Psychoneuroendocrinology (2015) 51, 219—226
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/psyneuen
ORIGINAL RESEARCH PAPER
Obesity and major depression: Body-mass index (BMI) is associated with a severe course of disease and specific neurostructural alterations Nils Opel a,1, Ronny Redlich a,1, Dominik Grotegerd a, Katharina Dohm a, Walter Heindel b, Harald Kugel b, Volker Arolt a, Udo Dannlowski a,c,∗ a
Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster Germany Department of Clinical Radiology, University of Münster, Germany c Department of Psychiatry, University of Marburg, Germany b
Received 11 July 2014; received in revised form 23 September 2014; accepted 2 October 2014
KEYWORDS Obesity; Body mass index; Mood disorders; MRI; Unipolar depression; Chronicity
Abstract Obesity is one of the most prevalent somatic comorbidities of major depressive disorder (MDD). Both disorders rank among the leading challenges in public health and have been independently characterized by gray matter alterations in partly overlapping brain structures. Hence, it appears crucial to investigate the possibility of a shared neurostructural correlate of this frequent comorbidity as well as its clinical implications. One hundred and fourty-four patients suffering from acute MDD and 141 healthy control subjects underwent structural MRI. Imaging data were analyzed using voxel-based morphometry (VBM). Body-mass-index (BMI) as well as state and course of disease were assessed. Higher BMI was associated with a highly comparable pattern of gray matter reductions in the medial prefrontal cortex, the orbitofrontal cortex, the caudate nucleus and the thalamus in MDD patients and healthy controls alike. In MDD-patients, BMI was associated with a more chronic course of disease and both BMI and chronicity of disorder were related to similar morphometric anomalies in medial prefrontal areas.
∗ Corresponding author at: Corresponding author at. Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster, Germany, Tel.: +49 251 8356601; fax: +49 251 8356612. E-mail address: [email protected] (U. Dannlowski). 1 This is to indicate that NO and RR contributed equally to the present work and should therefore both be regarded as first authors.
http://dx.doi.org/10.1016/j.psyneuen.2014.10.001 0306-4530/© 2014 Elsevier Ltd. All rights reserved.
220
N. Opel et al. In MDD, obese subjects might be characterized by a more chronic course of disease. Moreover, obesity and chronicity of disorder seem to share overlapping neurostructural anomalies in prefrontal areas involved in emotion regulation and impulse control. Hence, our data provide evidence for specific morphological alterations underlying this prevalent comorbidity. It further underlines the clinical importance of preventive measures against obesity accompanying MDD treatment. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction Obesity is one of the most prevalent somatic comorbidities of major depressive disorder (MDD) (De Wit et al., 2010). The prevalence of obesity is strongly elevated not only among subjects suffering from MDD but also in high-risk populations before onset of disease (Danese and Tan, 2013). A recent meta-analysis revealed that obesity increases the risk of depression and vice versa pointing to a reciprocal link between both depression and obesity (Luppino et al., 2010). The clinical implications of this comorbidity were underlined by an epidemiologic study showing that nutritional counseling and physical activity is accompanied by both weight loss and improvement of depressive symptoms in obese adolescents (Melnyk et al., 2013). Moreover, Kloiber et al. demonstrated that obese and overweight MDD patients suffer from poorer treatment outcome (Kloiber et al., 2007). Given that both disorders rank among the leading challenges in public health and considering the apparently reciprocal relationship of these conditions, investigation of common neurobiological underpinnings seems to be warranted. In MDD, a wealth of structural imaging findings elucidated the role of specific brain areas in the etiopathology of affective disorders (Cole et al., 2011; Phillips et al., 