Zur pathophysiologischen Bedeutung der Amygdala in der Affektregulation bei psychischen Störungen

L. Tebartz van Elst; K. Lieb

doi:10.1055/s-0038-1629938

Nervenheilkunde, Table of Contents

Nervenheilkunde 2005; 24(02): 89-98
DOI: 10.1055/s-0038-1629938

Original Article

Schattauer GmbH

Zur pathophysiologischen Bedeutung der Amygdala in der Affektregulation bei psychischen Störungen

On the role of amygdala pathology in affect regulation in psychiatric disorders

L. Tebartz van Elst

¹Universitätsklinikum Freiburg, Abteilung Psychiatrie und Psychotherapie

,

K. Lieb

¹Universitätsklinikum Freiburg, Abteilung Psychiatrie und Psychotherapie

› Author Affiliations

Abstract

Zusammenfassung

Die Amygdala (Mandelkern) spielt eine zentrale Rolle in der normalen und gestörten Affektregulation. In diesem Beitrag wird der Stand des Wissens zur Neuroanatomie und Pathophysiologie der Amygdala zusammenfassend vorgestellt. In einem zweiten thematischen Schwerpunkt werden die Konsequenzen von experimentellen Amygdalaläsionen beim Tier und von Läsionen beim Menschen referiert. Daran anschließend werden relevante Befunde aus der bildgebenden Forschung zur Rolle der Amygdala bei emotional-instabilen und impulsiven Syndromen vorgestellt. Abschließend wird in einem Integrationsversuch der Befunde ein Modell zur Rolle der Amygdala im Kontext der Affektregulation vorgeschlagen.

Summary

The amygdala plays a central role in the normal and pathological regulation of emotions. In a first section of this paper we summarise the present knowledge of the neuroanatomy and pathophysiology of the amygdala. We then analyse the neuropsychiatric consequences of amygdala lesions in animal models and in humans. Following this we present the latest neuroimaging findings related to amygdala dysfunction in impulsive and emotional-instable syndromes. Summarising the findings we try to develop a model of the role of the amygdala in general affect regulation.

