Skip to main content Accessibility help

Pituitary gland volume and psychosocial stress among children at elevated risk for schizophrenia

  • A. E. Cullen (a1) (a2), F. L. Day (a2), R. E. Roberts (a1), C. M. Pariante (a3) and K. R. Laurens (a1) (a4) (a5)...

Pituitary volume enlargements have been observed among individuals with first-episode psychosis. These abnormalities are suggestive of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, which may contribute to the development of psychosis. However, the extent to which these abnormalities characterize individuals at elevated risk for schizophrenia prior to illness onset is currently unclear, as volume increases, decreases and no volume differences have all been reported relative to controls. The current study aimed to determine whether antipsychotic-naive, putatively at-risk children who present multiple antecedents of schizophrenia (ASz) or a family history of illness (FHx) show pituitary volume abnormalities relative to typically developing (TD) children. An additional aim was to explore the association between pituitary volume and experiences of psychosocial stress.


ASz (n = 30), FHx (n = 22) and TD (n = 32) children were identified at age 9–12 years using a novel community-screening procedure or as relatives of individuals with schizophrenia. Measures of pituitary volume and psychosocial stress were obtained at age 11–14 years.


Neither ASz nor FHx children showed differences in pituitary volume relative to TD children. Among FHx children only, pituitary volume was negatively associated with current distress relating to negative life events and exposure to physical punishment.


The lack of pituitary volume abnormalities among ASz and FHx children is consistent with our previous work demonstrating that these children are not characterized by elevated diurnal cortisol levels. The findings imply that these biological markers of HPA axis hyperactivity, observed in some older samples of high-risk individuals, may emerge later, more proximally to disease onset.

