1 Boring Old Man

Of course 1boringoldman isn’t in the CME business and certainly can’t offer any kind of credits, but reading the articles in the series above [all freely available full text on-line] is definitely a valuable educational experience about any number of things.

Telomere length and cortisol reactivity in children of depressed mothers

by I H Gotlib, J LeMoult, N L Colich, L C Foland-Ross, J Hallmayer, J Joormann, J Lin and O M Wolkowitz

Molecular Psychatry. doi: 10.1038/mp.2014.119.

[full text on-line]

A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.

What can be done to reduce the risk of depression? In previous experiments, girls at risk for depression exhibited different patterns of brain activation during experimental mood regulation. In ongoing experiments, the Gotlib team is using neurofeedback to help these girls retrain their brain circuits and hopefully their stress responses. It will be a few years before we will know how much this intervention reduces risk for depression, but anything that prevents or slows the telomere shortening may be an early indication of success.

In this two-part blog post, I’ll document this process of amplification of the distortion of science from article to press release to subsequent coverage. In the first installment, I’ll provide a walkthrough commentary and critique of a flawed small study of telomere length among daughters of depressed women published in the prestigious Nature Publishing Group journal, Molecular Psychiatry. In the second, I will compare the article and press release to media coverage, specifically the personal blog of NIMH Director Thomas Insel. I warn the squeamish that I will whack some bad science and outrageous assumptions with demands for evidence and pelt the study, its press release, and Insel’s interpretation with contradictory evidence.  I’m devoting a two-part blog to this effort. Bad science with misogynist, mother bashing assumptions is being touted by the Director of NIMH as an example to be followed.

NIMH Director Thomas Insel should stick to his knitting. He has no business setting scientific directions for the field, as with the RDoC mandates. I suppose it is an occupational hazard of administrators to prefer a top-down management style. Problem is, science is a bottom-up business. His shallow hyping of the Gotlib-Wolkowitz report is a further reason to disqualify him.

Dr. Insel is on record with an amateurish view of how clinical science moves forward. See PubMed #22869033. When he says we should sidestep the issue of a gold standard he plainly doesn’t understand the iterative process of nosology or the related concept of convergent validity. He doesn’t seem to understand the need to advance nosology by incorporating biomarkers along with clinical symptoms in diagnostic definitions, as happened in general medicine. And he shows no understanding of the need for a Bayesian perspective on the interpretation of biomarkers as well as of definitional symptoms. When he proposes tracking biological markers across current diagnostic domains he ignores the central issue of pathophysiology. Consider where we would end up if, for instance, we lumped Cushing disease together with juvenile onset diabetes mellitus, Type II diabetes mellitus, severe psychological or physiological stress, metabolic syndrome, anorexia nervosa, and pregnancy on the basis of an abnormal glucose tolerance test, which these all can display.

The RDoC matrix that Dr. Insel insists should be adopted in new grant proposals to NIMH is a classic product of armchair scholastic theorizing. We are already seeing researchers bend like pretzels to make their proposals and journal submissions appear RDoC-friendly. The effect is contrived, to put it mildly. We can expect that the RDoC matrix eventually will go the way of the eccentrics and epicycles of 16th Century astronomy. The pressing issue is how much damage will be done before that happens? Director Insel and his lieutenants at NIMH need to get out of the way – their presumptuousness is breathtaking.