Schlüsselwörter

Amygdala - Extended Amygdala - Affektregulation - psychische Störungen

Keywords

amygdala - extended amygdala - affect regulation - psychiatric disorders

Full Text

References

Literatur
1 Delgado JMR. Offensive-defensive behaviour in free monkeys and chimpanzees induced by radio stimulation of the brain. In: Garattini S, Sigg EB. (eds.). Aggressive Behaviour Proceedings of the International Symposium on the Biology of Aggressive Behaviour. Amsterdam: Exerpta Medica; 1969: 109-19.
2 Klüver H, Bucy PC. Preliminary analysis of functions of the temporal lobes in monkeys. Arch Neurol Psychiatry 1939; 42: 979.
3 Downer JL. Changes in visual gnostic functions and emotional behavior following unilateral temporal pole damage in the “split brain” monkey. Nature 1961; 191: 50-1.
4 Adolphs R, Tranel D, Damasio AR. The human amygdala in social judgment. Nature 1998; 393: 470-4.
5 Aggleton JP. The contribution of the amygdala to normal and abnormal emotional states. Trends Neurosci 1993; 16: 328-33.
6 Broks P. Brain, self, and others: The neuropsychology of social cognition. Oxford: Oxford University Press; xii, 340 pp 1997: 98-123.
7 Gallagher M, Chiba AA. The amygdala and emotion. Cur Opin Neurobiol 1996; 6: 221-7.
8 Halgren E. Emotional neurophysiology of the amygdala within the context of human cognition. In: Aggleton JP. (ed.). The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction. Wiley; 1992: 191-228.
9 Kling AS, Brothers LA. The amygdala and social behavior. In: Aggleton JP. (ed.). The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York: Wiley; 1992: 353-77.
10 LeDoux JE. Emotions: Clues from the brain. Ann Rev Psychology 1995; 46: 209-35.
11 Rolls ET. Neurophysiology and functions of the primate amygdala. In: Aggleton JP. (ed.). The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction. New York: Wiley; 1992: 143-65.
12 Roozendaal B, Koolhaas JM, Bohus B. The role of the central amygdala in stress and adaption. Acta Physiol Scan 1997; (Suppl. 640): 51-4.
13 Tanaka T, Yoshida M, Yokoo H, Tomita M, Tanaka M. Expression of aggression attenuates both stress-induced gastric ulcer formation and increases in noradrenaline release in the rat amygdala assessed by intracerebral microdialysis. Pharmacol Biochem Behav 1998; 59: 27-31.
14 Tebartz van Elst L, Woermann F, Lemieux L, Thompson PJ, Trimble MR. Affective aggression in patients with temporal lobe epilepsy – a quantitative magnetic resonance study of the amygdala. Brain 2000; 123: 234-43.
15 Becker T, Elmer K, Schneider F, Schneider M, Grodd W, Bartels M, Heckers S, Beckmann H. Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia. Psychiatry Res 1996; 67: 135-43.
16 Bergin PS, Fish DR, Shorvon SD, Oatridge A, deSouza NM, Bydder GM. Magnetic resonance imaging in partial epilepsy: additional abnormalities shown with the fluid attenuated inversion recovery (FLAIR) pulse sequence. J Neurol Neurosurg Psychiatry 1995; 58: 439-43.
17 Bertram EH. Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy. Epilepsia 1997; 38: 95-105.
18 Boundy KL, Rowe CC, Black AB, Kitchener MI, Barnden LR, Sebben R, Kneebone A, Kassiou M, Katsifis A, Lambrecht R. Localization of temporal lobe epileptic foci with iodine-123 iododexetimide cholinergic neuroreceptor single-photon emission computed tomography. Neurology 1996; 47: 1015-20.
19 Cascino GD, Trenerry MR, Sharbrough FW, So EL, Marsh WR, Strelow DC. Depth electrode studies in temporal lobe epilepsy: relation to quantitative magnetic resonance imaging and operative outcome. Epilepsia 1995; 36: 230-5.
20 Cendes F, Andermann F, Gloor P, Gambardella A, Lopes-Cendes I, Watson C, Evans A, Carpenter S. Olivier Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy. Brain 1994; 117: 739-46.
21 Chung MH, Horoupian DS. Corpora amylacea: a marker for mesial temporal sclerosis. J Neuropathol Exp Neurol 1996; 55: 403-8.
