Atrofia global do hipocampo no transtorno depressivo maior: uma metanálise de estudos com ressonância magnética

Santos, Marcelo Antônio Oliveira; Bezerra, Lucas Soares; Carvalho, Ana Rita Marinho Ribeiro; Brainer-Lima, Alessandra Mertens

doi:10.1590/2237-6089-2017-0130

Acessibilidade / Reportar erro

Brasil

Trends in Psychiatry and Psychotherapy

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Review Article • Trends Psychiatry Psychother. 40 (4) • Oct-Dec 2018 • https://doi.org/10.1590/2237-6089-2017-0130 copiar

Atrofia global do hipocampo no transtorno depressivo maior: uma metanálise de estudos com ressonância magnética

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

Introdução:

O transtorno depressivo maior (TDM) é uma doença mental incapacitante caracterizada por episódios de pelo menos 2 semanas de mudanças claras no afeto, cognição e funções neurovegetativas. Vários estudos de neuroimagem, realizados através de imagem de ressonância magnética (IRM), examinaram mudanças morfométricas em pacientes com TDM, com resultados não conclusivos. Este estudo tem como objetivo revisar a literatura e realizar uma metanálise sobre o volume do hipocampo (VHc) em pacientes com TDM.

Métodos:

Estudos de VHc em pacientes com TDM foram identificados a partir dos principais bancos de dados (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO e SciELO) usando os seguintes termos: depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI e hippocampus.

Resultados:

Foi realizada uma metanálise de 29 estudos que preencheram os critérios específicos. A amostra foi composta por 1327 pacientes e 1004 indivíduos saudáveis. Os estudos foram altamente heterogêneos em relação a idade, gênero, idade do primeiro episódio e duração média da doença, mas o efeito combinado da depressão foi significativo em ambos os hipocampos. O TDM foi associado à atrofia do hipocampo à direita [-0,43; intervalo de confiança de 95% (IC95%) −0,66 a −0,21] e à esquerda (-0,40; IC95% −0,66 a −0,15).

Conclusões:

O TDM parece estar associado à atrofia global do VHc. Estudos longitudinais com maior tempo de seguimento, projetados para analisar a influência dos fatores sociodemográficos nessa relação, são necessários para obter evidências mais robustas.

