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Depression And Anxiety Are Triggered By Combination Of Environmental, Psychological, And Genetic Factors

a mother who is stressed outProblems like anxiety and depression are caused by psychological and environmental factors, and are known to be influenced by genetic proclivities. However, it is still not clear how each factor affects the brain’s functions to induce anxious and depressive symptoms. To shed light on these interactions, a team from the Centre Émotion-Remédiation et Réalité Virtuelle (Center for Emotion Remediation and Virtual Reality, CNRS / UPMC / CHU Pitié Salpêtrière) has investigated the amygdala, a part of the brain that is hyperactive in individuals suffering from anxiety and depression.

The researchers have shown that its activity can be modulated depending on the subject’s genetic makeup, personal history and cognition. These results suggest that the effects of psychotherapies on the cerebral activity of patients could vary according to their genetic traits. This work makes the cover story of the November 2011 issue of Human Brain Mapping.

Several studies published over the past decade point to the possibility that the 5-HTTLPR gene, which codes for the serotonin (a substance involved in emotional regulation) transporter, could play an important role in depression. The promoter of this gene can be in either long or short form, and the short version can accentuate the emotional impact of stressful events. Although this hypothesis remains controversial, it is accepted that the short form of the gene triggers a more intense activation of the amygdala, also known as the cerebellar tonsil, a brain structure involved in emotions and in the recognition of danger signals.

For this new project, the researchers studied the impact of psychological and environmental factors on the “genetic” effect by carrying out functional MRI brain scans on 45 healthy individuals, including carriers of both the short and long form of the gene. During the scans, the subjects were shown photographs of pleasant or unpleasant images and were asked either to indicate whether they found the effect pleasing or displeasing, or to think about the links between the images and themselves.

The results of the scans proved to be different depending on the form of the gene: carriers of the short form showed a higher activation of the amygdala when associating a photo with themselves than when deciding whether an image was pleasing or displeasing. The opposite was observed in the subjects who did not carry the short form. In other words, the activity of the amygdala varied according not only to the form of the gene, but also to the type of mental activity — whether it was an “objective” description of the image or an association with one’s personal history.

Prior to the scans, the subjects were interviewed about any negative events that may have occurred in their lives during the previous year, such as professional difficulties, separation, bereavement, etc. The results showed that the stress experienced during the year also affected the influence of the gene on the activation of the amygdala — such “genetic-environmental” interaction being itself modified by the individual’s mental activity.

The results show that while the subjects’ genetic makeup affects their brain functions, its influence is modulated by both personal history and psychological condition. Extrapolated to the field of depression, these results also suggest that psychotherapy — in particular, cognitive therapy, which consists in helping depressed patients to perceive the world differently — could have diverse cerebral effects depending on certain genes. Researchers are on the case.

Material adapted from CNRS (Délégation Paris Michel-Ange).

Cognitive Appraisal and Life Stress Moderate the Effects of the 5-HTTLPR Polymorphism on Amygdala Reactivity. Cédric Lemogne, Philip Gorwood, Claudette Boni, Mathias Pessiglione, Stéphane Lehéricy, and Philippe Fossati. Human Brain Mapping, November 2011.

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