Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-19T04:12:27.204Z Has data issue: false hasContentIssue false
  • English
  • Français

Altered microstructure integrity of the amygdala in schizophrenia: a bimodal MRI and DWI study

Published online by Cambridge University Press:  12 May 2010

B. Tomasino ,
M. Bellani ,
C. Perlini ,
G. Rambaldelli ,
R. Cerini ,
M. Isola ,
M. Balestrieri ,
S. Calì ,
A. Versace  and
R. Pozzi Mucelli
...Show all authors
B. Tomasino
Affiliation:
Scientific Institute IRCCS ‘E. Medea’, Udine, Italy
M. Bellani
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
C. Perlini
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
G. Rambaldelli
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
R. Cerini
Affiliation:
Department of Morphological and Biomedical Sciences, Section of Radiology, G.B. Rossi Hospital, University of Verona, Verona, Italy
M. Isola
Affiliation:
Department of Medical and Morphological Research, Section of Statistics, University of Udine, Udine, Italy
M. Balestrieri
Affiliation:
Inter-University Centre for Behavioural Neurosciences, Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine, Udine, Italy
S. Calì
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
A. Versace
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
R. Pozzi Mucelli
Affiliation:
Department of Morphological and Biomedical Sciences, Section of Radiology, G.B. Rossi Hospital, University of Verona, Verona, Italy
A. Gasparini
Affiliation:
Department of Morphological and Biomedical Sciences, Section of Radiology, G.B. Rossi Hospital, University of Verona, Verona, Italy
M. Tansella
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Centre for Behavioural Neurosciences, University of Verona, Verona, Italy
P. Brambilla*
Affiliation:
Scientific Institute IRCCS ‘E. Medea’, Udine, Italy Inter-University Centre for Behavioural Neurosciences, Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine, Udine, Italy
*
*Address for correspondence: P. Brambilla, Dipartimento di Patologia e Medicina Clinica e Sperimentale, Cattedra di Psichiatria, AOU, P. le S. Maria della Misericordia 15, 33100Udine, Italy. (Email: paolo.brambilla@uniud.it)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes.

Method

In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures.

Results

Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia.

Conclusions

We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.

Keywords

Apparent diffusion coefficientbraindiffusion-weighted magnetic resonance imagingmagnetic resonance imagingmorphometryschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 2 , February 2011 , pp. 301 - 311
Copyright
Copyright © Cambridge University Press 2010