2003). Particularly, gray matter volume reductions in structures involved in emotion processing were frequently found to be associated with MDD (Arnone et al., 2012; Cusi et al., 2012). However, only few studies have investigated neural correlates of obesity. In healthy participants, neuroimaging studies revealed associations between elevated body-massindex (BMI) and reduced gray and white matter, as well as loss of global brain volume (Mueller et al., 2012; Ward et al., 2005). More specifically, reductions of gray matter in prefrontal areas such as the superior frontal gyrus, the medial orbitofrontal gyrus and striatal areas are among the few available findings in obesity (Marqués-Iturria et al., 2013; Raji et al., 2010; Walther et al., 2010), much resembling neurostructural alterations reported in depressed patients. Furthermore, a recent tensor-based morphometry study indicated that BMI might be associated with comparable effects on brain structure in depressed patients (Cole et al., 2013). Taken together, there is evidence not only for a clinical but also for a neurostructural link between obesity and depression since gray matter reductions appear to affect overlapping brain regions in both conditions. Given the mutual negative impact of these disorders, especially the poorer treatment outcome, obese MDD-patients are likely to suffer from a more severe course of disease. Thus, further elucidation of common biological factors could be of great clinical importance. A potential neurobiological connection
between obesity and MDD might highlight the relevance of preventive measures against obesity and provide the basis for adjusted strategies in MDD treatment. Hence, in our present study we sought to clarify if, or to which extent BMI is associated with aberrations in cerebral structures and with differences in clinical appearance in MDD patients. We hypothesized that in patients and healthy controls alike BMI would be associated with specific neurostructural alterations. We further hypothesized that in MDD-patients BMI would be associated with a more chronic course of the disorder, and that both BMI and chronicity would be related to morphometric anomalies in similar cerebral areas.
2. Material and methods 2.1. Participants Our dataset comprised two samples: a psychiatric sample comprising n = 144 subjects suffering from acute major depressive disorder (MDD) according to DSM-IV criteria (American Psychiatric Association, APA, 2000) as diagnosed with the SCID-I interview (Wittchen et al., 1997). Additionally, a second sample of n = 141 healthy controls (HC), matched according to BMI (p = 0.70), age (p = 0.95) and sex (p = 0.86), was obtained from a larger ongoing study (see Table 1 for details). Patients were recruited from the inpatient service of the Department of Psychiatry, University of Muenster. For all analyses, six subjects had to be excluded due to anatomical abnormalities leaving n = 140 MDD patients (mean age = 37.6, SD = 11.8 years) and n = 139 HC (mean age = 37.7, SD = 12.0 years). Exclusion criteria for all participants were any neurological abnormalities, severe medical conditions, substance-related disorders or current benzodiazepine treatment. Furthermore, all participants had normal or corrected-to-normal vision, and had adequate knowledge of German and cognitive abilities (verbal IQ > 80; multiple-choice vocabulary intelligence test MWT-B; Lehrl, 2005). All HC subjects had no history of psychiatric illness, according to the SCID-Interview (Wittchen et al., 1997) and were free from any psychotropic medication. Subjects were screened for imaging safety concerns, and informed, written consent was obtained following the Declaration of Helsinki (World Medical Association, 1991). The experimental procedure was approved by the ethics committee of the Medical Faculty at the University of Münster. All participants received a financial compensation.
Obesity and major depression
221
Table 1 Sociodemographic and clinical characteristics of our study sample consisting of 140 currently depressed patients and 139 healthy controls. Means, standard deviations (SD) and group differences (as measured with t-tests or 2 -test).
