Schizophrenia and bipolar disorder are associated with opposite brain reward anticipation-associated response

Blunted and exaggerated neuronal response to rewards are hypothesized to be core features of schizophrenia spectrum disorders (SZ) and bipolar disorder (BD), respectively. Nonetheless, direct tests of this hypothesis, in which response between SZ and BD is compared in the same study, are lacking. Here we examined the functional correlates of reward processing during the Incentivized Control Engagement Task (ICE-T) using 3T fMRI. Reward-associated activation was examined in 49 healthy controls (HCs), 52 recent-onset individuals with SZ, and 22 recent-onset individuals with Type I BD using anterior cingulate (ACC), anterior insula, and ventral striatal regions of interest. Significant group X reward condition (neutral vs. reward) interactions were observed during reward anticipation in the dorsal ACC (F(2,120) = 4.21, P = 0.017) and right insula (F(2,120) = 4.77, P = 0.010). The ACC interaction was driven by relatively higher activation in the BD group vs. HCs (P = 0.007) and vs. individuals with SZ (P = 0.010). The insula interaction was driven by reduced activation in the SZ group relative to HCs (P = 0.018) and vs. people with BD (P = 0.008). A composite of reward anticipation-associated response across all associated ROIs also differed significantly by diagnosis (F(1,120) = 5.59, P = 0.02), BD > HC > SZ. No effects of group or group X reward interactions were observed during reward feedback. These results suggest that people with SZ and BD have opposite patterns of activation associated with reward anticipation but not reward receipt. Implications of these findings in regard to Research Domain Criteria-based classification of illness and the neurobiology of reward in psychosis are discussed.Subject terms: Schizophrenia, Bipolar disorder     

Promoting fit bodies,healthy eating and physical activity among Indigenous Australian men: a study protocol

Background  

Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia's Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a community-based investigation into the factors surrounding the health and body image of Indigenous Australian men.     

Elevated Liver Enzymes Indicating a Diagnosis of Limb-Girdle Muscular Dystrophy

A 27-year-old man presented to an internal medicine clinic to establish primary care. His past medical history was significant for elevated liver transaminases found during laboratory monitoring while taking isotretinoin for acne. He had an extensive workup spanning 7 years including serial hepatic function panels after withholding isotretinoin, viral serologies, and two liver biopsies, which eventually led to a diagnosis of an idiopathic elevation in serum transaminases. During his present evaluation, he endorsed complaints of significant muscle soreness with strenuous activity despite conditioning. Creatine kinase was found to be elevated at 11,778 U/l. Nerve conduction studies and electromyogram indicated a myopathy. DNA sequencing confirmed a diagnosis of limb-girdle muscular dystrophy. The aminotransferases are most notable for their association with liver pathology; however, they are also present in other tissues such as heart, kidney, and skeletal muscle. Muscle pathology, including the inherited muscular dystrophies, are often identified by elevations in creatine kinase, but can also be suggested by elevations of aminotransferases. This case illustrates that myopathies should be considered in patients with otherwise unexplained elevations in liver aminotransferases.     

Microsatellite markers for Longfin Dace, Agosia chrysogaster, a sentinel fish species in imperiled arid-land rivers of the Sonoran Desert

We isolated and characterized 16 microsatellite DNA loci in Longfin Dace, Agosia chrysogaster, a minnow native to Sonoran Desert streams (southwestern US and northwestern Mexico). After optimization, all primer pairs produced consistently scorable products. Genetic diversity metrics were determined for each locus using 50 individuals from two populations in the Gila River basin, New Mexico. Allelic richness ranged from 2 to 37 and observed heterozygosity ranged from 0.08 to 0.95 across loci. These microsatellites offer a powerful tool to study effects of habitat fragmentation, dewatering, and climate change on population connectivity and genetic diversity in this species. Moreover, Longfin Dace co-occurs with more geographically restricted and endangered desert fish species. Genetic information for Longfin Dace could provide an important comparative dataset to assist conservation and management of other imperiled fishes in the region.     

Synchronous extinction of North America's Pleistocene mammals

The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (≈13,800–11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 genera from this time interval is the result of sampling error or temporally staggered extinctions is unclear. Analysis of the chronology of extinctions suggests that sampling error can explain the absence of terminal Pleistocene last appearance dates for the remaining 19 genera. The extinction chronology of North American Pleistocene mammals therefore can be characterized as a synchronous event that took place 12,000–10,000 radiocarbon years B.P. Results favor an extinction mechanism that is capable of wiping out up to 35 genera across a continent in a geologic instant.     

Differentiating lexical form, meaning, and structure in the neural language system

A technique for studying the relationship between brain and language, which involves correlating scores on two continuous variables, signal intensity across the entire brains of brain-damaged patients and behavioral priming scores, was used to investigate a central issue in cognitive neuroscience: Are the components of the neural language system organized as a single undifferentiated process, or do they respond differentially to different types of linguistic structure? Differences in lexical structure, in the form of the regular and irregular past tense, have proven to be critical in this debate by contrasting a highly predictable rule-like process (e.g., jump-jumped) with an unpredictable idiosyncratic process typified by the irregulars (e.g., think-thought). The key issue raised by these contrasts is whether processing regular and irregular past tense forms differentially engages different aspects of the neural language system or whether they are processed within a single system that distinguishes between them purely on the basis of phonological and semantic differences. The correlational analyses provide clear evidence for a functional differentiation between different brain regions associated with the processing of lexical form, meaning, and morphological structure.     

Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes

Transition-state theory has led to the design of Immucillin-H (Imm-H), a picomolar inhibitor of purine nucleoside phosphorylase (PNP). In humans, PNP is the only route for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T cell-mediated immunosuppression. This study reports the biological effects and mechanism of action of Imm-H on malignant T cell lines and on normal activated human peripheral T cells. Imm-H inhibits the growth of malignant T cell leukemia lines with the induction of apoptosis. Imm-H also inhibits activated normal human T cells after antigenic stimulation in vitro. However, Imm-H did not inhibit malignant B cells, colon cancer cell lines, or normal human nonstimulated T cells, demonstrating the selective activity of Imm-H. The effects on leukemia cells were mediated by the cellular phosphorylation of deoxyguanosine and the accumulation of dGTP, an inhibitor of ribonucleotide diphosphate reductase. Cells were protected from the toxic effects of Imm-H when deoxyguanosine was absent or when deoxycytidine was present. Guanosine incorporation into nucleic acids was selectively blocked by Imm-H with no effect on guanine, adenine, adenosine, or deoxycytidine incorporation. Imm-H may have clinical potential for treatment of human T cell leukemia and lymphoma and for other diseases characterized by abnormal activation of T lymphocytes. The design of Imm-H from an enzymatic transition-state analysis exemplifies a powerful approach for developing high-affinity enzyme inhibitors with pharmacologic activity.