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Hippocampal subregion volume changes associated with antipsychotic treatment in first-episode psychosis

Published online by Cambridge University Press:  14 February 2017

K. Rhindress ,
D. G. Robinson ,
J. A. Gallego ,
R. Wellington ,
A. K. Malhotra  and
P. R. Szeszko
K. Rhindress*
Affiliation:
Department of Psychiatry, New York University School of Medicine, New York, NY, USA
D. G. Robinson
Affiliation:
Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA
J. A. Gallego
Affiliation:
Department of Psychiatry, Weill Cornell Medical College, White Plains, NY, USA
R. Wellington
Affiliation:
Department of Psychology, St John's University, Queens, NY, USA
A. K. Malhotra
Affiliation:
Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, USA Division of Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, NY, USA
P. R. Szeszko
Affiliation:
James J. Peters VA Medical Center, Bronx, NY, USA Icahn School of Medicine at Mount Sinai, New York, NY, USA
*
*Address for correspondence: K. Rhindress, Ph.D., Department of Psychiatry, Bellevue Hospital Center, 462 First Avenue, New York, NY 10016, USA. (Email: [email protected])
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Abstract

Background

Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.

Method

A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.

Results

Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.

Conclusions

This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

Keywords

Antipsychotic treatmentdendate gyrushippocampuspsychosissubiculum
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 10 , July 2017 , pp. 1706 - 1718
Copyright
Copyright © Cambridge University Press 2017 

