John van Geest Centre for Brain Repair

School of Clinical Medicine

Sections

 

In this section

 

Joe Herbert

Emeritus Professor of Neuroscience, University of Cambridge

Director of Graduate Training, Department of Clinical Neurosciences, University of Cambridge

Formerly chair, Graduate School of Biosciences

jh24@cam.ac.uk

My interests centre on the way hormones alter the function of the brain.  I focus on three principal areas:

1. The role of hormones in the ability of the adult brain to make new nerve cells (neurons) and repair the brain. Part of the brain called the hippocampus, which is known to be concerned with storing recent memory,  continues to make new neurons throughout adult life. HerbertHowever, the hippocampus is very vulnerable to injury; for example, it is one of the first parts of the brain to be affected by Alzheimer’s disease.  Its ability to make new neurons is very sensitive to a number of events, particularly the action of ‘stress’ hormones such as cortisol. Cortisol drastically reduces the formation of new neurons, whereas another hormone, DHEA, increases it and can offset some of the actions of cortisol. DHEA decreases in man with age, which may account for some of the memory difficulties associated with ageing.  Some drugs increase the formation of new nerve cells in the hippocampus: these include anti-depressants (such as Prozac) and this has suggested that their action on depression may, in some way, be related to the growth of new neurons in the hippocampus. We are studying these actions, as well as the ability of grafts of brain tissue to repair the damaged hippocampus.

2. The role of stress hormones (such as cortisol) in depression. My clinical work is carried out in collaboration with psychiatrists and psychologists interested in the risks for depression, particularly in young people (adolescents). Individuals with higher (though normal) levels of cortisol are at increased risk of depression if they experience adversity in their lives.  Furthermore, adversity early in life (for example, poor parenting) results in increased cortisol levels in these infants when they reach adolescence.  This may influence their susceptibility to mental illness.  Girls also have higher levels of cortisol than boys, and a greater incidence of depression. We are now studying how cortisol and other factors (eg social and psychological ones) interact with common variations in a person’s genes (such as those regulating serotonin or growth factors in the brain, such as  BDNF) to increase the risk for depression, or offer some protection against this serious illness in people experiencing severe adversities in their lives. We are also interested in why a history of chronic or repeated depression enhances the risk for subsequent Alzheimer’s disease.

3. Hormones and genes in financial decision-making.  People who work in high risk occupations, such as financial traders (but also airline pilots, surgeons, footballers and racing drivers etc)  have to make rapid decisions with important consequences both for themselves and for others.  In collaboration with economists and others I am studying how individual differences in hormones, particularly testosterone and cortisol, influence such decisions and the appetite for financial risk-taking, and how the genetic makeup of different traders also contributes to their success or otherwise under the severe pressure that such jobs entail.

Principal collaborators

  • Scarlett Pinnock, Brain Repair Centre, Cambridge
  • Ian Goodyer, Psychiatry, Cambridge
  • Valerie Dunne, Psychiatry, Cambridge
  • Tirril Harris, Psychiatry, St Thomas’ Hospital
  • Tom Craig, Psychiatry, St Thomas’ Hospital
  • Stephanie van Goozen, Psychology,Cardiff University
  • George Brown, St Thomas’ Hospital
  • Tim Croudace, York University
  • Lynne Murray, Reading University
  • Sarah Halligan, Reading University
  • Ed Roberts, Imperial College
  • Aldo Rusticini, University of Minnesota.
  • Jay Schulkin, University of Washington
  • Aviva Tolkovsky, Cambridge

Some recent books and papers.

Testosterone: the molecule that made history. Oxford University Press (in press)

The Minder Brain (How your brain keeps you alive, protects you from danger, and ensures that you reproduce).  World Scientific Press 2009

Owens, M, Herbert, J, Jones, PB, Sahakian, BJ, Wilkinson, PO, Dunn, VJ, Croudace, TJ, Goodyer, IM (2014) Elevated morning cortisol is a stratified population level biomarker for major depression in boys only with high depressive symptoms.  Proceedings of the National Academy of Sciences USA 111: 3638-3643

Herbert J (2013) Cortisol and depression: three questions for psychiatry. Psychol Med. 43 :449-69

Brown GW, Ban M, Craig TK, Harris TO, Herbert J, Uher R. (2013)  Serotonin transporter length polymorphism, childhood maltreatment and chronic depression: a specific gene-environment interaction. Depress Anxiety. 30: 5-13.

