Skip to main content Accessibility help
×
Home
Hostname: page-component-846f6c7c4f-msmtk Total loading time: 0.379 Render date: 2022-07-07T14:37:15.860Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

Inefficient cerebral recruitment as a vulnerability marker for schizophrenia

Published online by Cambridge University Press:  14 May 2012

E. B. Liddle*
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
A. T. Bates
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
D. Das
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
T. P. White
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
M. J. Groom
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
M. Jansen
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
G. M. Jackson
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
C. Hollis
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
P. F. Liddle
Affiliation:
Division of Psychiatry, Queen's Medical Centre, Nottingham, UK
*
*Address for correspondence: Dr E. B. Liddle, Division of Psychiatry, E Floor, South Block, Queen's Medical Centre, Nottingham NG7 2UH, UK. (Email: Elizabeth.Liddle@nottingham.ac.uk)

Abstract

Background

Patients with schizophrenia and their first-degree relatives exhibit both abnormally diminished and increased neural activation during cognitive tasks. In particular, excessive task-related activity is often observed when tasks are easy, suggesting that inefficient cerebral recruitment may be a marker of vulnerability for schizophrenia. This hypothesis might best be tested using a very easy task, thus avoiding confounding by individual differences in task difficulty.

Method

Eighteen people with schizophrenia, 18 unaffected full siblings of patients with schizophrenia and 26 healthy controls performed an easy auditory target-detection task in a 3-T magnetic resonance imaging (MRI) scanner. Groups were matched for accuracy on the task. Blood oxygen level-dependent (BOLD) responses to non-target stimuli in participants with vulnerability for schizophrenia (siblings and patients) were compared with those of healthy controls, and those of patients with those of unaffected siblings. BOLD responses to targets were compared with baseline, across groups.

Results

Subjects with vulnerability for schizophrenia showed significant hyperactivation to non-targets in brain areas activated by targets in all groups, in addition to reduced deactivation to non-targets in areas suppressed by targets in all groups. Siblings showed greater activation than patients to non-targets in the medial frontal cortex. Patients exhibited significantly longer reaction times (RTs) than unaffected siblings and healthy controls.