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References

Allen, KM, Fung, SJ, Shannon Weickert, C (2016). Cell proliferation is reduced in the hippocampus in schizophrenia. Australian and New Zealand Journal of Psychiatry 50, 473–480.CrossRefGoogle ScholarPubMed
Amaral, D, Lavenex, P (2006). Hippocampal neuroanatomy. In The Hippocampus Book (ed. Andersen, P, Morris, R, Amaral, D, Bliss, T and O'Keefe, J), pp. 37–115. Oxford University Press: New York.Google Scholar
Ardekani, BA, Bachman, AH (2009). Model-based automatic detection of the anterior and posterior commissures on MRI scans. NeuroImage 46, 677–682.Google Scholar
Arnold, SJ, Ivleva, EI, Gopal, TA, Reddy, AP, Jeon-Slaughter, H, Sacco, CB, Francis, AN, Tandon, N, Bidesi, AS, Witte, B, Poudyal, G, Pearlson, GD, Sweeney, JA, Clementz, BA, Keshavan, MS, Tamminga, CA (2015). Hippocampal volume is reduced in schizophrenia and schizoaffective disorder but not in psychotic bipolar I disorder demonstrated by both manual tracing and automated parcellation (FreeSurfer). Schizophrenia Bulletin 41, 233–249.Google Scholar
Barr, AM, Wu, CH, Wong, C, Hercher, C, Töpfer, E, Boyda, HN, Procyshyn, RM, Honer, WG, Beasley, CL (2013). Effects of chronic exercise and treatment with the antipsychotic drug olanzapine on hippocampal volume in adult female rats. Neuroscience 255, 147–157.Google Scholar
Bearden, CE, Thompson, PM, Avedissian, C, Klunder, AD, Nicoletti, M, Dierschke, N, Brambilla, P, Soares, JC (2009). Altered hippocampal morphology in unmedicated patients with major depressive illness. ASN Neuro 1, 265–273.CrossRefGoogle ScholarPubMed
Benes, FM (2015). Building models for postmortem abnormalities in hippocampus of schizophrenics. Schizophrenia Research 167, 73–83.CrossRefGoogle ScholarPubMed
Boccardi, M, Ganzola, R, Rossi, R, Sabattoli, F, Laakso, MP, Repo-Tiihonen, E, Vaurio, O, Könönen, M, Aronen, HJ, Thompson, PM, Frisoni, GB, Tiihonen, J (2010). Abnormal hippocampal shape in offenders with psychopathy. Human Brain Mapping 31, 438–447.Google Scholar
Bonavita, C, Ferrero, A, Cereseto, M, Velardez, M, Rubio, M, Wikinski, S (2003). Adaptive changes in the rat hippocampal glutamatergic neurotransmission are observed during long-term treatment with lorazepam. Psychopharmacology 166, 163–167.Google Scholar
Bonnici, HM, Chadwick, MJ, Kumaran, D, Hassabis, D, Weiskopf, N, Maguire, EA (2012). Multi-voxel pattern analysis in human hippocampal subfields. Frontiers in Human Neuroscience 6, 290.Google Scholar
Caine, SB, Geyer, MA, Swerdlow, NR (1992). Hippocampal modulation of acoustic startle and prepulse inhibition in the rat. Pharmacology, Biochemistry, and Behavior 43, 1201–1208.Google Scholar
Clerx, L, Jacobs, HI, Burgmans, S, Gronenschild, EH, Uylings, HB, Echávarri, C, Visser, PJ, Verhey, FR, Aalten, P (2013). Sensitivity of different MRI-techniques to assess gray matter atrophy patterns in Alzheimer's disease is region-specific. Current Alzheimer Research 10, 940–951.Google Scholar
Cole, J, Toga, AW, Hojatkashani, C, Thompson, P, Costafreda, SG, Cleare, AJ, Williams, SC, Bullmore, ET, Scott, JL, Mitterschiffthaler, MT, Walsh, ND, Donaldson, C, Mirza, M, Marquand, A, Nosarti, C, McGuffin, P, Fu, CH (2010). Subregional hippocampal deformations in major depressive disorder. Journal of Affective Disorders 126, 272–277.Google Scholar
Cousins, DA, Aribisala, B, Nicol Ferrier, I, Blamire, AM (2013). Lithium, gray matter, and magnetic resonance imaging signal. Biological Psychiatry 73, 652–657.Google Scholar
Das, T, Ivleva, EI, Wagner, AD, Stark, CE, Tamminga, CA (2014). Loss of pattern separation performance in schizophrenia suggests dentate gyrus dysfunction. Schizophrenia Research 159, 193–197.Google Scholar
