Skip to main content Accessibility help

Anterior hippocampal volume predicts affect-focused psychotherapy outcome

  • Benjamin Suarez-Jimenez (a1), Xi Zhu (a1), Amit Lazarov (a1) (a2), J. John Mann (a1) (a3), Franklin Schneier (a1) (a3), Andrew Gerber (a1) (a4), Jacques P. Barber (a5) (a6), Dianne L. Chambless (a6), Yuval Neria (a1) (a2), Barbara Milrod (a7) and John C. Markowitz (a1) (a2)...



The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)].


Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes.


Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome.


This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the ‘limbic’ AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.


Corresponding author

Author for correspondence: John C. Markowitz, E-mail:


Hide All

These authors contributed equally to this paper.



Hide All
Abdallah, CG, Wrocklage, KM, Averill, CL, Akiki, T, Schweinsburg, B, Roy, A, Martini, B, Southwick, SM, Krystal, JH and Scott, JC (2017) Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach. Translational Psychiatry 7, e1045.
Ashburner, J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38, 95113.
Ashburner, J and Friston, KJ (2005) Unified segmentation. Neuroimage 26, 839851.
Bandelow, B, Baldwin, D, Abelli, M, Altamura, C, Dell'Osso, B, Domschke, K, Fineberg, NA, Grünblatt, E, Jarema, M, Maron, E, Nutt, D, Pini, S, Vaghi, MM, Wichniak, A, Zai, G and Riederer, P (2016) Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics. World Journal of Biological Psychiatry 17, 321365.
Bandelow, B, Baldwin, D, Abelli, M, Bolea-Alamanac, B, Bourin, M, Chamberlain, SR, Cinosi, E, Davies, S, Domschke, K, Fineberg, N, Grünblatt, E, Jarema, M, Kim, YK, Maron, E, Masdrakis, V, Mikova, O, Nutt, D, Pallanti, S, Pini, S, Ströhle, A, Thibaut, F, Vaghi, MM, Won, E, Wedekind, D, Wichniak, A, Woolley, J, Zwanzger, P and Riederer, P (2017) Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition. World Journal of Biological Psychiatry 18, 162214.
Bannerman, DM, Grubb, M, Deacon, RM, Yee, BK, Feldon, J and Rawlins, JN (2003) Ventral hippocampal lesions affect anxiety but not spatial learning. Behavioural Brain Research 139, 197213.
Bannerman, DM, Sprengel, R, Sanderson, DJ, McHugh, SB, Rawlins, JN, Monyer, H and Seeburg, PH (2014) Hippocampal synaptic plasticity, spatial memory and anxiety. Nature Reviews Neuroscience 15, 181192.
Barlow, DH and Craske, MG (2006) Mastery of Your Anxiety and Panic, 4th Edn. New York: Oxford.
Barlow, DH, Gorman, JM, Shear, MK and Woods, SW (2000) Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: a randomized controlled trial. Journal of the American Medical Association 283, 25292536.
Blake, DD, Weathers, FW, Nagy, LM, Kaloupek, DG, Gusman, FD, Charney, DS and Keane, TM (1995) The development of a Clinician-Administered PTSD Scale. Journal of Traumatic Stress 8, 7590.
Brohawn, KH, Offringa, R, Pfaff, DL, Hughes, KC and Shin, LM (2010) The neural correlates of emotional memory in posttraumatic stress disorder. Biological Psychiatry 68, 10231030.
Busch, F, Milrod, B, Singer, M and Aronson, A (2012) Panic Focused Psychodynamic Psychotherapy: Extended Range: Psychodynamic Psychotherapy for Anxiety Disorders: A Transdiagnostic Treatment Manual. New York: Taylor & Francis.
Cerny, JA, Klosko, J and Barlow, DH (1985) Anxiety treatment project: combined relaxation and cognitive therapy treatment manual. Unpublished manuscript, the phobia and anxiety disorders clinic. New York, Albany: State University of New York.
Chen, AC and Etkin, A (2013) Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder. Neuropsychopharmacology 38, 18891898.
Corcoran, KA, Desmond, TJ, Frey, KA and Maren, S (2005) Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. Journal of Neuroscience 25, 89788987.
DiNardo, PA and Brown, TA (1995) Anxiety Disorders Interview Schedule For DSM-IV: Current Version (ADIS-IV). New York: Graywinds.
Doeller, CF, King, JA and Burgess, N (2008) Parallel striatal and hippocampal systems for landmarks and boundaries in spatial memory. Proceedings of the National Academy of Sciences of the USA 105, 59155920.
Driessen, M, Herrmann, J, Stahl, K, Zwaan, M, Meier, S, Hill, A, Osterheider, M and Petersen, D (2000) Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Archives of General Psychiatry 57, 11151122.
Etkin, A and Wager, TD (2007) Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 14761488.
Fanselow, MS and Dong, HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65, 719.
First, MB, Spitzer, RL, Gibbon, M and Williams, JB (1995) Structured Clinical Interview for DSM-IV Axis I Disorders -- Patient edition (SCID-I/P, Version 2.0). New York: New York State Psychiatric Institute, Biometrics Research Department.
Foa, EB and Rothbaum, BO (1998) Treating the Trauma of Rape: Cognitive-Behavioral Therapy for PTSD. New York: Guilford.
Fonagy, P and Target, M (1997) Attachment and reflective function: their role in self-organization. Developmental Psychopathology 9, 679700.
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Ismaylova, E, Di Sante, J, Gouin, JP, Pomares, FB, Vitaro, F, Tremblay, RE and Booij, L (2018) Associations between daily mood states and brain gray matter volume, resting-state functional connectivity and task-based activity in healthy adults. Frontiers in Human Neuroscience 12, 168.
