👤 Caroline Crombie

Acute exercise modulates circulating exerkines and affective states, yet it remains unclear whether mind-body exercise modalities, such as yoga, elicit responses observed in aerobic exercise. This study examined the acute effects of yoga, stretching, moderate-intensity aerobic exercise, and low-intensity aerobic exercise on exerkines and affect. Eighty-eight adults (52% female; mean age = 23.3 ± 5.79 years) were randomized to one of two study arms: aerobic exercise (moderate-intensity = 70-75% heart rate max and low-intensity = 40-50% heart rate max) or mind-body exercise (yoga and stretching). At two laboratory visits, participants completed 30-minutes of each condition within their assigned arm in a counterbalanced order. Venous blood collected immediately before and after exercise was analyzed for brain-derived neurotrophic factor (BDNF) and endocannabinoids (N-arachidonoylethanolamine [AEA], 2-arachidonoylglycerol [2-AG]). State anxiety and positive and negative affect were assessed pre- and post-exercise. Linear mixed-effects models tested pre-to-post changes and condition interactions. Moderate-intensity aerobic exercise increased circulating concentrations of AEA (b = 0.10, p = .005), while 2-AG and BDNF concentrations were unchanged across conditions. All four exercise conditions decreased state anxiety and negative affect, whereas only yoga, stretching, and moderate-intensity aerobic exercise increased positive affect. Pre-to-post AEA increases were correlated with changes in positive affect (b = 0.18, p = .041). In this randomized study-arm design, moderate-intensity aerobic exercise uniquely increased AEA, whereas affective improvements were observed across modalities. These findings implicate cardiovascular intensity in the endocannabinoid response to exercise, while diverse forms of acute exercise are associated with short-term affective benefits. Show less

Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in both a University College London (UCL) and a USA-based case-control sample. In this paper we report a statistically significant replication of the PCM1 association in a large Scottish case-control sample from Aberdeen. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine to isoleucine missense mutation in exon 24 which was likely to change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in 98 schizophrenic research subjects and controls out of 2246 case and control research subjects. Among the 98 carriers of rs370429, 67 were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both the London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422, which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Genotyping of the new variants discovered in the UCL case-control sample strengthened the evidence for allelic and haplotypic association (P=0.02-0.0002). Given the number and identity of the haplotypes associated with schizophrenia, further aetiological base pair changes must exist within and around the PCM1 gene. PCM1 protein has been shown to interact directly with the disrupted-in-schizophrenia 1 (DISC1) protein, Bardet-Biedl syndrome 4, and Huntingtin-associated protein 1, and is important in neuronal cell growth. In a separate study we found that clozapine but not haloperidol downregulated PCM1 expression in the mouse brain. We hypothesize that mutant PCM1 may be responsible for causing a subtype of schizophrenia through abnormal cell division and abnormal regeneration in dividing cells in the central nervous system. This is supported by our previous finding of orbitofrontal volumetric deficits in PCM1-associated schizophrenia patients as opposed to temporal pole deficits in non-PCM1-associated schizophrenia patients. Caution needs to be exercised in interpreting the actual biological effects of the mutations we have found without further cell biology. However, the DNA changes we have found deserve widespread genotyping in multiple case-control populations. Show less

Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.24% of cases and 0.015% of controls). These were significantly associated with a high odds ratio (P = 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia. Show less