Skip to main content Accessibility help

Functional brain-imaging correlates of negative affectivity and the onset of first-episode depression

  • C. G. Davey (a1) (a2), S. Whittle (a2), B. J. Harrison (a2), J. G. Simmons (a3), M. L. Byrne (a3), O. S. Schwartz (a3) and N. B. Allen (a3)...



The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala–sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression.


Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala–sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression.


The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala–sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala–sACC connectivity at follow-up.


Amygdala–sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological ‘scar’ hypothesis of depression.


Corresponding author

* Address for correspondence: Dr C. G. Davey, Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia. (Email:


Hide All
Adolphs, R (2010). What does the amygdala contribute to social cognition? Annals of the New York Academy of Sciences 1191, 4261.
Almeida, JR, Kronhaus, DM, Sibille, EL, Langenecker, SA, Versace, A, Labarbara, EJ, Phillips, ML (2011). Abnormal left-sided orbitomedial prefrontal cortical-amygdala connectivity during happy and fear face processing: a potential neural mechanism of female MDD. Frontiers in Psychiatry 2, 69.
An, X, Bandler, R, Ongur, D, Price, JL (1998). Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in macaque monkeys. Journal of Comparative Neurology 401, 455479.
Beckmann, M, Johansen-Berg, H, Rushworth, MF (2009). Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization. Journal of Neuroscience 29, 11751190.
Brown, BB (2004). Adolescents’ relationships with peers. In Handbook of Adolescent Psychology (ed. Lerner, R. M. and Steinberg, L. D.), pp. 363394. John Wiley & Sons: Hoboken, NJ.
Buckner, RL, Andrews-Hanna, JR, Schacter, DL (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences 1124, 138.
Clark, LA, Watson, D, Mineka, S (1994). Temperament, personality, and the mood and anxiety disorders. Journal of Abnormal Psychology 103, 103116.
Cloninger, CR, Przybeck, TR, Svrakic, DM (1991). The Tridimensional Personality Questionnaire: U.S. normative data. Psychological Reports 69, 10471057.
Connolly, CG, Wu, J, Ho, TC, Hoeft, F, Wolkowitz, O, Eisendrath, S, Frank, G, Hendren, R, Max, JE, Paulus, MP, Tapert, SF, Banerjee, D, Simmons, AN, Yang, TT (2013). Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biological Psychiatry 74, 898907.
Craske, MG, Waters, AM, Nazarian, M, Mineka, S, Zinbarg, RE, Griffith, JW, Naliboff, B, Ornitz, EM (2009). Does neuroticism in adolescents moderate contextual and explicit threat cue modulation of the startle reflex? Biological Psychiatry 65, 220226.
Cronbach, LJ, Furby, L (1970). How we should measure ‘change’: or should we? Psychological Bulletin 74, 6880.
Cunningham, WA, Arbuckle, NL, Jahn, A, Mowrer, SM, Abduljalil, AM (2010). Aspects of neuroticism and the amygdala: chronic tuning from motivational styles. Neuropsychologia 48, 33993404.
Ellis, LK, Rothbart, MK (2001). Revision of the Early Adolescent Temperament Questionnaire. Poster presented at the 2001 Biennial Meeting of the Society for Research in Child Development.
Fox, MD, Corbetta, M, Snyder, AZ, Vincent, JL, Raichle, ME (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proceedings of the National Academy of Sciences of the United States of America 103, 1004610051.
Freedman, LJ, Insel, TR, Smith, Y (2000). Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. Journal of Comparative Neurology 421, 172188.
Gotlib, IH, Sivers, H, Gabrieli, JD, Whitfield-Gabrieli, S, Goldin, P, Minor, KL, Canli, T (2005). Subgenual anterior cingulate activation to valenced emotional stimuli in major depression. Neuroreport 16, 17311734.
Haas, BW, Omura, K, Constable, RT, Canli, T (2007). Emotional conflict and neuroticism: personality-dependent activation in the amygdala and subgenual anterior cingulate. Behavioral Neuroscience 121, 249256.
Harrison, BJ, Soriano-Mas, C, Pujol, J, Ortiz, H, Lopez-Sola, M, Hernandez-Ribas, R, Deus, J, Alonso, P, Yucel, M, Pantelis, C, Menchon, JM, Cardoner, N (2009). Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Archives of General Psychiatry 66, 11891200.
Johansen-Berg, H, Gutman, DA, Behrens, TE, Matthews, PM, Rushworth, MF, Katz, E, Lozano, AM, Mayberg, HS (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cerebral Cortex 18, 13741383.
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980988.
Kotov, R, Gamez, W, Schmidt, F, Watson, D (2010). Linking ‘big’ personality traits to anxiety, depressive, and substance use disorders: a meta-analysis. Psychological Bulletin 136, 768821.
Lewinsohn, PM, Rohde, P, Seeley, JR (1998). Major depressive disorder in older adolescents: prevalence, risk factors, and clinical implications. Clinical Psychology Review 18, 765794.
Lewinsohn, PM, Steinmetz, JL, Larson, DW, Franklin, J (1981). Depression-related cognitions: antecedent or consequence? Journal of Abnormal Psychology 90, 213219.
Matthews, SC, Strigo, IA, Simmons, AN, Yang, TT, Paulus, MP (2008). Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder. Journal of Affective Disorders 111, 1320.
Monroe, SM, Harkness, KL (2011). Recurrence in major depression: a conceptual analysis. Psychological Review 118, 655674.
Norris, CJ, Larsen, JT, Cacioppo, JT (2007). Neuroticism is associated with larger and more prolonged electrodermal responses to emotionally evocative pictures. Psychophysiology 44, 823826.
Ongur, D, An, X, Price, JL (1998). Prefrontal cortical projections to the hypothalamus in macaque monkeys. Journal of Comparative Neurology 401, 480505.
Ongur, D, Price, JL (2000). The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cerebral Cortex 10, 206219.
Pezawas, L, Meyer-Lindenberg, A, Drabant, EM, Verchinski, BA, Munoz, KE, Kolachana, BS, Egan, MF, Mattay, VS, Hariri, AR, Weinberger, DR (2005). 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neuroscience 8, 828834.
Post, RM, Weiss, SR (1998). Sensitization and kindling phenomena in mood, anxiety, and obsessive-compulsive disorders: the role of serotonergic mechanisms in illness progression. Biological Psychiatry 44, 193206.
Price, JL, Drevets, WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192216.
Putnam, SP, Ellis, LK, Rothbart, MK (2001). The structure of temperament from infancy through adolescence. In Advances in Research on Temperament (ed. Eliasz, A. and Angleitner, A.), pp. 165182. Pabst Science: Lengerich, Germany.
Radloff, LS (1977). The CES-D scale: a self-reported depression scale for research in the general population. Applied Psychological Measurement 1, 385401.
Reynaud, E, El Khoury-Malhame, M, Rossier, J, Blin, O, Khalfa, S (2012). Neuroticism modifies psychophysiological responses to fearful films. PLoS ONE 7, e32413.
Rohde, P, Lewinsohn, PM, Seeley, JR (1994). Are adolescents changed by an episode of major depression? Journal of the American Academy of Child and Adolescent Psychiatry 33, 12891298.
Roy, AK, Shehzad, Z, Margulies, DS, Kelly, AM, Uddin, LQ, Gotimer, K, Biswal, BB, Castellanos, FX, Milham, MP (2009). Functional connectivity of the human amygdala using resting state fMRI. Neuroimage 45, 614626.
Rutter, M (1987). Temperament, personality and personality disorder. British Journal of Psychiatry 150, 443458.
Shea, MT, Leon, AC, Mueller, TI, Solomon, DA, Warshaw, MG, Keller, MB (1996). Does major depression result in lasting personality change? American Journal of Psychiatry 153, 14041410.
Shehzad, Z, Kelly, AM, Reiss, PT, Gee, DG, Gotimer, K, Uddin, LQ, Lee, SH, Margulies, DS, Roy, AK, Biswal, BB, Petkova, E, Castellanos, FX, Milham, MP (2009). The resting brain: unconstrained yet reliable. Cerebral Cortex 19, 22092229.
Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA (2001). Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biological Psychiatry 50, 651658.
Stein, JL, Wiedholz, LM, Bassett, DS, Weinberger, DR, Zink, CF, Mattay, VS, Meyer-Lindenberg, A (2007). A validated network of effective amygdala connectivity. Neuroimage 36, 736745.
Strelau, J (1982). Biologically determined dimensions of personality or temperament? Personality and Individual Differences 3, 355360.
Tellegen, A (1985). Structures of mood and personality and their relevance to assessing anxiety, with an emphasis on self-report. In Anxiety and the Anxiety Disorders, (ed. A. H. Tuma and J. D. Masur), pp. 681706. Lawrence Erlbaum Associates Inc.: Hillsdale, NJ.
van den Heuvel, MP, Hulshoff Pol, HE (2010). Exploring the brain network: a review on resting-state fMRI functional connectivity. European Neuropsychopharmacology 20, 519534.
Van Dijk, KR, Hedden, T, Venkataraman, A, Evans, KC, Lazar, SW, Buckner, RL (2010). Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. Journal of Neurophysiology 103, 297321.
Van Dijk, KR, Sabuncu, MR, Buckner, RL (2012). The influence of head motion on intrinsic functional connectivity MRI. Neuroimage 59, 431438.
Watson, D, Clark, LA (1984). Negative affectivity: the disposition to experience aversive emotional states. Psychological Bulletin 96, 465490.
Whittle, S, Yap, MB, Yucel, M, Fornito, A, Simmons, JG, Barrett, A, Sheeber, L, Allen, NB (2008). Prefrontal and amygdala volumes are related to adolescents’ affective behaviors during parent-adolescent interactions. Proceedings of the National Academy of Sciences USA 105, 36523657.
Wilson, S, Dirago, AC, Iacono, WG (2014). Prospective inter-relationships between late adolescent personality and major depressive disorder in early adulthood. Psychological Medicine 44, 567577.
Yap, MB, Allen, NB, Ladouceur, CD (2008). Maternal socialization of positive affect: the impact of invalidation on adolescent emotion regulation and depressive symptomatology. Child Development 79, 14151431.
Zald, DH, Mattson, DL, Pardo, JV (2002). Brain activity in ventromedial prefrontal cortex correlates with individual differences in negative affect. Proceedings of the National Academy of Sciences USA 99, 24502454.
Zeiss, AM, Lewinsohn, PM (1988). Enduring deficits after remissions of depression: a test of the scar hypothesis. Behaviour Research and Therapy 26, 151158.


Related content

Powered by UNSILO
Type Description Title
Supplementary materials

Davey Supplementary Material
Table S1 and Figures S1-S2

 PDF (4.6 MB)
4.6 MB

Functional brain-imaging correlates of negative affectivity and the onset of first-episode depression

  • C. G. Davey (a1) (a2), S. Whittle (a2), B. J. Harrison (a2), J. G. Simmons (a3), M. L. Byrne (a3), O. S. Schwartz (a3) and N. B. Allen (a3)...


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.