Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study

Romain Colle^{1

2

3}, Tomoyuki Segawa^{4

5

6}, Marie Chupin^{7

8

9

10

11

12}, Minh Ngoc Thien Kim Tran Dong^{13

14}, Patrick Hardy^{4

5

6}, Bruno Falissard¹⁵, Olivier Colliot^{7

8

9

10

11

12}, Denis Ducreux^{13

14}, Emmanuelle Corruble^{4

5

6}

Affiliations

¹ INSERM UMRS 1178, Team "Depression and Antidepressants", 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
² Faculté de Médecine Paris Sud, Univ. Paris-Sud, 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
³ Service de Psychiatrie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique-Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
⁴ INSERM UMRS 1178, Team "Depression and Antidepressants", 94275, Le Kremlin Bicêtre, France.
⁵ Faculté de Médecine Paris Sud, Univ. Paris-Sud, 94275, Le Kremlin Bicêtre, France.
⁶ Service de Psychiatrie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique-Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France.
⁷ INSERM U1127, F-75013, Paris, France.
⁸ CNRS, UMR 7225, 75013, Paris, France.
⁹ Sorbonne Universités, UPMC Univ. Paris 06, UMR S 1127, F-75013, Paris, France.
¹⁰ Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
¹¹ Inria, Aramis project-team, Centre de Recherche de Paris, Paris, France.
¹² Departments of Neuroradiology and Neurology, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013, Paris, France.
¹³ CNRS IR4M, UMR 8081, 94275, Le Kremlin Bicêtre, France.
¹⁴ Service de Neuroradiologie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France.
¹⁵ INSERM, Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, Villejuif, France.

PMID: 28202012
PMCID: PMC5312536
DOI: 10.1186/s12888-017-1233-2

Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study

Romain Colle et al. BMC Psychiatry. 2017.

. 2017 Feb 15;17(1):71.

doi: 10.1186/s12888-017-1233-2.

Authors

Affiliations

¹ INSERM UMRS 1178, Team "Depression and Antidepressants", 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
² Faculté de Médecine Paris Sud, Univ. Paris-Sud, 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
³ Service de Psychiatrie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique-Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France. romaincolle@hotmail.com.
⁴ INSERM UMRS 1178, Team "Depression and Antidepressants", 94275, Le Kremlin Bicêtre, France.
⁵ Faculté de Médecine Paris Sud, Univ. Paris-Sud, 94275, Le Kremlin Bicêtre, France.
⁶ Service de Psychiatrie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique-Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France.
⁷ INSERM U1127, F-75013, Paris, France.
⁸ CNRS, UMR 7225, 75013, Paris, France.
⁹ Sorbonne Universités, UPMC Univ. Paris 06, UMR S 1127, F-75013, Paris, France.
¹⁰ Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
¹¹ Inria, Aramis project-team, Centre de Recherche de Paris, Paris, France.
¹² Departments of Neuroradiology and Neurology, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013, Paris, France.
¹³ CNRS IR4M, UMR 8081, 94275, Le Kremlin Bicêtre, France.
¹⁴ Service de Neuroradiologie, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique Hôpitaux de Paris, 94275, Le Kremlin Bicêtre, France.
¹⁵ INSERM, Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, Villejuif, France.

PMID: 28202012
PMCID: PMC5312536
DOI: 10.1186/s12888-017-1233-2

Abstract

Background: Three studies assessed the association of early life adversity (ELA) and hippocampal volumes in depressed patients, of which one was negative and the two others did not control for several potential confounding variables. Since the association of ELA and hippocampal volumes differ in male and female healthy volunteers, we investigated the association of ELA and hippocampal volumes in depressed patients, while focusing specifically on sex and controlling for several relevant socio-demographic and clinical variables.

Methods: Sixty-three depressed in-patients treated in a psychiatric setting, with a current Major Depressive Episode (MDE) and a Major Depressive Disorder (MDD) were included and assessed for ELA. Hippocampal volumes were measured with brain magnetic resonance imaging (MRI) and automatic segmentation. They were compared between patients with (n = 28) or without (n = 35) ELA. After bivariate analyses, multivariate regression analyses tested the interaction of sex and ELA on hippocampal volume and were adjusted for several potential confounding variables. The subgroups of men (n = 26) and women (n = 37) were assessed separately.

Results: Patients with ELA had a smaller hippocampus than those without ELA (4.65 (±1.11) cm³ versus 5.25 (±1.01) cm³), bivariate: p = 0.03, multivariate: HR = 0.40, 95%CI [0.23;0.71], p = 0.002), independently from other factors. This association was found in men (4.43 (±1.22) versus 5.67 (±0.77) cm³), bivariate: p = 0.006, multivariate HR = 0.23, 95%CI [0.06;0.82], p = 0.03) but not in women.

Conclusion: ELA is associated with a smaller hippocampus in male but not female depressed in-patients. The reasons for this association should be investigated in further studies.

Keywords: Automated segmentation; Early life adversity; Hippocampal volume; MRI; Major depressive disorder; Major depressive episode; Sex.

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Figures

**Fig. 1**
Early life adversity and hippocampal volumes. Hippocampal volumes: m (sem) (cm3); ELA+: Patients with early life adversity; ELA-: Patients without early life adversity; p: p value controlled for sex, age, brain volumes, MRI acquisition method, age at onset of MDD, history of suicide attempts, previous antidepressant medication and HDRS

**Fig. 2**
Early life adversity and total hippocampal volumes in men and women. Hippocampal volumes: m (sem) (cm3); ELA+: Patients with early life adversity; ELA−: Patients without early life adversity; p: p value adjusted for age, brain volumes, MRI acquisition method, age at onset of MDD, history of suicide attempts, previous antidepressant medication and HDRS score

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Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study

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Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study

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Abstract

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