Ian H. Treasaden

Evidence from in vivo 31-phosphorus magnetic resonance spectroscopy phosphodiesters that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans.

BackgroundThis study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder.MethodsSamples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm3 voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra.ResultsThe ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs= 0.714, p < 0.05).ConclusionOur results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

Regional grey matter volumetric changes in forensic schizophrenia patients: an MRI study comparing the brain structure of patients who have seriously and violently offended with that of patients who have not

BackgroundThe aim was to carry out the first voxel-based morphometry study of grey matter changes in the whole brain in schizophrenia associated with a history of seriously and violently offending.MethodsStructural cerebral magnetic resonance imaging scans of 26 patients with schizophrenia were analyzed using voxel-based morphometry: 13 of the patients had seriously and violently offended directly as a result of schizophrenia prior to admission, the offences consisting of homicide, attempted murder or wounding with intent to cause grievous bodily harm; the other 13 patients did not have a history of violence. There was no history of comorbid psychoactive substance misuse disorder in any of the patients. Voxelwise generalized linear modelling was applied to the processed magnetic resonance data using permutation-based non-parametric testing, forming clusters at t > 2.3 and testing clusters for significance at p < 0.05, corrected for multiple comparisons across space.ResultsThe two groups of patients were matched with respect to age, gender and duration of illness, but the group with a history of serious violence was on average receiving a higher dose of antipsychotic medication than the group without a history of violence. There were local regions of reduced grey matter volume in the schizophrenia patient group with a history of serious and violent offending, compared with the schizophrenia patient group without such a history. Significant voxels (p < 0.05, corrected for multiple comparisons) were noted bilaterally in the cerebellum and in BA 39 and 40.ConclusionThese regions are important in verbal working memory. The cerebellum may integrate inputs from ventrolateral prefrontal cortex and parietal regions, providing a corrective signal that refines the process of rehearing the contents of the phonological store. A strong connection has been hypothesized between the supramarginal region corresponding to BA 39/40 and Brocas area, which may correspond largely to the arcuate fasciculus, with the connectional pattern of the language regions of this model fitting the network of parietotemporal-prefrontal connections that participate in working memory. Therefore our results point to the possibility of an abnormality in neural circuits involved in verbal working memory in this group of patients.

A comparison of oxidative stress in smokers and non-smokers: an in vivo human quantitative study of n-3 lipid peroxidation

BackgroundCigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath.MethodsSamples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry.ResultsThe two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75).ConclusionOur results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

Brain cell membrane motion-restricted phospholipids in patients with schizophrenia who have seriously and dangerously violently offended

This study directly assessed, for the first time, whether there was a change in brain cell motion-restricted membrane phospholipids in vivo in male forensic patients with schizophrenia who had seriously and violently offended (homicide, attempted murder, or wounding with intent to cause grievous bodily harm) while psychotic, by quantification of the broadband resonance signal from 31-phosphorus neurospectroscopy scans. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 15 such patients, who suffered from positive symptoms of schizophrenia, and in 12 age- and sex-matched normal control subjects. Spectra were obtained from 70 x 70 x 70 mm(3) voxels using an image-selected in vivo spectroscopy pulse sequence. There was no significant difference in the broad resonances between the two groups, with the mean (standard error) percentage broadband signal for the patients being 57.8 (5.6) and that for the control subjects 57.7 (6.0). The phosphomonoesters and phosphodiesters narrow signals also did not differ between the groups. These results suggest that patients with schizophrenia who have predominantly positive symptoms may not show neuroimaging-based signs compatible with the membrane phospholipid hypothesis of schizophrenia.

A human in vivo study of the extent to which 31-phosphorus neurospectroscopy phosphomonoesters index cerebral cell membrane phospholipid anabolism

The phosphomonoester narrow resonance of human in vivo 31-phosphorus neurospectroscopy studies is believed to index the anabolism of cell membrane phospholipids and has therefore been used to study phospholipid anabolism in the brain non-invasively. However, it is an indirect measure of phospholipid metabolism and although it does contain major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are important precursors of membrane phospholipids, many other metabolites, including sugar phosphates, can contribute to this region of the spectrum, and separation of these different peaks is not achieved with the present in vivo methodology. Recently, it has become possible to analyze signal directly from the cell membrane motion-restricted phospholipids by analysis of a broad resonance signal. We therefore hypothesized that there should be a positive correlation between the phosphomonoester narrow resonance and the broad resonance signal if the former does indeed index cell membrane phospholipid anabolism. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 54 human subjects, including normal volunteers and patients with schizophrenia in order to widen the range of phosphomonoester and broad resonance values. Spectra were obtained from 70x70x70mm(3) voxels using an image-selected in vivo spectroscopy pulse sequence. There was a highly significant positive correlation between the phosphomonoester resonances and the broad resonance signals (r=0.404, P<0.005). These results are consistent with the hypothesis that the phosphomonoester narrow resonance does indeed index cell membrane phospholipid anabolism in brain studies.