22 Connelly A, Van PW, Porter DA, Johnson CL, Duncan JS, Gadian DG. Proton magnetic resonance spectroscopy in MRI-negative temporal lobe epilepsy. Neurology 1998; 51: 61-6.
23 Hirsch E, Danober L, Simler S, Pereira dV, Maton B. Nehlig Marescaux C, Vergnes M. The amygdala is critical for seizure propagation from brainstem to forebrain. Neurosci 1997; 77: 975-84.
24 Kalviainen R, Salmenpera T, Partanen K, Vainio P, Riekkinen PS, Pitkanen A. MRI volumetry and T2 relaxometry of the amygdala in newly diagnosed and chronic temporal lobe epilepsy. Epilepsy Res 1997; 28: 39-50.
25 Miller LA, McLachlan RS, Bouwer MS, Hudson LP, Munoz DG. Amygdala sclerosis: preoperative indicators and outcome after temporal lobectomy. J Neurol Neurosurg Psychiatry 1994; 57: 1099-105.
26 Van Paesschen W, Connelly A, Johnson CL, Duncan JS. The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic resonance imaging study. Neurology 1996; 47: 1021-31.
27 Deakin FW, Simpson MD, Slater P, Hellewell JS. Familial and developmental abnormalities of front lobe function and neurochemistry in schizophrenia. J Psychopharmacol 1997; 11: 133-42.
28 Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J. Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry 1998; 55: 663-4.
29 Jacobsen LK, Giedd JN, Vaituzis AC, Hamburger SD, Rajapakse JC, Frazier JA, Kaysen D, Lenane MC, McKenna K, Gordon CT, Rapoport JL. Temporal lobe morphology in childhood-onset schizophrenia. Am J Psychiatry 1996; 153: 355-61.
30 Keshavan MS, Montrose DM, Pierri JN, Dick EL, Rosenberg D, Talagala L, Sweeney JA. Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies. Prog Neuro-Psychopharmacol Biol Psychiatry 1997; 21: 1285-95.
31 Lawrie SM, Abukmeil SS. Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 1998; 172: 110-20.
32 Nelson MD, Saykin AJ, Flashman LA, Riordan HJ. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry 1998; 55: 433-40.
33 O’Brien JT, Desmond P, Ames D, Schweitzer I, Chiu E, Tress B. Temporal lobe magnetic resonance imaging can differentiate Alzheimer’s disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment. Psychol Med 1997; 27: 1267-75.
34 Yeo RA, Hodde-Vargas J, Hendren RL, Vargas LA, Brooks WM, Ford CC, Gangestad SW, Hart BL. Brain abnormalities in schizophrenia-spectrum children: implications for a neurodevelopmental perspective. Psychiatry Res 1997; 76: 1-13.
35 Ebert D, Speck O, Konig A, Berger M, Hennig J. Hohagen 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Res 1997; 74: 173-6.
36 Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME. A functional anatomical study of unipolar depression. J Neurosci 1992; 12: 3628-41.
37 Ebert U, Koch M. Amygdala kindling does not change emotional responding as measured by the acoustic startle response in the rat. Brain Res 1996; 733: 193-202.
38 Strakowski SM, DeBello MP, Sax KW, Zimmermann ME, Shear PK, Hawikins JM, Larson ER. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999; 56: 254-60.
39 Ho AP, Gillin JC, Buchsbaum MS, Wu JC, Abel L, Bunney WE. Brain glucose metabolism during non-rapid eye movement sleep in major depression. Arch Gen Psychiatry 1996; 53: 645-52.
40 Morris JS, Friston KJ, Büchel C, Frith CD, Young AW, Calder AJ, Dolan RJ. A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain 1998; 121: 47-57.
41 Tebartz van Elst L, Woermann F, Lemieux L, Trimble MR. Amygdala enlargement in dysthymia – A volumetric study of patients with temporal lobe epilepsy. Biol Psychiatry 1999; 46: 1614-23.
42 Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Hippocampal volume reduction in major depression. Am J Psychiatry 2000; 157: 115-8.
43 Tebartz van Elst L, Ebert D, Trimble MR. Hippocampal and amygdala pathology in major depression. Am J Psychiatry 2001; 158: 652-3.
44 Mega MS, Cummings JL, Salloway S, Malloy P. The limbic system: an anatomic, phylogenetic, and clinical perspective. J Neuropsychiatry Clin Neurosci 1997; 9: 315-30.