Descritores:
Volume hipocampal; transtorno depressivo maior; RM; depressão

	Patients with depression					Healthy controls
Author and year	Age	Right volume	Left volume	N	Age	Right volume	Left volume	N
Meisenzhal 2010 ²⁷27. Meisenzahl EM, Seifert D, Bottlender R, Teipel S, Zetzsche T, Jäger M, et al. Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study. Eur Arch Psychiatry Clin Neurosci. 2010;260:127-37.	44 (12.3)	3770 (420)	3670 (410)	92	33.3 (12.2)	3940 (410)	3830 (410)	138
Posener 2003 ²⁸28. Posener JA, Wang L, Price JL, Gado MH, Province MA, Miller MI, et al. High-dimensional mapping of the hippocampus in depression. Am J Psychiatry. 2003;160:83-9.	33 (10.7)	2948.4 (446.7)	2546.00 (392.7)	27	33.2 (10.8)	2993.9 (414.2)	2475 (359.4)	42
Xia 2004 ³⁵35. Xia J, Chen J, Zhou Y, Zhang J, Yang B, Xia L, et al. Volumetric MRI analysis of the amygdala and hippocampus in subjects with major depression. J Huazhong Univ Sci Technolog Med Sci. 2004;24:500-2, 506.	39.5 (12)	3487.2 (62.9)	3109.8 (83.5)	22	35.4 (8.8)	3710.3 (36.6)	3352 (43.5)	13
Sheline 1996 ⁶6. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A. 1996;93:3908-13.	68.5 (10.4)	2283 (324)	2159 (301)	10	68.5 (9.5)	2577 (259)	2544 (333)	10
MacMaster 2004 ²⁵25. MacMaster FP, Kusumakar V. Hippocampal volume in early onset depression. BMC Med. 2004;2:2.	16.6 (1.8)	2540 (120)	2530 (90)	17	16.2 (1.6)	2880 (110)	3050 (110)	17
Eijndhoven 2009 ³³33. van Eijndhoven P, van Wingen G, van Oijen K, Rijpkema M, Goraj B, Jan Verkes R, et al. Amygdala volume marks the acute state in the early course of depression. Biol Psychiatry. 2009;65:812-8.	34.9 (11.5)	3848 (444)	3610 (372.5)	40	37.3 (12.7)	3881 (429)	3716 (364)	20
Saylam 2006 ¹²12. Saylam C, Üçerler H, Kitiş Ö, Ozand E, Gönül AS. Reduced hippocampal volume in drug-free depressed patients. Surg Radiol Anat. 2006;28:82-7.	33.4 (9.3)	2696.4 (194.4)	2638.7 (249.2)	24	30.1 (6.1)	2806.3 (256.8)	2786.7 (249.2)	24
Eker 2010 ¹⁸18. Eker C, Kitis O, Taneli F, Eker OD, Ozan E, Yucel K, et al. Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients. Eur Arch Psychiatry Clin Neurosci. 2010;260:527-33.	32.1 (9.3)	3310 (420)	3380 (350)	25	29.7 (6.4)	3110 (260)	3330 (300)	22
Vythilingam 2002 ³⁴34. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159:2072-80.	33.5 (7)	2884 (120.5)	3235.5 (111)	32	27 (5)	3037 (134)	3179 (123)	14
MacQueen 2003 ²⁶26. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci U S A. 2003;100:1387-92.	28.4 (11.8)	2793 (303.8)	2738 (301.1)	20	28.4 (11.5)	2784 (342.2)	2761 (368.4)	20
	35.9 (11.1)	2392 (256.7)	2381 (273.5)	17	36.2 (11.9)	2692 (190.1)	2703 (249)	17
Kaymak 2010 ²²22. Kaymak SU, Demir B, Şentürk S, Tatar I, Aldur MM, Uluğ B. Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders. Eur Arch Psychiatry Clin Neurosci. 2010;260:217-23.	32 (8.5)	2720 (320)	2850 (330)	20	29.3 (5.8)	3400 (250)	3520 (330)	15
Lange 2004 ²³23. Lange C, Irle E. Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med. 2004;34:1059-64.	34 (10)	2670 (500)	2790 (410)	17	32 (6)	3190 (370)	2990 (460)	17
Bearden 2009 ³⁷37. Bearden CE, Thompson PM, Avedissian C, Klunder AD, Nicoletti M, Dierschke N, et al. Altered hippocampal morphology in unmedicated patients with major depressive illness. ASN Neuro. 2009;1:AN20090026.	32.9 (11.9)	1911.1 (280.1)	1885.4 (230.8)	31	36.7 (10.7)	1828.9 (284.2)	1851.9 (326.8)	31
Rusch 2001 ²⁹29. Rusch BD, Abercrombie HC, Oakes TR, Schaefer SM, Davidson RJ. Hippocampal morphometry in depressed patients and control subjects: relations to anxiety symptoms. Biol Psychiatry. 2001;50:960-4.	33.2 (9.5)	2290 (300)	2170 (260)	25	37.4 (14.4)	2200 (240)	2130 (270)	15