Age Sex (m/f) BMI Verbal IQ HAMD BDI Number of episodes Time since first psychiatric symptoms (months) Duration since onset of depression (months) Time since first outpatient treatment (months) Time since first inpatient treatment (months) Total duration of inpatient treatment (weeks)
HC sample (n = 139)
MDD patients (n = 140)
Mean
SD
Range
Mean
37.59 61/ 78 25.74 114.81 0.89 1.78 n/a n/a n/a n/a n/a n/a
11.78 0.5 4.7 12.46 1.29 2.07
20—59
37.69 11.97 18—59 60/ 80 0.5 25.97 5.25 18—44 109.46 13.12 82—143 23.26 5.23 12—42 27.94 9.18 9—53 4.56 5.64 1—30 117.51 111.54 3—480 100.38 102.93 1—432 72.85 93.21 1—396 36.37 71.91 1—384 10.35 12.78 1—67
18—40 93—143 0—5 0—8
SD
p-value
Range 0.95 0.86 0.7 0.01
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/psyneuen
ORIGINAL RESEARCH PAPER
Obesity and major depression: Body-mass index (BMI) is associated with a severe course of disease and specific neurostructural alterations Nils Opel a,1, Ronny Redlich a,1, Dominik Grotegerd a, Katharina Dohm a, Walter Heindel b, Harald Kugel b, Volker Arolt a, Udo Dannlowski a,c,∗ a
Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster Germany Department of Clinical Radiology, University of Münster, Germany c Department of Psychiatry, University of Marburg, Germany b
Received 11 July 2014; received in revised form 23 September 2014; accepted 2 October 2014
KEYWORDS Obesity; Body mass index; Mood disorders; MRI; Unipolar depression; Chronicity
Abstract Obesity is one of the most prevalent somatic comorbidities of major depressive disorder (MDD). Both disorders rank among the leading challenges in public health and have been independently characterized by gray matter alterations in partly overlapping brain structures. Hence, it appears crucial to investigate the possibility of a shared neurostructural correlate of this frequent comorbidity as well as its clinical implications. One hundred and fourty-four patients suffering from acute MDD and 141 healthy control subjects underwent structural MRI. Imaging data were analyzed using voxel-based morphometry (VBM). Body-mass-index (BMI) as well as state and course of disease were assessed. Higher BMI was associated with a highly comparable pattern of gray matter reductions in the medial prefrontal cortex, the orbitofrontal cortex, the caudate nucleus and the thalamus in MDD patients and healthy controls alike. In MDD-patients, BMI was associated with a more chronic course of disease and both BMI and chronicity of disorder were related to similar morphometric anomalies in medial prefrontal areas.
∗ Corresponding author at: Corresponding author at. Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster, Germany, Tel.: +49 251 8356601; fax: +49 251 8356612. E-mail address: [email protected] (U. Dannlowski). 1 This is to indicate that NO and RR contributed equally to the present work and should therefore both be regarded as first authors.
http://dx.doi.org/10.1016/j.psyneuen.2014.10.001 0306-4530/© 2014 Elsevier Ltd. All rights reserved.
220
N. Opel et al. In MDD, obese subjects might be characterized by a more chronic course of disease. Moreover, obesity and chronicity of disorder seem to share overlapping neurostructural anomalies in prefrontal areas involved in emotion regulation and impulse control. Hence, our data provide evidence for specific morphological alterations underlying this prevalent comorbidity. It further underlines the clinical importance of preventive measures against obesity accompanying MDD treatment. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction Obesity is one of the most prevalent somatic comorbidities of major depressive disorder (MDD) (De Wit et al., 2010). The prevalence of obesity is strongly elevated not only among subjects suffering from MDD but also in high-risk populations before onset of disease (Danese and Tan, 2013). A recent meta-analysis revealed that obesity increases the risk of depression and vice versa pointing to a reciprocal link between both depression and obesity (Luppino et al., 2010). The clinical implications of this comorbidity were underlined by an epidemiologic study showing that nutritional counseling and physical activity is accompanied by both weight loss and improvement of depressive symptoms in obese adolescents (Melnyk et al., 2013). Moreover, Kloiber et al. demonstrated that obese and overweight MDD patients suffer from poorer treatment outcome (Kloiber et al., 2007). Given that both disorders rank among the leading challenges in public health and considering the apparently reciprocal relationship of these conditions, investigation of common neurobiological underpinnings seems to be warranted. In MDD, a wealth of structural imaging findings elucidated the role of specific brain areas in the etiopathology of affective disorders (Cole et al., 2011; Phillips et al., 2003). Particularly, gray matter