BACKGROUND: Resting brain connectivity is a crucial component of human behavior 
demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, 
a recently identified critical reproductive hormone, can alter activity in 
certain brain structures but its effects on resting brain connectivity and 
networks in humans remain elusive.
METHODS: We determined the effects of kisspeptin on resting brain connectivity 
(using functional neuroimaging) and behavior (using psychometric analyses) in 
healthy men, in a randomized double-blinded 2-way placebo-controlled study.
RESULTS: Kisspeptin's modulation of the default mode network (DMN) correlated 
with increased limbic activity in response to sexual stimuli (globus pallidus r 
= 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin's 
DMN modulation was greater in men with less reward drive (r = -0.489, P = 0.008) 
and predicted reduced sexual aversion (r = -0.499, P = 0.006), providing key 
functional significance. Kisspeptin also enhanced key mood connections including 
between the amygdala-cingulate, hippocampus-cingulate, and hippocampus-globus 
pallidus (all P < 0.05). Consistent with this, kisspeptin's enhancement of 
hippocampus-globus pallidus connectivity predicted increased responses to 
negative stimuli in limbic structures (including the thalamus and cingulate [all 
P < 0.01]).
CONCLUSION: Taken together, our data demonstrate a previously unknown role for 
kisspeptin in the modulation of functional brain connectivity and networks, 
integrating these with reproductive hormones and behaviors. Our findings that 
kisspeptin modulates resting brain connectivity to enhance sexual and emotional 
processing and decrease sexual aversion, provide foundation for kisspeptin-based 
therapies for associated disorders of body and mind.
FUNDING: NIHR, MRC, and Wellcome Trust.