23 research outputs found
Endogenous opioid peptides and epilepsy
In recent years a large number of pept:ides, many of which were
originall.y characterized in non-neural tissues, have been reported to be
present in the central nervous system ( CNS) . The detection of these
peptides within the CNS has raised many questions regarding their source
and mechanism of action.
In view of the accumulating information, it seems that the function of the
classical neurotransmitters in the CNS would be better clarified by
elucidating the role of the brain neuropeptides.
The classification of the major categories of the main peptides, as listed
below, is a some what arbitrary one as it is based on the first
localization of a given peptide, while the opioid peptide family is given
separately. For many of the peptides described in brain, their major
functional role is still unknown. However, even before the major
discoveries in the past decade, the opiates were known to possess selective
and unique pharmacological properties. It was well known that opiates were
effective in the treatment of pain and were useful as cough suppressants.
They are also known to depress respiration and blood pressure and to exert
an effect on behaviour, like euphoria, sedation and depression. The
diversity/complexity of their properties suggests that like the
catecholamines, endogenous opioids may have a basic, multisystem regulation
essential to the maintenance of homeostasis and to the survival of the
organism.
In the last years we have tried to reveal one of these petidergic secrets
and focussed our attention on the opioid pe~ides, more specifically in
relation to the excitatory phenomena which they might induce after systemic
or intraventricular administratio
Collaborative Mental Health Care Versus Care as Usual in a Primary Care Setting: A Randomized Controlled Trial
De samenhang tussen somatische en psychische (dys)functie
Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia
Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 Γ 10β5 and c.2702T > G [p.V901G], MAF 2.51 Γ 10β3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05β13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 Γ 10β8), viability (P = 8.9 Γ 10β7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 Γ 10β4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 Γ 10β5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia
Tryptophan Depletion Affects Heart Rate Variability and Impulsivity in Remitted Depressed Patients with a History of Suicidal Ideation
Cardiale disfunctie en ritmestoornisse
Serum BDNF Concentrations Show Strong Seasonal Variation and Correlations with the Amount of Ambient Sunlight
Contains fulltext :
109494.pdf (publisher's version ) (Open Access)Earlier findings show seasonality in processes and behaviors such as brain plasticity and depression that in part are regulated by Brain-Derived Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n's >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ss) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ss = -0.17, P<.0001). Effect sizes [Cohen's d] ranged from 0.27 to 0.66 for monthly significant differences. We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations (Pearson's correlation coefficients ranged: 0.05-0.18) and this could partly explain the observed monthly variation. These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression. Finally, the findings reported here should be taken into account when designing and interpreting studies on BDNF
Sodium valproate in the treatment of aggressive behavior in patients with dementia--a randomized placebo controlled clinical trial
OBJECTIVES: The efficacy and tolerability of sodium valproate 2 x 240 mg compared to placebo were investigated in aggressive behavior in dementia. DESIGN: A randomized, placebo controlled, double-blind cross-over design. The trial included a baseline period (one week); a placebo period (three weeks); a wash-out period with placebo (one week); and a treatment period with sodium valproate (three weeks). SETTING: A psychogeriatric short-stay ward at a psychiatric teaching hospital. PARTICIPANTS: Demented patients who met Patel's criteria for aggressive behavior and had a score of > or =3 on at least one of the items of the Social Dysfunction and Aggression scale-9 (SDAS-9). INTERVENTION: A fixed dose of sodium valproate 2 x 6 ml of a 40 mg/ml suspension (daily defined dose of 480 mg) was compared to placebo. MEASUREMENTS: Primary outcome variables were changes of the score of SDAS-9 and Clinical Global Impression scale (CGI) performed at the last week of each treatment period. RESULTS: Data of 42 patients (F=25 and M=17; age 80.4+/-6.8 years) were analyzed. Treatment with sodium valproate showed no differences compared to placebo on aggressive behavior. The mean plasma level of sodium valproate was 40.9+/-10.8 microg/ml. Regression analysis showed a trend for improvement between the plasma levels of sodium valproate and the SDAS-9 and the CGI scores. Adverse events were not related to the plasma levels of sodium valproate. Secondary outcome measurements showed significant improvement on restless, melancholic and anxious behavior; a trend for improvement was found on suspicious and dependent behavior. Possible limitations of this study are the low dose of sodium valproate, the relatively short treatment period (three weeks), and the absence of statistical corrections for multiple comparisons. CONCLUSION: This study showed no effect of sodium valproate 2 x 240 mg over placebo on aggressive behavior in dementi