What causes depression in discordant monozygotic twins? Molecular psych. Sept 2013


Stress is an important trigger for depression. What is the role of genetics in this? Kendler has argued against dichotomy between purely stress-induced and purely biologically mediated depressions, or combinations of the two alone.  He suggested 11 categories of ‘difference makers” (molecular genetics, systems neuroscience, aggregate genetic effects, neuropsychological factors, personality and attitudinal factors, trauma exposure, as well as social, political and cultural factors) to account for.

In their most recent paper Kendler and Halberstadt , ( ‘The road not taken: life experiences in monozygotic twin pairs discordant for major depression) examines the life of 12 monozygotic twins reared together rigorously discordant for lifetime major depressive disorder (MDD).Authors interviewed each twin pair together to provide a joint biography and to describe important differences in their life course that might provide environmental sources of their discordance for MDD. The identical twins remained exceedingly close to one another and were often each other’s best friend.


The most common event that emerged prior to the development of MDD in the affected twin was the traumatic loss of an important romantic relationship. (in 8/12). In 5 of these 8 cases,  temperamental differences such as impulsivity, dependency and stimulus seeking may have contributed to early marriages that ended poorly. In 3 pairs, outcome of marriage appeared ‘bad luck’. A single event ( accident) was the precipitant for Md in two twin pairs only. Occupational stress resulted in depression in two pairs.

A previous study by Kendler (Kendler and Gardner 2001)  among 72 pairs of femlae Monozygotic twins has shown that the lifetime stressor  most closely associated with the risk for MDD was a history of divorce (odds ratio 6.2).

In the accompanying editorial (Gold) highlight the ‘dysregulation of stress response’ as the key etiological process in depression.  In acute stress, the response ( anxiety, focused attention, activations of the CRH and sympathetic nervous systems, and inhibition of behaviors likely to be deleterious in threatening situations) affects sleep, sexual activity, eating, attention and  mood shifts to reduce distractions.There is accompanying activation of inflammatory responses and anti bleeding pathways.To conserve energy, the activities of growth hormone and gonadal axes are diminished.  Melancholic depression presents with symptoms that closely reflect these changes.

Conclusions: Kendler’s study tell us one important thing:  the basic importance of environmental influences on well-being and psychopathology. Authors assert that “our moods are not only due to genetic differences between us, but substantially shaped by our cumulative environmental experiences”.

Summary of the article

The road not taken: life experiences in monozygotic twin pairs discordant for major depression.

Kendler KS, Halberstadt LJ. Mol Psychiatry. 2013 Sep;18(9):975-84.





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