Differential Methylation Pattern of Schizophrenia Candidate Genes in Tetrahydrocannabinol-Consuming Treatment-Resistant Schizophrenic Patients Compared to Non-Consumer Patients and Healthy Controls.

BACKGROUND: Patients suffering from schizophrenic psychosis show reduced synaptic connectivity compared to healthy individuals. Furthermore, the use of cannabis often precedes the onset of schizophrenic psychosis. Therefore, we investigated whether consumption of cannabis has an impact on the methylation pattern of schizophrenia candidate genes concerned with the development and preservation of synapses and synaptic function. METHODS: Fifty blood samples of outpatients affected by treatment-resistant schizophrenic psychosis were collected in the outpatient department of Ch Ste Anne/INSERM (Paris, France). Extracted DNA was sent to the LMN/MHH (Hanover, Germany) where DNA samples were bisulfite converted. The methylation patterns of the promoter region of neuregulin 1 (NRG1), neurexin (NRXN1), disrupted in schizophrenia 1 (DISC1), and microtubule-associated-protein tau (MAPT) were then analysed by sequencing according to Sanger. RESULTS: In NRXN1 the group of non-consumer patients showed a methylation rate slightly lower than controls. In patients with preliminary use of tetrahydrocannabinol (THC) the NRXN1 promoter turned out to be methylated almost two times higher than in non-consumer patients. In MAPT, non-consumer patients showed a significant lower mean methylation rate in comparison to controls. In THC-consuming patients the difference compared with controls became less. NRG1 and DISC1 showed no significant differences between groups, whereas DISC1 appeared to be not methylated at all. CONCLUSION: In MAPT and NRXN1 mean methylation rates were lower in non-consumer patients compared with controls, which seems to be a compensatory mechanism. With consumption of THC, mean methylation rates were increased: in the case of MAPT compared with controls, and in NRXN1 even significantly beyond that. Methylation of NRG1 and DISC1 seems not to be affected by the psychiatric disorder or by consumption of THC.

Severe hair loss associated with psychotropic drugs in psychiatric inpatients-Data from an observational pharmacovigilance program in German-speaking countries.

BACKGROUND: The study aimed to investigate severe hair loss related to psychotropic drugs (PDs) by using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie (AMSP). METHODS: Data on PD utilization and reports of severe PD-related hair loss were collected in 83 psychiatric hospitals in Austria, Germany and Switzerland during the period 1993-2013. RESULTS: Out of 432,215 patients under surveillance, 404,009 patients were treated with PDs for the main indications of depression, schizophrenic disorder, neurosis, mania, and organic psychosis. Severe hair loss related to PD treatment was reported in 43 cases (0.01%). The rates of hair loss under antipsychotic drugs were slightly lower than the mean rates of all PDs and antidepressant drugs. Valproic acid was related to the highest risk. In 6 of the 43 cases, hair loss was imputed to multiple drugs, with 4 cases imputed to double drug combinations and 2 cases to triple combinations. Rates of severe hair loss under valproic acid (VPA) and lithium salts were distinctly lower as compared with the overall rates reported in literature. Severe hair loss under PD treatment was reported significantly more often in female patients than in male patients (p < 0.01). CONCLUSION: The rate of severe PD-related hair loss was very low in the present survey. The large number of patients included in this multicentre study allows for assessment and comparison of hair loss rates related to different PDs and groups of PDs and provides new and supplementary information on PD-related hair loss.

Reduced audiovisual integration in synesthesia--evidence from bimodal speech perception.

Recent research suggests synesthesia as a result of a hypersensitive multimodal binding mechanism. To address the question whether multimodal integration is altered in synesthetes in general, grapheme-colour and auditory-visual synesthetes were investigated using speech-related stimulation in two behavioural experiments. First, we used the McGurk illusion to test the strength and number of illusory perceptions in synesthesia. In a second step, we analysed the gain in speech perception coming from seen articulatory movements under acoustically noisy conditions. We used disyllabic nouns as stimulation and varied signal-to-noise ratio of the auditory stream presented concurrently to a matching video of the speaker. We hypothesized that if synesthesia is due to a general hyperbinding mechanism this group of subjects should be more susceptible to McGurk illusions and profit more from the visual information during audiovisual speech perception. The results indicate that there are differences between synesthetes and controls concerning multisensory integration--but in the opposite direction as hypothesized. Synesthetes showed a reduced number of illusions and had a reduced gain in comprehension by viewing matching articulatory movements in comparison to control subjects. Our results indicate that rather than having a hypersensitive binding mechanism, synesthetes show weaker integration of vision and audition.

