The effect of 5-HTTLPR and a serotonergic multi-marker score on amygdala,prefrontal and anterior cingulate cortex reactivity and habituation in a large,healthy fMRI cohort

Major depressive disorder (MDD) is characterized by low mood for at least two weeks. Impaired emotion regulation has been suggested to be the consequence of dysfunctional serotonergic regulation of limbic and prefrontal regions, especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The impact of genetic variation on brain function can be investigated with intermediate phenotypes. A suggested intermediate phenotype of MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other serotonergic genes have been associated with amygdala and prefrontal function during emotion recognition. Previously, it has been suggested that habituation is a more reliable index of emotion recognition than functional activation. We examined the relationship of genes involved in serotonergic signaling with amygdala as well as prefrontal functional activation and habituation during an emotion recognition task in 171 healthy subjects. While effects of 5-HTTLPR and of a serotonergic multi-marker score (5-HTTLPR, TPH1(rs1800532), TPH2(rs4570625), HTR1A(rs6295) and HTR2A(rs6311)) on amygdala activation did not withstand correction for multiple regions of interest, we observed a strong correlation of the multi-marker score and habituation in the amygdala, DLPFC, and ACC. We replicated a well-studied intermediate phenotype for association with 5-HTTLPR and provided additional evidence for polygenic involvement. Furthermore, we showed that task habituation may be influenced by genetic variation in serotonergic signaling, particularly by a serotonergic multi-marker score. We provided preliminary evidence that PFC activation is an important intermediate phenotype of MDD. Future studies are needed to corroborate the results in larger samples.     

Wie häufig werden Patienten mit depressiven Störungen in der hausärztlichen Praxis erkannt?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Hausärzte sind als Primärversorger für Patienten mit depressiven Störungen entscheidende Weichensteller...     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.     

Modified types of orbital exenteration,survival, and reconstruction

Graefe's Archive for Clinical and Experimental Ophthalmology - This study aims to analyse the various modifications of orbital exenteration. Patients undergoing orbital exenteration from March...     

Cognitive Impairment in Cocaine Users is Drug-Induced but Partially Reversible: Evidence from a Longitudinal Study

Cocaine users consistently display cognitive impairments. However, it is still unknown whether these impairments are cocaine-induced and if they are reversible. Therefore, we examined the relation between changing intensity of cocaine use and the development of cognitive functioning within 1 year. The present data were collected as part of the longitudinal Zurich Cocaine Cognition Study (ZuCo²St). Forty-eight psychostimulant-naive controls and 57 cocaine users (19 with increased, 19 with decreased, and 19 with unchanged cocaine use) were eligible for analysis. At baseline and after a 1-year follow-up, cognitive performance was measured by a global cognitive index and four neuropsychological domains (attention, working memory, declarative memory, and executive functions), calculated from 13 parameters of a broad neuropsychological test battery. Intensity of cocaine use was objectively determined by quantitative 6-month hair toxicology at both test sessions. Substantially increased cocaine use within 1 year (mean +297%) was associated with reduced cognitive performance primarily in working memory. By contrast, decreased cocaine use (−72%) was linked to small cognitive improvements in all four domains. Importantly, users who ceased taking cocaine seemed to recover completely, attaining a cognitive performance level similar to that of the control group. However, recovery of working memory was correlated with age of onset of cocaine use—early-onset users showed hampered recovery. These longitudinal data suggest that cognitive impairment might be partially cocaine-induced but also reversible within 1 year, at least after moderate exposure. The reversibility indicates that neuroplastic adaptations underlie cognitive changes in cocaine users, which are potentially modifiable in psychotherapeutical or pharmacological interventions.     

Cocaine use in Europe - a multi-centre study. Methodology and prevalence estimates

An increase in the use of cocaine and crack in several parts of Europe has raised the question whether this trend is similar to that of the USA in the 1980s. However, research in the field of cocaine use in Europe has been only sporadic. Therefore, a European multi-centre and multi-modal project was designed to study specific aspects of cocaine and crack use in Europe, in order to develop guidelines for public health strategies. Data on prevalence rates were analysed for the general population and for specific subgroups. Despite large differences between countries in the prevalence of cocaine use in the general population, most countries show an increase in the last few years. The highest rate with a lifetime prevalence of 5.2% was found for the United Kingdom, although with a plateau effect around the year 2000. With regard to specific subgroups, three groups seem to show a higher prevalence than the general population: (1) youth, especially in the party scene; (2) socially marginalized groups, such as homeless and prostitutes or those found in open drug scenes; (3) opiate-dependent patients in maintenance treatment who additionally use cocaine. Specific strategies need to be developed to address problematic cocaine use in these subgroups.