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Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk

Published online by Cambridge University Press:  30 April 2014

G. Modinos ,
P. Allen ,
M. Frascarelli ,
S. Tognin ,
L. Valmaggia ,
L. Xenaki ,
P. Keedwell ,
M. Broome ,
I. Valli  and
J. Woolley
...Show all authors
G. Modinos
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
P. Allen
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
M. Frascarelli
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
S. Tognin
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
L. Valmaggia
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
L. Xenaki
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
P. Keedwell
Affiliation:
Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
M. Broome
Affiliation:
Department of Psychiatry, University of Oxford, Oxford, UK
I. Valli
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
J. Woolley
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
J. M. Stone
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
A. Mechelli
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
M. L. Phillips
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA, USA
P. McGuire
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
P. Fusar-Poli*
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: P. Fusar-Poli, M.D., Ph.D., Department of Psychosis Studies, Institute of Psychiatry, Box PO 63, 16 De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])
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Abstract

Background.

The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown.

Method.

We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses.

Results.

The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive–compulsive disorder symptoms.

Conclusions.

Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.

Keywords

Anterior cingulate cortexco-morbiditygrey matter volumehigh riskneuroimagingschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 16 , December 2014 , pp. 3491 - 3501
Copyright
Copyright © Cambridge University Press 2014 

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References

APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Bora, E, Fornito, A, Pantelis, C, Yucel, M (2012). Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. Journal of Affective Disorders 138, 9–18.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, McGuire, P, Fusar-Poli, P, Radue, EW, Riecher-Rossler, A (2008). Anterior cingulate pathology in the prodromal stage of schizophrenia. NeuroImage 39, 553–554.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, Riecher-Rossler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, Gschwandtner, U, Haller, S, Pfluger, M, Rechsteiner, E, D'Souza, M, Stieglitz, RD, Radu, EW, McGuire, PK (2007). Regional gray matter volume abnormalities in the at risk mental state. Biological Psychiatry 61, 1148–1156.CrossRefGoogle ScholarPubMed
Broome, MR, Woolley, JB, Johns, LC, Valmaggia, LR, Tabraham, P, Gafoor, R, Bramon, E, McGuire, PK (2005). Outreach and support in south London (OASIS): implementation of a clinical service for prodromal psychosis and the at risk mental state. European Psychiatry 20, 372–378.CrossRefGoogle ScholarPubMed
Damasio, AR, Tranel, D, Damasio, H (1990). Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli. Behavioral Brain Research 41, 81–94.CrossRefGoogle ScholarPubMed
Demjaha, A, Valmaggia, L, Stahl, D, Byrne, M, McGuire, P (2012). Disorganization/cognitive and negative symptom dimensions in the at-risk mental state predict subsequent transition to psychosis. Schizophrenia Bulletin 38, 351–359.CrossRefGoogle ScholarPubMed
Drevets, WC (2000). Neuroimaging studies of mood disorders. Biological Psychiatry 48, 813–829.CrossRefGoogle ScholarPubMed
Drevets, WC (2001). Neuroimaging and neuropathological studies of depression: implications for the cognitive–emotional features of mood disorders. Current Opinion in Neurobiology 11, 240–249.CrossRefGoogle ScholarPubMed
First, M, Spitzer, R, Gibbon, M, Williams, JBW (1996). Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press: Washington, DC.Google Scholar
Folstein, MF, Folstein, SE, McHugh, PR (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189–198.CrossRefGoogle Scholar
Fornito, A, Yung, AR, Wood, SJ, Phillips, LJ, Nelson, B, Cotton, S, Velakoulis, D, McGorry, PD, Pantelis, C, Yucel, M (2008). Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals. Biological Psychiatry 64, 758–765.CrossRefGoogle ScholarPubMed
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 a). The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry 70, 107–120.CrossRefGoogle Scholar
Fusar-Poli, P, Borgwardt, S, Crescini, A, Deste, G, Kempton, MJ, Lawrie, S, McGuire, P, Sacchetti, E (2011). Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neuroscience and Biobehavioral Reviews 35, 1175–1185.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Byrne, M, Badger, S, Valmaggia, LR, McGuire, PK (2013 b). Outreach and support in South London (OASIS), 2001–2011: ten years of early diagnosis and treatment for young individuals at high clinical risk for psychosis. European Psychiatry 28, 315–326.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Carpenter, WT, Woods, SW, McGlashan, TH (2014 a). Attenuated psychosis syndrome: ready for DSM-5.1? Annual Review of Clinical Psychology. Published online 17 January 2014 . doi:10.1146/annurev-clinpsy-032813-153645.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Nelson, B, Valmaggia, L, Yung, AR, McGuire, PK (2014 b). Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis. Schizophrenia Bulletin 40, 120–131.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Radua, J, McGuire, P, Borgwardt, S (2012). Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies. Schizophrenia Bulletin 38, 1297–1307.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Valmaggia, L, McGuire, P (2007). Can antidepressants prevent psychosis? Lancet 370, 1746–1748.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Yung, AR, McGorry, P, van Os, J (2014 c). Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention. Psychological Medicine 44, 17–24.CrossRefGoogle ScholarPubMed
Hercher, C, Canetti, L, Turecki, G, Mechawar, N (2010). Anterior cingulate pyramidal neurons display altered dendritic branching in depressed suicides. Journal of Psychiatric Research 44, 286–293.CrossRefGoogle ScholarPubMed
Ho, BC, Alicata, D, Ward, J, Moser, DJ, O'Leary, DS, Arndt, S, Andreasen, NC (2003). Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. American Journal of Psychiatry 160, 142–148.CrossRefGoogle ScholarPubMed
Lahti, AC, Holcomb, HH, Weiler, MA, Medoff, DR, Frey, KN, Hardin, M, Tamminga, CA (2004). Clozapine but not haloperidol re-establishes normal task-activated rCBF patterns in schizophrenia within the anterior cingulate cortex. Neuropsychopharmacology 29, 171–178.CrossRefGoogle Scholar
Mechelli, A, Riecher-Rossler, A, Meisenzahl, EM, Tognin, S, Wood, SJ, Borgwardt, SJ, Koutsouleris, N, Yung, AR, Stone, JM, Phillips, LJ, McGorry, PD, Valli, I, Velakoulis, D, Woolley, J, Pantelis, C, McGuire, P (2011). Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Archives of General Psychiatry 68, 489–495.CrossRefGoogle ScholarPubMed
Meisenzahl, EM, Koutsouleris, N, Gaser, C, Bottlender, R, Schmitt, GJ, McGuire, P, Decker, P, Burgermeister, B, Born, C, Reiser, M, Moller, HJ (2008). Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study. Schizophrenia Research 102, 150–162.CrossRefGoogle ScholarPubMed
Mishara, AL, Fusar-Poli, P (2013). The phenomenology and neurobiology of delusion formation during psychosis onset: Jaspers, Truman symptoms, and aberrant salience. Schizophrenia Bulletin 39, 278–286.CrossRefGoogle ScholarPubMed
O'Connor, R, Sota, M, Cortesi, M, Fusar-Poli, P (2007). Quetiapine as a first-choice agent in subjects at high-risk to psychosis? Medical Hypotheses 69, 230.CrossRefGoogle ScholarPubMed
Pan, LA, Hassel, S, Segreti, AM, Nau, SA, Brent, DA, Phillips, ML (2013). Differential patterns of activity and functional connectivity in emotion processing neural circuitry to angry and happy faces in adolescents with and without suicide attempt. Psychological Medicine 43, 2129–2142.CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, Yung, AR, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGuire, PK (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281–288.CrossRefGoogle ScholarPubMed
Radua, J, Borgwardt, S, Crescini, A, Mataix-Cols, D, Meyer-Lindenberg, A, McGuire, PK, Fusar-Poli, P (2012). Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neuroscience and Biobehavioral Reviews 36, 2325–2333.CrossRefGoogle ScholarPubMed
Radua, J, van den Heuvel, OA, Surguladze, S, Mataix-Cols, D (2010). Meta-analytical comparison of voxel-based morphometry studies in obsessive–compulsive disorder vs other anxiety disorders. Archives of General Psychiatry 67, 701–711.CrossRefGoogle ScholarPubMed
Rajkowska, G, Miguel-Hidalgo, JJ, Wei, J, Dilley, G, Pittman, SD, Meltzer, HY, Overholser, JC, Roth, BL, Stockmeier, CA (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry 45, 1085–1098.CrossRefGoogle ScholarPubMed
Sacher, J, Neumann, J, Funfstuck, T, Soliman, A, Villringer, A, Schroeter, ML (2012). Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. Journal of Affective Disorders 140, 142–148.CrossRefGoogle Scholar
Salokangas, RK, Ruhrmann, S, von Reventlow, HG, Heinimaa, M, Svirskis, T, From, T, Luutonen, S, Juckel, G, Linszen, D, Dingemans, P, Birchwood, M, Patterson, P, Schultze-Lutter, F, Klosterkötter, J; EPOS Group (2012). Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries. Schizophrenia Research 138, 192–197.CrossRefGoogle ScholarPubMed
Schennach-Wolff, R, Jager, M, Seemuller, F, Obermeier, M, Messer, T, Laux, G, Pfeiffer, H, Naber, D, Schmidt, LG, Gaebel, W, Huff, W, Heuser, I, Maier, W, Lemke, MR, Ruther, E, Buchkremer, G, Gastpar, M, Moller, HJ, Riedel, M (2009). Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders. Schizophrenia Research 113, 210–217.CrossRefGoogle ScholarPubMed
Schroeter, ML, Abdul-Khaliq, H, Krebs, M, Diefenbacher, A, Blasig, IE (2008). Serum markers support disease-specific glial pathology in major depression. Journal of Affective Disorders 111, 271–280.CrossRefGoogle ScholarPubMed
Schroeter, ML, Abdul-Khaliq, H, Sacher, J, Steiner, J, Blasig, IE, Mueller, K (2010). Mood disorders are glial disorders: evidence from in vivo studies. Cardiovascular Psychiatry and Neurology 2010, 780 645.Google ScholarPubMed
Snitz, BE, MacDonald, A 3rd, Cohen, JD, Cho, RY, Becker, T, Carter, CS (2005). Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. American Journal of Psychiatry 162, 2322–2329.CrossRefGoogle Scholar
Song, XW, Dong, ZY, Long, XY, Li, SF, Zuo, XN, Zhu, CZ, He, Y, Yan, CG, Zang, YF (2011). REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS ONE 6, e25 031.CrossRefGoogle Scholar
Spellmann, I, Riedel, M, Schennach, R, Seemuller, F, Obermeier, M, Musil, R, Jager, M, Schmauss, M, Laux, G, Pfeiffer, H, Naber, D, Schmidt, LG, Gaebel, W, Klosterkotter, J, Heuser, I, Maier, W, Lemke, MR, Ruther, E, Klingberg, S, Gastpar, M, Moller, HJ (2012). One-year functional outcomes of naturalistically treated patients with schizophrenia. Psychiatry Research 198, 378–385.CrossRefGoogle ScholarPubMed
Thompson, A, Nelson, B, Yung, A (2011). Predictive validity of clinical variables in the “at risk” for psychosis population: international comparison with results from the North American Prodrome Longitudinal Study. Schizophrenia Research 126, 51–57.CrossRefGoogle ScholarPubMed
Torres-Platas, SG, Hercher, C, Davoli, MA, Maussion, G, Labonte, B, Turecki, G, Mechawar, N (2011). Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides. Neuropsychopharmacology 36, 2650–2658.CrossRefGoogle ScholarPubMed
Tsuang, MT, Van Os, J, Tandon, R, Barch, DM, Bustillo, J, Gaebel, W, Gur, RE, Heckers, S, Malaspina, D, Owen, MJ, Schultz, S, Carpenter, W (2013). Attenuated psychosis syndrome in DSM-5. Schizophrenia Research 150, 31–35.CrossRefGoogle ScholarPubMed
Valmaggia, LR, Stahl, D, Yung, AR, Nelson, B, Fusar-Poli, P, McGorry, PD, McGuire, PK (2013). Negative psychotic symptoms and impaired role functioning predict transition outcomes in the at-risk mental state: a latent class cluster analysis study. Psychological Medicine 43, 2311–2325.CrossRefGoogle Scholar
van Os, J, Murray, RM (2013). Can we identify and treat “schizophrenia light” to prevent true psychotic illness? British Medical Journal 346, f304.CrossRefGoogle ScholarPubMed
Velthorst, E, Nelson, B, Wiltink, S, de Haan, L, Wood, SJ, Lin, A, Yung, AR (2013). Transition to first episode psychosis in ultra high risk populations: does baseline functioning hold the key? Schizophrenia Research 143, 132–137.CrossRefGoogle ScholarPubMed
Wagner, G, Koch, K, Schachtzabel, C, Schultz, CC, Sauer, H, Schlosser, RG (2011). Structural brain alterations in patients with major depressive disorder and high risk for suicide: evidence for a distinct neurobiological entity? Neuroimage 54, 1607–1614.CrossRefGoogle ScholarPubMed
Wagner, G, Schultz, CC, Koch, K, Schachtzabel, C, Sauer, H, Schlosser, RG (2012). Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior. Journal of Psychiatric Research 46, 1449–1455.CrossRefGoogle ScholarPubMed
Wood, SJ, Pantelis, C, Velakoulis, D, Yucel, M, Fornito, A, McGorry, PD (2008). Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophrenia Bulletin 34, 322–329.CrossRefGoogle ScholarPubMed
Wulff, K, Dijk, DJ, Middleton, B, Foster, RG, Joyce, EM (2012). Sleep and circadian rhythm disruption in schizophrenia. British Journal of Psychiatry 200, 308–316.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, McGorry, PD, McFarlane, CA, Francey, S, Harrigan, S, Patton, GC, Jackson, HJ (1998). Prediction of psychosis. A step towards indicated prevention of schizophrenia. British Journal of Psychiatry. Supplement 172, 14–20.CrossRefGoogle ScholarPubMed
Yung, AR, Woods, SW, Ruhrmann, S, Addington, J, Schultze-Lutter, F, Cornblatt, BA, Amminger, GP, Bechdolf, A, Birchwood, M, Borgwardt, S, Cannon, TD, de Haan, L, French, P, Fusar-Poli, P, Keshavan, M, Klosterkotter, J, Kwon, JS, McGorry, PD, McGuire, P, Mizuno, M, Morrison, AP, Riecher-Rossler, A, Salokangas, RK, Seidman, LJ, Suzuki, M, Valmaggia, L, van der Gaag, M, Wood, SJ, McGlashan, TH (2012). Whither the attenuated psychosis syndrome? Schizophrenia Bulletin 38, 1130–1134.CrossRefGoogle ScholarPubMed
Yung, AR, Yuen, HP, McGorry, PD, Phillips, LJ, Kelly, D, Dell'Olio, M, Francey, SM, Cosgrave, EM, Killackey, E, Stanford, C, Godfrey, K, Buckby, J (2005). Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States. Australian and New Zealand Journal of Psychiatry 39, 964–971.CrossRefGoogle ScholarPubMed
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