Sex differences in serotonin-hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight.
The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown.



Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite).



In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite.



This study suggests sex differences in serotonin-hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight.
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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J
Melasch
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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M
Rullmann
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.
A
A
Hilbert
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
J
J
Luthardt
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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GA
Becker
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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M
Patt
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Medical Department III, University Hospital Leipzig, Leipzig, Germany.
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Stumvoll
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Medical Department III, University Hospital Leipzig, Leipzig, Germany.
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Blüher
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.|Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
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Villringer
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.|Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
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Arelin
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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PM
Meyer
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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Bresch
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
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O
Sabri
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
S
S
Hesse
IFB Adiposity Diseases, University Medical Centre, Leipzig, Germany.|Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.|Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.|BG University Clinic Bergmannsheil, Department of Neurology, Ruhr University Bochum, Bochum, Germany.
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Pleger
D000328:Adult; D003863:Depression / Q000503:physiopathology*; D005260:Female; D005858:Germany; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D000072078:Positron Emission Tomography Computed Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D011594:Psychometrics; D011788:Quality of Life; D015203:Reproducibility of Results; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D013851:Thinness / Q000378:metabolism*; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D015430:Weight Gain
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin