Neural correlates of psychotherapy in anxiety and depression: a meta-analysis
Open accessAbstract
Several studies have used neuroimaging methods to identify neural change in brain networks associated to emotion regulation after psychotherapy of depression and anxiety. In the present work we adopted a meta-analytic technique specific to neuroimaging data to evaluate the consistence of empirical findings and assess models of therapy that have been proposed in the literature. Meta-analyses were conducted with the Activation Likelihood Estimation technique, which evaluates the overlap between foci of activation across studies. The analysis included 16 studies found in Pubmed (200 foci of activation and 193 patients). Separate meta-analyses were conducted on studies of 1) depression, post-traumatic stress disorder and panic disorder investigated with rest state metabolism (6 studies, 70 patients); 2) depression, post-traumatic stress disorder and panic disorder investigated with task-related activation studies (5 studies, 65 patients); 3) the previous studies considered jointly; and 4) phobias investigated with studies on exposure-related activation (5 studies, 57 patients). Studies on anxiety and depression gave partially consistent results for changes in the dorsomedial prefrontal cortex and in the posterior cingulated gyrus/precuneus. Several areas of change in the temporal lobes were also observed. Studies on the therapy of phobia were consistent with a reduction of activity in medial temporal areas. The cluster of change in the prefrontal cortex may refer to increased recruitment of control processes, as hypothesized by influential models of emotion regulation changes due to psychotherapy. However, not all areas associated with controlled emotion regulation were detected in the meta-analysis, while involvement of midline structures suggested changes in self-related information processing. Changes in phobia were consistent with reduced reactivity to phobic stimuli.
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The same theory is used to model therapeutic response across depression and anxiety disorders.
“Both disorders were included due to high levels of comorbidity between the conditions (Brown et al., 2001; Kaufman and Charney, 2000), overlapping symptoms, both responding to similar therapies (Ressler and Mayberg, 2007), and the same theory being used to model therapeutic response across disorders (Messina et al., 2013).”
From Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety (2018) · cites this paper as Messina et al., 2013
Paradigm type can affect results.
“due to evidence that paradigm type can effect results (Fu et al., 2007; Messina et al., 2013; Palmer et al., 2015; Whitfield-Gabrieli et al., 2011).”
From Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety (2018) · cites this paper as Messina et al., 2013
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PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation
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Frederickson, J., Messina, I., & Grecucci, A. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.02054 · Cited by 70 · see citing works
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Ke, J., Zhang, L., Qi, R., Li, W., Hou, C., Zhong, Y., He, Z., Li, L., & Lu, G. (2015) · Acta Radiologica · doi:10.1177/0284185115585848 · Cited by 58 · see citing works
Mental Imagery and Brain Regulation—New Links Between Psychotherapy and Neuroscience
Skottnik, L., & Linden, D. E. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00779 · Cited by 61 · see citing works
Functional neuroimaging of psychotherapeutic processes in anxiety and depression
Lueken, U., & Hahn, T. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000218 · Cited by 52 · see citing works
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Boosting psychological change: Combining non-invasive brain stimulation with psychotherapy
Tatti, E., Phillips, A., Paciorek, R., Romanella, S. M., Dèttore, D., Lorenzo, G. D., Ruffini, G., Rossi, S., & Santarnecchi, E. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104867 · Cited by 49 · see citing works
Mori, A., Okamoto, Y., Okada, G., Takagaki, K., Jinnin, R., Takamura, M., Kobayakawa, M., & Yamawaki, S. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.09.036 · Cited by 49 · see citing works
Schrammen, E., Roesmann, K., Rosenbaum, D., Redlich, R., Harenbrock, J., Dannlowski, U., & Leehr, E. J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104895 · Cited by 49 · see citing works