Kaplan, R, Horner, AJ, Bandettini, PA, Doeller, CF and Burgess, N (2014) Human hippocampal processing of environmental novelty during spatial navigation. Hippocampus 24, 740750.
Kessler, RC, Sonnega, A, Bromet, E, Hughes, M and Nelson, CB (1995) Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry 52, 10481060.
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005 a) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593602.
Kessler, RC, Chiu, WT, Demler, O and Walters, EE (2005 b) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617627.
Lazarov, A, Zhu, X, Suarez-Jimenez, B, Rutherford, BR and Neria, Y (2017) Resting-state functional connectivity of anterior and posterior hippocampus in posttraumatic stress disorder. Journal of Psychiatric Research 94, 1522.
Management of Posttraumatic Stress Disorder Work Group (2017) VA/DOD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Version 3.0–2017. Available at (Accessed 13 May 2018).
Markowitz, JC (2016) IPT for PTSD: Interpersonal Psychotherapy for Posttraumatic Stress Disorder. New York: Oxford University Press.
Markowitz, JC, Milrod, B, Bleiberg, KL and Marshall, RD (2009) Interpersonal factors in understanding and treating posttraumatic stress disorder. Journal of Psychiatric Practice 15, 133140.
Markowitz, JC, Petkova, E, Neria, Y, Van Meter, P, Zhao, Y, Hembree, E, Lovell, K, Biyanova, T and Marshall, RD (2015) Is exposure necessary? A randomized clinical trial of interpersonal psychotherapy for PTSD. American Journal of Psychiatry 172, 430440.
Markowitz, JC, Neria, Y, Lovell, K, Van Meter, PE and Petkova, E (2017) History of sexual trauma moderates psychotherapy outcome for posttraumatic stress disorder. Depression and Anxiety 34, 692700.
Milrod, B, Busch, F, Cooper, A and Shapiro, T (1997) Manual of Panic-Focused Psychodynamic Psychotherapy. Washington, DC: American Psychiatric Association Press.
Milrod, B, Chambless, DL, Gallop, R, Busch, FN, Schwalberg, M, McCarthy, KS, Gross, C, Sharpless, BA, Leon, AC and Barber, JP (2016) Psychotherapies for panic disorder: a tale of two sites. Journal of Clinical Psychiatry 77, 927935.
Neria, Y, Nandi, A and Galea, S (2008) Post-traumatic stress disorder following disasters: a systematic review. Psychological Medicine 38, 467480.
Neria, Y, DiGrande, L and Adams, BG (2011) Posttraumatic stress disorder following the September 11, 2001, terrorist attacks: a review of the literature among highly exposed populations. American Psychologist 66, 429446.
North, CS, Suris, AM, Davis, M and Smith, RP (2009) Toward validation of the diagnosis of posttraumatic stress disorder. American Journal of Psychiatry 166, 3441.
O'Doherty, DC, Chitty, KM, Saddiqui, S, Bennett, MR and Lagopoulos, J (2015) A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Research 232, 133.
Patel, R, Spreng, NR, Shin, LM and Girard, TA (2012) Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neuroscience & Biobehavioral Reviews 36, 21302142.
Poppenk, J, Evensmoen, HR, Moscovitch, M and Nadel, L (2013) Long-axis specialization of the human hippocampus. Trends in Cognitive Science 17, 230240.
Quirk, GJ and Mueller, D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33, 5672.
Rubin, M, Shvil, E, Papini, S, Chhetry, BT, Helpman, L, Markowitz, JC, Mann, JJ and Neria, Y (2016) Greater hippocampal volume is associated with PTSD treatment response. Psychiatry Research 252, 3639.
Shear, MK, Brown, TA, Barlow, DH, Money, R, Sholomskas, DE, Woods, SW, Gorman, JM and Papp, LA (1997) Multicenter collaborative panic disorder severity scale. American Journal of Psychiatry 154, 15711575.
Small, SA, Schobel, SA, Buxton, RB, Witter, MP and Barnes, CA (2011) A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nature Reviews Neuroscience 2011, 585601.
Stein, MB, Koverola, C, Hanna, C, Torchia, MG and McClarty, B (1997) Hippocampal volume in women victimized by childhood sexual abuse. Psychological Medicine 27, 951959.
Vythilingam, M, Heim, C, Newport, J, Miller, AH, Anderson, E, Bronen, R, Brummer, M, Staib, L, Vermetten, E, Charney, DS, Nemeroff, CB and Bremner, JD (2002) Childhood trauma associated with smaller hippocampal volume in women with major depression. American Journal of Psychiatry 159, 20722080.
Weathers, FW, Keane, TM and Davidson, JRT (2001) Clinician-Administered PTSD Scale: a review of the first ten years of research. Depression and Anxiety 13, 132156.
Zarei, M, Beckmann, CF, Binnewijzend, MA, Schoonheim, MM, Oghabian, MA, Sanz-Arigita, EJ, Scheltens, P, Matthews, PM and Barkhof, F (2013) Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease. Neuroimage 66, 2835.
Zeidman, P and Maguire, EA (2016) Anterior hippocampus: the anatomy of perception, imagination, and episodic memory. Nature Reviews Neuroscience 17, 173182.


Related content

Powered by UNSILO

Anterior hippocampal volume predicts affect-focused psychotherapy outcome

  • Benjamin Suarez-Jimenez (a1), Xi Zhu (a1), Amit Lazarov (a1) (a2), J. John Mann (a1) (a3), Franklin Schneier (a1) (a3), Andrew Gerber (a1) (a4), Jacques P. Barber (a5) (a6), Dianne L. Chambless (a6), Yuval Neria (a1) (a2), Barbara Milrod (a7) and John C. Markowitz (a1) (a2)...


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.