Dice, LR (1945). Measures of the amount of ecologic association between species. Ecology 26, 297–302.Google Scholar
Donix, M, Burggren, AC, Suthana, NA, Siddarth, P, Ekstrom, AD, Krupa, AK, Bookheimer, SY (2010). Family history of Alzheimer's disease and hippocampal structure in healthy people. American Journal of Psychiatry 167, 1399–1406.CrossRefGoogle ScholarPubMed
Ebdrup, BH, Skimminge, A, Rasmussen, H, Aggernaes, B, Oranje, B, Lublin, H, Baaré, W, Glenthøj, B (2011). Progressive striatal and hippocampal volume loss in initially antipsychotic-naïve, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. International Journal of Neuropsychopharmacology 14, 69–82.CrossRefGoogle ScholarPubMed
Ekstrom, AD, Bazih, AJ, Suthana, NA, Al-Hakim, R, Ogura, K, Zeineh, M, Burggren, AC, Bookheimer, SY (2009). Advances in high-resolution imaging and computational unfolding of the human hippocampus. NeuroImage 47, 42–49.Google Scholar
Faghihi, F, Moustafa, AA (2015). A computational model of pattern separation efficiency in the dentate gyrus with implications in schizophrenia. Frontiers in Systems Neuroscience 9, 42.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1998). Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Patient Edition (SCID-I/P), version 2.0. Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (2001). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
Fischl, B, Dale, AM (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences of the United States of America 97, 11050–11055.Google Scholar
Fischl, B, van der Kouwe, A, Destrieux, C, Halgren, E, Ségonne, F, Salat, DH, Busa, E, Seidman, LJ, Goldstein, J, Kennedy, D, Caviness, V, Makris, N, Rosen, B, Dale, AM (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex 14, 11–22.Google Scholar
Fresnoza, S, Paulus, W, Nitsche, MA, Kuo, MF (2014). Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans. Journal of Neuroscience 34, 2744–2753.Google Scholar
Frey, BN, Andreazza, AC, Nery, FG, Martins, MR, Quevedo, J, Soares, JC, Kapczinski, F (2007). The role of hippocampus in the pathophysiology of bipolar disorder. Behavioural Pharmacology 18, 419–430.Google Scholar
Frisoni, GB, Ganzola, R, Canu, E, Rüb, U, Pizzini, FB, Alessandrini, F, Thompson, PM (2008). Mapping local hippocampal changes in Alzheimer's disease and normal ageing with MRI at 3 Tesla. Brain 131, 3266–3276.Google Scholar
Fusar-Poli, P, Perez, J, Broome, M, Borgwardt, S, Placentino, A, Caverzasi, E, Cortesi, M, Veggiotti, P, Politi, P, Barale, F, McGuire, P (2007). Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews 31, 465–484.Google Scholar
Gao, XM, Sakai, K, Roberts, RC, Conley, RR, Dean, B, Tamminga, CA (2000). Ionotropic glutamate receptors and expression of N-methyl-d-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia. American Journal of Psychiatry 157, 1141–1149.Google Scholar
Greene, JR (1996). The subiculum: a potential site of action for novel antipsychotic drugs? Molecular Psychiatry 1, 380–387.Google Scholar
Haukvik, UK, Westlye, LT, Mørch-Johnsen, L, Jørgensen, KN, Lange, EH, Dale, AM, Melle, I, Andreassen, OA, Agartz, I (2015). In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder. Biological Psychiatry 77, 581–588.Google Scholar
Kawano, M, Sawada, K, Shimodera, S, Ogawa, Y, Kariya, S, Lang, DJ, Inoue, S, Honer, WG (2015). Hippocampal subfield volumes in first episode and chronic schizophrenia. PLOS ONE 10, e0117785.Google Scholar
Kerchner, GA, Hess, CP, Hammond-Rosenbluth, KE, Xu, D, Rabinovici, GD, Kelley, DAC, Vigneron, DB, Nelson, SJ, Miller, BL (2010). Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI. Neurology 75, 1381–1387.Google Scholar