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

Addington, J, Addington, D (2000). Neurocognitive and social functioning in schizophrenia: a 2.5 year follow-up study. Schizophrenia Research 44, 47–56.CrossRefGoogle ScholarPubMed
Adolphs, R, Gosselin, F, Buchanan, TW, Tranel, D, Schyns, P, Damasio, AR (2005). A mechanism for impaired fear recognition after amygdala damage. Nature 433, 68–72.CrossRefGoogle ScholarPubMed
Aggleton, JP (2000). The Amygdala: A Functional Analysis. Oxford University Press: Oxford.CrossRefGoogle Scholar
Aggleton, JP, Young, AW (2000). The enigma of the amygdala: on its contribution to human emotion. In Cognitive Neuroscience of Emotion (ed. Lane, R. D., Nadel, L., Ahern, G. L., Allen, J. J. B., Kaszniak, A. W., Rapcsak, S. Z. and Schwartz, G. E.), pp. 106–128. Oxford University Press: New York.Google Scholar
Aleman, A, Kahn, RS (2005). Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia? Progress in Neurobiology 77, 283–298.Google ScholarPubMed
Altshuler, LL, Bartzokis, G, Grieder, T, Curran, J, Jimenez, T, Leight, K, Wilkins, J, Gerner, R, Mintz, J (2000). An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biological Psychiatry 48, 147–162.CrossRefGoogle ScholarPubMed
Amaddeo, F, Burti, L, Ruggeri, M, Tansella, M (2009). Long-term monitoring and evaluation of a new system of community-based psychiatric care. Integrating research, teaching and practice at the University of Verona. Annali dell'Istituto Superiore di Sanità 45, 43–53.Google ScholarPubMed
Amaddeo, F, Tansella, M (2009). Information systems for mental health. Epidemiologia e Psichiatria Sociale 18, 1–4.CrossRefGoogle ScholarPubMed
Anderson, JE, Wible, CG, McCarley, RW, Jakab, M, Kasai, K, Shenton, ME (2002). An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia. Schizophrenia Research 58, 123–134.CrossRefGoogle ScholarPubMed
Ardekani, BA, Bappal, A, D'Angelo, D, Ashtari, M, Lencz, T, Szeszko, PR, Butler, PD, Javitt, DC, Lim, KO, Hrabe, J, Nierenberg, J, Branch, CA, Hoptman, MJ (2005). Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia. Neuroreport 16, 1455–1459.CrossRefGoogle ScholarPubMed
Basser, PJ, Jones, DK (2002). Diffusion-tensor MRI: theory, experimental design and data analysis – a technical review. NMR in Biomedicine 15, 456–467.CrossRefGoogle ScholarPubMed
Bellani, M, Brambilla, P (2008). Social cognition, schizophrenia and brain imaging. Epidemiologia e Psichiatria Sociale 17, 117–119.CrossRefGoogle ScholarPubMed
Bellani, M, Marzi, CA, Brambilla, P (2009). Interhemispheric communication in schizophrenia. Epidemiologia e Psichiatria Sociale 18, 104–106.CrossRefGoogle ScholarPubMed
Birbaumer, N, Grodd, W, Diedrich, O, Klose, U, Erb, M, Lotze, M, Schneider, F, Weiss, U, Flor, H (1998). fMRI reveals amygdala activation to human faces in social phobics. Neuroreport 9, 1223–1226.CrossRefGoogle ScholarPubMed
Bogerts, B, Meertz, E, Schonfeldt-Bausch, R (1985). Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Archives of General Psychiatry 42, 784–791.CrossRefGoogle ScholarPubMed
Brambilla, P, Harenski, K, Nicoletti, M, Sassi, RB, Mallinger, AG, Frank, E, Kupfer, DJ, Keshavan, MS, Soares, JC (2003). MRI investigation of temporal lobe structures in bipolar patients. Journal of Psychiatry Research 37, 287–295.CrossRefGoogle ScholarPubMed
Breier, A, Buchanan, RW, Elkashef, A, Munson, RC, Kirkpatrick, B, Gellad, F (1992). Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. Archives of General Psychiatry 49, 921–926.CrossRefGoogle ScholarPubMed
Chance, SA, Esiri, MM, Crow, TJ (2002). Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings. British Journal of Psychiatry 180, 331–338.CrossRefGoogle ScholarPubMed
Cohen, J (1988). Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates: Hillsdale, NJ.Google Scholar
Das, P, Kemp, AH, Flynn, G, Harris, AW, Liddell, BJ, Whitford, TJ, Peduto, A, Gordon, E, Williams, LM (2007). Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia. Schizophrenia Research 90, 284–294.CrossRefGoogle ScholarPubMed