Vakili 2000 ¹⁰10. Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry. 2017;47:1087-90.	38.5 (10)	2610 (580)	2640 (550)	38	40.3 (10.4)	2600 (510)	2460 (380)	20
Mervaala 2000 ⁸8. Mervaala E, Föhr J, Könönen M, Valkonen-Korhonen M, Vainio P, Partanen K, et al. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000;30:117-25.	42.2 (12.2)	3462 (405)	3104 (391)	34	42.1 (14.6)	3700 (467)	3441 (436)	17
Cole 2010 ¹⁷17. Cole J, Toga AW, Hojatkashani C, Thompson P, Costafreda SG, Cleare AJ, et al. Subregional hippocampal deformations in major depressive disorder. J Affect Disord. 2010;126:272-7.	41.9 (8.9)	1860 (220)	1770 (260)	37	42.2 (9)	2080 (280)	1980 (290)	37
Bremner 2000 ⁹9. 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 (8)	982 (269)	940 (208)	16	45 (10)	1113 (194)	1166 (248)	16
Frodl 2008 ¹⁹19. Frodl T, Jäger M, Smajstrlova I, Born C, Bottlender R, Palladino T, et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci. 2008;33:423-30.	45 (11.1)	3850 (330)	3780 (380)	30	46.3 (13.1)	3830 (420)	3760 (400)	30
Hickie 2005 ²⁰20. Hickie I, Naismith S, Ward PB, Turner K, Scott E, Mitchell P, et al. Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. Br J Psychiatry. 2005;186:197-202.	53.5 (13.5)	3000 (400)	2900 (400)	66	55.8 (10)	3300 (600)	3300 (500)	20
von Gunten 2000 ¹¹11. von Gunten A, Fox NC, Cipolotti L, Ron MA. A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. J Neuropsychiatry Clin Neurosci. 2000;12:493-8.	57.6 (13.9)	2597.9 (244)	2498.6 (294.8)	14	58.1 (11.4)	2699.5 (312.7)	2644.4 (409.9)	14
Janssen 2004 ²¹21. Janssen J, Pol HEH, de Leeuw F, Schnack HG, Lampe IK, Kok RM, et al. Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. J Neurol Neurosurg Psychiatry. 2007;78:638-40.	64 (10.9)	2840 (390)	3100 (370)	28	62.37 (11.3)	3120 (450)	3200 (520)	41
Steffens 2000 ¹³13. Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KRR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One. 2008;3:e1837.	71.4 (8.4)	3300 (440)	3170 (440)	66	67.1 (5)	2980 (390)	2920 (360)	18
Zhao 2008 ¹³13. Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KRR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One. 2008;3:e1837.	66 (5.5)	3660 (560)	3435 (550)	61	69 (5.5)	3720 (590)	3510 (620)	43
Taylor 2005 ³¹31. Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, et al. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry. 2005;62:537.	70 (7.3)	3090 (420)	2950 (430)	135	69.4 (6.3)	3120 (440)	2960 (450)	83
Avila 2011 ³⁶36. Avila R, Ribeiz S, Duran FLS, Arrais JPJ, Moscoso MAA, Bezerra DM, et al. Effect of temporal lobe structure volume on memory in elderly depressed patients. Neurobiol Aging. 2011;32:1857-67.	70 (6.67)	3099.3 (489.9)	3439.7 (405.3)	48	70.2 (7.2)	3099.8 (271.6)	3446.5 (334.2)	31
Ballmaier 2008 ¹⁴14. Ballmaier M, Narr KL, Toga AW, Elderkin-Thompson V, Thompson PM, Hamilton L, et al. Hippocampal morphology and sistinguishing late-onset from early-onset elderly depression. Am J Psychiatry. 2008;165:229-37.	71.1 (7.6)	1127.5 (231.1)	1116.1 (222)	46	72.3 (6.9)	1308.4 (245.6)	1272.7 (275.6)	34
Lloyd 2004 ²⁴24. Lloyd AJ, Ferrier IN, Barber R, Gholkar A, Young AH, O'Brien JT. Hippocampal volume change in depression: late- and early-onset illness compared. Br J Psychiatry. 2004;184:488-95.	74 (6.3)	2800 (500)	2700 (400)	51	73.1 (6.7)	3000 (400)	2800 (400)	39
Sawyer 2013 ³⁰30. Sawyer K, Corsentino E, Sachs-Ericsson N, Steffens DC. Depression, Hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls. Aging Ment Health. 2012;16:753-62.	70 (7.5)	3070 (420)	2930 (410)	238	70,4 (6.2)	3110 (430)	2950 (420)	146

