Monday, February 04, 2008

30 is the new 70

44 is the age of depression, say researchers

By Richard Alleyne

The biggest lows of our lives are experienced in middle age, according to new research that concludes that Britons are at their most depressed aged 44.

Scientists believe that although we are closer to death as pensioners and powerless in youth, it is the "reality check" years of our 40s that are the most depressing.
I'm not writing about that article, which was based on a finding to appear in the journal, Social Science & Medicine (available online as a preprint on David G. Blanchflower's website). Instead, this post is about another downhill slide that does not recover as one ages.

A new imaging paper applied the technique of deformation field morphometry 1 to the MR images from a group of male subjects 18-51 years to quantify the effects of aging on neuroanatomical regions of interest (Pieperhoff et al., 2008). Although this paper is notable for technical reasons, it isn't the first to demonstrate how much your brain deteriorates by the age of 30 (e.g., Gur et al., 2002; Fotenos et al., 2005). In fact, the latter authors noted that
Whole-brain volume differences were detected by age 30.

Figure 2 of Pieperhoff et al., 2008. Horizontal sections of the reference brain with statistical maps, showing the t values of age-related volume decline and increase. t values were calculated by a two-sided t test for a linear regression in the voxels of the LVR [local volume ratio] maps, depending on age. The statistical map is thresholded according to a significance level of p less than .01.

The latest findings, in brief:
Age-related volume declines in circumscribed brain regions are detected, which are part of functionally defined systems, i.e., the sensorimotor system, encompassing the cerebellum, thalamus, somatosensory and motor cortices, and the prefrontal system, encompassing the anterior cingulate as well as the lateral and basomedial frontal cortices. Regions belonging to other functional systems, such as the auditory system or the visual system, did not show such age–volume relationships.
The ventricles showed a pronounced widening. Remarkably, these volume differences occur at a relatively early period of the human life span.
So maybe the hippies were right when they said, "don't trust anyone over 30"...


1 According to the authors:
Deformation field morphometry (DFM) is a highly automatized technique based on the nonlinear transformation (i.e., registration) of individual three-dimensional (3D) magnetic resonance (MR) images to a reference image. Each "source" MR image is warped to a reference image such that the differences between them are minimized, yielding a deformation field. The analysis of deformation fields enables quantification of the shape of human brains at the voxel level. Thus, this technique has the potential to detect local structural differences between brains. Various algorithms based on substantially different mathematical approaches have been proposed for DFM. The accuracy of the registrations may differ significantly between currently used algorithms (Crivello et al., 2002). In the present study, we applied an algorithm that is based on an elastic, nonlinear deformation of the source MR images (Hömke, 2006).

Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. (2005). Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 64:1032-9.

Gur RC, Gunning-Dixon FM, Turetsky BI, Bilker WB, Gur RE. (2002). Brain region and sex differences in age association with brain volume: a quantitative MRI study of healthy young adults.
Am J Geriatr Psychiatry 10:72-80.

Pieperhoff P, Homke L, Schneider F, Habel U, Shah NJ, Zilles K, Amunts K. (2008). Deformation Field Morphometry Reveals Age-Related Structural Differences between the Brains of Adults up to 51 Years. Journal of Neuroscience, 28(4), 828-842. DOI: 10.1523/JNEUROSCI.3732-07.2008

Age-related differences in the anatomical structure of the brains from 51 healthy male subjects (age: 18-51 years) were analyzed by deformation field morphometry in a cross-sectional study. The magnetic resonance images of the brains were nonlinearly registered onto the image of a reference brain: the registration algorithm simulated an elastic deformation of each brain (source brain) so that the voxelwise intensity differences with the reference brain were minimized. A three-dimensional deformation field was calculated for each source brain that encoded the anatomical differences between the source brain and the reference brain. Maps of voxelwise volume differences between each subject's brain and the reference brain were analyzed. They showed age-related differences in anatomically defined regions of interest. Major volume decreases were found in the white matter and nuclei of the cerebellum, as well as in the ventral thalamic nuclei and the somatosensory and motor cortices, including the underlying white matter. These findings suggest that aging between the second and sixth decade predominantly affects subcortical nuclei and cortical areas of the sensorimotor system, forming the cortico-rubro-cerebello-thalamo-cortical pathway. Additionally, a pronounced age-related decline in volume was observed in the rostral anterior cingulate, orbitofrontal, and lateral prefrontal cortices. Almost no differences were observed in the occipital and temporal lobes. The ventricles showed a pronounced widening. Remarkably, these volume differences occur at a relatively early period of the human life span. It may be speculated that these structural differences accompany or precede differences in sensorimotor functions and behavior.


Blanchflower DG, Oswald AJ (in press). Is Well-being U-Shaped over the Life Cycle?
Social Science & Medicine, 2008.

We present evidence that psychological well-being is U-shaped through life. A difficulty with research on this issue is that there are likely to be omitted cohort effects (earlier generations may have been born in, say, particularly good or bad times). First, using data on 500,000 randomly sampled Americans and West Europeans, the paper designs a test that can control for cohort effects. Holding other factors constant, we show that a typical individual’s happiness reaches its minimum -- on both sides of the Atlantic and for both males and females -- in middle age. Second, evidence is provided for the existence of a similar U-shape through the life-course in East European, Latin American and Asian nations. Third, a U-shape in age is found in separate well-being regression equations in 72 developed and developing nations. Fourth, using measures that are closer to psychiatric scores, we document a comparable well-being curve across the life cycle in two other data sets: (i) in GHQ-N6 mental health levels among a sample of 16,000 Europeans, and (ii) in reported depression and anxiety levels among 1 million U.K. citizens. Fifth, we discuss some apparent exceptions, particularly in developing nations, to the U-shape. Sixth, we note that American male birth-cohorts seem to have become progressively less content with their lives. Our paper’s results are based on regression equations in which other influences, such as demographic variables and income, are held constant.

Figure 1 of Blanchflower & Oswald, in press. The incidence of self-reported depression in the UK Labour Force Survey. Here the data are pooled for men and women across the period 2004Q2-2007Q1. The sample is for those aged 16-70. There are approximately one million observations (n=972,464), and the estimates are weighted using the person weights so are nationally representative.

Figure 3 of Fotenos et al., 2005. Cross-sectional and longitudinal plots of whole-brain volume, normalized for head size. (A) Cross-sectional plot of normalized whole-brain volume (nWBV) across the adult lifespan. The line represents the best-fit polynomial regression of all nondemented individuals and is referred to as the cross-sectional, nondemented aging curve.

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