volume reductions in structures involved in emotion processing were frequently found to be associated with MDD (Arnone et al., 2012; Cusi et al., 2012). However, only few studies have investigated neural correlates of obesity. In healthy participants, neuroimaging studies revealed associations between elevated body-massindex (BMI) and reduced gray and white matter, as well as loss of global brain volume (Mueller et al., 2012; Ward et al., 2005). More specifically, reductions of gray matter in prefrontal areas such as the superior frontal gyrus, the medial orbitofrontal gyrus and striatal areas are among the few available findings in obesity (Marqués-Iturria et al., 2013; Raji et al., 2010; Walther et al., 2010), much resembling neurostructural alterations reported in depressed patients. Furthermore, a recent tensor-based morphometry study indicated that BMI might be associated with comparable effects on brain structure in depressed patients (Cole et al., 2013). Taken together, there is evidence not only for a clinical but also for a neurostructural link between obesity and depression since gray matter reductions appear to affect overlapping brain regions in both conditions. Given the mutual negative impact of these disorders, especially the poorer treatment outcome, obese MDD-patients are likely to suffer from a more severe course of disease. Thus, further elucidation of common biological factors could be of great clinical importance. A potential neurobiological connection
between obesity and MDD might highlight the relevance of preventive measures against obesity and provide the basis for adjusted strategies in MDD treatment. Hence, in our present study we sought to clarify if, or to which extent BMI is associated with aberrations in cerebral structures and with differences in clinical appearance in MDD patients. We hypothesized that in patients and healthy controls alike BMI would be associated with specific neurostructural alterations. We further hypothesized that in MDD-patients BMI would be associated with a more chronic course of the disorder, and that both BMI and chronicity would be related to morphometric anomalies in similar cerebral areas.
2. Material and methods 2.1. Participants Our dataset comprised two samples: a psychiatric sample comprising n = 144 subjects suffering from acute major depressive disorder (MDD) according to DSM-IV criteria (American Psychiatric Association, APA, 2000) as diagnosed with the SCID-I interview (Wittchen et al., 1997). Additionally, a second sample of n = 141 healthy controls (HC), matched according to BMI (p = 0.70), age (p = 0.95) and sex (p = 0.86), was obtained from a larger ongoing study (see Table 1 for details). Patients were recruited from the inpatient service of the Department of Psychiatry, University of Muenster. For all analyses, six subjects had to be excluded due to anatomical abnormalities leaving n = 140 MDD patients (mean age = 37.6, SD = 11.8 years) and n = 139 HC (mean age = 37.7, SD = 12.0 years). Exclusion criteria for all participants were any neurological abnormalities, severe medical conditions, substance-related disorders or current benzodiazepine treatment. Furthermore, all participants had normal or corrected-to-normal vision, and had adequate knowledge of German and cognitive abilities (verbal IQ > 80; multiple-choice vocabulary intelligence test MWT-B; Lehrl, 2005). All HC subjects had no history of psychiatric illness, according to the SCID-Interview (Wittchen et al., 1997) and were free from any psychotropic medication. Subjects were screened for imaging safety concerns, and informed, written consent was obtained following the Declaration of Helsinki (World Medical Association, 1991). The experimental procedure was approved by the ethics committee of the Medical Faculty at the University of Münster. All participants received a financial compensation.
Obesity and major depression
221
Table 1 Sociodemographic and clinical characteristics of our study sample consisting of 140 currently depressed patients and 139 healthy controls. Means, standard deviations (SD) and group differences (as measured with t-tests or 2 -test).
Age Sex (m/f) BMI Verbal IQ HAMD BDI Number of episodes Time since first psychiatric symptoms (months) Duration since onset of depression (months) Time since first outpatient treatment (months) Time since first inpatient treatment (months) Total duration of inpatient treatment (weeks)
HC sample (n = 139)
MDD patients (n = 140)
Mean
SD
Range
Mean
37.59 61/ 78 25.74 114.81 0.89 1.78 n/a n/a n/a n/a n/a n/a
11.78 0.5 4.7 12.46 1.29 2.07
20—59
37.69 11.97 18—59 60/ 80 0.5 25.97 5.25 18—44 109.46 13.12 82—143 23.26 5.23 12—42 27.94 9.18 9—53 4.56 5.64 1—30 117.51 111.54 3—480 100.38 102.93 1—432 72.85 93.21 1—396 36.37 71.91 1—384 10.35 12.78 1—67
18—40 93—143 0—5 0—8
SD
p-value
Range 0.95 0.86 0.7 0.01
