The capacity of cognitive tests to detect generalized anxiety disorder (GAD): A pilot study.

Cognitive impairment remains understudied in generalized anxiety disorder (GAD), despite the high prevalence and substantial burden associated with this disorder. We aimed to assess cognitive impairment in patients with GAD and evaluate the ability of cognitive tests to detect this disorder. Because of its high rate of comorbidity, we also examined how other anxiety disorders and current major depressive episodes affected our results. We tested 263 consecutive general practice outpatients. We used the GAD-7 and the Mini International Neuropsychiatric Interview (MINI) to detect anxiety and mood disorders. We assessed cognitive performance with the Stroop test, a facial emotion recognition test, and the trail-making test (TMT). Compared to patients without GAD, patients with GAD were significantly slower to complete the TMT(B-A) and faster to recognize emotions, especially negative ones such as disgust and anger. When controlling for other anxiety disorders and current major depressive episode, GAD retained a significant effect on the TMT(B-A), but not on the emotion recognition test. The TMT(B-A) could detect GAD with good accuracy (area under the curve (AUC) = 0.83, maximal Youden's index = 0.56), which was by no means comparable to the GAD-7 (AUC = 0.97, Youden's index = 0.81). While it is not efficient enough to replace the GAD-7 as a diagnostic tool, the capacity of the TMT(B-A) to detect GAD emphasizes the importance of cognitive flexibility impairment in GAD.

Influence of the human body odor compound HMHA on face perception.

Body odors convey information about the individuals, but the mechanisms are not fully understood yet. As far as human reproduction is concerned, molecules that are produced in sexually dimorphic amounts could be possible chemosignals. 3-hydroxy-3-methylhexanoic acid (HMHA) is one of them-more typical of men. Here, we investigated the possibility that the perception of gender and attractiveness in human faces could be implicitly influenced by this compound. Clearly feminine, ambiguous and clearly masculine faces were primed with an odor of HMHA, a control odor or air. Based on 100-ms face presentation, 40 raters had to identify the face's gender as quickly as possible and provide attractiveness evaluations. 3-hydroxy-3-methylhexanoic acid tended to be perceived as less pleasant and induced lower sniff duration in women compared with men. As to the effects of HMHA on face perception (vs. control conditions), we found that gender identification and the associated response time were unaffected by HMHA. Attractiveness of the faces, however, increased in presence of HMHA, but not in a sex-specific manner and only for unattractive faces with ambiguous gender. In sum, this study found no evidence in favor of a possible role of this sexually dimorphic compound in intrasexual competition nor in intersexual attraction.

Early effects predict trajectories of response to esketamine in treatment-resistant depression.

BACKGROUND: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability. METHODS: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response. RESULTS: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %. LIMITATIONS: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings. CONCLUSIONS: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response.

BDNF CpG methylation and serum levels covary during alcohol withdrawal in patients with alcohol use disorder: A pilot study.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) levels vary in various conditions including alcohol use disorder (AUD). We aimed to identify drivers of these variations. METHODS: Twelve patients with AUD were assessed at hospitalisation for alcohol withdrawal and four months later. We looked for associations between the change in serum BDNF levels and (1) length of abstinence, (2) anxiety (Hamilton Anxiety Scale) and depression (Beck-Depression Inventory), (3) one functional BDNF genotype (rs6265) and (4) methylation levels of 12 CpG sites within the BDNF gene (located in exons I, IV and IX). RESULTS: While abstinence remained, serum BDNF level increased. This increase correlated with the variation of methylation levels of the BDNF gene, and more specifically of exon I. We found no significant effect of length of abstinence, rs6265, depression or anxiety on serum BDNF level. CONCLUSIONS: Epigenetic regulation of the BDNF gene may be involved in variations of BDNF blood level associated with alcohol abstinence.

Associated and intermediate factors between genetic variants of the dopaminergic D2 receptor gene and harmful alcohol use in young adults.

Dopamine receptor D2 (DRD2) and ankyrin repeat and kinase domain-containing protein 1 (ANKK1) genes have received considerable attention for their involvement in alcohol use disorder (AUD), but many questions remain on their exact role. We conducted a population-based case-control and genetic association study in a large sample of young adults. Our aim was to assess the association between DRD2 and ANKK1 single nucleotide polymorphisms (SNPs) and harmful alcohol use, disentangling associated and possible intermediate factors. A total of 1841 college students from the French region Champagne-Ardennes, aged between 18 and 21 years and who reported at least one lifetime alcohol consumption, were included in this study. Allele frequencies were analysed according to harmful alcohol use (assessed through the Alcohol Use Disorder Identification Test [AUDIT] questionnaire). Different substance use disorders, including nicotine and cannabis dependences, were also assessed through questionnaires, as was a list of potential associated factors (e.g., major depressive episode, conduct disorder, attention-deficit/hyperactivity disorder [ADHD], school failure, sugar consumption, sexual trauma, parents' use of alcohol, tobacco or cannabis). We found that DRD2 rs1800498 was associated with harmful alcohol use. Many factors were detected, but a global path analysis revealed that DRD2 rs1800498 had a significant direct effect on harmful alcohol use and that early age at first alcohol consumption and depressive symptoms moderated this effect. This study suggests an interplay between harmful alcohol use, DRD2 genotypes and other risk factors that, with a full understanding, could be useful for preventive purposes.

