Skip to main content Accessibility help

Hippocampal volume as marker of daily life stress sensitivity in psychosis

  • D. Collip (a1), P. Habets (a1), M. Marcelis (a1), E. Gronenschild (a1), T. Lataster (a1), M. Lardinois (a1), N. A. Nicolson (a1) and I. Myin-Germeys (a1)...



Reduced hippocampal size and increased stress sensitivity are associated with psychotic disorder and familial risk for psychosis. However, to what degree the hippocampus is implicated in daily life stress reactivity has not yet been examined. The current study investigated (i) whether familial risk (the contrast between controls, patients and siblings of patients) moderated the relationship between hippocampal volume (HV) and emotional daily stress reactivity and (ii) whether familial risk (the contrast between controls and siblings of patients) moderated the relationship between HV and cortisol daily stress reactivity.


T1-weighted magnetic resonance imaging (MRI) scans were acquired from 20 patients with schizophrenia, 37 healthy siblings with familial risk for schizophrenia and 32 controls. Freesurfer 5.0.0 was used to measure HV. The experience sampling method (ESM), a structured momentary assessment technique, was used to assess emotional stress reactivity, that is the effect of momentary stress on momentary negative affect (NA). In addition, in the control and sibling groups, cortisol stress reactivity was assessed using momentary cortisol levels extracted from saliva.


Multilevel linear regression analyses revealed a significant three-way interaction between group, HV and momentary stress in both the model of NA and the model of cortisol. Increased emotional stress reactivity was associated with smaller left HV in patients and larger total HV in controls. In line with the results in patients, siblings with small HV demonstrated increased emotional and cortisol stress reactivity compared to those with large HV.


HV may index risk and possibly disease-related mechanisms underlying daily life stress reactivity in psychotic disorder.


Corresponding author

*Address for correspondence: I. Myin-Germeys, Ph.D., Department of Psychiatry and Neuropsychology, Maastricht University, PO Box 616 (VIJV1), 6200 MD Maastricht, The Netherlands. (Email:


Hide All
Andreasen, NC, Flaum, M, Arndt, S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615623.
APA (2000). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC.
Boos, H, Aleman, A, Cahn, W, Pol, HH, Kahn, RS (2007). Brain volumes in relatives of patients with schizophrenia: a meta-analysis. Archives of General Psychiatry 64, 297304.
Buchanan, TW, Tranel, D, Kirschbaum, C (2009). Hippocampal damage abolishes the cortisol response to psychosocial stress in humans. Hormones and Behavior 56, 4450.
Cahn, W, Pol, HE, Lems, EB, van Haren, NE, Schnack, HG, van der Linden, JA, Schothorst, PF, van Engeland, H, Kahn, RS (2002). Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59, 10021010.
Collip, D, Nicolson, N, Lardinois, M, Lataster, T, van Os, J, Myin-Germeys, I (2011). Daily cortisol, stress reactivity and psychotic experiences in individuals at above average genetic risk for psychosis. Psychological Medicine 41, 23052315.
Corcoran, C, Walker, E, Huot, R, Mittal, V, Tessner, K, Kestler, L, Malaspina, D (2003). The stress cascade and schizophrenia: etiology and onset. Schizophrenia Bulletin 29, 671692.
Csikszentmihalyi, M, Larson, R (1987). Validity and reliability of the Experience-Sampling Method. Journal of Nervous and Mental Disease 175, 526536.
Dale, AM, Fischl, B, Sereno, MI (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. NeuroImage 9, 179194.
Fischl, B, Dale, AM (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences USA 97, 1105011055.
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, van der Kouwe, A, Killiany, R, Kennedy, D, Klaveness, S, Montillo, A, Makris, N, Rosen, B, Dale, AM (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341355.
Fischl, B, Sereno, MI, Dale, AM (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. NeuroImage 9, 195207.
Fischl, B, Van Der Kouwe, A, Destrieux, C, Halgren, E, Ségonne, F, Salat, DH, Busa, E, Seidman, LJ, Goldstein, J, Kennedy, D (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex 14, 1122.
Geuze, E, Vermetten, E, Bremner, JD (2005). MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Molecular Psychiatry 10, 160184.
Green, AS, Rafaeli, E, Bolger, N, Shrout, PE, Reis, HT (2006). Paper or plastic? Data equivalence in paper and electronic diaries. Psychological Methods 11, 87105.
Gunduz-Bruce, H, Szeszko, PR, Gueorguieva, R, Ashtari, M, Robinson, DG, Kane, JM, Bilder, RM (2007). Cortisol levels in relation to hippocampal sub-regions in subjects with first episode schizophrenia. Schizophrenia Research 94, 281287.
Habets, P, Marcelis, M, Gronenschild, E, Drukker, M, van Os, J (2011). Reduced cortical thickness as an outcome of differential sensitivity to environmental risks in schizophrenia. Biological Psychiatry 69, 487494.
Han, X, Jovicich, J, Salat, D, van der Kouwe, A, Quinn, B, Czanner, S, Busa, E, Pacheco, J, Albert, M, Killiany, R, Maguire, P, Rosas, D, Makris, N, Dale, A, Dickerson, B, Fischl, B (2006). Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. NeuroImage 32, 180194.
Hruschka, DJ, Kohrt, BA, Worthman, CM (2005). Estimating between- and within-individual variation in cortisol levels using multilevel models. Psychoneuroendocrinology 30, 698714.
Jacobs, N, Myin-Germeys, I, Derom, C, Delespaul, P, van Os, J, Nicolson, NA (2007). A momentary assessment study of the relationship between affective and adrenocortical stress responses in daily life. Biological Psychology 74, 6066.
Jacobs, N, Nicolson, NA, Derom, C, Delespaul, P, van Os, J, Myin-Germeys, I (2005). Electronic monitoring of salivary cortisol sampling compliance in daily life. Life Sciences 76, 24312443.
Jacobson, L, Sapolsky, R (1991). The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocrine Reviews 12, 118134.
Jovicich, J, Czanner, S, Greve, D, Haley, E, van der Kouwe, A, Gollub, R, Kennedy, D, Schmitt, F, Brown, G, Macfall, J, Fischl, B, Dale, A (2006). Reliability in multi-site structural MRI studies: effects of gradient non-linearity correction on phantom and human data. NeuroImage 30, 436443.
Kahn, R, Linszen, H, van Os, J, Wiersma, D, Bruggeman, R, Cahn, W, de Haan, L, Krabbendam, L, Myin-Germeys, I (2011). Evidence that familial liability for psychosis is expressed as differential sensitivity to cannabis: an analysis of patient-sibling and sibling-control pairs. Archives of General Psychiatry 68, 138147.
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.
Knoops, AJG, Gerritsen, L, van der Graaf, Y, Mali, WPTM, Geerlings, MI (2010). Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. Biological Psychiatry 67, 11911198.
Lataster, T, Collip, D, Lardinois, M, van Os, J, Myin-Germeys, I (2010). Evidence for a familial correlation between increased reactivity to stress and positive psychotic symptoms. Acta Psychiatrica Scandinavica 122, 395404.
Lawrie, SM, McIntosh, AM, Hall, J, Owens, DG, Johnstone, EC (2008). Brain structure and function changes during the development of schizophrenia: the evidence from studies of subjects at increased genetic risk. Schizophrenia Bulletin 34, 330340.
Liu, J, Chaplin, TM, Wang, F, Sinha, R, Mayes, LC, Blumberg, HP (2012). Stress reactivity and corticolimbic response to emotional faces in adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 51, 304312.
Lupien, SJ, De Leon, M, De Santi, S, Convit, A, Tarshish, C, Nair, NPV, Thakur, M, McEwen, BS, Hauger, RL, Meaney, MJ (1998). Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nature Neuroscience 1, 6973.