45 Charney DS, Deutch A. A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders. Crit Rev Neurobiol 1996; 10: 419-46.
46 Alheid GF, de Olmos JS, Beltramino CA. Amygdala and extended amygdala. In: Paxinos G. ed. The Rat Nervous System. San Diego: Academic Press; 1995: 495-578.
47 Amaral DG, Price JL, Pitkänen A, Carmichael ST. Anatomical Organisation of the primate amygdaloid complex. In: Aggleton JP. ed. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York: Wiley-Liss, Inc; 1992: 1-66.
48 Pitkänen A, Savander V, LeDoux JE. Organisation of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala. Trends Neurosci 1997; 20: 517-23.
49 Kosmal A, Malinowska M, Kowalska DM. Thalamic and amygdaloid connections of the auditory association cortex of the superior temporal gyrus in rhesus monkey (Macaca mulatta). Acta Neurobiolog Exp 1997; 57: 165-88.
50 Alheid GF, Beltramino CA, De OJ, Forbes MS, Swanson DJ, Heimer L. The neuronal organization of the supracapsular part of the stria terminalis in the rat: the dorsal component of the extended amygdala. Neurosci 1998; 84: 967-96.
51 Alheid GF, Heimer L. New perspectives of basal forebrain organisation of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopedal components of substantia inominata. Neurosci 1988; 27: 1-39.
52 Alheid GF, Heimer L. Theories of basal forebrain organisation and the emotional motor system. In: Holstege G, Bandler R, Saper CD. Progress in Brain Research. Amsterdam: Elsevier; 1996. (107) 461-84.
53 Heimer L, Alheid GF, de Olmos JS, Groenewegen HJ, Haber SN, Harlan RE, Zahm DS. The accumbens: beyond the core-shell dichotomy. J Neuropsychiatry Clin Neurosci 1997; 9: 354-81.
54 Tebartz van Elst L, Trimble M. R. Neuropsychiatric aspects of basal forebrain functional-anatomical systems. 7th World Congress of Biological Psychiatry. 2001
55 LaBar KS, Gatenby JC, Gore JC, LeDoux JE, Phelps EA. Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 1998; 20: 937-45.
56 Dickson DW. Pick’s disease: a modern approach. Brain Path 1998; 8: 339-54.
57 Morris JS, Ohman A, Dolan RJ. Conscious and unconscious emotional learning in the human amygdala. Nature 1998; 393: 467-70.
58 Onaka T, Yagi K. Role of noradrenergic projections to the bed nucleus of the stria terminalis in neuroendocrine and behavioral responses to fear-related stimuli in rats. Brain Res 1998; 788: 287-93.
59 Fallon JH, Ciofi P. Distribution of monoamines within the amygdala. In: Aggleton JP. ed. The amygdala. Neurobiological aspects of emotion, memory, and mental dysfunction. New York: Wiley Liss; 1990: 97-114.
60 Mehler W. R. Subcortical afferent connections of the amygdala in the monkey. Neurology 1980; 190: 733-62.
61 Dennis T, Dubois A, Benavides J, Scatton B. Distribution of central omega 1 (benzodiazepine1) and omega 2 (benzodiazepine2) receptor subtypes in the monkey and human brain. An autoradiographic study with [3H] flunitrazepam and the omega 1 selective ligand [3H]zolpidem. J Pharmacol Exp Therap 1988; 247: 309-22.
62 Aggleton JP. The functional effects of amygdala lesions in humans: a comparison with findings from monkeys. In: Aggleton JP. ed. The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction. Wiley; 1992: 485-503.
63 Tran-Nguyen LT, Fuchs RA, Coffey GP, Baker DA, O’Dell LE, Neisewander JL. Time-dependent changes in cocaine-seeking behavior and extracellular dopamine levels in the amygdala during cocaine withdrawal. Neuropsychopharmacol 1998; 19: 48-59.
64 Davis MD. Neurobiology of fear responses: the role of the amygdala. J Neuropsychiatry Clin Neurosci 1997; 9: 382-402.
65 Kim JJ, Fanselow MS. Modality-specific retrograde amnesia of fear. Science 1992; 256: 675-7.
66 LeDoux JE, Romanski LM, Xagoraris AE. Indelibility of subcortical emotional memories. J Cog Neurosci 1989; 1: 238-43.