Knable, MB, Barci, BM, Webster, MJ, Meador-Woodruff, J, Torrey, EF; Stanley Neuropathology Consortium (2004). Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Molecular Psychiatry 9, 609–620.CrossRefGoogle ScholarPubMed
Koolschijn, PC, van Haren, NE, Cahn, W, Schnack, HG, Janssen, J, Klumpers, F, Hulshoff Pol, HE, Kahn, RS (2010). Hippocampal volume change in schizophrenia. Journal of Clinical Psychiatry 71, 737–744.Google Scholar
Krzystanek, M, Bogus, K, Pałasz, A, Krzystanek, E, Worthington, JJ, Wiaderkiewicz, R (2015). Effects of long-term treatment with the neuroleptics haloperidol, clozapine and olanzapine on immunoexpression of NMDA receptor subunits NR1, NR2A and NR2B in the rat hippocampus. Pharmacological Reports 67, 965–969.Google Scholar
La Joie, R, Fouquet, M, Mézenge, F, Landeau, B, Villain, N, Mevel, K, Pélerin, A, Eustache, F, Desgranges, B, Chételat, G (2010). Differential effect of age on hippocampal subfields assessed using a new high-resolution 3 T MR sequence. NeuroImage 53, 506–514.CrossRefGoogle ScholarPubMed
Leucht, S, Samara, M, Heres, S, Patel, MX, Furukawa, T, Cipriani, A, Geddes, J, Davis, JM (2015). Dose equivalents for second-generation antipsychotic drugs: the classical mean dose method. Schizophrenia Bulletin 41, 1397–1402.Google Scholar
Lodge, DJ, Grace, AA (2011). Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia. Trends in Pharmacological Sciences 32, 507–513.Google Scholar
Malykhin, NV, Lebel, RM, Coupland, NJ, Wilman, AH, Carter, RC (2010). In vivo quantification of hippocampal subfields using 4.7 T fast spin echo imaging. NeuroImage 49, 1224–1230.Google Scholar
Mamah, D, Harms, MP, Barch, D, Styner, M, Lieberman, JA, Wang, L (2012). Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Frontiers in Psychiatry 3, 96.Google Scholar
McClure, RK, Styner, M, Maltbie, E, Lieberman, JA, Gouttard, S, Gerig, G, Shi, X, Zhu, H (2013). Localized differences in caudate and hippocampal shape are associated with schizophrenia but not antipsychotic type. Psychiatry Research 211, 1–10.Google Scholar
Meyer, FF, Louilot, A (2011). Latent inhibition-related dopaminergic responses in the nucleus accumbens are disrupted following neonatal transient inactivation of the ventral subiculum. Neuropsychopharmacology 36, 1421–1432.Google Scholar
Monte-Silva, K, Kuo, MF, Thirugnanasambandam, N, Liebetanz, D, Paulus, W, Nitsche, MA (2009). Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans. Journal of Neuroscience 29, 6124–6131.Google Scholar
Mueller, SG, Laxer, KD, Barakos, J, Cheong, I, Garcia, P, Weiner, MW (2009). Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: preliminary results. Epilepsia 50, 1474–1483.Google Scholar
Mueller, SG, Schuff, N, Yaffe, K, Madison, C, Miller, B, Weiner, MW (2010). Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease. Human Brain Mapping 31, 1339–1347.Google Scholar
Mueller, SG, Stables, L, Du, AT, Schuff, N, Truran, D, Cashdollar, N, Weiner, MW (2007). Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4 T. Neurobiology of Aging 28, 719–726.Google Scholar
Mueller, SG, Weiner, MW (2009). Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal subfields. Hippocampus 19, 558–564.Google Scholar
Newton, SS, Duman, RS (2007). Neurogenic actions of atypical antipsychotic drugs and therapeutic implications. CNS Drugs 21, 715–725.CrossRefGoogle ScholarPubMed
Overall, JE, Gorham, DR (1962). The Brief Psychiatric Rating Scale. Psychological Reports 10, 799–812.Google Scholar
Panenka, WJ, Khorram, B, Barr, AM, Smith, GN, Lang, DJ, Kopala, LC, Vandorpe, RA, Honer, WG (2007). A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia. Schizophrenia Research 94, 288–292.Google Scholar