Olfactory bulb volume and cortical thickness evolve during sommelier training.

Brain plasticity is essential for experts to acquire the abilities they need. Sommeliers are olfaction experts who display differences in olfactory regions in the brain that correlate with greater olfactory abilities. While most studies on this topic are cross-sectional, we used a longitudinal design and invited 17 sommelier students at the start and end of their training then to compare them to 17 control students to study the effects of training-related brain plasticity. After a year and a half, 5 sommelier students and 4 control students dropped out, leading to 12 sommelier students versus 13 controls. We used magnetic resonance imaging to measure cortical thickness and olfactory bulb volume, as this structure plays a crucial role in olfactory processing. We used the Sniffin' Sticks test to evaluate olfactory performance. During training, olfactory bulb volume increased in sommelier students while there was no significant change in the control group. We also observed that thickness of right entorhinal cortex increased, and cortical thickness decreased in other cerebral regions. Our olfactory tests did not reveal any significant changes in sommelier students. In conclusion, this is the first longitudinal study to report an increase in olfactory bulb volume in olfaction experts in line with the notion of effects of ecological training-related brain plasticity. The mixed results about cortical thickness might be explained by a "overproduction-pruning" model of brain plasticity, according to which the effects of training-related plasticity are non-linear and simultaneously involve different processes.

Pupil psychosensory reflex in response to own and standardised silhouettes in patients with anorexia nervosa.

OBJECTIVE: This study aimed to assess the physiological response of patients with anorexia nervosa (AN) to different types of silhouettes using pupillometry. METHODS: We measured the pupil psychosensory reflex (PSR) of 42 patients with AN and 35 healthy controls in response to standardised body silhouettes and to pictures of their own silhouettes digitally modified to represent different body mass indices (BMI). Perceptual distortion and body dissatisfaction were assessed using Anamorphic Micro Software©. Twenty-three of the recruited patients were tested up to four times during an inpatient treatment programme to assess the impact of weight gain. RESULTS: PSR correlated with the subjective rating of emotional arousal in controls but not in patients. Own silhouettes and standardised silhouettes triggered a different pupil response both in patients with AN and in controls. With pictures of their own silhouettes, pupil response to underweight stimuli differed from pupil response to normal weight or overweight stimuli in both groups. Weight gain was associated with an increase in PSR, an improvement of ideal BMI and a decrease of body dissatisfaction, but no change in perceptual distortion. CONCLUSION: Our findings support the idea that pupillometry could be a useful tool to assess the physiological state of patients with AN.

Influence of gender and culture on the perception of acidic compounds of human body odor.

There is increasing evidence that human body odor is involved in interpersonal communication. However, among the wide variety of substances excreted by the human body that might act as chemosignals, much attention has been granted to androstenes to the detriment of other categories. Here, we focused on the acidic fraction of human body odor. We investigated men and women's perceptual descriptions and detection thresholds of the sexually dimorphic (male) compound 3-hydroxy-3-methylhexanoic acid (HMHA) in two contrasted cultures, France and Madagascar. Perceptual responses to HMHA in both countries were very similar. HMHA proved to be more typical of body odor than another chemically-related major compound of human body odor 3MHA (3-methylhex-2-enoic acid also known as 3M2H). A significant portion of the samples studied (between 8 and 19%) was likely to be anosmic to HMHA (and to 3MHA: 25%). Although differences would be expected between men and women's perceptual responses to HMHA, based on the assumption that this compound would have a function in human partner choice, no sex differences were found for any of the perceptual variables. However, in Malagasy women, perceived intensity of HMHA was higher in participants who were in the fertile phase of the menstrual cycle. Whether HMHA is relevant in the perception of a potential partner thus requires further explorations, with more implicit approaches for example and/or by investigating the repercussions of HMHA specific anosmia on interpersonal relationships.

Smell training improves olfactory function and alters brain structure.