Study	MRI tracing method	Condition	Follow-up	Hippocampal atrophy	Symptom assessment	Females in the sample (%)
Meisenzhal 2010 ²⁷27. Meisenzahl EM, Seifert D, Bottlender R, Teipel S, Zetzsche T, Jäger M, et al. Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study. Eur Arch Psychiatry Clin Neurosci. 2010;260:127-37.	Software	FE, RMD	No	Bilateral	HAM-D	58.3
Posener 2003 ²⁸28. Posener JA, Wang L, Price JL, Gado MH, Province MA, Miller MI, et al. High-dimensional mapping of the hippocampus in depression. Am J Psychiatry. 2003;160:83-9.	Manual	MDD	No	No	HAM-D, CGI	55.8
Xia 2004 ³⁵35. Xia J, Chen J, Zhou Y, Zhang J, Yang B, Xia L, et al. Volumetric MRI analysis of the amygdala and hippocampus in subjects with major depression. J Huazhong Univ Sci Technolog Med Sci. 2004;24:500-2, 506.	Manual	MDD	No	Bilateral	HAM-D	51.4
Sheline 1996 ⁶6. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A. 1996;93:3908-13.	Manual	RMD	No	Bilateral	HAM-D	100.0
MacMaster 2004 ²⁵25. MacMaster FP, Kusumakar V. Hippocampal volume in early onset depression. BMC Med. 2004;2:2.	Semi-auto	MDD	No	Bilateral	CDRS	52.9
Eijndhoven 2009 ³³33. van Eijndhoven P, van Wingen G, van Oijen K, Rijpkema M, Goraj B, Jan Verkes R, et al. Amygdala volume marks the acute state in the early course of depression. Biol Psychiatry. 2009;65:812-8.	Software	FE	No	No	HAM-D	50.0
Saylam 2006 ¹²12. Saylam C, Üçerler H, Kitiş Ö, Ozand E, Gönül AS. Reduced hippocampal volume in drug-free depressed patients. Surg Radiol Anat. 2006;28:82-7.	Manual	DF MDD	No	Left	HAM-D	75.0
Eker 2010 ¹⁸18. Eker C, Kitis O, Taneli F, Eker OD, Ozan E, Yucel K, et al. Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients. Eur Arch Psychiatry Clin Neurosci. 2010;260:527-33.	Software	FE	No	No	HAM-D	74.4
Vythilingam 2002 ³⁴34. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159:2072-80.	Manual	MDD	No	Left	HAM-D, ZDS	100.0
MacQueen 2003 ²⁶26. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci U S A. 2003;100:1387-92.	Manual	FE, RMD	No	Bilateral	HAM-D, CGI, BDI-II	51.9
Kaymak 2010 ²²22. Kaymak SU, Demir B, Şentürk S, Tatar I, Aldur MM, Uluğ B. Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders. Eur Arch Psychiatry Clin Neurosci. 2010;260:217-23.	Software	MDD	No	Bilateral	HAM-D	100.0
Lange 2004 ²³23. Lange C, Irle E. Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med. 2004;34:1059-64.	Not clear	MDD	No	Not clear	HAM-D, BDI-II	100.0
Bearden 2009 ³⁷37. Bearden CE, Thompson PM, Avedissian C, Klunder AD, Nicoletti M, Dierschke N, et al. Altered hippocampal morphology in unmedicated patients with major depressive illness. ASN Neuro. 2009;1:AN20090026.	Manual	MDD	No	Left	HAM-D	77.0
Rusch 2001 ²⁹29. Rusch BD, Abercrombie HC, Oakes TR, Schaefer SM, Davidson RJ. Hippocampal morphometry in depressed patients and control subjects: relations to anxiety symptoms. Biol Psychiatry. 2001;50:960-4.	Software	MDD	No	No	HAM-D	57.5
Vakili 2000 ¹⁰10. Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry. 2017;47:1087-90.	Manual	MDD	No	No	HAM-D	55.3
Mervaala 2000 ⁸8. Mervaala E, Föhr J, Könönen M, Valkonen-Korhonen M, Vainio P, Partanen K, et al. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000;30:117-25.	Manual	DR MDD	No	Left	HAM-D	56.9