Peleg-Raibstein, D, Feldon, J, Meyer, U (2012). Behavioral animal models of antipsychotic drug actions. Handbook of Experimental Pharmacology 212, 361–406.Google Scholar
Perez, SM, Lodge, DJ (2014). New approaches to the management of schizophrenia: focus on aberrant hippocampal drive of dopamine pathways. Drug Design, Development and Therapy 8, 887–896.Google Scholar
Ramos-Miguel, A, Honer, WG, Boyda, HN, Sawada, K, Beasley, CL, Procyshyn, RM, Barr, AM (2015). Exercise prevents downregulation of hippocampal presynaptic proteins following olanzapine-elicited metabolic dysregulation in rats: distinct roles of inhibitory and excitatory terminals. Neuroscience 301, 298–311.Google Scholar
Reuter, M, Schmansky, NJ, Rosas, HD, Fischl, B (2012). Within-subject template estimation for unbiased longitudinal image. NeuroImage 61, 1402–1418.Google Scholar
Rhindress, K, Ikuta, T, Wellington, R, Malhotra, AK, Szeszko, PR (2015). Delineation of hippocampal subregions using T1-weighted magnetic resonance images at 3 Tesla. Brain Structure and Function 220, 3259–3272.Google Scholar
Rizos, E, Papathanasiou, MA, Michalopoulou, PG, Laskos, E, Mazioti, A, Kastania, A, Vasilopoulou, K, Nikolaidou, P, Margaritis, D, Papageorgiou, C, Liappas, I (2014). A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia. PLOS ONE 9, e87997.CrossRefGoogle Scholar
Sakurai, H, Bies, RR, Stroup, ST, Keefe, RS, Rajji, TK, Suzuki, T, Mamo, DC, Pollock, BG, Watanabe, K, Mimura, M, Uchida, H (2013). Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data. Schizophrenia Bulletin 39, 564–574.CrossRefGoogle ScholarPubMed
Schobel, SA, Lewandowski, NM, Corcoran, CM, Moore, H, Brown, T, Malaspina, D, Small, SA (2009). Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Archives of General Psychiatry 66, 938–946.Google Scholar
Shohamy, D, Mihalakos, P, Chin, R, Thomas, B, Wagner, AD, Tamminga, C (2010). Learning and generalization in schizophrenia: effects of disease and antipsychotic drug treatment. Biological Psychiatry 67, 926–932.Google Scholar
Steiner, J, Brisch, R, Schiltz, K, Dobrowolny, H, Mawrin, C, Krzyżanowska, M, Bernstein, HG, Jankowski, Z, Braun, K, Schmitt, A, Bogerts, B, Gos, T (2016). GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: a post-mortem study. Schizophrenia Research 177, 10–17.CrossRefGoogle ScholarPubMed
Szeszko, PR, Goldberg, E, Gunduz-Bruce, H, Ashtari, M, Robinson, D, Malhotra, AK, Lencz, T, Bates, J, Crandall, DT, Kane, JM, Bilder, RM (2003). Smaller anterior hippocampal formation volume in antipsychotic-naïve patients with first-episode schizophrenia. American Journal of Psychiatry 160, 2190–2197.Google Scholar
Tamminga, CA, Stan, AD, Wagner, AD (2010). The hippocampal formation in schizophrenia. American Journal of Psychiatry 167, 1178–1193.Google Scholar
Terry, AV Jr., Gearhart, DA, Mahadik, SP, Warsi, S, Waller, JL (2006). Chronic treatment with first or second generation antipsychotics in rodents: effects on high affinity nicotinic and muscarinic acetylcholine receptors in the brain. Neuroscience 140, 1277–1287.CrossRefGoogle ScholarPubMed
Thomas, BP, Welch, EB, Niederhauser, BD, Whetsell, WO Jr., Anderson, AW, Gore, JC, Avison, MJ, Creasy, JL (2008). High-resolution 7 T MRI of the human hippocampus in vivo . Journal of Magnetic Resonance Imaging 28, 1266–1272.Google Scholar
