Trial of Sertraline to Treat Children With Fragile X Syndrome

The Autism Diagnostic Observation Schedule (ADOS-2) assesses and diagnoses autism spectrum disorder. This test was administered at baseline and at the six-month follow-up visit. The choice to administer Module 1 or Module 2 depends on the verbal ability of each subject: Module 1 is used for children who are 31 months and older and/or who do not consistently use phrase speech, and Module 2 is used for children of any age who use phrase speech but are not verbally fluent. The scoring algorithm gives an overall total, which ranges from 0 to 28. The higher the score, the higher the level of autism-related symptoms. The overall total ranges from 0 to 28. On Module 1, for children with few to no words, scores at 11 and above indicate autism spectrum; for children with some words, the cutoff is scores 8 and above. On Module 2, the cutoff for autism spectrum is 7 or above for kids under 5 years, and 8 or above for those 5 years and older.

The Visual Analog Scale will be used to measure the severity of three specific behavioral symptoms chosen by the caregiver(s). Parents mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. The parents choose two key behaviors that they want to target for this trial (e.g., aggression, hyperarousal, anxiety, hyperactivity) and the third target measurement is language/communication. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 6-month visit. The calculated distance in cm between the baseline and 6-month visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

There are several eye tracking measures, each intended to measure different outcomes including social gaze, social reciprocity, and attention. All stimuli are presented on a Tobii T120 binocular eye tracker monitor. The system consists of a high-resolution camera embedded in a 17-inch TFT monitor. Stimuli consist of sixty colored photographs of adult human face (equal numbers of males and females, different races and ethnicities) from the NimStim Face Stimulus Set, each showing a calm, happy, or fearful expression, and sixty scrambled versions of the face images. Shown here are the averaged response times (in seconds) to the presented stimuli, at the baseline visit.

The Preschool Language Scale-fifth edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, Theory of Mind, as well as emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the baseline visit.

The Sensory Processing Measure - Preschool (SPM-P) is a questionnaire that was used to measure specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old. The SPM-P provides norm-referenced standard scores for two higher level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

The Sensory Profile is designed to measure sensory-related difficulties. This measure will be administered to the primary caregiver of each subject to measure the caregiver's sensory ability and its impact on the subject. Of the four subscales scored in the Sensory Profile, the "Sensation Seeking" subscale mean raw scores for the placebo and treatment groups are reported here. This subscale has a raw scores range from 0 to 95, with scores 0-6 indicating that the child is sensation seeking much less than others, 7-19 less than others, 20-47 just like the majority of others, 48-60 more than others, and 61-95 much more than others.

The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups baseline. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean baseline raw scores from the Visual Reception scale. This scale's raw scores range from 0 to 50. The lower the score on this scale, the weaker the child's ability for visual reception; the higher the score, the greater the ability for visual reception.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean raw scores from the Fine Motor scale at the baseline visit. This scale's raw scores range from 0 to 49. The lower the score on this scale, the weaker the child's fine motor skills; the higher the score, the greater the child's fine motor skills.

The Autism Diagnostic Observation Schedule (ADOS-2) assesses and diagnoses autism spectrum disorder. This test was administered at baseline and at the six-month follow-up visit. The choice to administer Module 1 or Module 2 depends on the verbal ability of each subject: Module 1 is used for children who are 31 months and older and/or who do not consistently use phrase speech, and Module 2 is used for children of any age who use phrase speech but are not verbally fluent. The scoring algorithm gives an overall total, which ranges from 0 to 28. The higher the score, the higher the level of autism-related symptoms. The overall total ranges from 0 to 28. On Module 1, for children with few to no words, scores at 11 and above indicate autism spectrum; for children with some words, the cutoff is scores 8 and above. On Module 2, the cutoff for autism spectrum is 7 or above for kids under 5 years, and 8 or above for those 5 years and older.

The Visual Analog Scale will be used to measure the severity of three specific behavioral symptoms chosen by the caregiver(s). Parents mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. The parents choose two key behaviors that they want to target for this trial (e.g., aggression, hyperarousal, anxiety, hyperactivity) and the third target measurement is language/communication. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the 6-month visit. The calculated distance in cm between the baseline and 6-month visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side, at the 6-month visit. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

There are several eye tracking measures, each intended to measure different outcomes including social gaze, social reciprocity, and attention. All stimuli are presented on a Tobii T120 binocular eye tracker monitor. The system consists of a high-resolution camera embedded in a 17-inch TFT monitor. Stimuli consist of sixty colored photographs of adult human face (equal numbers of males and females, different races and ethnicities) from the NimStim Face Stimulus Set, each showing a calm, happy, or fearful expression, and sixty scrambled versions of the face images. Shown here are the averaged response times (in seconds) to the presented stimuli, at the 6-month follow-up visit.

The Preschool Language Scale-fifth edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, Theory of Mind, as well as emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the 6-month follow-up visit.