[Permanent disability and death among German workers with depression]. / Invalidität und Tod bei Erwerbsfähigen mit Depressionen.

OBJECTIVE: It was the aim of this study to estimate effects of depression on permanent disability and death in a statutory health insurance population. METHODS: Data from 128,001 clients were used with a mean follow up of 6.4 years. Excess risks were calculated with Cox regression models adjusted for age, gender, education and job classification. RESULTS: Outpatient treatment for depression was associated with an elevated relative risk for permanent disability, but inpatient treatment even more so. Life table analysis suggests higher risks of early retirement for males who get ill early in life. Depression treated solely in an outpatient setting may be associated with lower mortality early in life, but this was only significant for women. CONCLUSIONS: Outpatient treatment should include an emphasis on occupational functioning, but also a gender-specific approach is needed.

Decreased galanin serum levels are associated with alcohol-craving during withdrawal.

BACKGROUND: The hypothalamic galanin expression has been associated with increased intake of carbohydrates and fats in preclinical studies. The appetite stimulating effect of galanin is thought to underlie the positive association between alcohol consumption and hypothalamic galanin expression observed in preclinical studies. METHODS: In this pilot study we investigated alterations in galanin serum levels (33 male patients) in alcohol-dependent patients during alcohol withdrawal (days 1, 7 and 14) in comparison to healthy controls (19 male controls). In order to assess the putative association between appetite regulation, galanin serum levels and alcohol consumption we additionally investigated the serum levels of insulin, glucose and triglycerides. RESULTS: The galanin serum levels on day 1 of alcohol withdrawal were significantly reduced in the alcohol-dependent patients (T=-3.302, p=0.002) and increased significantly from day 1 to day 14 of alcohol withdrawal (F=6.437, p=0.002). We found a significant negative association between the galanin serum levels and alcohol craving measured by the Obsessive Compulsive Drinking Scale (OCDS) (r=-0.449, p=0.009) and the obsessive subscale of the OCDS (r=-0.521, p=0.002) on day 1 of alcohol withdrawal. There was no association between the galanin serum levels and the parameters of energy homeostasis (triglycerides, cholesterol, insulin, and glucose) investigated. CONCLUSIONS: Acute alcohol withdrawal was associated with decreased galanin serum levels in this pilot study. There was no association between the galanin serum levels and the parameters of energy homeostasis. Further research of galanin serum levels in active drinkers will be necessary to clarify the putative association between galanin serum levels, appetite regulation and alcohol consumption.

[Who gets how much psychiatric outpatient care and why?]. / Wer erhält wie viel Versorgung in der Institutsambulanz und warum?

AIMS: To elucidate the connections between individual aspects and patients' concerns and the care effort provided in a clinic for the sickest among outpatients. METHODS: Clients of one health insurer were followed for six months (n = 339) in a "Institutsambulanz" or "PIA". All treatment activities, which involved roughly 100,000 working minutes, were recorded. Sociodemographic data, the diagnoses, the individual needs and idiosyncracies, symptoms and case history were noted for multivariate analysis. RESULTS: The linear regression model with the best fit (n = 251, r (2) = 0.512, p < 0.001) included six variables. Lower efforts: living in nursing home (beta = - 0.319; p < 0.001), higher age (beta = - 0.238; p < 0.001), legal incapacity (beta = - 0.165, p = 0.006), own work income (beta = - 0.100; p = 0.044); higher efforts: inpatient stays prior to study treatment (lifetime: beta = 0.181; p = 0.001; number of days in last two years: beta = 0.193; p < 0.001). Treatment aims, functional deficits, and diagnoses did not have a significant influence. CONCLUSIONS: Younger patients who wish for an independent life despite of a grave psychiatric disorder may effectuate higher treatment efforts. Treatments administered to nursing-home inhabitants are far less complex, although these patients are even sicker. The current reimbursement mechanism may serve as a disincentive towards care administration according to individual need.