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Reduced overflow of BDNF from the brain is linked with suicide risk in depressive illness

Molecular Psychiatry volume 12, pages 981–983 (2007)Cite this article

Neurotrophic factors are thought to play an important role in the development of major depressive disorder (MDD). The neurotrophic hypothesis of depression suggests that stress increases the susceptibility to depressive illness via increased hypothalamic–pituitary–adrenal axis activation, in turn decreasing neurotrophic factors that are required for hippocampal neuronal survival and function.1 Postmortem studies have investigated neurotrophic factors in suicide patients revealing decreased brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus2 and leptin in the hypothalamus.3 In suicidal patients, BDNF and neurotrophin-4 levels were reduced in cerebrospinal fluid.4 Recently, low peripheral plasma BDNF concentrations were shown to be associated with suicide behaviour in patients with MDD.5 Studies utilizing peripheral indices of brain-derived products present methodological complications in that many neurotransmitters and neuromodulators are released from sites other than the brain.6 Indeed, in humans, BDNF has been identified in platelets7 and endothelial cells,8 rendering it difficult to extrapolate directly peripheral BDNF levels to activity in the brain. To circumvent this issue, we used direct internal jugular vein blood sampling methodology6 to examine the relationship between brain BDNF production and suicide risk in unmedicated patients with MDD.

Nineteen subjects (8 men/11 women, aged 46±3 years, BMI 26±1) meeting DSM-IV diagnostic criteria for MDD were recruited from the community via media advertisement. Patients were either newly diagnosed or with a past history of MDD who had suffered a recent relapse and were on no antidepressant medication or therapy. All subjects were screened for underlying physical illness. Exclusion criteria included comorbid medical conditions such as pre-existing heart disease, diabetes, medicated hypertension, epilepsy, alcohol/drug dependence, infectious blood diseases, comorbid psychotic disorders, eating disorders, mental retardation, dementia (MMSE <23) and personality disorders. All patients had a psychiatric interview and were evaluated using the full Mini International Neuropsychiatric Interview (MINI). Hamilton depression rating scale (Ham D; 17 items) was used to monitor depression severity. Eligibility for entry were determined by Ham D>18, major depression diagnosis on MINI and by patients being judged to have a significant major depression as the primary illness at psychiatric interview. Clinician-rated suicide risk was assessed using the suicidality score on the MINI. This comprises thoughts about planning and previous attempts, gaining a score of current suicide risk. Low risk was classified as 1–5 points; medium as 6–9 points; and high as over 10 points. Ethics approval was obtained from the Alfred Hospital Human Research Ethics Committee, and written informed consent was obtained from each participant before the study. Following completion of the study, patients were referred to a psychiatrist for clinical management.

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Authors and Affiliations

  1. Human Neurotransmitters Laboratory, Baker Heart Research Institute, Melbourne, VIC, Australia

    T Dawood, J Anderson, D Barton, E Lambert, M Esler, E Hotchkin, D Haikerwal & G Lambert

  2. Wynn Department of Cardiology, Baker Heart Research Institute, Melbourne, VIC, Australia

    D Kaye

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  1. T Dawood
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  2. J Anderson
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  3. D Barton
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  4. E Lambert
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  5. M Esler
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  6. E Hotchkin
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  7. D Haikerwal
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  8. D Kaye
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  9. G Lambert
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Correspondence to T Dawood.

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Dawood, T., Anderson, J., Barton, D. et al. Reduced overflow of BDNF from the brain is linked with suicide risk in depressive illness. Mol Psychiatry 12, 981–983 (2007). https://doi.org/10.1038/sj.mp.4002059

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