Fabien Gierski

Executive functions in adult offspring of alcohol-dependent probands: toward a cognitive endophenotype?

BACKGROUND Executive function (EF) impairment in alcohol dependence (AD) has been related to the toxic effects of alcohol on frontal lobes. However, this impairment could be partially present before the onset of the disease and might constitute a vulnerability factor. Although a considerable body of research has investigated executive functioning among AD patients, much less attention has been directed toward high-risk individuals. Most studies were carried out among children or adolescents, and very few were conducted in adults. The aim of this study was to examine EF in a group of adult offspring of AD individuals. METHODS One hundred and fifty-five nonalcoholic adults with (family history positive [FHP]) or without (family history negative [FHN]) family history of AD were included in the study. All participants were screened for past and current psychiatric diagnoses, and alcohol, tobacco, and other substance use. They were compared on self-rated impulsiveness using the Barratt Impulsiveness Scale-11 (BIS-11) and EF using a neuropsychological test battery. RESULTS Group comparison revealed that FHP participants had significantly higher BIS-11 scores than the FHN participants, while neuropsychological examination revealed lower EF scores for FHP participants. Hierarchical regression analysis revealed that the number of AD family members was a predictor of EF results, whereas impulsiveness was not. CONCLUSIONS Nonalcoholic adult offspring of AD individuals showed increased impulsiveness and decreased EF, suggesting weakness of 2 distinct neurobehavioral decision systems. Findings support evidence that EF weaknesses may qualify as a suitable endophenotype candidate for AD.

Surgical treatment by electrical stimulation of the auditory cortex for intractable tinnitus

Tinnitus is a public health issue in France. Around 1% of the population is affected and 30,000 people are handicapped in their daily life. The treatments available for disabling tinnitus have until now been disappointing. We are reporting on the surgical treatment by electrical stimulation of the auditory cortex of a female patient affected by disabling tinnitus that resisted classical treatments. The tinnitus appeared suddenly 10 years ago after a left ear tympanoplasty. The acouphenometry measures revealed a bilateral tinnitus, predominant on the right side, constant, with high frequency (6000 Hz). Transcranial magnetic stimulation (TMS) was performed at first with several supraliminal and infraliminal protocols. This showed promising results. Anatomic and functional magnetic resonance imaging (fMRI) of the auditory cortex before and after repetitive TMS (rTMS) demonstrated a modification of the cortical activity and where the ideal location for a cortical electrode might be, to straddle primary and secondary auditory cortex. After these investigations, two quadra polar electrodes (Resume, Medtronic Ltd, Hertfordshire, UK), connected to a stimulating device implanted under the skin (Synergy, Medtronic Ltd), were extradurally implanted. The surgical procedure was similar to the one performed for analgesic cortical stimulation. No surgical complications were reported. The activation of the stimulator provided a reduction of 65% of the tinnitus impact, with a persistent effect on the right side. The feasibility of the cortical stimulation in symptomatic treatment of tinnitus was proven by this preparatory work. The middle- and long-term therapeutic effects remain to be evaluated.

Altered white matter integrity in whole brain and segments of corpus callosum, in young social drinkers with binge drinking pattern.

Binge drinking is associated with impaired cognitive functioning, but the relationship of cognitive impairments and white matter integrity is less known. We used diffusion tensor imaging (DTI) to investigate the relationships of binge drinking, whole brain white matter integrity and cognitive performance during young adulthood (18 to 25 years), a period of continued brain development in two sessions 1 year apart. Binge drinkers (n = 20) and non‐binge drinkers (n = 20) underwent DTI and completed measures of spatial working memory and motor impulsivity. Fractional anisotropy (FA), a measure derived from DTI, was estimated from whole brain and from five segments of the corpus callosum (CC): prefrontal, premotor/supplementary motor, motor, (SMA) sensory and parietal/temporal/occipital (PTO). FA was lower for binge than for non‐binge men but not women at Session 1 and 2 for all measurements except for FA in the motor segment, which was significantly increased from Session 1 to Session 2. Lower FA in the prefrontal and PTO CC segments was associated with higher binge score, whereas lower FA in all five segments was associated with greater drug use in men and worse spatial working memory both in men and women. These findings extend the literature by showing that in early adulthood, binge drinking and drug use are linked with degradations in neural white matter and that compromised white matter at this period of brain development is linked with impaired cognitive functioning.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and its implication in executive functions in adult offspring of alcohol-dependent probands

Impairment of executive functions (EFs) mediated by the prefrontal lobe is regarded as a cognitive endophenotype of alcohol dependence, being observed both in probands and in healthy offspring. Given its impact on the anatomy of the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may well be involved in this specific endophenotype. Forty-six healthy adult children of alcoholics (HACA) and 82 healthy controls (HC) took part in the study. All the participants were assessed with the Diagnostic Interview for Genetic Studies, and their family histories of alcohol and substance use were assessed with the Family Informant Schedule and Criteria. The Trail Making Test, Arithmetic Switching Task, Stroop Color-Word Test and Wisconsin Card Sorting Test were administered to assess EFs. An overall executive factor score was calculated using factorial analyses. Genotyping of the BDNF Val66Met polymorphism was performed using the TaqMan® allelic discrimination assay. HACA had significantly lower EFs performance than HC. Genetic analysis showed that BDNF genotype distributions were in Hardy-Weinberg equilibrium in the HACA and HC. Genotype and allele distributions did not differ significantly between the two groups. Participants with the Met allele performed significantly more poorly than participants with the Val allele, and a group by allele interaction was observed, the BDNF Met allele being associated with a poorer executive factor score in the HACA group. These results suggest that the BDNF Val66Met polymorphism may contribute to alcohol dependence vulnerability via lower EFs performance.