67 Teich AH, McCabe PM, Gentile CC, Schneiderman LS, Winters RW. Auditory cortex lesions prevent the extinction of Pavlovian differential heart rate conditioning to tonal stimuli in rabbits. Brain Res 1989; 480: 210-8.
68 Dicks P, Myers RE, Kling A. Uncus and amygdala lesions: effects on social behavior in the free ranging rhesus monkey. Science 1969; 165: 69-71.
69 Davis M, Rainnie D, Cassell M. Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci 1994; 17: 208-14.
70 Henke PG. The amygdala and restraint ulcers in rats. J Comp Physiol Psychol 1980; 94: 313-23.
71 Beaulieux S, Dipaolo T, Barden N. Control of ACTH secretion by central nucleus of the amygdala: Implications of the serotonergic system and its relevance to the glucocorticoid delayed negative feedback mechanism. Neuroendocrinol 1986; 44: 247.
72 Hood TW, Siegfried J, Wieser HG. The role of stereotactic amygdalotomy in the treatment of temporal lobe epilepsy associated with behavioral disorders. Appl Neurophysiol 1983; 46: 19-25.
73 Small IF, Heimburger RF, Small JG, Milstein V, Moore DF. Follow-up of stereotaxic amygdalotomy for seizure and behavior disorders. Biol Psychiatry 1977; 12: 401-11.
74 Ramamurthi B. Stereotactic operation in behaviour disorders. Amygdalotomy and hypothalamotomy. Acta Neurochir Suppl (Wien.) 1988; 44: 152-7.
75 Mark VH, Sweet WH, Ervin FR. The effect of amygdalotomy on violent behavior in patients with temporal lobe epilepsy. In: Hitchcock E, Laitinen L, Vaernet K. (eds.). Psychosurgery. Springfield, Illinois: Charles C. Thomas Publisher; 1972: 139-55.
76 Tranel D, Hyman BT. Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990; 47: 349-55.
77 Hitchcock E, Laitinen L, Vaernet K. (eds). Psychosurgery. Springfield, Illinois: Charles C. Thomas Publisher; 1972
78 Siebert M, Markowitsch HJ, Bartel P. Amygdala, affect and cognition: evidence from 10 patients with Urbach-Wiethe disease. Brain 2003; 126: 2627-37.
79 Tranel D, Hyman BT. Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990; 47: 349-55.
80 Monopolis S, Lion JR. Problems in the diagnosis of intermittent explosive disorder. Am J Psychiatry 1983; 140: 1200-2.
81 Tebartz van Elst L, Woermann F, Lemieux L, Thompson PJ, Trimble MR. Affective aggression in patients with temporal lobe epilepsy – a quantitative magnetic resonance study of the amygdala. Brain 2000; 123: 234-43.
82 Ashburner J, Friston KJ. Voxel-based morphometry – the methods. NeuroImage 2000; 11: 805-21.
83 Woermann F, Tebartz van Elst L, Koepp MJ, Free S, Thompson PJ, Trimble MR, Duncan JS. Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy. An objective voxel-by-voxel analysis of automatically segmented MRI. J Neurol Neurosurg Psychiatry 2000; 68: 162-9.
84 Tebartz van Elst L, Ebert D, Trimble MR. Dual brain pathology in patients with affective aggression. Arch Gen Psychiatry 2001; 58: 1187-8.
85 Tebartz van Elst L, Thiel T, Hesslinger B, Lieb K, Bohus M, Hennig J, Ebert D. Subtle Prefrontal Neuropathology in a Pilot Magnetic Resonance Spectroscopy Study in Patients with Borderline Personality Disorder. J Neuropsychiatry Clin Neurosci 2001; 13: 511-4.
86 Hesslinger B, Thiel T, Tebartz van Elst L, Hennig J, Ebert D. Attention-deficit disorder in adults with and without hyperactivity – Where is the difference? A study using short echo 1H-magnetic-resonance spectroscpoy. Neurosci Let 2001; 304: 117-9.
87 Hesslinger B, Tebartz van Elst L, Thiel T, Haegele K, Hennig J, Ebert D. Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder. Neurosci Let 2002; 328: 319-21.
88 Tebartz van Elst L, Hesslinger B, Thiel T, Geiger E, Haegele K, Lemieux L, Lieb K, Bohus M, Hennig J, Ebert D. Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study. Biol Psychiatry 2003; 54: 163-71.
89 Rusch N, Tebartz van Elst L, Ludaescher P, Wilke M, Huppertz HJ, Thiel T, Schmahl C, Bohus M, Lieb K, Hesslinger B, Hennig J, Ebert D. A voxel-based morphometric MRI study in female patients with borderline personality disorder. Neuroimage 2003; 20: 385-92.
