Prof. Joe Herbert

Neurogenesis in the adult hippocampus. The brown spots are newly-formed cells.

Regulation of neurogenesis in the adult brain

Contrary to traditional ideas, the adult brain does make new neurons, but only in very restricted areas. One of these is the dentate gyrus of the hippocampus. Here new neurons are continually formed, grow axons, and make new connections with the hippocampal pyramidal cells (CA3). The hippocampus is known to be concerned with certain forms of memory (such as 'episodic' memory) but whether or how the formation of new neurons influences these functions is still rather uncertain. However, we do know
that the rate of new cell proliferation, and the survival of newly-formed neurons, is greatly altered by a number of factors. One set of these are steroid hormones from the adrenal. Glucocorticoids, such as cortisol in man, dramatically decrease neurogenesis. Since these hormones are secreted during stress, it may be that some of the adverse effects of stress are related to reduced neurogenesis. Dehydroepiandrosterone (DHEA) is another adrenal steroid, plentiful in man. DHEA stimulates neurogenesis. It also decreases with age in humans, and this may be related to declining cognitive function in older people. Antidepressant drugs that up-regulate serotonin (eg SSRIs) increase neurogenesis, which has suggested that depression or recovery from it may be related to the formation of new neurons.This is moderated by glucocorticoids, which are altered in many cases of depression. Since our clinical programme has identified individual differences in cortisol and DHEA as risk factors for subsequent depression, these cross-disciplinary experimental studies chime well with our clinical interests.

Our clinical work focuses on risk factors for depression in both adolescents (in which the illness often starts) and adult women (who are particularly prone to depression). We combine psychological measures (such as emotionality or self-esteem) with social ones (current or past family or other difficulties,) with hormonal measures (cortisol and DHEA in the saliva) and, mostly recently, polymorphisms in certain genes associated either with steroids or serotonin. We have established, for example, that
individuals with particularly high levels of cortisol on the morning, together with the experience of a sudden adverse 'life event' (usually a loss of some sort) are most likely to become depressed. Furthermore, these levels are related to a polymorphism in the serotonin transporter. Currently we have large prospective studies going on both in adolescents and in adult women. We hope to define the risk factors for this serious and common illness, and see how they interact, thus paving the way for preventative measures.

Colleagues

Dr Scarlett Pinnock (Research Associate)
Dr Diane Bamber (Research Associate)
Valerie Dunne (Research Assistant)
Sarah Cleary (Senior technician)
Jayn Wright(technician)
Min Lui (Research student)
Samaher Al-Ahmed (Research student)

Main collaborators

Prof Ian Goodyer (Dept Psychiatry, Cambridge)
Dr Tirril Harris (Psychiatry, St Thomas’ Hospital)
Dr Alan Ogilvie (Psychiatry, University of Oxford)
Dr Stephanie van Goozen (Cardiff University )
Prof Peter Jones (Psychiatry, Cambridge)
Dr Manuela Martinez (Psychobiology, University of Valencia)
Prof Lynne Murray (Psychology, University of Reaqding)
Dr Sarah Halligan (Psychology, University of Reading)

Support: Programme and project grants from the Wellcome Trust.

Recent Book: The Minder Brain  www.theminderbrain.com.   World Scientific Press
[How your brain keeps you alive, protects you from danger, and ensures that you reproduce].

References:

S.L Halligan , J. Herbert, I. Goodyer, L. Murray (2007) Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents. Biol Psychiatry 62, 40-46

S.B. Pinnock, R. Balendra, M. Chan, L.T Hunt, T. Turner-Stokes,J.Herbert (2007) Interactions between nitric oxide and corticosterone in the regulation of progenitor cell proliferation in the dentate gyrus of the adult rat. Neuropsychopharmacology 32 493-504

J. Herbert, I.M. Goodyer, A.B. Grossman, M.H. Hastings, E.R de Kloet, S.L. Lightman, S.J. Lupien, B. Roozendaal, J.R. Seckl (2006) Do corticosteroids damage the brain? J Neuroend.18, 393-411

G-J Huang and J Herbert (2005) Serotonin modulates the suppressive effects of corticosterone on proliferating progenitor cells in the dentate gyrus of the hippocampus in the adult rat. Neuropsychopharmacology. 30 :231-41.

EY Wong, J Herbert (2005) Roles of mineralocorticoid and glucocorticoid receptors in the regulation of progenitor proliferation in he adult hippocampus. Eur J Neurosci.;22 :785-92.

R N Carter, S B Pinnock and J Herbert (2004) Does the amygdala modulate adaptation to stress? Neuroscience 126, 9-19

S L Halligan, J Herbert, I M Goodyer, L Murray (2004) Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biol Psychiatry 55, 376-381

C F Hatfield, J Herbert, E J W van Someren, J R Hodges, M H Hastings (2004) Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer?s disease. Brain 127, 1061-1074

Y Temel, A Helmy, S Pinnock and J Herbert (2003) Effect of serotonin depletion on the neuronal, endocrine and behavioural responses to corticotropin-releasing factor in the rat. Neurosci Letters 338, 139-142

I M Goodyer, J Herbert and A Tamplin (2003) Psychoendocrine antecedents of persistent first-episode major depression in adolescents: a community-based longitudinal enquiry. Psychol Med. 33, 601-610

K Karishma and J Herbert (2002) Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly-formed neurons and prevents corticosterone-induced suppression. Eur. J Neurosci. 16, 445-453