Conclusions

Inefficient cerebral recruitment is a vulnerability marker for schizophrenia, marked by reduced suppression of brain areas normally deactivated in response to task stimuli, and increased activation of areas normally activated in response to task stimuli. Moreover, siblings show additional activation in the medial frontal cortex that may be protective.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Bebbington, PE, Nayani, T (1995). The Psychosis Screening Questionnaire. International Journal of Methods in Psychiatric Research 5, 1119.Google Scholar
Byrne, M, Agerbo, E, Mortensen, P (2002). Family history of psychiatric disorders and age at first contact in schizophrenia: an epidemiological study. British Journal of Psychiatry 181, s19s25.CrossRefGoogle Scholar
Callicott, JH, Egan, MF, Mattay, VS, Bertolino, A, Bone, AD, Verchinksi, B, Weinberger, DR (2003). Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. American Journal of Psychiatry 160, 709719.CrossRefGoogle ScholarPubMed
Egan, MF, Goldberg, TE, Gscheidle, T, Weirich, M, Rawlings, R, Hyde, TM, Bigelow, L, Weinberger, DR (2001). Relative risk for cognitive impairments in siblings of patients with schizophrenia. Biological Psychiatry 50, 98107.CrossRefGoogle ScholarPubMed
Fletcher, PC, McKenna, PJ, Frith, CD, Grasby, PM, Friston, KJ, Dolan, RJ (1998). Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging. Archives of General Psychiatry 55, 10011008.CrossRefGoogle ScholarPubMed
Friston, KJ, Worsley, KJ, Frackowiak, RSJ, Mazziotta, JC, Evans, AC (1993). Assessing the significance of focal activations using their spatial extent. Human Brain Mapping 1, 210220.CrossRefGoogle Scholar
Garrity, AG, Pearlson, GD, McKiernan, K, Lloyd, D, Kiehl, KA, Calhoun, VD (2007). Aberrant ‘default mode’ functional connectivity in schizophrenia. American Journal of Psychiatry 164, 450457.CrossRefGoogle Scholar
Glahn, DC, Ragland, JD, Abramoff, A, Barrett, J, Laird, AR, Bearden, CE, Velligan, DI (2005). Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Human Brain Mapping 25, 6069.CrossRefGoogle Scholar
Goghari, VM (2011). Executive functioning-related brain abnormalities associated with the genetic liability for schizophrenia: an activation likelihood estimation meta-analysis. Psychological Medicine 41, 12391252.CrossRefGoogle ScholarPubMed
Green, DM, Swets, JA (1966). Signal Detection Theory and Psychophysics. Wiley: New York.Google Scholar
Hasenkamp, W, James, GA, Boshoven, W, Duncan, E (2011). Altered engagement of attention and default networks during target detection in schizophrenia. Schizophrenia Research 125, 169173.CrossRefGoogle Scholar
Karlsgodt, KH, Glahn, DC, van Erp, TGM, Therman, S, Huttunen, M, Manninen, M, Kaprio, J, Cohen, MS, Lönnqvist, J, Cannon, TD (2007). The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophrenia Research 89, 191197.CrossRefGoogle ScholarPubMed
Karlsgodt, KH, Sanz, J, van Erp, TGM, Bearden, CE, Nuechterlein, KH, Cannon, TD (2009). Re-evaluating dorsolateral prefrontal cortex activation during working memory in schizophrenia. Schizophrenia Research 108, 143150.CrossRefGoogle Scholar
Heinz, A, Schlagenhauf, F (2010). Dopaminergic dysfunction in schizophrenia: salience attribution revisited. Schizophrenia Bulletin 36, 472485.CrossRefGoogle ScholarPubMed
Kapur, S (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 1323.CrossRefGoogle Scholar
Liddle, PF, Ngan, ETC, Duffield, G, Kho, K, Warren, AJ (2002). Signs and Symptoms of Psychotic Illness (SSPI): a rating scale. British Journal of Psychiatry 180, 4550.CrossRefGoogle ScholarPubMed
MacDonald, AW, Thermenos, HW, Barch, DM, Seidman, LJ (2009). Imaging genetic liability to schizophrenia: systematic review of fMRI studies of patients' nonpsychotic relatives. Schizophrenia Bulletin 35, 11421162.CrossRefGoogle ScholarPubMed
Mannell, MV, Franco, AR, Calhoun, VD, Cañive, JM, Thoma, RJ, Mayer, AR (2010). Resting state and task-induced deactivation: a methodological comparison in patients with schizophrenia and healthy controls. Human Brain Mapping 31, 424437.Google ScholarPubMed
Manoach, DS (2003). Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophrenia Research 60, 285298.CrossRefGoogle ScholarPubMed
McKiernan, KA, Kaufman, JN, Kucera-Thompson, J, Binder, JR (2003). A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging. Journal of Cognitive Neuroscience 15, 394408.CrossRefGoogle ScholarPubMed