Davis, KA, Kwon, A, Cardenas, VA, Deicken, RF (2004). Decreased cortical gray and cerebral white matter in male patients with familial bipolar I disorder. Journal of Affective Disorders 82, 475–485.Google ScholarPubMed
Davis, M, Whalen, PJ (2001). The amygdala: vigilance and emotion. Molecular Psychiatry 6, 13–34.CrossRefGoogle ScholarPubMed
DeLisi, LE, Szulc, KU, Bertisch, H, Majcher, M, Brown, K, Bappal, A, Branch, CA, Ardekani, BA (2006). Early detection of schizophrenia by diffusion weighted imaging. Psychiatry Research 148, 61–66.CrossRefGoogle ScholarPubMed
Drevets, WC (1998). Functional neuroimaging studies of depression: the anatomy of melancholia. Annual Review of Medicine 49, 341–361.CrossRefGoogle ScholarPubMed
Drevets, WC (1999). Prefrontal cortical–amygdalar metabolism in major depression. In Annals of the New York Academy of Sciences: Advancing from the Ventral Striatum to the Extended Amygdala, vol. 877 (ed. McGinty, J. F.), pp. 614–637. New York Academy of Sciences: New York.Google Scholar
Exner, C, Boucsein, K, Degner, D, Irle, E, Weniger, G (2004). Impaired emotional learning and reduced amygdala size in schizophrenia: a 3-month follow-up. Schizophrenia Research 71, 493–503.CrossRefGoogle ScholarPubMed
Fahim, C, Stip, E, Mancini-Marie, A, Mensour, B, Boulay, LJ, Leroux, JM, Beaudoin, G, Bourgouin, P, Beauregard, M (2005). Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study. Psychiatry Research 140, 1–15.CrossRefGoogle ScholarPubMed
Galloway, NR, Tong, KA, Ashwal, S, Oyoyo, U, Obenaus, A (2008). Imaging improves outcome prediction in pediatric traumatic brain injury. Journal of Neurotrauma 25, 1153–1162.CrossRefGoogle ScholarPubMed
Garakani, A, Mathew, SJ, Charney, DS (2006). Neurobiology of anxiety disorders and implications for treatment. Mount Sinai Journal of Medicine 73, 941–949.Google ScholarPubMed
Garcia-Marti, G, Aguilar, EJ, Lull, JJ, Marti-Bonmati, L, Escarti, MJ, Manjon, JV, Moratal, D, Robles, M, Sanjuan, J (2008). Schizophrenia with auditory hallucinations: a voxel-based morphometry study. Progress in Neuro-Psychopharmacology, Biological Psychiatry 32, 72–80.CrossRefGoogle ScholarPubMed
Gur, RE, Turetsky, BI, Cowell, PE, Finkelman, C, Maany, V, Grossman, RI, Arnold, SE, Bilker, WB, Gur, RC (2000). Temporolimbic volume reductions in schizophrenia. Archives of General Psychiatry 57, 769–775.CrossRefGoogle ScholarPubMed
Heckers, S, Heinsen, H, Heinsen, YC, Beckmann, H (1990). Limbic structures and lateral ventricle in schizophrenia. A quantitative postmortem study. Archives of General Psychiatry 47, 1016–1022.CrossRefGoogle ScholarPubMed
Hirayasu, Y, Shenton, ME, Salisbury, DF, Dickey, CC, Fischer, IA, Mazzoni, P, Kisler, T, Arakaki, H, Kwon, JS, Anderson, JE, Yurgelun-Todd, D, Tohen, M, McCarley, RW (1998). Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects. American Journal of Psychiatry 155, 1384–1391.CrossRefGoogle ScholarPubMed
Hou, DJ, Tong, KA, Ashwal, S, Oyoyo, U, Joo, E, Shutter, L, Obenaus, A (2007). Diffusion-weighted magnetic resonance imaging improves outcome prediction in adult traumatic brain injury. Journal of Neurotrauma 24, 1558–1569.CrossRefGoogle ScholarPubMed
Hulshoff Pol, HE, Schnack, HG, Mandl, RC, van Haren, NE, Koning, H, Collins, DL, Evans, AC, Kahn, RS (2001). Focal gray matter density changes in schizophrenia. Archives of General Psychiatry 58, 1118–1125.CrossRefGoogle ScholarPubMed
Irwan, R, Sijens, PE, Potze, JH, Oudkerk, M (2005). Correlation of proton MR spectroscopy and diffusion tensor imaging. Magnetic Resonance Imaging 23, 851–858.CrossRefGoogle ScholarPubMed
Joyal, CC, Laakso, MP, Tiihonen, J, Syvalahti, E, Vilkman, H, Laakso, A, Alakare, B, Rakkolainen, V, Salokangas, RK, Hietala, J (2003). The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naive patients. Biological Psychiatry 54, 1302–1304.CrossRefGoogle ScholarPubMed
