Inferior frontal white matter volume and suicidality in schizophrenia.

The neurobiology of suicidality in schizophrenia is largely unknown. We therefore assessed gray and white matter volumes associated with past suicidality and current self-aggression in schizophrenia. Fifty-five outpatients with schizophrenia (n=55) and healthy controls (n=55), matched for age, gender and handedness, were recruited. Ten patients had a life-time history of one or more suicide attempts. Current self-aggression was assessed using the Modified Overt Aggression Scale. High resolution structural magnetic resonance images were analyzed by voxel-based morphometry. We found significantly larger inferior frontal white matter volumes bilaterally in patients with a previous suicide attempt as compared with those patients without a history of suicidality. No other significant white or gray matter volume differences were observed. White matter volume in these regions did not differ between healthy controls and those patients without a previous suicide attempt. Furthermore, among patients, the level of current self-aggression showed a significant positive correlation with white matter volume in the same regions. Inferior frontal white matter alterations in fronto-temporo-limbic circuits may be associated with suicidality and self-aggression in schizophrenia.

Plasma dehydroepiandrosterone levels are strongly increased in schizophrenia.

Dehydroepiandrosterone has been recently recognized as neuroactive steroid with several vital neurophysiological activities on membrane receptors, such as N-methyl-d-aspartate, and gamma-aminobutyric acid receptors and on genomic androgen receptors. DHEA does also have an antiglucocorticoid effect. So far, the relevance of this neuroactive steroid to psychiatric disorders is not well known. In this study, plasma levels of DHEA were determined with a highly sensitive and specific gas-chromatography/mass-spectrometry method in 23 outpatients suffering from Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia compared with 23 healthy control subjects matched for age and sex. Plasma levels of DHEA were found to be strongly elevated in the group of schizophrenic patients (mean+/-SD=90.9+/-61.4 nmol/l) compared to that of control subjects (mean+/-SD=24.0+/-17.9 nmol/l) and the difference was highly significant (t=5.018, df=44, p<0.0001). This statistically significant difference was also found when we divided the groups of schizophrenics and controls in subgroups of males (t=4.536, df=24, p=0.0001) and females (t=2.777, df=18, p=0.0124). These results suggest that DHEA may have some role in the pathophysiology of schizophrenia due to its complex mechanism of action in the brain involving genomic and non-genomic components. Therefore, its study may provide further understanding of the pathophysiology of psychoses and open new avenues for their treatment.

Preliminary evidence for an association between aggressive and hostile behaviour and 3alpha,5alpha-tetrahydroprogesterone plasma levels in schizophrenia.

OBJECTIVE: Because it has been suggested that agents acting on the gamma-aminobutyric acid-A (GABA(A)) receptor complex, such as the neuroactive steroid 3!#!alpha;,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), may be biologic modulators of aggression, we aimed to measure 3alpha,5alpha-THP plasma concentrations in subjects with schizophrenia in order to investigate a possible relation with aggressive and hostile behaviour. METHODS: Eight outpatients with schizophrenia diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), were included. Aggression and hostility were assessed using the Modified Overt Aggression Scale and the paranoid/belligerence symptom cluster of the Positive and Negative Syndrome Scale. Plasma samples were obtained 1 hour before psychometric assessment and were quantified for 3alpha,5alpha-THP using a highly sensitive and specific combined analysis by gas chromatography-mass spectrometry. RESULTS: Increased aggressiveness and hostility were associated with increased 3alpha,5alpha-THP plasma levels (Pearson r = 0.72, p = 0.043 and Pearson r = 0.72, p = 0.041, respectively). CONCLUSIONS: These preliminary results suggest that the neuroactive steroid 3alpha,5alpha-THP may affect aggression and hostility in humans.

[Assessment of working conditions in health care workers]. / La valutazione della condizione lavorativa in popolazioni del settore sanitario.

OBJECTIVE: Validation and first use of a self-completed questionnaire to assess opinion on working conditions in health professionals. METHODS: The questionnaire consisted of 40 items. It was developed via review of the literature and two focus groups. A reliability test-retest study was performed on 45 health professionals with different roles. Factorial validity and internal consistency of each derived subscale were evaluated on a wide sample of 514 professionals. In addition, the opinion of the health care professionals was evaluated and possible relationships were tested between total and subscale scores and the following variables: age, sex, professional role and years in the job. RESULTS: Weighted kappa was higher than 0.60 for 95% of the items, higher than 0.70 for 43% and higher than 0.80 for 20%. Factor analysis revealed that six factors--work content and organisation, physical fatigue, relationships, mental stress, hours of work, and physical environment--explained 57% of total variance. Cronbach's alpha coefficient of the subscales ranged from 0.70 to 0.91. Low levels of satisfaction in dfferent job aspects were found among general hospital staff. They were particularly dissatisfied with personal growth and development, fairness in incentives, dissemination of information, environment, support of new ideas and skills, career opportunities. In particular, satisfaction differed among the various professional roles. DISCUSSION: The questionnaire was found reliable and had a coherent factor structure, with six factors or subscales that showed good internal consistency. This questionnaire may be useful to assess satisfaction with work in health care staff. The preliminary results of its use suggest that satisfaction with different aspects of work is low.

Chronic schizophrenia as a brain misconnection syndrome: a white matter voxel-based morphometry study.

It has been hypothesized that schizophrenia could be due to a defect of neural circuitry, that is a misconnection between different cerebral areas, particularly those involved in language processing and production. A group of 28 patients with chronic schizophrenia were investigated in order to detect differences in locations of white matter voxel signal intensity in comparison with a control group of 28 normal subjects matched for age, gender and educational level. Voxel-based morphometry was used to assess the white matter of the brain. Significant voxel signal hypointensity was identified in schizophrenic patients bilaterally (mainly in the left hemisphere) in the post-central gyrus and superior temporal gyrus and unilaterally (in the left hemisphere) in the inferior frontal gyrus-pars triangularis and pars pretriangularis, the medial orbital gyrus, the lateral orbital gyrus and the rectus gyrus. Thus, the white matters of these cerebral areas were structurally modified particularly in the left hemisphere and in those structures that control language and hearing processes.

Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia.

Schizophrenia or schizoaffective disorders are quite common features in patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS) as a result of hemizygosity of chromosome 22q11.2. We evaluated the PCQAP gene, which maps within the DGS/VCFS interval, as a potential candidate for schizophrenia susceptibility. PCQAP encodes for a subunit of the large multiprotein complex PC2, which exhibits a coactivator function in RNA polymerase II mediated transcription. Using a case-control study, we searched association between schizophrenia and the intragenic coding trinucleotide polymorphism. The distribution of the CAG repeat alleles was significantly different between patients and controls with the Mann-Whitney test (z = -2.5694, P = 0.0051; schizophrenics: n = 378, W = 161,002.5, Mean rank = 425.9325; controls: n = 444, W = 177,250.5, Mean rank = 399.2128). This result may indicate a possible involvement of the multiprotein complex PC2 in schizophrenia susceptibility.