Training and repeated exposure to odorants leads to enhanced olfactory sensitivity. So far, the efficacy of intensive olfactory training on olfactory function in a healthy population and its underlying neurobiological basis remain poorly known. This study investigated the effects of a 6-week intensive and well-controlled olfactory training on olfactory function and brain structure/neuroplasticity. Thirty-six healthy young individuals were recruited and randomly distributed in three groups: (1) 12 participants underwent daily intensive olfactory training of at least 20 min that included an (a) odor intensity classification task, an (b) odor quality classification task and an (c) target odor detection task, (2) 12 participants underwent an equivalent visual control training, and (3) 12 control individuals did not participate in any training. Before and after the training period, all participants performed a series of olfactory tests and those from groups 1 and 2 underwent structural magnetic resonance (MR) imaging, from which we obtained measures such as cortical thickness and tissue density. Participants improved in the respectively trained tasks throughout the 6-weeks training period. Those who underwent olfactory training improved general olfactory function compared to control participants, especially in odor identification, thus showing intramodal transfer. Further, MR imaging analysis revealed that olfactory training led to increased cortical thickness in the right inferior frontal gyrus, the bilateral fusiform gyrus and the right entorhinal cortex. This research shows that intensive olfactory training can generally improve olfactory function and that this improvement is associated with changes in the structure of olfactory processing areas of the brain.

Can the Identification of Odorants Within a Mixture Be Trained?

Identifying odors within mixtures is a difficult task: humans are able to recognize only up to 4 odors within a mixture. We wanted to test the effects of olfactory training on this ability. We used 7 odorants to create 35 olfactory stimuli of 1, 2, 3, 4, or 5 odorants. The task consisted of identifying the odorants present within the mixture. We trained novices on this task for 5 days: they came to the laboratory to perform the task once a day before coming back for the final testing. Then, we compared them to sommeliers, thus olfaction experts, and untrained novices. Results showed that sommeliers outperformed the other groups with mixtures of up to 4 odorants but not with mixtures of 5 odorants. The short olfactory training allowed trained participants to perform as well as sommeliers when it came to identifying single odorants but was not enough to improve their performance when stimuli were mixtures of 2 or more odorants. This study supports the idea that the number of odors we can recognize within a mixture is limited but suggests training can improve the performance: a short olfactory training is enough to enhance the ability to identify single odorants, whereas expertise refines identification ability of mixtures of up to 4 odorants.

Early-blind Individuals Show Impaired Performance in Wine Odor Categorization.

Blind individuals display superior sensory abilities in other modalities, yet results remain contradictory regarding their performance on olfactory tasks. Using complex ecological olfactory tasks, we evaluated the impact of blindness on olfactory performance. We tested 12 early-blind individuals (M = 49, SD = 13.09) and 12 sighted controls (M = 49, SD = 14.31) who were all blindfolded. Based solely on the wine odors, participants evaluated 24 pairs of wine and determined if both samples belonged to the same category (red wine, white wine, or rosé wine) or not (odor categorization), and if so, whether they were identical or not (odor differentiation). Then, they had to classify 15 different wines (5 red, 5 white and 5 rosé) into red, white, and rosé wines (odor classification). Blind individuals (d': M = 1.3, SD = 1.2) presented lower scores compared to sighted controls (M = 2.2 SD = 0.8; p < .05) in the odor categorization task, but no group difference was observed for the other tasks. For all participants, red wine odors were the easiest to classify (1.8 ±â€¯1.0), followed by white wine odors (0.5 ±â€¯0.6) and finally rosé wine odors (blind and sighted; F[2; 44] = 11.9, p < .001). In summary, early-blind individuals had a harder time to categorize wine odors. This could be explained by a different construction of internal reference categories for wine in early-blind individuals. Finally, this research is in line with the notion of the absence of higher olfactory sensitivity in blind individuals.

Nostril Differences in the Olfactory Performance in Health and Disease.

In the past few decades, several olfactory tests have been developed to assess olfactory performance and detect disorders. Contrary to other sensory systems, both nostrils are usually tested together; we hypothesized that monorhinal testing may reveal side differences in sensitivity which may be useful for the diagnosis of olfactory dysfunction. Using the "Sniffin' Sticks" test, we assessed olfactory function of 458 participants (278 healthy controls, 180 hyposmic patients), one nostril after the other, with 3 different tasks. For each participant and each task, we compared the scores obtained with both nostrils, and defined the best and worst nostrils. Thus we were able to establish normative data and to define cut-off values. Our results suggest that scores obtained with the worst nostril are the most efficient in detecting an olfactory disorder. This supports the importance of monorhinal testing, as it can allow an earlier and more accurate diagnosis than birhinal testing. This may be especially useful in the context of early detection of neurodegenerative diseases.