Juranek, J, Filipek, PA, Berenji, GR, Modahl, C, Osann, K, Spence, MA (2006). Association between amygdala volume and anxiety level: magnetic resonance imaging (MRI) study in autistic children. Journal of Child Neurology 21, 1051–1058.CrossRefGoogle ScholarPubMed
Kalus, P, Slotboom, J, Gallinat, J, Wiest, R, Ozdoba, C, Federspiel, A, Strik, WK, Buri, C, Schroth, G, Kiefer, C (2005). The amygdala in schizophrenia: a trimodal magnetic resonance imaging study. Neuroscience Letters 375, 151–156.CrossRefGoogle ScholarPubMed
Keshavan, MS, Diwadkar, VA, Rosenberg, DR (2005). Developmental biomarkers in schizophrenia and other psychiatric disorders: common origins, different trajectories? Epidemiologia e Psichiatria Sociale 14, 188–193.CrossRefGoogle ScholarPubMed
Kosaka, H, Omori, M, Murata, T, Iidaka, T, Yamada, H, Okada, T, Takahashi, T, Sadato, N, Itoh, H, Yonekura, Y, Wada, Y (2002). Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study. Schizophrenia Research 57, 87–95.CrossRefGoogle ScholarPubMed
LaBar, KS, LeDoux, JE, Spencer, DD, Phelps, EA (1995). Impaired fear conditioning following unilateral temporal lobectomy in humans. Journal of Neuroscience 15, 6846–6855.CrossRefGoogle ScholarPubMed
Lawrie, SM, Abukmeil, SS (1998). Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172, 110–120.CrossRefGoogle ScholarPubMed
LeDoux, J (1998). Fear and the brain: where have we been, and where are we going? Biological Psychiatry 44, 1229–1238.CrossRefGoogle ScholarPubMed
LeDoux, JE (1996). The Emotional Brain: The Mysterious Underpinnings of Emotional Life. Simon and Schuster: New York.Google Scholar
LeDoux, JE (2000). Emotion circuits in the brain. Annual Review of Neuroscience 23, 155–184.CrossRefGoogle ScholarPubMed
Leitman, DI, Hoptman, MJ, Foxe, JJ, Saccente, E, Wylie, GR, Nierenberg, J, Jalbrzikowski, M, Lim, KO, Javitt, DC (2007). The neural substrates of impaired prosodic detection in schizophrenia and its sensorial antecedents. American Journal of Psychiatry 164, 474–482.CrossRefGoogle ScholarPubMed
Leitman, DI, Loughead, J, Wolf, DH, Ruparel, K, Kohler, CG, Elliott, MA, Bilker, WB, Gur, RE, Gur, RC (2008). Abnormal superior temporal connectivity during fear perception in schizophrenia. Schizophrenia Bulletin 34, 673–678.CrossRefGoogle ScholarPubMed
Levitt, JG, Blanton, RE, Caplan, R, Asarnow, R, Guthrie, D, Toga, AW, Capetillo-Cunliffe, L, McCracken, JT (2001). Medial temporal lobe in childhood-onset schizophrenia. Psychiatry Research 108, 17–27.CrossRefGoogle ScholarPubMed
Marsh, L, Suddath, RL, Higgins, N, Weinberger, DR (1994). Medial temporal-lobe structures in schizophrenia – relationship of size to duration of illness. Schizophrenia Research 11, 225–238.CrossRefGoogle ScholarPubMed
McCarley, RW, Wible, CG, Frumin, M, Hirayasu, Y, Levitt, JJ, Fischer, IA, Shenton, ME (1999). MRI anatomy of schizophrenia. Biological Psychiatry 45, 1099–1119.CrossRefGoogle ScholarPubMed
Morris, JS, Friston, KJ, Buchel, C, Frith, CD, Young, AW, Calder, AJ, Dolan, RJ (1998 a). A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain 121, 47–57.CrossRefGoogle ScholarPubMed
Morris, JS, Ohman, A, Dolan, RJ (1998 b). Conscious and unconscious emotional learning in the human amygdala. Nature 393, 467–470.CrossRefGoogle ScholarPubMed
Nakamae, T, Narumoto, J, Shibata, K, Matsumoto, R, Kitabayashi, Y, Yoshida, T, Yamada, K, Nishimura, T, Fukui, K (2008). Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive–compulsive disorder: a diffusion tensor imaging study. Progress in Neuro-psychopharmacology and Biological Psychiatry 32, 1221–1226.CrossRefGoogle ScholarPubMed
Namiki, C, Hirao, K, Yamada, M, Hanakawa, T, Fukuyama, H, Hayashi, T, Murai, T (2007). Impaired facial emotion recognition and reduced amygdalar volume in schizophrenia. Psychiatry Research 156, 23–32.CrossRefGoogle ScholarPubMed
