural magnetic resonance imaging (MRI), clinical evaluations, and neuropsychological examinations of executive functions with the Color Trail Test (CTT) and the Wisconsin Card Sorting Test (WCST). This study used an automated surface-based method (FreeSurfer) to measure cortical thickness and to generate the thickness maps for each subject. Statistical comparisons were performed using a general linear model. Compared with healthy controls, subjects with MDD showed the largest area of cortical thinning in the prefrontal cortex. This study also noted smaller areas of cortical thinning in the bilateral inferior parietal cortex, left middle temporal gyrus, left entorhinal cortex, left lingual cortex, and right postcentral gyrus. Regression analysis demonstrated cortical thinning in several frontoparietal regions, predicting worse executive performance measured by CTT 2, though the patterns of cortical thickness/executive performance correlation differed in healthy controls and MDD subjects. In conclusion, the results provide further evidence for the significant role of a prefrontal structural deficit and an aberrant structural/functional relationship in patients with MDD.
Psychiatry Research 04/2012; 202(3):206-13. DOI:10.1016/j.pscychresns.2011.07.011 · 2.47 Impact Factor
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