Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-02T21:28:25.800Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  26 February 2014

C. A. Webb*
Affiliation:
McLean Hospital, Harvard Medical School, Belmont, MA, USA
M. Weber
Affiliation:
McLean Hospital, Harvard Medical School, Belmont, MA, USA
E. A. Mundy
Affiliation:
McLean Hospital, Harvard Medical School, Belmont, MA, USA
W. D. S. Killgore
Affiliation:
McLean Hospital, Harvard Medical School, Belmont, MA, USA
*
* 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: [email protected])

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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

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

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.Google Scholar
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry – the methods. NeuroImage 11, 805821.Google Scholar
Beck, AT, Alford, BA (2009). Depression: Causes and Treatments. University of Pennsylvania Press: Philadelphia.Google Scholar
Beck, AT, Steer, RA (1993). Beck Depression Inventory Manual. Harcourt Brace: San Antonio.Google Scholar
Beck, AT, Steer, RA, Brown, GK (1996). Beck Depression Inventory Manual, 2nd edn. Harcourt Brace: San Antonio.Google Scholar
Beck, AT, Steer, RA, Carbin, MG (1988). Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clinical Psychology Review 8, 77100.Google Scholar
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.Google Scholar
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.Google Scholar
Boes, AD, McCormick, LM, Coryell, WH, Nopoulos, P (2008). Cortex volume correlates with depressed mood in normal healthy children. Biological Psychiatry 63, 391397.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, 918.Google Scholar
Bush, G, Luu, P, Posner, MI (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences 4, 215222.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 8593.CrossRefGoogle ScholarPubMed
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.Google Scholar
Eugene, F, Joormann, J, Cooney, RE, Atlas, LY, Gotlib, IH (2010). Neural correlates of inhibitory deficits in depression. Psychiatry Research 181, 3035.Google Scholar
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.Google Scholar
Field, A (2009 a). Discovering Statistics Using SPSS, 3rd edn., pp. 138139. Sage Publications, Inc.: Thousand Oaks, CA.Google Scholar
Field, A (2009 b). Discovering Statistics Using SPSS, 3rd edn., pp. 154156. Sage Publications, Inc.: Thousand Oaks, CA.Google Scholar
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.Google Scholar
Goeleven, E, De Raedt, R, Baert, S, Koster, EH (2006). Deficient inhibition of emotional information in depression. Journal of Affective Disorders 93, 149157.Google Scholar
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.Google Scholar
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.CrossRefGoogle ScholarPubMed
Hayasaka, S, Phan, KL, Liberzon, I, Worsley, KJ, Nichols, TE (2004). Nonstationary cluster-size inference with random field and permutation methods. NeuroImage 22, 676687.Google Scholar
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.Google Scholar
Joormann, J (2004). Attentional bias in dysphoria: the role of inhibitory processes. Cognition and Emotion 18, 125147.Google Scholar
Killgore, WD (1999). Empirically derived factor indices for the Beck Depression Inventory. Psychological Reports 84, 10051013.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
Killgore, WD, Yurgelun-Todd, DA (2006). Ventromedial prefrontal activity correlates with depressed mood in adolescent children. Neuroreport 17, 167171.Google Scholar
Kim, MJ, Hamilton, JP, Gotlib, IH (2008). Reduced caudate gray matter volume in women with major depressive disorder. Psychiatry Research 164, 114122.Google Scholar
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.Google Scholar
Kline, RB (2005). Principles and Practice of Structural Equation Modeling, 2nd edn., pp. 5051. Guilford Press: New York.Google Scholar
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.Google Scholar
Lai, CH (2013). Gray matter volume in major depressive disorder: a meta-analysis of voxel-based morphometry studies. Psychiatry Research 211, 3746.Google Scholar
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.Google Scholar
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.Google Scholar
Mayberg, HS (1997). Limbic–cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry 9, 471481.Google Scholar
Morey, LC (1991). Personality Assessment Inventory. Psychological Assessment Resources Inc.: Lutz, FL.Google Scholar
Morey, LC (2007). Personality Assessment Inventory: Professional Manual, 2nd edn. Psychological Assessment Resources Inc.: Lutz, FL.Google Scholar
Nolen-Hoeksema, S (1991). Responses to depression and their effects on the duration of depressive episodes. Journal of Abnormal Psychology 100, 569582.Google Scholar
Nolen-Hoeksema, S, Wisco, BE, Lyubomirsky, S (2008). Rethinking rumination. Perspectives on Psychological Science 3, 400424.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
Pizzagalli, DA (2011). Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 36, 183206.Google Scholar
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.Google Scholar
Price, JL, Drevets, WC (2009). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192216.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Shafritz, KM, Collins, SH, Blumberg, HP (2006). The interaction of emotional and cognitive neural systems in emotionally guided response inhibition. NeuroImage 31, 468475.Google Scholar
Sharot, T, Riccardi, MA, Raio, CM, Phelps, EA (2007). Neural mechanisms mediating optimism bias. Nature 450, 102105.Google Scholar
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.Google ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
Vogt, B, Vogt, L, Farber, NB, Bush, G (2005). Architecture and neurocytology of monkey cingulate gyrus. Journal of Comparative Neurology 485, 218239.Google Scholar
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.CrossRefGoogle ScholarPubMed
Warner-Schmidt, JL, Duman, RS (2006). Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16, 239249.Google Scholar
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.Google Scholar
World Health Organization (1993). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. World Health Organization: Geneva.Google Scholar
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.Google Scholar
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.Google Scholar