Maxwell, ME (1992). Family Interview for Genetic Studies (FIGS): Manual For FIGS. Clinical Neurogenetics Branch, Intramural Research Program, National Institute of Mental Health: Bethesda, MD.
Meador-Woodruff, J, Greden, J (1988). Effects of psychotropic medications on hypothalamic-pituitary-adrenal regulation. Neurologic Clinics 6, 225234.
Meltzer, HY, Koenig, JI, Nash, JF, Gudelsky, GA (1989). Melperone and clozapine: neuroendocrine effects of atypical neuroleptic drugs. Acta Psychiatrica Scandinavica. Supplementum 352, 2429.
Mondelli, V, Dazzan, P, Hepgul, N, Di Forti, M, Aas, M, D'Albenzio, A, Di Nicola, M, Fisher, H, Handley, R, Marques, TR, Morgan, C, Navari, S, Taylor, H, Papadopoulos, A, Aitchison, KJ, Murray, RM, Pariante, CM (2010 a). Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment. Schizophrenia Research 116, 234242.
Mondelli, V, Pariante, CM, Navari, S, Aas, M, D'Albenzio, A, Di Forti, M, Handley, R, Hepgul, N, Marques, TR, Taylor, H, Papadopoulos, AS, Aitchison, KJ, Murray, RM, Dazzan, P (2010 b). Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis. Schizophrenia Research 119, 7578.
Myin-Germeys, I, Delespaul, P, van Os, J (2005). Behavioural sensitization to daily life stress in psychosis. Psychological Medicine 35, 733741.
Myin-Germeys, I, Oorschot, M, Collip, D, Lataster, J, Delespaul, P, van Os, J (2009). Experience sampling research in psychopathology: opening the black box of daily life. Psychological Medicine 39, 15331547.
Myin-Germeys, I, van Os, J (2007). Stress-reactivity in psychosis: evidence for an affective pathway to psychosis. Clinical Psychology Review 27, 409424.
Myin-Germeys, I, van Os, J, Schwartz, JE, Stone, AA, Delespaul, PA (2001). Emotional reactivity to daily life stress in psychosis. Archives of General Psychiatry 58, 11371144.
NIMH Genetics Initiative (1992). Family Interview for Genetic Studies (FIGS). National Institute of Mental Health: Rockville, MD.
Oorschot, M, Kwapil, T, Delespaul, P, Myin-Germeys, I (2009). Momentary assessment research in psychosis. Psychological Assessment 21, 498505.
Pariante, CM (2008). Pituitary volume in psychosis: the first review of the evidence. Journal of Psychopharmacology 22, 7681.
Pruessner, JC, Dedovic, K, Pruessner, M, Lord, C, Buss, C, Collins, L, Dagher, A, Lupien, SJ (2010). Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populations – 2008 Curt Richter Award Winner. Psychoneuroendocrinology 35, 179191.
Pruessner, M, Pruessner, JC, Hellhammer, DH, Bruce Pike, G, Lupien, SJ (2007). The associations among hippocampal volume, cortisol reactivity, and memory performance in healthy young men. Psychiatry Research 155, 110.
Sapolsky, RM (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of General Psychiatry 57, 925935.
Schulze, K, McDonald, C, Frangou, S, Sham, P, Grech, A, Toulopoulou, T, Walshe, M, Sharma, T, Sigmundsson, T, Taylor, M (2003). Hippocampal volume in familial and nonfamilial schizophrenic probands and their unaffected relatives. Biological Psychiatry 53, 562570.
Segonne, F, Dale, AM, Busa, E, Glessner, M, Salat, D, Hahn, HK, Fischl, B (2004). A hybrid approach to the skull stripping problem in MRI. NeuroImage 22, 10601075.
Seidman, LJ, Faraone, SV, Goldstein, JM, Kremen, WS, Horton, NJ, Makris, N, Toomey, R, Kennedy, D, Caviness, VS, Tsuang, MT (2002). Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Archives of General Psychiatry 59, 839849.
StataCorp (2009). STATA/SE Statistical Software, Release 11. Stata Corporation: College Station, TX.
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510518.
Stefanis, N, Frangou, S, Yakeley, J, Sharma, T, O'Connell, P, Morgan, K, Sigmudsson, T, Taylor, M, Murray, R (1999). Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biological Psychiatry 46, 697702.
Stein, MB, Koverola, C, Hanna, C, Torchia, M, McClarty, B (1997). Hippocampal volume in women victimized by childhood sexual abuse. Psychological Medicine 27, 951959.
Stone, AA, Shiffman, S, Schwartz, JE, Broderick, JE, Hufford, MR (2002). Patient non-compliance with paper diaries. British Medical Journal 324, 11931194.
Szeszko, PR, Betensky, JD, Mentschel, C, Gunduz-Bruce, H, Lencz, T, Ashtari, M, Malhotra, AK, Bilder, RM (2006). Increased stress and smaller anterior hippocampal volume. NeuroReport 177, 18251828.
Teicher, MH, Anderson, CM, Polcari, A (2012). Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proceedings of the National Academy of Sciences USA 109, E563E572.
Tessner, KD, Walker, EF, Dhruv, SH, Hochman, K, Hamann, S (2007). The relation of cortisol levels with hippocampus volumes under baseline and challenge conditions. Brain Research 1179, 7078.
Vita, A, De Peri, L, Silenzi, C, Dieci, M (2006). Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophrenia Research 82, 7588.
WHO (1990). Composite International Diagnostic Interview (CIDI). World Health Organization: Geneva.
Wik, G (1995). Effects of neuroleptic treatment on cortisol and 3-methoxy-4-hydroxyphenylethyl glycol levels in blood. Journal of Endocrinology 144, 425429.
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 1625.


Hippocampal volume as marker of daily life stress sensitivity in psychosis

  • D. Collip (a1), P. Habets (a1), M. Marcelis (a1), E. Gronenschild (a1), T. Lataster (a1), M. Lardinois (a1), N. A. Nicolson (a1) and I. Myin-Germeys (a1)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.