Herbert J, Ban M, Brown GW, Harris TO, Ogilvie A, Uher R, Craig TK. (2012) Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women. Brit J Psychiatry. 201:313-9

St Clair MC, Goodyer IM, Dunn V, Herbert J, Jones PB, Croudace T. (2012) Depressive symptoms during adolescence: comparison between epidemiological and high risk sampling.  Soc Psychiatry Psychiatr Epidemiol.47:1333-41

Chen, X, Lepier A, Berninger B, TolkovskyA.M., Herbert J. (2012) Cultured subventricular zone progenitor cells transduced with neurogenin-2 become mature glutamatergic neurons and integrate into the dentate gyrus. PLoS ONE. 2012. 7(2): e31547

Russ, SJ.,  Herbert, J.,  Cooper, PJ., Gunnar, MR., Goodyer, IM., Croudace, T., Murray, LM. (2012)  Cortisol levels in response to starting school in children at increased risk for social phobia. Psychoneuroendocrinology, 37, 462-474

Chen X, Tolkovsky AM, Herbert J (2011) Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat. PLoS One. 2011 Feb 16;6(2):e17072.

Landt J, Ball SL, Holland AJ, Hon J, Owen A, Treppner P, Herbert J. (2011) Age-related changes in plasma dehydroepiandrosterone levels in adults with Down’s syndrome and the risk of dementia. J Neuroendocrinol. 23(5):450-5

Liu JX, Pinnock SB, Herbert J. (2011) Novel control by the CA3 region of the hippocampus on neurogenesis in the dentate gyrus of the adult rat. PLoS One. 2011 Mar 18;6(3):e17562.

Dunn VJ, Abbott RA, Croudace TJ, Wilkinson P, Jones PB, Herbert J, Goodyer IM (2011) Profiles of family-focused adverse experiences through childhood and early adolescence: the ROOTS project a community investigation of adolescent mental health. BMC Psychiatry. 2011 Jul 7;11:109

Russ SJ, Herbert J, Cooper P, Gunnar MR, Goodyer I, Croudace T, Murray L (2011) Cortisol levels in response to starting school in children at increased risk for social phobia. Psychoneuroendocrinology

Gilhooley MJ.,  Pinnock SB, Herbert J. (2011) Rhythmic expression of per1 in the dentate gyrus is suppressed by corticosterone: Implications for neurogenesis. Neuroscience Letters 489 177-181

Pinnock SB, Blake AM, Platt NJ, Herbert J (2010) The roles of BDNF, pCREB and Wnt3a in the latent period preceding activation of progenitor cell mitosis in the adult dentate gyrus by fluoxetine. PLoS ONE 5, e13652

Goodyer IM, Croudace T, Dudbridge F, Ban M, Herbert J. (2010) Polymorphisms in BDNF (Val66met) and rHTTLPR, morning cortisol and subsequent depression in at-risk adolescents.  Br J Psychiatry 97, 365-71

AlAhmed S, Herbert J.(2010) Effect of agomelatine and its interaction with the daily corticosterone rhythm on progenitor cell proliferation in the dentate gyrus of the adult rat.  Neuropharmacology, 59, 375-379

Murray L, Halligan SL, Goodyer I, Herbert J. (2010) Disturbances in early parenting of depressed mothers and cortisol secretion in offspring: a preliminary study.  J. Affect Dis. 122, 218-223

Goodyer IM, Bacon A, Ban M, Croudace T, Herbert J.(2009) Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents. Brit J Psychiatry 195, 39-45

Pinnock SB, Lazic SE, Wong HT, Wong IH, Herbert J. (2009) Synergistic effects of dehydroepiandrosterone and fluoxetine on proliferation of progenitor cells in the dentate gyrus of the adult male rat.  Neuroscience, 158, 1644-1651

Fairchild G, van Goozen SH, Stollery SJ, Brown J, Gardiner J, Herbert J, Goodyer IM (2008) Cortisol diurnal rhythm and stress reactivity in male adolescents with early-onset or adolescence-onset conduct disorder . Biol Psychiatry 64, 599-606

Pinnock SB, Herbert J (2008) Brain-derived neurotropic factor and neurogenesis in the adult rat dentate gyrus: interactions with corticosterone. Eur. J. Neursci. 27, 2493-500

Coates JM, Herbert J (2008) Endogenous steroids and financial risk taking on a London trading floor. Proc Natl. Acad. Sci USA 105, 6167-72

Gurnell EM, Hunt PJ, Curran SE, Conway CL, Pullenayegum EM, Huppert FA, Compston JE, Herbert J, Chatterjee VK.(2008) Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial.  J Clin Endocrin Metab. 93, 400-9

Halligan SL, Herbert J, Goodyer I, Murray L (2007) Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents. Biol Psychiat. 63, 40-6

Pinnock SB, Balendra R, Chan M, Hunt LT, Turner-Stokes T, Herbert J (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

Herbert J, Goodyer IM, Grossman AB, Hastings MH, de Kloet ER, Lightman SL, Lupien SJ, Roozendaal B, Seckl JR. (2006) Do corticosteroids damage the brain? J Neuroendocrinol. 18, 393-411

<< Back to Principal investigators