Skip to main content Accessibility help
×
Home

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

  • G. Modinos (a1), P. Allen (a1), M. Frascarelli (a1), S. Tognin (a1), L. Valmaggia (a1), L. Xenaki (a1), P. Keedwell (a2), M. Broome (a3), I. Valli (a1), J. Woolley (a1), J. M. Stone (a1), A. Mechelli (a1), M. L. Phillips (a4), P. McGuire (a1) and P. Fusar-Poli (a1)...

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.

Copyright

Corresponding author

* 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: paolo.fusar-poli@kcl.ac.uk)

References

Hide All
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.
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, 918.
Borgwardt, SJ, McGuire, P, Fusar-Poli, P, Radue, EW, Riecher-Rossler, A (2008). Anterior cingulate pathology in the prodromal stage of schizophrenia. NeuroImage 39, 553554.
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, 11481156.
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, 372378.
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, 8194.
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, 351359.
Drevets, WC (2000). Neuroimaging studies of mood disorders. Biological Psychiatry 48, 813829.
Drevets, WC (2001). Neuroimaging and neuropathological studies of depression: implications for the cognitive–emotional features of mood disorders. Current Opinion in Neurobiology 11, 240249.
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.
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, 189198.
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, 758765.
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, 107120.
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, 11751185.
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, 315326.
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.
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, 120131.
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, 12971307.
Fusar-Poli, P, Valmaggia, L, McGuire, P (2007). Can antidepressants prevent psychosis? Lancet 370, 17461748.
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, 1724.
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, 286293.
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, 142148.
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, 171178.
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, 489495.
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, 150162.
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, 278286.
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.
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, 21292142.
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, 281288.
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, 23252333.
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, 701711.
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, 10851098.
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, 142148.
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, 192197.
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, 210217.
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, 271280.
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.
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, 23222329.
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.
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, 378385.
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, 5157.
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, 26502658.
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, 3135.
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, 23112325.
van Os, J, Murray, RM (2013). Can we identify and treat “schizophrenia light” to prevent true psychotic illness? British Medical Journal 346, f304.
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, 132137.
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, 16071614.
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, 14491455.
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, 322329.
Wulff, K, Dijk, DJ, Middleton, B, Foster, RG, Joyce, EM (2012). Sleep and circadian rhythm disruption in schizophrenia. British Journal of Psychiatry 200, 308316.
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, 1420.
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, 11301134.
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, 964971.

Keywords

Type Description Title
WORD
Supplementary materials

Modinos Supplementary Material
Supplementary Material

 Word (2.4 MB)
2.4 MB

Metrics

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