An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)

A particularly important family of antioxidant defence enzymes in the body are the glutathione peroxidases, which remove H(2)O(2) by coupling its reduction to H(2)O with oxidation of reduced glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of unknown aetiology. Since many of the symptoms relate to cerebral functioning, it would seem probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in myalgic encephalomyelitis. Cerebral proton neurospectroscopy was carried out at a magnetic field strength of 3T in 26 subjects; spectra were obtained from 20x20x20mm(3) voxels using a point-resolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis patients was 2.703 (SD 2.311) which did not differ significantly from that in age- and gender-matched normal controls who did not have any history of neurological or other major medical disorder (5.191, SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic encephalomyelitis. At the present time, based on the results of this study, there is no evidence to support the suggestion that, by taking glutathione supplements, an improvement in the brain-related symptomatology of myalgic encephalomyelitis may occur.

Clinical experience of the use of triptorelin as an antilibidinal medication in a high-security hospital

Paraphilias (disorders of sexual preference), in particular paedophilia, have been increasingly recognised as a major problem in Western countries and are associated with significant human and material costs. Various treatments have been used to manage sex offenders with varying success. Gonadotropin-releasing hormone (GnRH) agonists, such as triptorelin, a depot injection, cause castration-equivalent testosterone levels in men and are emerging as an effective treatment option in cases of severe paraphilia. Triptorelin has recently received a licence in the UK for use in sex offenders. We surveyed the literature on prescribing protocols for triptorelins use as an antilibidinal medication and compared them with actual prescribing practice in a high-security hospital, which enabled us to suggest improvements in practice with regard to pre-treatment considerations and appropriate monitoring during therapy. Our study highlights the need and proposes a treatment protocol for the safe administration of long-term triptorelin therapy for paraphilia.

A systematic review of the heritability of specific psychopathic traits using Hare’s two-factor model of psychopathy

BACKGROUND There have been no systematic reviews that investigated the heritability of the two-factor model of psychopathy: interpersonal-affective and behavioral. Our review aimed, first, to examine the heritability of general psychopathic traits and, second, if genetic influences were suggested, to determine the heritability of various traits related to the interpersonal-affective and behavioral factors of psychopathy. METHOD A systematic literature search was conducted using articles from the PsycINFO, Embase, Global Health, Medline, PubMed, Web of Science, and Scopus databases (January of 1980 to December of 2015) in order to identify eligible literature that reported on the heritability of psychopathy-related traits. Papers were also found via manual examination and reference tracking. Papers were subjected to exclusion criteria and quality appraisal. We identified a total of 24 studies. RESULTS Our results were grouped into three categories: general, interpersonal-affective, and behavioral. All these areas demonstrated modest to high heritability. The highest heritability values were found in studies investigating callous-unemotional behaviors. CONCLUSIONS Heritability was found for all the psychopathic traits. Future research should include endophenotypic approaches that explore gene-environment correlations, which could aid in identification of the behavioral phenotype that is most amenable to early intervention by way of moderation of genetic risk.

Provision of spiritual and pastoral care facilities in a high-security hospital and their increased use by those of Muslim compared to Christian faith

The relationship between religion and psychiatry remains controversial amongst British psychiatrists. We looked at the provision of spiritual and pastoral care facilities in a high-security hospital and the role of faith chaplains with particular reference to the Muslim minority group. There was a significantly higher uptake of pastoral care services amongst those of Muslim faith compared to Church of England and Roman Catholic Christians. Possible reasons for this are discussed. Resources allocated for the Muslim faith group were limited and heavily dependent on the availability of the Muslim faith chaplain. Our study highlighted the need for clearly defined standards for the provision of spiritual and pastoral care within high-secure psychiatric hospitals, and by implication other NHS psychiatric settings, a re-examination of the role of the faith chaplain in relation to the clinical team, and raised questions about the equitable allocation of resources between various faith groups within the hospital.

EPA in schizophrenia and violence

This lecture will describe the role of EPA in schizophrenia and violence by first considering fatty acid metabolism abnormalities in violence and in schizophrenia. The results of the first 31-phosphorus magnetic resonance spectroscopy study of cerebral metabolism in patients with schizophrenia who have seriously and dangerously violently offended will then be described, which found a significantly lower beta-NTP and significantly higher gamma-NTP level in the patient group compared with age- and gender-matched control subjects. To explore these findings further, the relationship between these neurospectroscopy results and the volumetric niacin response (VNR) was studied. A significant negative correlation (Spearman r = -0.78, P < 0.005) was found between the VNR and cerebral Pi. The implications of this finding will be discussed. The further findings of our group relating to motion-restricted membrane phospholipids in the brain, measures of oxidative stress and changes in brain structure in patients with schizophrenia who have seriously and dangerously violently offended will be detailed. Finally, the implications of our results for the role of EPA in schizophrenia and violence will be described.