Hypothalamic-Pituitary and Thyroid Function in Chronic Alcoholics with Neurological Complications

Endocrinological tests were performed in 14 chronic alcoholic men with signs of intellectual impairment and/or peripheral neuropathy. All had been abstinent from alcohol for at least 1 month. Basal serum growth hormone (GH) was consistently increased in only one patient whereas the GH responses to insulin hypoglycemia stimulation was normal in all patients. Thyroid function values (T4, T3, rT3, TSH) were normal in all patients whereas baseline serum prolactin values were significantly increased in alcoholics as compared with a control group. In a combined TRH- and GnRH-stimulation tests, GH-responses were also normal whereas TSH and prolactin responses were blunted or absent in about half of the patients, the responses correlating significantly (p less than 0.01). It is concluded that disturbances in the hypothalamic-pituitary axis may occur in chronic alcoholics with nervous impairment independently of the physical deterioration, which often is associated with chronic alcoholism.     

The 5‐HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans

The cerebral serotonin (5‐HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5‐HT type 4 receptor (5‐HT₄R) facilitates memory and learning and further that the 5‐HT₄R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5‐HT₄R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [¹¹C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5‐HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BP_ND, (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BP_ND and delayed recall (p = 0.014). These findings provide evidence that the 5‐HT₄R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory. Hum Brain Mapp 34:3066–3074, 2013. © 2012 Wiley Periodicals, Inc.     

Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: Concept and standards of the EARLYSTIM-study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD) with disabling motor complications. However, stimulation may be beneficial at an earlier stage of PD when motor fluctuations and dyskinesia are only mild and psychosocial competence is still maintained. The EARLYSTIM trial was conducted in patients with recent onset of levodopa-induced motor complications (≤3 years) whose social and occupational functioning remained preserved. This is called ‘early’ here. The study was a randomized, multicenter, bi–national pivotal trial with a 2 year observation period. Quality of life was the main outcome measure, and a video-based motor score was a blinded secondary outcome of the study. Motor, neuropsychological, psychiatric and psychosocial aspects were captured by established scales and questionnaires. The patient group randomized here is the earliest in the disease course and the youngest recruited in controlled DBS trials so far. The methodological innovation for DBS-studies of this study lies in novel procedures developed and used for monitoring best medical treatment, neurosurgical consistency, best management of stimulation programming, blinded video assessment of motor disability, and prevention of suicidal behaviors.     

Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma - a single centre's experience

Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and correlation with pathologic and clinical characteristics, including response to Rituximab-containing chemotherapy and survival, in an unselected cohort of patients with LBCL. Translocations involving BCL2 and MYC loci were examined with fluorescent in situ hybridization (FISH) in 157 patients with diffuse large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). The incidence of DH was 11% in the total cohort, 7% of primary LBCL and 21% of transformed LBCL. DH lymphomas were all GCB immunophenotype and were more often BCLU. No clinical characteristics were correlated with the presence of DH, which also had no impact on overall response rate (ORR), relapse rate or overall survival (OS). However, sub-stratification of DH lymphomas by FISH indicated a possible inferior survival related to immunoglobulin MYC translocation partner gene. Screening of patients with BCLU and DLBCL of GCB type for DH BCL2/MYC translocation including MYC translocation partner gene may provide important prognostic information.     

Common mental disorders and long‐term sickness absence in a general working population. The Hordaland Health Study

Objective: To examine and compare the prospective effect of the common mental disorders (CMD) anxiety and depression on duration and recurrence of sickness absence (SA), and to investigate whether the effect of CMD on SA is detectable over time. Method: Information from a large epidemiological health study (N = 13 436) was linked with official records of SA episodes lasting ≥16 days up to 6 years after participation. Common mental disorders were assessed with the Hospital Anxiety and Depression Scale (HADS). Associations were analysed with Cox regression and multinomial logistic regression models controlling for potential covariates. Results: Comorbid anxiety and depression, and anxiety only were significant risk factors for SA after adjusting for covariates, whilst depression only was not. Anxiety and depression were stronger predictors for longer duration of SA episodes compared with shorter duration and associated with more frequent recurrence of SA. There was a general trend toward the effect of CMD on SA becoming weaker over time; however, the effect of anxiety only on SA remained stable throughout the follow‐up. Conclusion: Common mental disorders are long‐lasting predictors of onset, duration and recurrence of SA. Anxiety appears to be a more important contributor to long‐term SA than previously described in the literature.     

Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia

Prefrontal serotonin 2A receptors (5‐HT_2ARs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5‐HT_2AR at clinical relevant doses, and activation of 5‐HT_2A receptors by lysergic acid diethylamide (LSD) and LSD‐like drugs induces a schizophrenia‐like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well‐established model for schizophrenia‐like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5‐HT_2ARs. As a measure of 5‐HT_2AR functionality, we used the 5‐HT_2AR agonist 2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced head‐twitch response (HTR) and mRNA expression of the immediate‐early genes (IEGs) activity‐related cytoskeletal associated‐protein (Arc), c‐fos, and early growth response protein 2 (egr‐2) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5‐day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated with changes in 5‐HT_2AR binding. Also, binding of the 5‐HT_1AR and the 5‐HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration produces changes in the brain that result in an increase in the absolute effect of DOI. Therefore, neurotransmission involving the 5‐HT_2AR could contribute to the behavioral deficits observed after PCP treatment. © 2013 Wiley Periodicals, Inc.