Narr, KL, Sharma, T, Woods, RP, Thompson, PM, Sowell, ER, Rex, D, Kim, S, Asuncion, D, Jang, S, Mazziotta, J, Toga, AW (2003). Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age. American Journal of Psychiatry 160, 2169–2180.CrossRefGoogle ScholarPubMed
Nasrallah, HA, Skinner, TE, Schmalbrock, P, Robitaille, PM (1994). Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study. British Journal of Psychiatry 165, 481–485.CrossRefGoogle ScholarPubMed
Nelson, MD, Saykin, AJ, Flashman, LA, Riordan, HJ (1998). Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Archives of General Psychiatry 55, 433–440.CrossRefGoogle ScholarPubMed
Niemann, K, Hammers, A, Coenen, VA, Thron, A, Klosterkotter, J (2000). Evidence of a smaller left hippocampus and left temporal horn in both patients with first episode schizophrenia and normal control subjects. Psychiatry Research 99, 93–110.CrossRefGoogle ScholarPubMed
Niu, L, Matsui, M, Zhou, SY, Hagino, H, Takahashi, T, Yoneyama, E, Kawasaki, Y, Suzuki, M, Seto, H, Ono, T, Kurachi, M (2004). Volume reduction of the amygdala in patients with schizophrenia: a magnetic resonance imaging study. Psychiatry Research 132, 41–51.CrossRefGoogle ScholarPubMed
Oepen, G, Funfgeld, M, Holl, T, Zimmermann, P, Landis, T, Regard, M (1987). Schizophrenia – an emotional hypersensitivity of the right cerebral hemisphere. International Journal of Psychophysiology 5, 261–264.CrossRefGoogle ScholarPubMed
Pakkenberg, B (1990). Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Archives of General Psychiatry 47, 1023–1028.CrossRefGoogle ScholarPubMed
Pearlson, GD, Barta, PE, Powers, RE, Menon, RR, Richards, SS, Aylward, EH, Federman, EB, Chase, GA, Petty, RG, Tien, AY (1997). Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biological Psychiatry 41, 1–14.CrossRefGoogle ScholarPubMed
Phelps, EA, O'Connor, KJ, Cunningham, WA, Funayama, ES, Gatenby, JC, Gore, JC, Banaji, MR (2000). Performance on indirect measures of race evaluation predicts amygdala activation. Journal of Cognitive Neuroscience 12, 729–738.CrossRefGoogle ScholarPubMed
Ray, KM, Wang, H, Chu, Y, Chen, YF, Bert, A, Hasso, AN, Su, MY (2006). Mild cognitive impairment: apparent diffusion coefficient in regional gray matter and white matter structures. Radiology 24, 197–205.CrossRefGoogle Scholar
Rovaris, M, Bozzali, M, Iannucci, G, Ghezzi, A, Caputo, D, Montanari, E, Bertolotto, A, Bergamaschi, R, Capra, R, Mancardi, GL, Martinelli, V, Comi, G, Filippi, M (2002). Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis – a diffusion-tensor magnetic resonance imaging study. Archives of Neurology 59, 1406–1412.CrossRefGoogle ScholarPubMed
Ruggeri, M, Koeter, M, Schene, A, Bonetto, C, Vazquez-Barquero, JL, Becker, T, Knapp, M, Knudsen, HC, Tansella, M, Thornicroft, G (2005). Factor solution of the BPRS-expanded version in schizophrenic outpatients living in five European countries. Schizophrenia Research 75, 107–117.CrossRefGoogle ScholarPubMed
Schneider, F, Weiss, U, Kessler, C, Salloum, JB, Posse, S, Grodd, W, Muller-Gartner, HW (1998). Differential amygdala activation in schizophrenia during sadness. Schizophrenia Research 34, 133–142.CrossRefGoogle ScholarPubMed
Shenton, ME, Kikinis, R, Jolesz, FA, Pollak, SD, Lemay, M, Wible, CG, Hokama, H, Martin, J, Metcalf, D, Coleman, M, McCarley, RW (1992). Abnormalities of the left temporal-lobe and thought-disorder in schizophrenia – a quantitative magnetic-resonance-imaging study. New England Journal of Medicine 327, 604–612.CrossRefGoogle ScholarPubMed
Shin, YW, Kwon, JS, Ha, TH, Park, HJ, Kim, DJ, Hong, SB, Moon, WJ, Lee, JM, Kim, IY, Kim, SI, Chung, EC (2006). Increased water diffusivity in the frontal and temporal cortices of schizophrenic patients. Neuroimage 30, 1285–1291.CrossRefGoogle ScholarPubMed
Staal, WG, Pol, HEH, Schnack, HG, Hoogendoorn, MLC, Jellema, K, Kahn, RS (2000). Structural brain abnormalities in patients with schizophrenia and their healthy siblings. American Journal of Psychiatry 157, 416–421.CrossRefGoogle ScholarPubMed