Cole 2010 ¹⁷17. Cole J, Toga AW, Hojatkashani C, Thompson P, Costafreda SG, Cleare AJ, et al. Subregional hippocampal deformations in major depressive disorder. J Affect Disord. 2010;126:272-7.	Software	MDD	No	Bilateral	HAM-D	75.7
Bremner 2000 ⁹9. 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.	Not clear	MDD	No	Left	Not Clear	37.5
Frodl 2008 ¹⁹19. Frodl T, Jäger M, Smajstrlova I, Born C, Bottlender R, Palladino T, et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci. 2008;33:423-30.	Software	MDD	3 years	Left increase ^* * Left hippocampal volume increased after a 3-year follow-up in use of antidepressants.	HAM-D	66.0
Hickie 2005 ²⁰20. Hickie I, Naismith S, Ward PB, Turner K, Scott E, Mitchell P, et al. Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. Br J Psychiatry. 2005;186:197-202.	Manual	LOS, EOS	No	Bilateral	HAM-D	64.0
von Gunten 2000 ¹¹11. von Gunten A, Fox NC, Cipolotti L, Ron MA. A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. J Neuropsychiatry Clin Neurosci. 2000;12:493-8.	Manual	MDD	No	No	HADS	57.1
Janssen 2004 ²¹21. Janssen J, Pol HEH, de Leeuw F, Schnack HG, Lampe IK, Kok RM, et al. Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. J Neurol Neurosurg Psychiatry. 2007;78:638-40.	Software	MDD	No	Right	MADRS	100.0
Steffens 2000 ¹³13. Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KRR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One. 2008;3:e1837.	Software	GD	No	Right	CESD, DDES	71.4
Zhao 2008 ¹³13. Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KRR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One. 2008;3:e1837.	Software	MDD	No	No	MADRS	53.7
Taylor 2005 ³¹31. Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, et al. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry. 2005;62:537.	Software	LOS, EOS	No	Right	DDES	70.6
Avila 2011 ³⁶36. Avila R, Ribeiz S, Duran FLS, Arrais JPJ, Moscoso MAA, Bezerra DM, et al. Effect of temporal lobe structure volume on memory in elderly depressed patients. Neurobiol Aging. 2011;32:1857-67.	Manual	LOS, EOS	No	Left	MADRS, HAM-D	72.2
Ballmaier 2008 ¹⁴14. Ballmaier M, Narr KL, Toga AW, Elderkin-Thompson V, Thompson PM, Hamilton L, et al. Hippocampal morphology and sistinguishing late-onset from early-onset elderly depression. Am J Psychiatry. 2008;165:229-37.	Manual	LOS, EOS	No	Bilateral	HAM-D	66.3
Lloyd 2004 ²⁴24. Lloyd AJ, Ferrier IN, Barber R, Gholkar A, Young AH, O'Brien JT. Hippocampal volume change in depression: late- and early-onset illness compared. Br J Psychiatry. 2004;184:488-95.	Software	LOS, EOS	No	Bilateral	MADRS, GDS	75.0
Sawyer 2013 ³⁰30. Sawyer K, Corsentino E, Sachs-Ericsson N, Steffens DC. Depression, Hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls. Aging Ment Health. 2012;16:753-62.	Software	MDD	10 years COHORT	Right	DDES, CESD	69.0

Associação de Psiquiatria do Rio Grande do Sul Av. Ipiranga, 5311/202, 90610-001 Porto Alegre RS/ Brasil, Tel./Fax: (55 51) 3024 4846 - Porto Alegre - RS - Brazil
E-mail: trends@aprs.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Correspondence: Marcelo Antônio Oliveira Santos, Rua Jonathas de Vasconcelos, 316, Boa Viagem, 51021-140 - Recife, PE - Brazil, E-mail: marcelosantos.med@gmail.com