Stéphanie Miot

OPA1 R445H mutation in optic atrophy associated with sensorineural deafness

The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network. Ann Neurol 2005

VGLUT3 (Vesicular Glutamate Transporter Type 3) Contribution to the Regulation of Serotonergic Transmission and Anxiety

Three different subtypes of H+-dependent carriers (named VGLUT1–3) concentrate glutamate into synaptic vesicles before its exocytotic release. Neurons using other neurotransmitter than glutamate (such as cholinergic striatal interneurons and 5-HT neurons) express VGLUT3. It was recently reported that VGLUT3 increases acetylcholine vesicular filling, thereby, stimulating cholinergic transmission. This new regulatory mechanism is herein designated as vesicular-filling synergy (or vesicular synergy). In the present report, we found that deletion of VGLUT3 increased several anxiety-related behaviors in adult and in newborn mice as early as 8 d after birth. This precocious involvement of a vesicular glutamate transporter in anxiety led us to examine the underlying functional implications of VGLUT3 in 5-HT neurons. On one hand, VGLUT3 deletion caused a significant decrease of 5-HT1A-mediated neurotransmission in raphe nuclei. On the other hand, VGLUT3 positively modulated 5-HT transmission of a specific subset of 5-HT terminals from the hippocampus and the cerebral cortex. VGLUT3- and VMAT2-positive serotonergic fibers show little or no 5-HT reuptake transporter. These results unravel the existence of a novel subset of 5-HT terminals in limbic areas that might play a crucial role in anxiety-like behaviors. In summary, VGLUT3 accelerates 5-HT transmission at the level of specific 5-HT terminals and can exert an inhibitory control at the raphe level. Furthermore, our results suggest that the loss of VGLUT3 expression leads to anxiety-associated behaviors and should be considered as a potential new target for the treatment of this disorder.

The vesicular glutamate transporter VGLUT3 contributes to protection against neonatal hypoxic stress

•  Hypoxic stress is an important cause of morbidity and mortality in neonates. •  We examined the role of VGLUT3, an atypical transporter of glutamate present in serotonergic neurons involved in breathing and heat production, in the response to hypoxia. •  The respiratory responses to chemical stimuli and the turnover of serotonin in the brainstem were impaired in newborn mice lacking VGLUT3. •  Under cold conditions, metabolic rate, body temperature, baseline breathing and the ventilatory response to hypoxia were disrupted. •  Thus, VGLUT3 expression is required for optimal response to hypoxic stress in neonates.

Links between sensory processing, adaptive behaviours, and attention in children with autism spectrum disorder: A systematic review

Atypical sensory processing has been described in autism spectrum disorder. The goal of this systematic review is to investigate the links between sensory processing, adaptive behaviours, and attention skills in children with autism spectrum disorder. The PRISMA guidelines were followed and a search was conducted using electronic databases: Medline, PsychInfo and Eric. Among the 11 studies about sensory processing that were selected, 7 investigated the association with adaptive behaviours and 5 with attention. Atypical sensory processing was reported in 82% to 97% of the participants with ASD, depending on the study. This review found a significant impact of sensory abnormalities on adaptive behaviour. In addition, we found interrelations between sensory processing and attention skills. However, the current literature is too limited to definitively conclude the direction of these interactions and the theories concerning perceptive functioning are conflicting.

Coping strategies of parents of children with autism spectrum disorder: a systematic review

To deal with stress, parents of children with ASD use coping strategies that help to tackle the challenging situations of raising their child. This systematic review examines parental coping strategy’s questionnaires, factors which influence these coping strategies, interactions between these strategies and perceived stress and their impact on parental quality of life. According to PRISMA guidelines, an electronic search was conducted on Medline, PsycInfo and Eric: 156 articles were identified and 11 studies were selected. Many types of self-reported questionnaires were used to assess parental coping strategies. Studies highlighted that parents of a child with ASD used more avoidance strategies and less social support-seeking strategies than those of typical children. Furthermore, problem-focused coping protects parental stress and quality of life, that on the contrary, emotion-focused coping is a risk factor for alteration. Our systematic review illustrates the need to adapt psychoeducational interventions for parents of children with ASD.

Adaptive trajectories and early risk factors in the autism spectrum: A 15-year prospective study: Adaptive trajectories and risk factors in autism

Little is known about long‐term outcomes. We investigate the adaptive trajectories and their risk factors in ASD. Data were obtained from 281 children prospectively followed untill adulthood. The final sample consisted of 106 individuals. Vineland scores were collected at baseline (T1), 3 (T2), 10 (T3), and 15 (T4) years later. A group‐based method was used to identify homogeneous patterns of adaptive skills trajectories. Results show that among the children initially categorized as autistic, 82.6% remained over the ADOS diagnostic threshold, 11.9% converted to atypical autism, and 5.4% fell under the ADOS threshold. Most atypical autism diagnoses were unstable. Most (81.7%) autistic participants had an ID at inclusion. At T1, 59.3% were nonverbal, but only 39% at T4. Most changes occurred between 4 and 8 years of age. Approximately 25% of participants exhibited a “high” growth trajectory, in which progress continues throughout adolescence, and 75% a “low” growth trajectory, characterized by greater autistic symptoms, intellectual disability, and lower language abilities reflected by high CARS scores, low apparent DQ, and speech difficulties, which mostly, but not always, predicted low trajectories. Our findings suggest that the adaptive prognosis of autism is mostly poor in this cohort, biased toward intellectual disability. However, changes in diagnostic, speech, and adaptive status are not uncommon, even for indivduals with low measured intelligence or apparent intellectual disability, and are sometimes difficult to predict. Autism Research 2018, 11: 1455–1467.