90 Schmahl CG, Vermetten E, Elzinga BM, Douglas BJ. Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Res 2003; 122: 193-8.
91 Driessen M, Herrmann J, Stahl K, Zwaan M, Meier S, Hill A, Osterheider M, Petersen D. Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 2000; 57: 1115-22.
92 Donegan NH, Sanislow CA, Blumberg HP, Fulbright RK, Lacadie C, Skudlarski P, Gore JC, Olson IR, McGlashan TH, Wexler BE. Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry 2003; 54: 1284-93.
93 Herpertz SC, Dietrich TM, Wenning B, Krings T, Erberich SG, Willmes K, Thron A, Sass H. Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study. Biol Psychiatry 2001; 50: 292-8.
94 Driessen M, Beblo T, Mertens M, Piefke M, Rullkoetter N, Silva-Saavedra A, Reddemann L, Rau H, Markowitsch HJ, Wulff H, Lange W, Woermann FG. Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder. Biol Psychiatry 2004; 55: 603-11.
95 Exner C, Boucsein K, Degner D, Irle E, Weniger G. Impaired emotional learning and reduced amygdala size in schizophrenia: a 3-month follow-up. Schizophr Res 2004; 71: 493-503.
96 Joyal CC, Laakso MP, Tiihonen J, Syvalahti E, Vilkman H, Laakso A, Alakare B, Rakkolainen V, Salokangas RK, Hietala J. The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naive patients. Biol Psychiatry 2003; 54: 1302-4.
97 Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR. Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings. Neuropsychopharmaco 2004; 29: 826-32.
98 Szeszko PR, Robinson D, Alvir JM, Bilder RM, Lencz T, Ashtari M, Wu H, Bogerts B. Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry 1999; 56: 913-9.
99 Tebartz van Elst L, Woermann F, Lemieux L, Trimble MR. Amygdala enlargement in dysthymia – A volumetric study of patients with temporal lobe epilepsy. Biol Psychiatry 1999; 46: 1614-23.
100 Strakowski SM, DeBello MP, Sax KW, Zimmermann ME, Shear PK, Hawikins JM, Larson ER. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999; 56: 254-60.
101 Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J. Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch of Gen Psychiatry 1998; 55: 663-4.
102 Frodl T, Meisenzahl E, Zetsche T, Bottlender R, Born C, Groll C, Jager M, Leinsinger G, Hahn K, Moeller HJ. Enlargement of the amygdala in patients with a first episode of major depression. Biol Psychiatry 2002; 51: 708-14.
103 Frodl T, Meisenzahl EM, Zetzsche T, Born C, Jager M, Groll C, Bottlender R, Leinsinger G, Moller HJ. Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Biol Psychiatry 2003; 53: 338-44.
104 De Bellis MD, Casey BJ, Dahl RE, Birmaher B, Williamson DE, Thomas KM, Axelson DA, Frustaci K, Boring AM, Hall J, Ryan ND. A pilot study of amygdala volumes in pediatric generalized anxiety disorder. Biol Psychiatry 2001; 48: 51-7.
105 Tebartz van Elst L, Baeumer D, Lemieux L, Woermann FG, Koepp M, Krishnamoorthy S, Thompson PJ, Ebert D, Trimble MR. Amygdala pathology in psychosis of epilepsy: A magnetic resonance imaging study in patients with temporal lobe epilepsy. Brain 2002; 125: 140-9.
106 Tebartz van Elst L, Trimble M. Amygdala pathology in schizophrenia and psychoses of epilepsy. Curr Opin Psychiatry 2003; 16: 321-6.
107 Blumer D. Dysphoric disorders and paroxysmal affects: recognition and treatment of epilepsy-related psychiatric disorders. Harv Rev Psychiatry 2000; 8: 8-17.
108 Alexander GE. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1986; 9: 357-81.
109 Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor,“prefrontal” and “limbic” functions. Prog Brain Res 1990; 85: 119-46.
110 Mega MS, Cummings JL. Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci 1994; 6: 358-70.
111 Bhatnagar S, Dallman M. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neurosci 1998; 84: 1025-39.