Neural differences in self-perception during illness and after weight-recovery in anorexia nervosa
McAdams, C. J., Jeon-Slaughter, H., Evans, S., Lohrenz, T., Montague, P. R., & Krawczyk, D. C. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw092 · Cited by 40 · see citing works
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Kira, I. A., Alpay, E. H., Ayna, Y. E., Shuwiekh, H. A. M., Ashby, J. S., & Türkeli, A. (2021) · Current Psychology · doi:10.1007/s12144-021-01743-2 · Cited by 46 · see citing works
Structural changes induced by electroconvulsive therapy are associated with clinical outcome
Mulders, P. C. R., Llera, A., Beckmann, C. F., Vandenbulcke, M., Stek, M. L., Sienaert, P. A., Redlich, R., Petrides, G., Oudega, M. L., Oltedal, L., et al. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.02.020 · Cited by 41 · see citing works
Predictive Neuroimaging Markers of Psychotherapy Response: A Systematic Review
Chakrabarty, T., Ogrodniczuk, J. S., & Hadjipavlou, G. A. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000132 · Cited by 40 · see citing works
Neuroimaging findings as predictors of treatment outcome of psychotherapy in anxiety disorders
Santos, V. A., Carvalho, D. D., Van Ameringen, M., Nardi, A. E., & Freire, R. C. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.04.001 · Cited by 34 · see citing works
Winter, D. (2016) · Borderline Personality Disorder and Emotion Dysregulation · doi:10.1186/s40479-016-0047-z · Cited by 36 · see citing works
Cristea, I. A., Karyotaki, E., Hollon, S. D., Cuijpers, P., & Gentili, C. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.03.022 · Cited by 34 · see citing works
Abnormal default system functioning in depression: implications for emotion regulation
Messina, I., Bianco, F., Cusinato, M., Calvo, V., & Sambin, M. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.00858 · Cited by 33 · see citing works
Resting State Functional Connectivity and Outcomes of Psychotherapies for Late-Life Depression
Solomonov, N., Victoria, L. W., Dunlop, K., Respino, M., Hoptman, M. J., Zilcha‐Mano, S., Oberlin, L. E., Liston, C. M., Areán, P. A., Gunning, F. M., et al. (2020) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2020.04.008 · Cited by 34 · see citing works
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Schwarzmeier, H., Leehr, E. J., Böhnlein, J., Seeger, F. R., Roesmann, K., Gathmann, B., Herrmann, M. J., Siminski, N., Junghöfer, M., Straube, T., et al. (2019) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1812 · Cited by 33 · see citing works
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Monachesi, B., Grecucci, A., Ghomroudi, P. A., & Messina, I. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1187092 · Cited by 32 · see citing works
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Significant change events in psychodynamic psychotherapy: Is cognition or emotion more important?
McCarthy, K. L., Caputi, P., & Grenyer, B. F. S. (2017) · Psychology and Psychotherapy Theory Research and Practice · doi:10.1111/papt.12116 · Cited by 31 · see citing works
Schwartzmann, B., Quilty, L. C., Dhami, P., Uher, R., Allen, T. A., Kloiber, S. M., Lam, R. W. M., Frey, B. N., Milev, R. V., Müller, D. J., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-35179-4 · Cited by 31 · see citing works
Doll, A., Sorg, C., Manoliu, A., Wöller, A. A., Meng, C., Förstl, H., Zimmer, C., Wohlschläger, A. M., & Riedl, V. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00677 · Cited by 30 · see citing works
Kalsi, N., Altavilla, D., Tambelli, R., Aceto, P., Trentini, C., Di Giorgio, C., & Lai, C. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.00927 · Cited by 26 · see citing works
Ng, M. Y., DiVasto, K. A., Cootner, S., Gonzalez, N.-A.-R., & Weisz, J. R. (2023) · Clinical Psychology: Science and Practice · doi:10.1111/cpsp.12367 · Cited by 25 · see citing works
Cuijpers, P., & Gentili, C. (2017) · Research in Psychotherapy: Psychopathology, Process and Outcome · doi:10.4081/ripppo.2017.273 · Cited by 24 · see citing works
Neuronal correlates of spider phobia in a combined fNIRS-EEG study
Rosenbaum, D., Leehr, E. J., Kroczek, A., Rubel, J. A., Int-Veen, I., Deutsch, K., Maier, M. J., Hudak, J., Fallgatter, A. J., & Ehlis, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-69127-3 · Cited by 24 · see citing works
Ghomroudi, P. A., Scaltritti, M., & Grecucci, A. (2023) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-023-01076-6 · Cited by 21 · see citing works
Altered Gray Matter Volumes in Post-Stroke Depressive Patients after Subcortical Stroke
Hong, W., Zhao, Z., Wang, D., Li, M., Tang, C., Li, Z., Xu, R. H., & Chan, C. C. H. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102224 · Cited by 19 · see citing works
Increased Risk of Developing Depression in Disability after Stroke: A Korean Nationwide Study
Choi, H. L., Yang, K., Han, K., Kim, B., Chang, W. H., Kwon, S., Jung, W., Yoo, J. E., Jeon, H. J., & Shin, D. W. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20010842 · Cited by 19 · see citing works
Saccenti, D., Lauro, L. J. R., Crespi, S. A., Moro, A. S., Vergallito, A., Grgič, R. G., Pretti, N., Lamanna, J., & Ferro, M. (2024) · Neural Plasticity · doi:10.1155/np/7853199 · Cited by 15 · see citing works
Bielczyk, N., Buitelaar, J. K., Glennon, J. C., & Tiesinga, P. H. E. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00029 · Cited by 18 · see citing works
Boeker, H., & Krähenmann, R. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00247 · Cited by 16 · see citing works
Baroni, M., Frumento, S., Cesari, V., Gemignani, A., Menicucci, D., & Rutigliano, G. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.023 · Cited by 17 · see citing works
Krysta, K., Krzystanek, M., Janas-Kozik, M. H., Klasik, A., & Krupka-Matuszczyk, I. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1282-3 · Cited by 18 · see citing works
Chapter 4. Psychoneuroendocrinology
Sforzini, L., Weston, F. I., & Pariante, C. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as04 · Cited by 16 · see citing works
Principal component analysis and neural predictors of emotion regulation
Klumpp, H., Bhaumik, R., Kinney, K. L., & Fitzgerald, J. M. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.024 · Cited by 15 · see citing works
Cortical oxygenation during exposure therapy – in situ fNIRS measurements in arachnophobia
Rosenbaum, D., Leehr, E. J., Rubel, J. A., Maier, M. J., Pagliaro, V., Deutsch, K., Hudak, J., Metzger, F. G., Fallgatter, A. J., & Ehlis, A. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102219 · Cited by 15 · see citing works
Anxiety Comorbidities: Mood Disorders, Substance Use Disorders, and Chronic Medical Illness
Rogers, A. H., Wieman, S. T., & Baker, A. W. (2019) · Current clinical psychiatry · doi:10.1007/978-3-030-30687-8_5 · Cited by 15 · see citing works
Using Cognitive Neuroscience to Improve Mental Health Treatment: A Comprehensive Review
Wojtalik, J. A., Eack, S. M., Smith, M. J., & Keshavan, M. S. (2018) · Journal of the Society for Social Work and Research · doi:10.1086/697566 · Cited by 16 · see citing works
Neurobiological Mechanisms of Metacognitive Therapy – An Experimental Paradigm
Winter, L., Alam, M., Heissler, H. E., Saryyeva, A., Milakara, D., Jin, X., Heitland, I., Schwabe, K., Krauss, J. K., & Kahl, K. G. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00660 · Cited by 13 · see citing works
Cera, N., Monteiro, J., Esposito, R., Francesco, G. D., Cordes, D., Caldwell, J., & Cieri, F. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.1029256 · Cited by 12 · see citing works
Sosic-Vasic, Z., Abler, B., Grön, G., Plener, P. L., & Straub, J. (2017) · Neuroreport · doi:10.1097/wnr.0000000000000770 · Cited by 12 · see citing works
Ambresin, G., Leuzinger-Bohleber, M., Fischmann, T., Axmacher, N., Hattingen, E., Bansal, R., & Peterson, B. S. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-05287-6 · Cited by 10 · see citing works
Decoding acceptance and reappraisal strategies from resting state macro networks
Ghomroudi, P. A., Siugzdaite, R., Messina, I., & Grecucci, A. (2024) · Scientific Reports · doi:10.1038/s41598-024-68490-9 · Cited by 10 · see citing works
The crossroads of anxiety: distinct neurophysiological maps for different symptomatic groups
Gerez, M., Suarez, E., Serrano, C., Castanedo, L., & Tello, A. (2016) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s89651 · Cited by 10 · see citing works
Berne’s Theory of Cathexis and Its Links to Modern Neuroscience
Messina, I., & Sambin, M. (2015) · Transactional Analysis Journal · doi:10.1177/0362153714566596 · Cited by 9 · see citing works
Tunnell, N. C., Ritz, T., Wilhelm, F. H., Roth, W. T., & Meuret, A. E. (2020) · Behavior Therapy · doi:10.1016/j.beth.2020.03.003 · Cited by 9 · see citing works
Messina, I., Spataro, P., Sorella, S., & Grecucci, A. (2023) · Brain Sciences · doi:10.3390/brainsci13060878 · Cited by 9 · see citing works
Welcome biological breakthroughs, supply psychosocial insights
