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Repeated episodes of depression: what are the effects on the brain?

Depression is not an ordinary case of the blues—it causes lasting changes to the intellectual functions unless it is managed. According to the results of a study carried out by Philip Gorwood (Inserm Unit 894, “Psychiatry and Neurosciences Center”, Mental and Brain illness Clinic – CMME, Saint Anne’s Hospital, Paris), people who have already experienced two or more depressive episodes perform routine cognitive tasks that require attention, concentration and speed abnormally slowly. These results, published in the journal European Neuropsychopharmacology, appear to confirm that depression may be a “neurotoxic” illness. Preventing recurrences is therefore clearly essential.



Depression is a common illness that has affected, affects or will affect at least one person out of ten. it is characterised by a permanent sadness, a loss of motivation and pleasure, and altered appetite, sleep and libido. Diagnosis corresponds to specific criteria established by international psychiatric standards. Although different types of management, based on drugs and psychotherapy, have been shown to be effective, the risk of recurrence is high, even after several years of remission.

The consequences of these repeated recurrences are a source of concern for physicians and researchers. Although it has already been proven that there is psychomotor retardation in depressed people (this is indeed one of the diagnostic criteria for the illness), there was until now no indication that this change could persist following a depressive episode.

To find out more, researchers at Inserm carried out a study in more than 2,000 patients who had experienced between 1 and over 5 depressive episodes during their lives. In order to assess their cognitive abilities, they measured the speed in performing a simple test (TMT: trail making test), which consists of linking numbered circles distributed in a disordered manner on a sheet of paper. The test was performed twice for each patient: during the depressive episode, and then 6 weeks later, by which time a good proportion of these patients were in complete remission (with no residual depressive symptoms).

Just after a first episode of depression, the time to perform this test was 35 seconds. These performances were almost identical among people undergoing the second depressive episodes in their lives. However, for people who had already had a history of 2, 3 or more depressive episodes, this time was considerably longer, even in subjects who had recovered (1 min 20 sec instead of 35 sec).

“Several other variables offer a potential explanation (age, education level, occupation, etc.), but if these parameters are adjusted, our results remain extremely robust,” explains Philip Gorwood.

Trails_Screenshot2 test TMA

Fig 1: Sample TMT    
Fig 2: Speed of performing TMT during and after depression, according to the number of depressive episodes previously experienced.

This result is the first to show in such a simple manner the “neurotoxic” effects of depression. It also supports the daily observations made by physicians, and the conclusions of earlier epidemiological studies indicating that depression is an illness that becomes worse with time. The researchers therefore judge that after treatment, prevention of recurrence must be one of the priorities for management.

Moreover, this study might also provide an explanation for this vicious circle: the more depressive episodes I have experienced, the more likely I am to have a recurrence. If speed and efficacy are increasingly altered with the number of recurrences, we imagine that it will become more difficult to adapt to new situations. For example, a worker at a computer, showing limited attention span, oversights in the tasks required, and general slowness in carrying out his/her work, will have lower self-esteem and less recognition from his/her work colleagues, which could make him/her more vulnerable to recurrences of his/her depression in the event of any stress.

Finally, the fact that these cognitive impairments may occur as a sequela of depression might also be considered as an argument in favour of the use of “cognitive remediation.” This therapy is based on the controlled stimulation of the impaired cognitive functions in order to reduce the risk of recurrence. It is widely used in schizophrenia and addiction, but is rarely used to treat depressive disorders.”

Researcher Contact

Philip Gorwood

Unité Inserm 894 "Centre de Psychiatrie et de Neurosciences (CPN)
Chef de service CMME, Hopital Sainte-Anne

 Tel (33) (0)1 57 27 77 61 // 01 45 65 85 72
e-mail: rf.mresni@doowrog.pilihp ou rf.enna-etnias-hc@doowrog.p


Psychomotor retardation is a scar of past depressive episodes, revealed by simple Cognitive tests

P.Gorwood a,b, S.Richard-Devantoyc, F.Baylé d, M.L.Cléry-Melun a

a CMME (GroupeHospitalierSainte-Anne), Université Paris Descartes,Paris,France
b INSERM U894, Centre of Psychiatry and Neurosciences,Paris 75014,France
c Department of Psychiatry and Douglas Mental Health University Institute, McGill Group for Suicide Studies, Mc Gill University,Montreal, Quebec, Canada
d SHU (GroupeHospitalierSainte-Anne),7 rue Cabanis,Paris75014,France

European Neuropsychopharmacology.