Linear association between social anxiety symptoms and neural activations to angry faces: from subclinical to clinical levels

Social anxiety disorder (SAD), which is characterized by the fear of being rejected and negatively evaluated, involves altered brain activation during the processing of negative emotions in a social context. Although associated temperament traits, such as shyness or behavioral inhibition, have been studied, there is still insufficient knowledge to support the dimensional approach, which assumes a continuum from subclinical to clinical levels of social anxiety symptoms. This study used functional magnetic resonance imaging (fMRI) to examine the neural bases of individual differences in social anxiety. Our sample included participants with both healthy/subclinical as well as clinical levels of social anxiety. Forty-six participants with a wide range of social anxiety levels performed a gender decision task with emotional facial expressions during fMRI scanning. Activation in the left anterior insula and right lateral prefrontal cortex in response to angry faces was positively correlated with the level of social anxiety in a regression analysis. The results substantiate, with a dimensional approach, those obtained in previous studies that involved SAD patients or healthy and subclinical participants. It may help to refine further therapeutic strategies based on markers of social anxiety.

Differential bilateral involvement of the parietal gyrus during predicative metaphor processing: an auditory fMRI study.

Despite the growing literature on figurative language processing, there is still debate as to which cognitive processes and neural bases are involved. Furthermore, most studies have focused on nominal metaphor processing without any context, and very few have used auditory presentation. We therefore investigated the neural bases of the comprehension of predicative metaphors presented in a brief context, in an auditory, ecological way. The comprehension of their literal counterparts served as a control condition. We also investigated the link between working memory and verbal skills and regional activation. Comparisons of metaphorical and literal conditions revealed bilateral activation of parietal areas including the left angular (lAG) and right inferior parietal gyri (rIPG) and right precuneus. Only verbal skills were associated with lAG (but not rIPG) activation. These results indicated that predicative metaphor comprehension share common activations with other metaphors. Furthermore, individual verbal skills could have an impact on figurative language processing.

Association study between reward dependence and a functional BDNF polymorphism in adult women offspring of alcohol-dependent probands.

Thirty-five healthy adult women offspring of alcohol-dependent probands (AWOA) were compared with 63 healthy controls to test whether personality dimensions on the Temperament and Character Inventory questionnaire were associated with the brain-derived neurotrophic factor Val66Met polymorphism in offspring. We found a significantly lower reward dependence score in AWOA compared with the controls. The brain-derived neurotrophic factor Val66Met polymorphism may be involved in this difference as the lower reward dependence score was found only in AWOA carrying the Val allele.

Remediation of context-processing deficits in schizophrenia: preliminary data with ambiguous sentences

Background Processing of contextual information is essential for the establishment of good interpersonal relations and communicational interactions. Nevertheless, it is known that schizophrenic patients present impairments in the processing of contextual information. The aim of this study is to explore the influence of the remediation of context processing in schizophrenic patients. Methods Thirty-one schizophrenic patients and 28 matched healthy participants were included in this study. All participants were assessed on verbal knowledge (Mill-Hill test) and depression intensity (Beck Depression Scale 21 items). Schizophrenic patients were also assessed on thought, language, and communication disorders (Thought, Language and Communication scale). All participants completed a disambiguation task with two different levels of contextualization (high or low context) and a context-processing remediation task containing social scenarios that included ambiguous words and were presented with two different types of instruction: with or without context explanation. Results For the disambiguation task, results showed no effect of group, but a main effect of context, with better performances in the high-context than the low-context condition. For the context-processing remediation task, results showed a main effect of group: The performance of schizophrenic patients who had received explanations differed from that both of healthy participants and of schizophrenic patients who had not received explanations. Conclusion This study revealed that for all participants, the structuring of context had a positive effect on the contextual integration of ambiguous words. Concerning the remediation task, explanations about the strategies that could be used to take context into account improved the schizophrenic patients’ performances. This allows us to consider new methods of remediation that could improve social interaction in schizophrenia.

Impact of switching or initiating antipsychotic treatment on body weight during a 6-month follow-up in a cohort of patients with schizophrenia.

Objective Although weight gain is one of the most widely studied adverse effects of second-generation antipsychotics, only relatively few studies have specifically evaluated the long-term effect of switching antipsychotic medication on body weight. We aimed to evaluate the impact of switching antipsychotics on body mass index (BMI) during a 6-month follow-up period in a large cohort of patients with schizophrenia. Method Data came from a 6-month prospective naturalistic survey in 6007 patients with schizophrenia. Results We prospectively studied the effect on BMI of initiating or switching antipsychotic medication after 6 months of treatment among 3801 patients with schizophrenia in a real-life setting. Patients who were being treated with clozapine or olanzapine at baseline were more likely to experience a decrease in BMI during the follow-up period than the patients who were being treated with a conventional antipsychotic (odds ratio, 2.25 and 1.68, respectively). Patients treated with aripiprazole and, to a lesser extent, those treated with risperidone were more likely to experience a decrease in BMI during follow-up than patients treated with conventional antipsychotics (odds ratio, 2.96 and 2.06, respectively). Conclusions Our findings suggest that switching antipsychotics could be an effective strategy for reducing or preventing weight gain.

Depression, anxiety and personality dimensions in female first-degree relatives of alcohol-dependent probands.

A total of 136 with or without first-degree relatives with alcohol dependence were compared according to lifetime prevalence of psychiatric disorders and personality dimensions. Family history positive women showed significant higher prevalence rates of depression and agoraphobia, and exhibited lower scores on Reward Dependence, Self-Directedness and Cooperativeness dimensions.