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510–518.CrossRefGoogle ScholarPubMed
Stein, MB, Simmons, AN, Feinstein, JS, Paulus, MP (2007). Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. American Journal of Psychiatry 164, 318–327.CrossRefGoogle ScholarPubMed
Sweet, RA, Henteleff, RA, Zhang, W, Sampson, AR, Lewis, DA (2009). Reduced dendritic spine density in auditory cortex of subjects with schizophrenia. Neuropsychopharmacology 34, 374–389.CrossRefGoogle ScholarPubMed
Syková, E (2004). Diffusion properties of the brain in health and disease. Neurochemistry International 45, 453–466.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-naive patients with first-episode schizophrenia. American Journal of Psychiatry 160, 2190–2197.CrossRefGoogle ScholarPubMed
Takahashi, H, Koeda, M, Oda, K, Matsuda, T, Matsushima, E, Matsuura, M, Asai, K, Okubo, Y (2004). An fMRI study of differential neural response to affective pictures in schizophrenia. Neuroimage 22, 1247–1254.CrossRefGoogle ScholarPubMed
Talarovicova, A, Krskova, L, Kiss, A (2007). Some assessments of the amygdala role in suprahypothalamic neuroendocrine regulation: a minireview. Endocrine Regulations 41, 155–162.Google ScholarPubMed
Tanskanen, P, Veijola, JM, Piippo, UK, Haapea, M, Miettunen, JA, Pyhtinen, J, Bullmore, ET, Jones, PB, Isohanni, MK (2005). Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort. Schizophrenia Research 75, 283–294.CrossRefGoogle ScholarPubMed
Taylor, SF, Liberzon, I, Decker, LR, Koeppe, RA (2002). A functional anatomic study of emotion in schizophrenia. Schizophrenia Research 58, 159–172.CrossRefGoogle ScholarPubMed
Taylor, WD, Hsu, E, Krishnan, KR, MacFall, JR (2004). Diffusion tensor imaging: background, potential, and utility in psychiatric research. Biological Psychiatry 55, 201–207.CrossRefGoogle ScholarPubMed
Tebartz, van Elst L, Bäumer, D, Ebert, D, Trimble, MR (2004). Chronic antidopaminergic medication might affect amygdala structure in patients with schizophrenia. Pharmacopsychiatry 37, 217–220.CrossRefGoogle Scholar
Velakoulis, D, Wood, SJ, Wong, MT, McGorry, PD, Yung, A, Phillips, L, Smith, D, Proffitt, T, Desmond, P, Pantelis, C (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Archives of General Psychiatry 63, 139–149.CrossRefGoogle ScholarPubMed
Ventura, J, Nuechterlein, KH, Subotnik, KL (2000). Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale. Psychiatry Research 97, 129–135.CrossRefGoogle Scholar
Vita, A, De Peri, L, Silenzi, C, Dieci, A (2006). Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophrenia Research 82, 75–88.CrossRefGoogle ScholarPubMed
Whittaker, JF, Deakin, JF, Tomenson, B (2001). Face processing in schizophrenia: defining the deficit. Psychological Medicine 31, 499–507.CrossRefGoogle ScholarPubMed
WHO (1992). Schedules for Clinical Assessment in Neuropsychiatry. World Health Organization: Geneva.Google Scholar
WHO (1996). Schede di valutazione clinica in neuropsichiatria. SCAN 2.1 (M. Tansella, M. Nardini, series editors). Il Pensiero Scientifico Editore: Roma.Google Scholar
Williams, LM, Brown, KJ, Das, P, Boucsein, W, Sokolov, EN, Brammer, MJ, Olivieri, G, Peduto, A, Gordon, E (2004). The dynamics of cortico-amygdala and autonomic activity over the experimental time course of fear perception. Brain Research. Cognitive Brain Research 21, 114–123.CrossRefGoogle Scholar
Wright, IC, Ellison, ZR, Sharma, T, Friston, KJ, Murray, RM, McGuire, PK (1999). Mapping of grey matter changes in schizophrenia. Schizophrenia Research 35, 1–14.CrossRefGoogle ScholarPubMed
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed
Zetzsche, T, Frodl, T, Preuss, UW, Schmitt, G, Seifert, D, Leinsinger, G, Born, C, Reiser, M, Moller, HJ, Meisenzahl, EM (2006). Amygdala volume and depressive symptoms in patients with borderline personality disorder. Biological Psychiatry 60, 302–310.CrossRefGoogle ScholarPubMed