Corresponding author
* Address for correspondence: A. E. Cullen and K. R. Laurens, Department of Health Service and Population Research, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London SE5 8AF, UK. (Email:
Hide All
Afifi, TO, Mota, NP, Dasiewicz, P, MacMillan, HL, Sareen, J (2012). Physical punishment and mental disorders: results from a nationally representative US sample. Pediatrics 130, 184192.
Borges, S, Gayer-Anderson, C, Mondelli, V (2013). A systematic review of the activity of the hypothalamic–pituitary–adrenal axis in first episode psychosis. Psychoneuroendocrinology 38, 603611.
Bradley, AJ, Dinan, TG (2010). A systematic review of hypothalamic–pituitary–adrenal axis function in schizophrenia: implications for mortality. Journal of Psychopharmacology 24, 91118.
Büschlen, J, Berger, GE, Borgwardt, SJ, Aston, J, Gschwandtner, U, Pflueger, MO, Kuster, P, Radu, EW, Stieglitz, RD, Riecher-Rossler, A (2011). Pituitary volume increase during emerging psychosis. Schizophrenia Research 125, 4148.
Carskadon, MA, Acebo, C (1993). A self-administered rating scale for pubertal development. Journal of Adolescent Health 14, 190195.
Chong, RY, Uhart, M, McCaul, ME, Johnson, E, Wand, GS (2008). Whites have a more robust hypothalamic–pituitary–adrenal axis response to a psychological stressor than blacks. Psychoneuroendocrinology 33, 246254.
Collip, D, Nicolson, NA, 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.
Cullen, AE, Fisher, HL, Roberts, RE, Pariante, CM, Laurens, KR (2014 a). Daily stressors and negative life events in children at elevated risk of developing schizophrenia. British Journal of Psychiatry 204, 354360.
Cullen, AE, Zunszain, PA, Dickson, H, Roberts, RE, Fisher, HL, Pariante, CM, Laurens, KR (2014 b). Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: relationship to psychosocial stress and cognition. Psychoneuroendocrinology 46, 113.
Fisher, HL, Caspi, A, Poulton, R, Meier, MH, Houts, R, Harrington, H, Arseneault, L, Moffitt, TE (2013). Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study. Psychological Medicine 43, 20772086.
Fusar-Poli, P, Borgwardt, S, Bechdolf, A, Addington, J, Riecher-Rossler, A, Schultze-Lutter, F, Keshavan, M, Wood, S, Ruhrmann, S, Seidman, LJ, Valmaggia, L, Cannon, T, Velthorst, E, De Haan, L, Cornblatt, B, Bonoldi, I, Birchwood, M, McGlashan, T, Carpenter, W, McGorry, P, Klosterkotter, J, McGuire, P, Yung, A (2013). The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry 70, 107120.
Garner, B, Chanen, AM, Phillips, L, Velakoulis, D, Wood, SJ, Jackson, HJ, Pantelis, C, McGorry, PD (2007). Pituitary volume in teenagers with first-presentation borderline personality disorder. Psychiatry Research: Neuroimaging 156, 257261.
Garner, B, Pariante, CM, Wood, SJ, Velakoulis, D, Phillips, L, Soulsby, B, Brewer, WJ, Smith, DJ, Dazzan, P, Berger, GE, Yung, AR, van den Buuse, M, Murray, R, McGorry, PD, Pantelis, C (2005). Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis. Biological Psychiatry 58, 417423.
Goodman, R (2001). Psychometric properties of the strengths and difficulties questionnaire. Journal of the American Academy of Child and Adolescent Psychiatry 40, 13371345.
Habets, P, Collip, D, Myin-Germeys, I, Gronenschild, E, van Bronswijk, S, Hofman, P, Lataster, T, Lardinois, M, Nicolson, NA, van Os, J, Marcelis, M (2012). Pituitary volume, stress reactivity and genetic risk for psychotic disorder. Psychological Medicine 42, 15231533.
Heubeck, B, O'Sullivan, C (1998). An exploration into the nature, frequency and impact of school hassles in the middle school years. Australian Psychologist 33, 130137.
Klomp, A, Koolschijn, PC, Hulshoff Pol, HE, Kahn, RS, Haren, NE (2012). Hypothalamus and pituitary volume in schizophrenia: a structural MRI study. International Journal of Neuropsychopharmacology 15, 281288.
Laurens, KR, Hobbs, MJ, Sutherland, M, Green, MJ, Mould, GL (2012). Psychotic-like experiences in a community sample of 8,000 children aged 9–11 years: an item response theory analysis. Psychological Medicine 47, 14951506.
Laurens, KR, Hodgins, S, Maughan, B, Murray, RM, Rutter, ML, Taylor, EA (2007). Community screening for psychotic-like experiences and other putative antecedents of schizophrenia in children aged 9–12 years. Schizophrenia Research 90, 130146.
Laurens, KR, Hodgins, S, Taylor, E, Murray, RM (2011). Is earlier intervention for schizophrenia possible?: Identifying antecedents of schizophrenia in children aged 9–12 years. In Schizophrenia: The Final Frontier (ed. David, A. S., McGuffin, P. and Kapur, S.), pp. 1932. Psychology Press: London.
Lipsey, MW, Wilson, DB (2001). Practical Meta-Analysis. Sage Publications: Thousand Oaks, CA.
MacMaster, FP, El-Sheikh, R, Upadhyaya, AR, Nutche, J, Rosenberg, DR, Keshavan, M (2007). Effect of antipsychotics on pituitary gland volume in treatment-naive first-episode schizophrenia: a pilot study. Schizophrenia Research 92, 207210.
Marsman, R, Nederhof, E, Rosmalen, JG, Oldehinkel, AJ, Ormel, J, Buitelaar, JK (2012). Family environment is associated with HPA-axis activity in adolescents. The TRAILS study. Biological Psychology 89, 460466.
Maxwell, ME (1992). Family Interview for Genetic Studies. National Institute of Mental Health: St Louis, MO.