Mendrek, A, Laurens, KR, Kiehl, KA, Ngan, ETC, Stip, E, Liddle, PF (2004). Changes in distributed neural circuitry function in patients with first-episode schizophrenia. British Journal of Psychiatry 185, 205214.CrossRefGoogle ScholarPubMed
Miller, TJ, McGlashan, TH, Rosen, JL, Cadenhead, K, Ventura, J, McFarlane, W, Perkins, DO, Pearlson, GD, Woods, SW (2003). Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin 29, 703715.CrossRefGoogle ScholarPubMed
Minzenberg, MJ, Laird, AR, Thelen, S, Carter, CS, Glahn, DC (2009). Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry 66, 811822.CrossRefGoogle Scholar
Mortensen, PB, Pedersen, CB, Westergaard, T, Wohlfahrt, J, Ewald, H, Mors, O, Andersen, PK, Melbye, M (1999). Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340, 603608.CrossRefGoogle ScholarPubMed
ONS (2004). The National Statistics Socio-Economic Classification User Manual. Office for National Statistics.Google Scholar
Palaniyappan, L, Liddle, PF (2012). Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. Journal of Psychiatry and Neuroscience 37, 1727.CrossRefGoogle ScholarPubMed
Potkin, SG, Turner, JA, Brown, GG, McCarthy, G, Greve, DN, Glover, GH, Manoach, DS, Belger, A, Diaz, M, Wible, CG, Ford, JM, Mathalon, DH, Gollub, R, Lauriello, J, O'Leary, D, van Erp, TGM, Toga, AW, Preda, A, Lim, KO; FBIRN (2009). Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study. Schizophrenia Bulletin 35, 1931.CrossRefGoogle ScholarPubMed
Raichle, ME, Snyder, AZ (2007). A default mode of brain function: a brief history of an evolving idea. NeuroImage 37, 10831090; discussion 1097-1099.CrossRefGoogle ScholarPubMed
Raine, A (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17, 555564.CrossRefGoogle ScholarPubMed
Ridderinkhof, KR, Ullsperger, M, Crone, EA, Nieuwenhuis, S (2004). The role of the medial frontal cortex in cognitive control. Science 306, 443447.CrossRefGoogle ScholarPubMed
Schafer, JL, Olsen, MK (1998). Multiple imputation for multivariate missing-data problems: a data analyst's perspective. Multivariate Behavioral Research 33, 545571.CrossRefGoogle ScholarPubMed
Seeley, WW, Menon, V, Schatzberg, AF, Keller, J, Glover, GH, Kenna, H, Reiss, AL, Greicius, MD (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience 27, 23492356.CrossRefGoogle ScholarPubMed
Seidman, LJ, Thermenos, HW, Poldrack, RA, Peace, NK, Koch, JK, Faraone, SV, Tsuang, MT (2006). Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: an fMRI study of working memory. Schizophrenia Research 85, 5872.CrossRefGoogle Scholar
Tan, H-Y, Callicott, JH, Weinberger, DR (2007). Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cerebral Cortex 17 (Suppl. 1), i171i181.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.CrossRefGoogle ScholarPubMed
White, TP, Joseph, V, Francis, ST, Liddle, PF (2010a). Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia. Schizophrenia Research 123, 105115.CrossRefGoogle Scholar
White, TP, Joseph, V, O'Regan, E, Head, KE, Francis, ST, Liddle, PF (2010b). Alpha-gamma interactions are disturbed in schizophrenia: a fusion of electroencephalography and functional magnetic resonance imaging. Clinical Neurophysiology 121, 14271437.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S, Thermenos, HW, Milanovic, S, Tsuang, MT, Faraone, SV, McCarley, RW, Shenton, ME, Green, AI, Nieto-Castanon, A, LaViolette, P, Wojcik, J, Gabrieli, JDE, Seidman, LJ (2009). Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proceedings of the National Academy of Sciences USA 106, 12791284.CrossRefGoogle ScholarPubMed
Wing, JK, Babor, T, Brugha, T, Burke, J, Cooper, JE, Giel, R, Jablenski, A, Regier, D, Sartorius, N (1990). SCAN: Schedules for Clinical Assessment in Neuropsychiatry. Archives of General Psychiatry 47, 589593.CrossRefGoogle ScholarPubMed
Woods, SW (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663667.CrossRefGoogle ScholarPubMed
13
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Inefficient cerebral recruitment as a vulnerability marker for schizophrenia
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Inefficient cerebral recruitment as a vulnerability marker for schizophrenia
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Inefficient cerebral recruitment as a vulnerability marker for schizophrenia
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *