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Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

  • C. A. Webb (a1), M. Weber (a1), E. A. Mundy (a1) and W. D. S. Killgore (a1)

Abstract

Background

Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.

Method

To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants.

Results

The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression.

Conclusions

Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

Copyright

Corresponding author

* Address for correspondence: C. A. Webb, Ph.D., Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. (Email: cwebb@mclean.harvard.edu)

References

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Abe, O, Yamasue, H, Kasai, K, Yamada, H, Aoki, S, Inoue, H, Takei, K, Suga, M, Matsuo, K, Kato, T, Masutani, Y, Ohtomo, K (2010). Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression. Psychiatry Research 181, 6470.
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry – the methods. NeuroImage 11, 805821.
Beck, AT, Alford, BA (2009). Depression: Causes and Treatments. University of Pennsylvania Press: Philadelphia.
Beck, AT, Steer, RA (1993). Beck Depression Inventory Manual. Harcourt Brace: San Antonio.
Beck, AT, Steer, RA, Brown, GK (1996). Beck Depression Inventory Manual, 2nd edn. Harcourt Brace: San Antonio.
Beck, AT, Steer, RA, Carbin, MG (1988). Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clinical Psychology Review 8, 77100.
Bielau, H, Trubner, K, Krell, D, Agelink, MW, Bernstein, HG, Stauch, R, Baumann, B (2005). Volume deficits of subcortical nuclei in mood disorders: a postmortem study. European Archives of Psychiatry and Clinical Neuroscience 255, 401412.
Blair, KS, Otero, M, Teng, C, Jacobs, M, Odenheimer, S, Pine, DS, Blair, RJ (2013). Dissociable roles of ventromedial prefrontal cortex (vmPFC) and rostral anterior cingulate cortex (rACC) in value representation and optimistic bias. NeuroImage 78, 103110.
Boes, AD, McCormick, LM, Coryell, WH, Nopoulos, P (2008). Cortex volume correlates with depressed mood in normal healthy children. Biological Psychiatry 63, 391397.
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.
Bush, G, Luu, P, Posner, MI (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences 4, 215222.
Caetano, SC, Hatch, JP, Brambilla, P, Sassi, RB, Nicoletti, M, Mallinger, AG, Frank, E, Kupfer, DJ, Keshaven, MS, Soares, JC (2004). Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Research 132, 141147.
Cohen, RA, Grieve, S, Hoth, KF, Paul, RH, Sweet, L, Tate, D, Williams, LM (2006). Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biological Psychiatry 59, 975982.
Cuijpers, P, de Graaf, R, van Dorsselaer, S (2004). Minor depression: risk profiles, functional disability, health care use and risk of developing major depression. Journal of Affective Disorders 79, 7179.
D'Avanzato, C, Joormann, J, Siemer, M, Gotlib, IH (2013). Emotion regulation in depression and anxiety: examining diagnostic specificity and stability of strategy use. Cognitive Therapy and Research 37, 968980.
DeRubeis, RJ, Webb, CA, Tang, TZ, Beck, AT (2010). Cognitive therapy. In Handbook of Cognitive–Behavioral Therapies, 3rd edn. (ed. Dobson, K. S.), pp. 277316. Guilford: New York.
Dotson, VM, Davatzikos, C, Kraut, MA, Resnick, SM (2009). Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study. Journal of Psychiatry and Neuroscience 34, 367375.
Du, MY, Wu, QZ, Yue, Q, Li, J, Liao, Y, Kuang, WH, Gong, QY (2012). Voxelwise meta-analysis of gray matter reduction in major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 36, 1116.
Elliott, R, Sahakian, BJ, Michael, A, Paykel, ES, Dolan, RJ (1998). Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression. Psychological Medicine 28, 559571.
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 8593.
Etkin, A, Egner, T, Peraza, DM, Kandel, ER, Hirsch, J (2006). Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron 51, 871882.
Eugene, F, Joormann, J, Cooney, RE, Atlas, LY, Gotlib, IH (2010). Neural correlates of inhibitory deficits in depression. Psychiatry Research 181, 3035.
Fergusson, DM, Horwood, LJ, Ridder, EM, Beautrais, AL (2005). Subthreshold depression in adolescence and mental health outcomes in adulthood. Archives of General Psychiatry 62, 6672.
Field, A (2009 a). Discovering Statistics Using SPSS, 3rd edn., pp. 138139. Sage Publications, Inc.: Thousand Oaks, CA.
Field, A (2009 b). Discovering Statistics Using SPSS, 3rd edn., pp. 154156. Sage Publications, Inc.: Thousand Oaks, CA.
First, M, Spitzer, R, Gibbon, M, Williams, J (2001). Structured Clinical Interview for DSM-IV-TR – Axis I Disorders, Research Version, Patient Edition with Psychotic Screen (SCID-I/P W/PSY SCREEN). Biometrics Research, New York State Psychiatric Institute: New York.
Goeleven, E, De Raedt, R, Baert, S, Koster, EH (2006). Deficient inhibition of emotional information in depression. Journal of Affective Disorders 93, 149157.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Hayakawa, YK, Sasaki, H, Takao, H, Mori, H, Hayashi, N, Kunimatsu, A, Ohtomo, K (2013). Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging. Journal of Affective Disorders 144, 263268.
Hayasaka, S, Phan, KL, Liberzon, I, Worsley, KJ, Nichols, TE (2004). Nonstationary cluster-size inference with random field and permutation methods. NeuroImage 22, 676687.
Holmes, AJ, Bogdan, R, Pizzagalli, DA (2010). Serotonin transporter genotype and action monitoring dysfunction: a possible substrate underlying increased vulnerability to depression. Neuropsychopharmacology 35, 11861197.
Joormann, J (2004). Attentional bias in dysphoria: the role of inhibitory processes. Cognition and Emotion 18, 125147.
Killgore, WD (1999). Empirically derived factor indices for the Beck Depression Inventory. Psychological Reports 84, 10051013.
Killgore, WD, Schwab, ZJ, Kipman, M, DelDonno, SR, Weber, M (2012 a). Voxel-based morphometric gray matter correlates of daytime sleepiness. Neuroscience Letters 518, 1013.
Killgore, WD, Schwab, ZJ, Weber, M, Kipman, M, Deldonno, SR, Weiner, MR, Rauch, SL (2013). Daytime sleepiness affects prefrontal regulation of food intake. NeuroImage 71, 216223.
Killgore, WD, Schwab, ZJ, Weiner, MR (2012 b). Self-reported nocturnal sleep duration is associated with next-day resting state functional connectivity. Neuroreport 23, 741745.
Killgore, WD, Yurgelun-Todd, DA (2006). Ventromedial prefrontal activity correlates with depressed mood in adolescent children. Neuroreport 17, 167171.
Kim, MJ, Hamilton, JP, Gotlib, IH (2008). Reduced caudate gray matter volume in women with major depressive disorder. Psychiatry Research 164, 114122.
Klein, DN, Glenn, CR, Kosty, DB, Seeley, JR, Rohde, P, Lewinsohn, PM (2013). Predictors of first lifetime onset of major depressive disorder in young adulthood. Journal of Abnormal Psychology 122, 16.
Kline, RB (2005). Principles and Practice of Structural Equation Modeling, 2nd edn., pp. 5051. Guilford Press: New York.
Koolschijn, PC, van Haren, NE, Lensvelt-Mulders, GJ, Hulshoff Pol, HE, Kahn, RS (2009). Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human Brain Mapping 30, 37193735.
Lai, CH (2013). Gray matter volume in major depressive disorder: a meta-analysis of voxel-based morphometry studies. Psychiatry Research 211, 3746.
Lee, HY, Tae, WS, Yoon, HK, Lee, BT, Paik, JW, Son, KR, Ham, BJ (2011). Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: an optimized voxel-based morphometry study. Journal of Affective Disorders 133, 128136.
MacQueen, GM, Campbell, S, McEwen, BS, Macdonald, K, Amano, S, Joffe, RT, Nahmias, C, Young, LT (2003). Course of illness, hippocampal function, and hippocampal volume in major depression. Proceedings of the National Academy of Sciences USA 100, 13871392.
Mayberg, HS (1997). Limbic–cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry 9, 471481.
Morey, LC (1991). Personality Assessment Inventory. Psychological Assessment Resources Inc.: Lutz, FL.
Morey, LC (2007). Personality Assessment Inventory: Professional Manual, 2nd edn. Psychological Assessment Resources Inc.: Lutz, FL.
Nolen-Hoeksema, S (1991). Responses to depression and their effects on the duration of depressive episodes. Journal of Abnormal Psychology 100, 569582.
Nolen-Hoeksema, S, Wisco, BE, Lyubomirsky, S (2008). Rethinking rumination. Perspectives on Psychological Science 3, 400424.
Northoff, G, Heinzel, A, de Greck, M, Bermpohl, F, Dobrowolny, H, Panksepp, J (2006). Self-referential processing in our brain – a meta-analysis of imaging studies on the self. NeuroImage 31, 440457.
Palomero-Gallagher, N, Mohlberg, H, Zilles, K, Vogt, B (2008). Cytology and receptor architecture of human anterior cingulate cortex. Journal of Comparative Neurology 508, 906926.
Pizzagalli, DA (2011). Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 36, 183206.
Pizzagalli, DA, Peccoralo, LA, Davidson, RJ, Cohen, JD (2006). Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: a 128-channel EEG study. Human Brain Mapping 27, 185201.
Price, JL, Drevets, WC (2009). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192216.
Prisciandaro, JJ, Roberts, JE (2009). A comparison of the predictive abilities of dimensional and categorical models of unipolar depression in the National Comorbidity Survey. Psychological Medicine 39, 10871096.
Ries, ML, Wichmann, A, Bendlin, BB, Johnson, SC (2009). Posterior cingulate and lateral parietal gray matter volume in older adults with depressive symptoms. Brain Imaging and Behavior 3, 233239.
Santesso, DL, Bogdan, R, Birk, JL, Goetz, EL, Holmes, AJ, Pizzagalli, DA (2012). Neural responses to negative feedback are related to negative emotionality in healthy adults. Social Cognitive and Affective Neuroscience 7, 794803.
Serra-Blasco, M, Portella, MJ, Gómez-Ansón, B, de Diego-Adeliño, J, Vives-Gilabert, Y, Puigdemont, D, Granell, E, Santos, A, Alvarez, E, Pérez, V (2013). Effects of illness duration and treatment resistance on grey matter abnormalities in major depression. British Journal of Psychiatry 202, 434440.
Shafritz, KM, Collins, SH, Blumberg, HP (2006). The interaction of emotional and cognitive neural systems in emotionally guided response inhibition. NeuroImage 31, 468475.
Sharot, T, Riccardi, MA, Raio, CM, Phelps, EA (2007). Neural mechanisms mediating optimism bias. Nature 450, 102105.
Southwick, SM, Morgan, CA 3rd, Nicolaou, AL, Charney, DS (1997). Consistency of memory for combat-related traumatic events in veterans of Operation Desert Storm. American Journal of Psychiatry 154, 173177.
Strunk, DR, Lopez, H, DeRubeis, RJ (2006). Depressive symptoms are associated with unrealistic negative predictions of future life events. Behaviour Research and Therapy 44, 861882.
Taki, Y, Kinomura, S, Awata, S, Inoue, K, Sato, K, Ito, H, Fukuda, H (2005). Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry. Journal of Affective Disorders 88, 313320.
Tang, Y, Wang, F, Xie, G, Liu, J, Li, L, Su, L, Liu, Y, Hu, X, He, Z, Blumberg, HP (2007). Reduced ventral anterior cingulate and amygdala volumes in medication-naive females with major depressive disorder: a voxel-based morphometric magnetic resonance imaging study. Psychiatry Research 156, 8386.
Treadway, MT, Grant, MM, Ding, Z, Hollon, SD, Gore, JC, Shelton, RC (2009). Early adverse events, HPA activity and rostral anterior cingulate volume in MDD. PLoS One 4, e4887.
Vasic, N, Walter, H, Hose, A, Wolf, RC (2008). Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study. Journal of Affective Disorders 109, 107116.
Veerman, JL, Dowrick, C, Ayuso-Mateos, JL, Dunn, G, Barendregt, JJ (2009). Population prevalence of depression and mean Beck Depression Inventory score. British Journal of Psychiatry 195, 516519.
Vogt, B, Vogt, L, Farber, NB, Bush, G (2005). Architecture and neurocytology of monkey cingulate gyrus. Journal of Comparative Neurology 485, 218239.
Wagner, G, Koch, K, Schachtzabel, C, Schultz, CC, Sauer, H, Schlsser, 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.
Warner-Schmidt, JL, Duman, RS (2006). Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16, 239249.
Webb, CA, Schwab, ZJ, Weber, M, DelDonno, S, Kipman, M, Weiner, MR, Killgore, WDS (2013). Convergent and divergent validity of integrative versus mixed model measures of emotional intelligence. Intelligence 41, 149156.
World Health Organization (1993). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. World Health Organization: Geneva.
Yoshimura, S, Ueda, K, Suzuki, S, Onoda, K, Okamoto, Y, Yamawaki, S (2009). Self-referential processing of negative stimuli within the ventral anterior cingulate gyrus and right amygdala. Brain and Cognition 69, 218225.
Zou, K, Deng, W, Li, T, Zhang, B, Jiang, L, Huang, C, Sun, X (2010). Changes of brain morphometry in first-episode, drug-naive, non-late-life adult patients with major depression: an optimized voxel-based morphometry study. Biological Psychiatry 67, 186188.

Keywords

Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

  • C. A. Webb (a1), M. Weber (a1), E. A. Mundy (a1) and W. D. S. Killgore (a1)

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