Mittal, VA, Dhruv, S, Tessner, KD, Walder, DJ, Walker, EF (2007). The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol. Biological Psychiatry 61, 11791186.
Mondelli, V, Dazzan, P, Gabilondo, A, Tournikioti, K, Walshe, M, Marshall, N, Schulze, KK, Murray, RM, McDonald, C, Pariante, CM (2008). Pituitary volume in unaffected relatives of patients with schizophrenia and bipolar disorder. Psychoneuroendocrinology 33, 10041012.
Nicolo, JP, Berger, GE, Garner, BA, Velakoulis, D, Markulev, C, Kerr, M, McGorry, PD, Proffitt, TM, McConchie, M, Pantelis, C, Wood, SJ (2010). The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study. Schizophrenia Research 116, 4954.
Office for National Statistics (2010). Neighbourhood Statistics by Local Authority. National Statistics.
Pariante, CM (2008). Pituitary volume in psychosis: the first review of the evidence. Journal of Psychopharmacology 22, 7681.
Pariante, CM, Dazzan, P, Danese, A, Morgan, KD, Brudaglio, F, Morgan, C, Fearon, P, Orr, K, Hutchinson, G, Pantelis, C, Velakoulis, D, Jones, PB, Leff, J, Murray, RM (2005). Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study. Neuropsychopharmacology 30, 19231931.
Pariante, CM, Vassilopoulou, K, Velakoulis, D, Phillips, L, Soulsby, B, Wood, SJ, Brewer, W, Smith, DJ, Dazzan, P, Yung, AR, Zervas, IM, Christodoulou, GN, Murray, R, McGorry, PD, Pantelis, C (2004). Pituitary volume in psychosis. British Journal of Psychiatry 185, 510.
Romo-Nava, F, Hoogenboom, WS, Pelavin, PE, Alvarado, JL, Bobrow, LH, Macmaster, FP, Keshavan, M, McCarley, RW, Shenton, ME (2013). Pituitary volume in schizophrenia spectrum disorders. Schizophrenia Research 146, 301307.
Sassi, RB, Nicoletti, M, Brambilla, P, Harenski, K, Mallinger, AG, Frank, E, Kupfer, DJ, Keshavan, MS, Soares, JC (2001). Decreased pituitary volume in patients with bipolar disorder. Biological Psychiatry 50, 271280.
Shah, JL, Malla, AK (2015). Much ado about much: stress, dynamic biomarkers and HPA axis dysregulation along the trajectory to psychosis. Schizophrenia Research 162, 253260.
Shah, JL, Tandon, N, Howard, ER, Mermon, D, Miewald, JM, Montrose, DM, Keshavan, MS (2015). Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia. Psychological Medicine. Published online: 07 07 2015 . doi:10.1017/S003329171500077X.
Shelton, KK, Frick, PJ, Wootton, JM (1996). Assessment of parenting practices in families of elementary school-age children. Journal of Clinical Child Psychology 25, 317329.
Sugranyes, G, Thompson, JL, Corcoran, CM (2012). HPA-axis function, symptoms, and medication exposure in youths at clinical high risk for psychosis. Journal of Psychiatric Research 46, 13891393.
Takahashi, T, Nakamura, K, Nishiyama, S, Furuichi, A, Ikeda, E, Kido, M, Nakamura, Y, Kawasaki, Y, Noguchi, K, Seto, H, Suzuki, M (2013). Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia. Psychiatry and Clinical Neurosciences 67, 540548.
Takahashi, T, Suzuki, M, Velakoulis, D, Lorenzetti, V, Soulsby, B, Zhou, SY, Nakamura, K, Seto, H, Kurachi, M, Pantelis, C (2009). Increased pituitary volume in schizophrenia spectrum disorders. Schizophrenia Research 108, 114121.
Takahashi, T, Zhou, SY, Nakamura, K, Tanino, R, Furuichi, A, Kido, M, Kawasaki, Y, Noguchi, K, Seto, H, Kurachi, M, Suzuki, M (2011). Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 35, 177183.
Thomas, LA, De Bellis, MD (2004). Pituitary volumes in pediatric maltreatment-related posttraumatic stress disorder. Biological Psychiatry 55, 752758.
Upadhyaya, AR, El-Sheikh, R, MacMaster, FP, Diwadkar, VA, Keshavan, MS (2007). Pituitary volume in neuroleptic-naive schizophrenia: a structural MRI study. Schizophrenia Research 90, 266273.
Walker, E, Mittal, V, Tessner, K (2008). Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia. Annual Review of Clinical Psychology 4, 189216.
Walker, EF, Diforio, D (1997). Schizophrenia: a neural diathesis–stress model. Psychological Review 104, 667685.
Walker, EF, Trotman, HD, Pearce, BD, Addington, J, Cadenhead, KS, Cornblatt, BA, Heinssen, R, Mathalon, DH, Perkins, DO, Seidman, LJ, Tsuang, MT, Cannon, TD, McGlashan, TH, Woods, SW (2013). Cortisol levels and risk for psychosis: initial findings from the North American Prodrome Longitudinal Study. Biological Psychiatry 74, 410417.
Walker, EF, Walder, DJ, Reynolds, F (2001). Developmental changes in cortisol secretion in normal and at-risk youth. Development and Psychopathology 13, 721732.
Walter, A, Studerus, E, Smieskova, R, Tamagni, C, Rapp, C, Borgwardt, SJ, Riecher-Rossler, A (2015). Pituitary gland volume in at-risk mental state for psychosis: a longitudinal MRI analysis. CNS Spectrums 20, 122129.
Wechsler, D (1999). Wechsler Abbreviated Scale of Intelligence (WASI) Manual. Psychological Corporation: San Antonio, TX.
Wilke, M, Holland, SK, Altaye, M, Gaser, C (2008). Template-O-Matic: a toolbox for creating customized pediatric templates. Neuroimage 41, 903913.
Zammit, S, Kounali, D, Cannon, M, David, AS, Gunnell, D, Heron, J, Jones, PB, Lewis, S, Sullivan, S, Wolke, D, Lewis, G (2013). Psychotic experiences and psychotic disorders at age 18 in relation to psychotic experiences at age 12 in a longitudinal population-based cohort study. American Journal of Psychiatry 170, 742750.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



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