Abstract
BACKGROUND: Leptin is derived in adipose tissue and circulates in the body to play a key role in metabolism and energy regulation. In non-psychiatric populations, there is evidence that leptin levels are associated with neurocognitive performance. The production of its circulating soluble binding receptor increases during exercise, which has been associated with neuroplasticity and memory enhancement. The soluble leptin receptor (SLR) is the main leptin binding protein in blood in humans, which serves as an antagonist of the transport of leptin to the brain. Cognitive deficits are well established in schizophrenia, even early in the course of the disorder. However, the question as to whether leptin plays a role in the well-observed cognitive deficits in schizophrenia is unanswered. We examined the relationship between soluble leptin receptor levels and cognitive deficits assessed with the MATRICS Consensus Cognitive Battery (MCCB) prior to participation in a longitudinal study of a combined cognitive training and aerobic exercise program intended to improve cognition and functional outcomes in these young-adult schizophrenia patients. METHODS: The participants were 48 first-episode adult-onset schizophrenia patients treated at the UCLA Aftercare Research Program. Plasma soluble leptin R levels were measured by solid phase sandwich ELISA (D0BR00, R&D Systems) using a Molecular Devices SpectraMax M2 plate reader, and concentrations calculated using a 5-Parameter Logistic Nonlinear Regression Model (SoftMax Pro software). The MATRICS Consensus Cognitive Battery (MCCB) was administered contemporaneously with the plasma blood draw during study baseline, prior to the randomized treatment conditions. RESULTS: Higher plasma soluble leptin receptor levels were significantly correlated in cross-sectional analyses with lower MCCB overall composite cognitive index scores (r= -.33, P=.03). Post-hoc analyses of the individual MCCB domains found 4 of the 7 to be significantly correlated with leptin levels (Speed of Processing (r = -34, P=.02), Attention/Vigilance (r = -34, P=.02), Verbal Learning and Memory (r = -30, P=.04), and Social Cognition (r = -30, P=.04). Soluble leptin receptor levels were not, however, significantly associated Working Memory (r = -19, P=.20), Visual Learning and Memory (r = -.21, P=.15), or Reasoning and Problem Solving (r = -07, P=.63). DISCUSSION: These results indicate certain cognitive deficits after onset of schizophrenia are moderately associated with soluble leptin receptor levels, even early in the course of the disorder. The higher incidence of the leptin receptor levels is thought to have an impact on lower rates of bioavailability of leptin to cross the blood-brain barrier and thus lend to improved neuroplasticity. Weight very commonly increases over time on antipsychotic medication. These findings are consistent with the known association between weight, and in particular, adipose tissue, and leptin. The negative impact of weight increase on cognitive functioning is rarely considered in the treatment of schizophrenia. However, these findings suggest that they should be an area of concern. Future reports will examine the effects of an exercise intervention on both leptin and cognition.