Leptin regulates fatty acid metabolism in liver, skeletal muscle, and pancreas by partitioning fatty acids into oxidation rather than triacylglycerol (TG) storage. Although leptin receptors are present in the heart, it is not known whether leptin also regulates cardiac fatty acid metabolism. To determine whether leptin directly regulates cardiac fatty acid metabolism, isolated working rat hearts were perfused with 0.8 mM [9,10-3 H]palmitate and 5 mM [1-14 C]glucose to measure palmitate and glucose oxidation rates. Leptin (60 ng/ml) significantly increased palmitate oxidation rates 60% above control hearts (p < 0.05) and decreased TG content by 33% (p < 0.05) over the 60-min perfusion period. In contrast, there was no difference in glucose oxidation rates between leptin-treated and control hearts. Although leptin did not affect cardiac work, oxygen consumption increased by 30% (p < 0.05) and cardiac efficiency was decreased by 42% (p < 0.05). AMP-activated protein kinase (AMPK) plays a major role in the regulation of cardiac fatty acid oxidation by inhibiting acetyl-CoA carboxylase (ACC) and reducing malonyl-CoA levels. Leptin has also been shown to increase fatty acid oxidation in skeletal muscle through the activation of AMPK. However, we demonstrate that leptin had no significant effect on AMPK activity, AMPK phosphorylation state, ACC activity, or malonyl-CoA levels. AMPK activity and its phosphorylation state were also unaffected after 5 and 10 min of perfusion in the presence of leptin. The addition of insulin (100 microunits/ml) to the perfusate reduced the ability of leptin to increase fatty acid oxidation and decrease cardiac TG content. These data demonstrate for the first time that leptin activates fatty acid oxidation and decreases TG content in the heart. We also show that the effects of leptin in the heart are independent of changes in the AMPK-ACC-malonyl-CoA axis.Leptin is a peptide hormone synthesized by adipocytes (1) that plays a key role in the regulation of appetite and energy expenditure through its actions in the hypothalamus (reviewed in Ref. 2). Accumulating evidence now suggests that leptin can also regulate energy homeostasis through direct actions on peripheral lipid and glucose metabolism (reviewed in Ref. 3). In liver, skeletal muscle, and pancreas, leptin partitions fatty acids toward fatty acid oxidation rather than TG 1 storage. For instance, in vivo elevation of leptin levels in normal rats leads to a depletion of TG content in liver, skeletal muscle, and pancreas without an increase in plasma fatty acids or ketones, suggesting intracellular oxidation (4). Furthermore, leptin treatment of isolated muscle results in increased fatty acid oxidation and decreased incorporation of fatty acids into TG (5-7). The mechanism by which leptin increases fatty acid oxidation and decreases TG content in peripheral tissues is not completely understood. Recently, leptin was suggested to acutely increase fatty acid oxidation in skeletal muscle through the activation of AMP-activated protein kinas...

Motivation and negative symptom research has recently been hampered by a series of inconsistent findings, leading to calls for a greater consensus on the type of measures used across studies. To inform this issue, we conducted a meta-analysis that quantified the association between motivation measures (self-report, performance-based) and clinician-rated negative symptom measures as well as a series of moderator analyses to develop a greater understanding of the measurement factors impacting this relationship. Forty-seven eligible studies with people with schizophrenia-spectrum disorders were included. Using a random-effects meta-analytic model, a small but significant overall effect size emerged between motivation and clinician-rated negative symptoms (r = −.18). Several significant moderators were identified, including the generation of negative symptom measures such that there was a significantly stronger relationship between motivation and secondgeneration (r = −.38) than first-generation negative symptom measures (r = −.17). Further, the type of performance-based measure used moderated the relationship, with effort discounting tasks most strongly related to negative symptoms (r = −.44). The domain of motivation assessed (intrinsic, extrinsic, amotivation) also moderated the relationship. These findings help to identify sources of inconsistencies observed in prior studies and point to both second-generation and effort discounting tasks as the most promising types of measures, particularly for those interested in validating motivation measures or assessing the effectiveness of motivation treatments. Although additional research is needed, our results suggest that using these measures may help to reduce inconsistencies across studies and move the field forward.

Impairments in metacognition or the ability to form integrated senses of self and others have been linked to deficits in laboratory-based measures of social functioning in schizophrenia. This study examined whether self-reported social functioning was related to metacognition in 88 adults in a nonacute phase of schizophrenia. Concurrent assessments were made of metacognition with the Metacognition Assessment Scale–Abbreviated, social functioning with the Social Functioning Scale, symptoms with the Positive and Negative Syndrome Scale, and neurocognition with the Wisconsin Card Sorting Task. Univariate correlations revealed that self-reported social functioning was related to metacognition. Symptom severity was linked to interpersonal relationships, and overall metacognition was found to significantly moderate that relationship such that the effects of symptoms on function grew less as metacognitive capacity was stronger, independent of the effects of neurocognition. This may suggest the potential of metacognitive interventions to titrate the negative effects of symptoms on social function.

Objective: Preliminary research has suggested that mental health clinicians who work with people with severe mental illness may experience associative stigma, and the Clinician Associative Stigma Scale (CASS; Yanos, Vayshenker, DeLuca, & O'Connor, 2017) was recently developed and tested in a cross-sectional, online sample to examine this construct. The purpose of the present study was to further investigate the CASS's psychometric properties, examining associations with measures of burnout, job satisfaction, and "turnover intention" with service providers in a setting directly working with people with severe mental illness (i.e., a community mental health center). Furthermore, we examined these associations over a 6-month period to assess predictive validity of the measure. Method: Participants were 68 providers working in a large community mental health center in a midwestern city. Participants completed the CASS as well as measures of burnout, job satisfaction, and turnover intention at 2 points in time (baseline and 6 months later). Results: The CASS significantly predicted burnout (emotional exhaustion and personal accomplishment) and job satisfaction when examined cross-sectionally, even after controlling for demographic characteristics. Longitudinal analyses showed that increased associative stigma was associated with increased burnout and lower job satisfaction over time. Conclusions and Implications for Practice: Associative stigma may have negative consequences for mental health service providers, as well as the consumers they serve, and the CASS appears to be a useful tool to study this phenomenon. Associative stigma may be an appropriate target for interventions designed to reduce burnout among mental health providers. Impact and ImplicationsAssociative stigma is frequently experienced by providers working with people with serious mental illness and is associated with increased burnout and decreased job satisfaction. Associative stigma may be one mechanism by which providers' empathy for persons with severe mental illness is eroded and should be targeted in intervention.