Tripathi, A., Trivedi, J., & Tekkalaki, B. V. (2014) · Mens Sana monographs · doi:10.4103/0973-1229.130315 · Cited by 8 · see citing works
Plasticity-augmented psychotherapy for refractory depressive and anxiety disorders
Choi, K., & Kim, Y. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.04.003 · Cited by 8 · see citing works
Sheline, Y. I., Thase, M. E., Hembree, E. A., Balderston, N. L., Nitchie, F. J., Batzdorf, A. S., Makhoul, W., & Lynch, K. G. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02945-x · Cited by 9 · see citing works
Chapter 50. Treatment of Anxiety Disorders
Choi, S., & Stein, M. B. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as50 · Cited by 7 · see citing works
Moritz, S., Xie, J., Lion, D., Penney, D., & Jelinek, L. (2021) · Cognitive Neuropsychiatry · doi:10.1080/13546805.2021.1967733 · Cited by 6 · see citing works
Role of Cognitive Control in Psychotherapy: An Integrated Review
Kashyap, H., Mehta, U. M., Reddy, R. P., & Bharath, R. D. (2022) · Indian Journal of Psychological Medicine · doi:10.1177/02537176221128611 · Cited by 7 · see citing works
Sun, Q., Xiong, N., Wang, Y., Xia, Z., Chen, J., Yan, C., & Sun, H. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.07.005 · Cited by 5 · see citing works
The American Psychiatric Association Publishing Textbook of Psychopharmacology
Schatzberg, A. F., & Nemeroff, C. B. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523 · Cited by 5 · see citing works
Rubart, A., Hohagen, F., & Zurowski, B. (2018) · PPmP - Psychotherapie · Psychosomatik · Medizinische Psychologie · doi:10.1055/a-0598-4972 · Cited by 5 · see citing works
Chapter 49. Treatment of Bipolar Disorder
Strakowski, S. M., & Keck, P. E. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as49 · Cited by 5 · see citing works
Waters, A. M., Cao, Y., Kershaw, R., Kerbler, G. M., Shum, D., Zimmer‐Gembeck, M. J., Craske, M. G., Bradley, B. P., Mogg, K., Pine, D. S., et al. (2018) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2018.02.004 · Cited by 5 · see citing works
The Neural Signature of Psychological Interventions in Persons With Cancer: A Scoping Review
Rossini, P. G., Ostacoli, L., Pagani, M., Malandrone, F., Oliva, F., Cominu, L., Annetta, M. C., & Carletto, S. (2022) · Integrative Cancer Therapies · doi:10.1177/15347354221096808 · Cited by 4 · see citing works
Tressoldi, P. E., Facco, E., & Lucangeli, D. (2016) · ScienceOpen Research · doi:10.14293/s2199-1006.1.sor-socsci.ay054b.v1 · Cited by 4 · see citing works
Effects of Psychotherapy on Brain Activation Patterns in Anxiety Disorders
Straube, T. (2016) · Zeitschrift für Psychologie · doi:10.1027/2151-2604/a000240 · Cited by 4 · see citing works
Chapter 57. Treatment of Eating Disorders
Agras, W. S. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as57 · Cited by 4 · see citing works
Chapter 55. Treatment of Alcohol Use Disorder
Mason, B. J., Ritvo, E. C., & Bonci, A. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as55 · Cited by 3 · see citing works
Leehr, E. J., Seeger, F. R., Böhnlein, J., Gathmann, B., Straube, T., Roesmann, K., Junghöfer, M., Schwarzmeier, H., Siminski, N., Herrmann, M. J., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02799-x · Cited by 3 · see citing works
Sweeney, T. (2016) · Nottingham ePrints (University of Nottingham) · Cited by 3 · see citing works
Frontal Lobe Moderators and Mediators of Response to Exposure Therapy in PTSD
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- Authors
- Messina, I., Sambin, M., Palmieri, A., & Viviani, R.
- Affiliations
- University of Padua (IT)
- Universität Innsbruck (AT)
- Corresponding author
- Messina, Irene
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-11
- Volume
- 8
- Issue
- 9
- Pages
- e74657
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3770681
- OpenAlex
- W2147566726
- Cited by
- 176
- References
- 108
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 77 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 7 · 2013: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- psychotherapy, neural correlates, anxiety, depression, emotion regulation, post-traumatic stress disorder, panic disorder, phobia, exposure therapy, dorsomedial prefrontal cortex, posterior cingulate cortex, precuneus, medial temporal lobe, self-referential processing
- MeSH terms
- Anxiety, Brain, Brain Mapping, Depression, Emotions, Humans, Implosive Therapy, Phobic Disorders, Psychotherapy, Stress Disorders, Post-Traumatic, Likelihood Functions, Panic Disorder, Neuroimaging
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