van Erp, TG, Hibar, DP, Rasmussen, JM, Glahn, DC, Pearlson, GD, Andreassen, OA, Agartz, I, Westlye, LT, Haukvik, UK, Dale, AM, Melle, I, Hartberg, CB, Gruber, O, Kraemer, B, Zilles, D, Donohoe, G, Kelly, S, McDonald, C, Morris, DW, Cannon, DM, Corvin, A, Machielsen, MW, Koenders, L, de Haan, L, Veltman, DJ, Satterthwaite, TD, Wolf, DH, Gur, RC, Gur, RE, Potkin, SG, Mathalon, DH, Mueller, BA, Preda, A, Macciardi, F, Ehrlich, S, Walton, E, Hass, J, Calhoun, VD, Bockholt, HJ, Sponheim, SR, Shoemaker, JM, van Haren, NE, Pol, HE, Ophoff, RA, Kahn, RS, Roiz-Santiañez, R, Crespo-Facorro, B, Wang, L, Alpert, KI, Jönsson, EG, Dimitrova, R, Bois, C, Whalley, HC, McIntosh, AM, Lawrie, SM, Hashimoto, R, Thompson, PM, Turner, JA (2016). Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Molecular Psychiatry 21, 547–553.Google Scholar
Van Leemput, K, Bakkour, A, Benner, T, Wiggins, G, Wald, LL, Augustinack, J, Dickerson, BC, Golland, P, Fischl, B (2009). Automated segmentation of hippocampal subfields from ultra-high resolution in vivo MRI. Hippocampus 19, 549–557.Google Scholar
Vernon, AC, Natesan, S, Modo, M, Kapur, S (2011). Effect of chronic antipsychotic treatment on brain structure: a serial magnetic resonance imaging study with ex vivo and postmortem confirmation. Biological Psychiatry 69, 936–944.Google Scholar
Vijayraghavan, S, Wang, M, Birnbaum, SG, Williams, GV, Arnsten, AF (2007). Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nature Neuroscience 10, 376–384.Google Scholar
Wang, Z, Neylan, TC, Mueller, SG, Lenoci, M, Truran, D, Marmar, CR, Weiner, MW, Schuff, N (2010). Magnetic resonance imaging of hippocampal subfields in posttraumatic stress disorder. Archives of General Psychiatry 67, 296–303.Google Scholar
Weinberger, DR, Radulescu, E (2016). Finding the elusive psychiatric “lesion” with 21st-century neuroanatomy: a note of caution. American Journal of Psychiatry 173, 27–33.Google Scholar
Wellington, RL, Bilder, RM, Napolitano, B, Szeszko, PR (2013). Effects of age on prefrontal subregions and hippocampal volumes in young and middle-aged healthy humans. Human Brain Mapping 34, 2129–2140.CrossRefGoogle Scholar
Wenger, E, Mårtensson, J, Noack, H, Bodammer, NC, Kühn, S, Schaefer, S, Heinze, HJ, Düzel, E, Bäckman, L, Lindenberger, U, Lövdén, M (2014). Comparing manual and automatic segmentation of hippocampal volumes: reliability and validity issues in younger and older brains. Human Brain Mapping 35, 4236–4248.Google Scholar
Wieshmann, UC, Symms, MR, Mottershead, JP, MacManus, DG, Barker, GJ, Tofts, PS, Revesz, T, Stevens, JM, Shorvon, SD (1999). Hippocampal layers on high resolution magnetic resonance images: real or imaginary? Journal of Anatomy 195, 131–135.Google Scholar
Winterburn, JL, Pruessner, JC, Chavez, S, Schira, MM, Lobaugh, NJ, Voineskos, AN, Chakravarty, MM (2013). A novel in vivo atlas of human hippocampal subfields using high-resolution 3 T magnetic resonance imaging. NeuroImage 74, 254–265.Google Scholar
Woods, SW (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663–667.CrossRefGoogle ScholarPubMed
Xie, J, Alcantara, D, Amenta, N, Fletcher, E, Martinez, O, Persianinova, M, DeCarli, C, Carmichael, O (2009). Spatially localized hippocampal shape analysis in late-life cognitive decline. Hippocampus 19, 526–532.Google Scholar
Yang, C, Wu, S, Lu, W, Bai, Y, Gao, H (2015). Brain differences in first-episode schizophrenia treated with quetiapine: a deformation-based morphometric study. Psychopharmacology 232, 369–377.Google Scholar
Yushkevich, PA, Piven, J, Hazlett, HC, Smith, RG, Ho, S, Gee, JC, Gerig, G (2006). User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. NeuroImage 31, 1116–1128.Google Scholar
Yushkevich, PA, Wang, H, Pluta, J, Das, SR, Craige, C, Avants, BB, Weiner, MW, Mueller, S (2010). Nearly automatic segmentation of hippocampal subfields in vivo focal T2-weighted MRI. NeuroImage 53, 1208–1224.Google Scholar
Zierhut, KC, Graßmann, R, Kaufmann, J, Steiner, J, Bogerts, B, Schiltz, K (2013). Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain 136, 804–814.Google Scholar