The Sensory Processing Measure - Preschool (SPM-P) is a questionnaire that was used to measure specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old. The SPM-P provides norm-referenced standard scores for two higher level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). The SPM-P was administered to the caregiver at baseline and again at the 6-month follow-up visit. Reported here is the Social Participation subscale mean raw score from the 6-month visit, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

The Sensory Profile is designed to measure sensory-related difficulties. This measure will be administered to the primary caregiver of each subject to measure the caregiver's sensory ability and its impact on the subject. Of the four subscales scored in the Sensory Profile, the "Sensation Seeking" subscale mean raw scores for the placebo and treatment groups are reported here. This subscale has a raw scores range from 0 to 95, with scores 0-6 indicating that the child is sensation seeking much less than others, 7-19 less than others, 20-47 just like the majority of others, 48-60 more than others, and 61-95 much more than others.

The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at the 6-month visit. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean raw scores from the Visual Reception scale at the 6-month follow-up visit. This scale's raw scores range from 0 to 50. The lower the score on this scale, the weaker the child's ability for visual reception; the higher the score, the greater the ability for visual reception.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean baseline age-equivalent scores from the Visual Reception scale. This scale's age-equivalent scores for each of the five scales are calculated from the raw scores for each scale, using the MSEL Age Equivalents table. Age-equivalent scores for each scale range from 0 to 70 months, with lower scores indicating that a child's visual reception is at a level typical of younger ages, and higher scores indicating that a child's visual reception is at a level typical of older ages.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean age-equivalent scores from the Visual Reception scale at the 6-month follow-up visit. This scale's age-equivalent scores for each of the five scales are calculated from the raw scores for each scale, using the MSEL Age Equivalents table. Age-equivalent scores for each scale range from 0 to 70 months, with lower scores indicating that a child's visual reception is at a level typical of younger ages, and higher scores indicating that a child's visual reception is at a level typical of older ages.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean raw scores from the Fine Motor scale at the 6-month follow-up visit. This scale's raw scores range from 0 to 49. The lower the score on this scale, the weaker the child's fine motor skills; the higher the score, the greater the child's fine motor skills.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean baseline age-equivalent scores from the Fine Motor scale. This scale's age-equivalent scores for each of the five scales are calculated from the raw scores for each scale, using the MSEL Age Equivalents table. Age-equivalent scores for each scale range from 0 to 70 months, with lower scores indicating that a child's fine motor skills are at a level typical of younger ages, and higher scores indicating that a child's fine motor skills are at a level typical of older ages.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the mean age-equivalent scores from the Fine Motor scale at the 6-month follow-up visit. This scale's age-equivalent scores for each of the five scales are calculated from the raw scores for each scale, using the MSEL Age Equivalents table. Age-equivalent scores for each scale range from 0 to 70 months, with lower scores indicating that a child's fine motor skills are at a level typical of younger ages, and higher scores indicating that a child's fine motor skills are at a level typical of older ages.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor (not administered because it was out of age range for most subjects), visual reception, fine motor, receptive language and expressive language. Based on the raw score obtained by the participant in each scale, the scoring software computes T scores for each scale separately. Each scale's T score has a range of 20 to 80, a mean of 50, and a standard deviation of 10, and the lower the T score, the lower the child's cognitive and developmental ability. Cognitive T score sum is the sum of the T scores for each scale administered; since 4 scales were administered, the sum's range is 80 to 320, with lower sums indicating lower overall ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit, and mean baseline cognitive T score sums for the placebo and treatment groups are shown here.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor (not administered because it was out of age range for most subjects), visual reception, fine motor, receptive language and expressive language. Based on the raw score obtained by the participant in each scale, the scoring software computes T scores for each scale separately. Each scale's T score has a range of 20 to 80, a mean of 50, and a standard deviation of 10, and the lower the T score, the lower the child's cognitive and developmental ability. Cognitive T score sum is the sum of the T scores for each scale administered; since 4 scales were administered, the sum's range is 80 to 320, with lower sums indicating lower overall ability. The MSEL was administered at the baseline and 6-month follow-up visits, and mean cognitive T score sums from the 6-month follow-up visit for the placebo and treatment groups are shown here.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language and expressive language. Based on the raw score obtained by the participant in each scale, the scoring software computes T scores, percentile ranks, and age equivalents for each scale separately, as well as a cognitive T score sum and summary age-equivalent score to characterize overall early developmental ability. Summary age-equivalent scores range from 0 to 70 months, with lower scores indicating that a child's ability is at a level typical of younger ages, and higher scores indicating that a child's ability is at a level typical of older ages. The MSEL was administered at the baseline visit and at the 6-month follow-up visit, and mean baseline summary age-equivalent scores for the placebo and treatment groups are shown here.

The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language and expressive language. Based on the raw score obtained by the participant in each scale, the scoring software computes T scores, percentile ranks, and age equivalents for each scale separately, as well as a cognitive T score sum and summary age-equivalent score to characterize overall early developmental ability. Summary age-equivalent scores range from 0 to 70 months, with lower scores indicating that a child's ability is at a level typical of younger ages, and higher scores indicating that a child's ability is at a level typical of older ages. The MSEL was administered at the baseline visit and at the 6-month follow-up visit, and mean summary age-equivalent scores at the 6-month follow-up visit for the placebo and treatment groups are shown here.