Behavior Problems and Social Competence in Fragile X Syndrome: A Systematic Review

Cregenzán-Royo, Olga; Gasca, Carme Brun i; Fornieles, Albert

doi:10.3390/genes13020280

Cited by 19 publications

(23 citation statements)

References 191 publications

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“…Social deficits are a common feature of both ASD and FXS 56 . In our FXS groups, FXS mice exhibited an increased total time spent in physical contact with a cage mate during their initial adjustment to the new environment, but this behavior normalized to levels like controls in later stages.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Group Behavior of Fragile X Mice in Unfamiliar Environments

Giua,

Strauss,

Lassalle

et al. 2023

Preprint

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Fragile X Syndrome (FXS) stands out as a prominent cause of inherited intellectual disability and a prevalent disorder closely linked to autism. FXS is characterized by substantial alterations in social behavior, encompassing social withdrawal, avoidance of eye contact, heightened social anxiety, increased arousal levels, language deficits, and challenges in regulating emotions. Conventional behavioral assessments primarily focus on short-term interactions within controlled settings. In this study, we conducted a comprehensive examination of the adaptive group behavior of FXS mice over a three-day period, without introducing experimental interventions or task-based evaluations. The data unveiled intricate behavioral anomalies, with the most significant changes manifesting during the initial adaptation to unfamiliar environments. Notably, certain behaviors exhibited a gradual return to typical patterns over time. This dynamic FXS phenotype exhibited heightened activity, featuring increased exploration, amplified social interest, and an unconventional approach to social interactions characterized by a higher frequency of shorter engagements. These findings contribute to the growing understanding of social behavior in individuals with FXS and underscore the significance of comprehending their adaptive responses in various environmental contexts.

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Section: Discussionmentioning

confidence: 99%

Adaptive Group Behavior of Fragile X Mice in Unfamiliar Environments

Giua,

Strauss,

Lassalle

et al. 2023

Preprint

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“…FD44-treated FXS mice showed the low level of aggressiveness similar to their WT counterparts (Figure 3D). As in other syndromic forms of autism, social behavior deficits are common in FXS (Cregenzán-Royo et al, 2022). Among all the tests available to study socialization in mice, the one that evaluates the greatest number of aspects of socialization, including recognition, motivation, and memory, is the one in which the mouse is confronted with a familiar or an unknown conspecific.…”

Section: Figurementioning

confidence: 99%

The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes

Cogram

Fernández-Beltrán²,

Casarejos³

et al. 2022

Front. Neurosci.

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Fragile X syndrome (FXS) is caused by the loss of function of Fragile X mental retardation protein (FMRP). FXS is one of the leading monogenic causes of intellectual disability (ID) and autism. Although it is caused by the failure of a single gene, FMRP that functions as an RNA binding protein affects a large number of genes secondarily. All these genes represent hundreds of potential targets and different mechanisms that account for multiple pathological features, thereby hampering the search for effective treatments. In this scenario, it seems desirable to reorient therapies toward more general approaches. Neuronal calcium sensor 1 (NCS-1), through its interaction with the guanine-exchange factor Ric8a, regulates the number of synapses and the probability of the release of a neurotransmitter, the two neuronal features that are altered in FXS and other neurodevelopmental disorders. Inhibitors of the NCS-1/Ric8a complex have been shown to be effective in restoring abnormally high synapse numbers as well as improving associative learning in FMRP mutant flies. Here, we demonstrate that phenothiazine FD44, an NCS-1/Ric8a inhibitor, has strong inhibition ability in situ and sufficient bioavailability in the mouse brain. More importantly, administration of FD44 to two different FXS mouse models restores well-known FXS phenotypes, such as hyperactivity, associative learning, aggressive behavior, stereotype, or impaired social approach. It has been suggested that dopamine (DA) may play a relevant role in the behavior and in neurodevelopmental disorders in general. We have measured DA and its metabolites in different brain regions, finding a higher metabolic rate in the limbic area, which is also restored with FD44 treatment. Therefore, in addition to confirming that the NCS-1/Ric8a complex is an excellent therapeutic target, we demonstrate the rescue effect of its inhibitor on the behavior of cognitive and autistic FXS mice and show DA metabolism as a FXS biochemical disease marker.

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“…www.nature.com/scientificreports/ Moreover, a direct association was also observed between the MMP-9 active form and the ADAMS score. Interestingly, anxiety is among neuropsychiatric FXS associated symptoms 34,[51][52][53] and inhibition of MMP-9 activity by minocycline showed an improvement of anxiety in individuals with FXS 18,54 . No significant association was obtained between MMP-9 plasma active or total forms and ABAS and SCQ scores suggesting that upregulation of MMP-9 active form might rather contribute to FXS-associated aberrant behavior and mood profile than to the cognitive dysfunction.…”

Section: Participants Of Our Cohort)mentioning

confidence: 99%

Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome

Laroui

Galarneau

Abolghasemi

et al. 2022

Sci Rep

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High plasma matrix metalloproteases-9 (MMP-9) levels have been reported in Fragile X Syndrome in a limited number of animal and human studies. Since the results obtained are method-dependent and not directly comparable, the clinical utility of MMP-9 measurement in FXS remains unclear. This study aimed to compare quantitative gel zymography and ELISA and to determine which method better discriminates abnormal MMP-9 levels of individuals with FXS from healthy controls and correlates with the clinical profile. The active and total forms of MMP-9 were quantified respectively, by gel zymography and ELISA in a cohort of FXS (n = 23) and healthy controls (n = 20). The clinical profile was assessed for the FXS group using the Aberrant Behavior Checklist FXS adapted version (ABC-CFX), Adaptive Behavior Assessment System (ABAS), Social Communication Questionnaire (SCQ), and Anxiety Depression and Mood Scale questionnaires. Method comparison showed a disagreement between gel zymography and ELISA with a constant error of − 0.18 [95% CI: − 0.35 to − 0.02] and a proportional error of 2.31 [95% CI: 1.53 to 3.24]. Plasma level of MMP-9 active form was significantly higher in FXS (n = 12) as compared to their age-sex and BMI matched controls (n = 12) (p = 0.039) and correlated with ABC-CFX (rs = 0.60; p = 0.039) and ADAMS (rs = 0.57; p = 0.043) scores. As compared to the plasma total form, the plasma MMP-9 active form better enables the discrimination of individuals with FXS from controls and correlates with the clinical profile. Our results highlight the importance of choosing the appropriate method to quantify plasma MMP-9 in future FXS clinical studies.

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Behavior Problems and Social Competence in Fragile X Syndrome: A Systematic Review

Cited by 19 publications

References 191 publications

Adaptive Group Behavior of Fragile X Mice in Unfamiliar Environments

Adaptive Group Behavior of Fragile X Mice in Unfamiliar Environments

The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes

Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome

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