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MRI Reveals Brain Development Differences in Children with Fragile X

By MedImaging International staff writers
Posted on 09 Jun 2010
Image: Image: Light micrograph an X chromosome (purple) with fragile X syndrome, a genetic cause of mental retardation (Photo courtesy of CMSP).
Image: Image: Light micrograph an X chromosome (purple) with fragile X syndrome, a genetic cause of mental retardation (Photo courtesy of CMSP).
Fragile X syndrome is the most common known cause of autism and inherited intellectual disability. Now, researchers using sophisticated, noninvasive imaging techniques have demonstrated how the brains of very young boys with fragile X syndrome differ from those of young boys without it, providing vital information for the development of treatments for the condition.

In a longitudinal study published online May 3, 2010, in the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS), researchers from the Stanford University School of Medicine and collaborators from the University of North Carolina-Chapel Hill (UNC; NC, USA) tracked anatomic changes that, over time, progressively differentiate the brains of children with fragile X syndrome from those of children without it.

Triggered by a mutation in a gene located on the X chromosome, fragile X syndrome affects about one in every 4,000 people, with more significant symptoms occurring in males than females. This disorder's genetics and neurobiology are relatively well understood, hastening the pace with which potential drug therapies have been moving through the pharmaceutical pipeline, said the study's senior author, Allan Reiss, M.D., a Stanford professor of psychiatry and behavioral sciences and professor of radiology.

Dr. Reiss, who directs the Center for Interdisciplinary Brain Sciences Research at Stanford, has been studying fragile X syndrome for more than 20 years. "A number of years ago, we saw new treatments quickly coming down the line,” he said. "So we wanted to provide information that could be used to guide those treatments.” Application of these new findings might enable scientists and clinicians to tell if a therapy is working in the very youngest of children diagnosed with this condition.

Fragile X syndrome alone accounts for approximately 2% - 3% of all cases of autism, making it the most common known, specific genetic risk factor for that disorder, although not all people with fragile X syndrome develop autism. Autism is increasingly viewed as not a single disease but a spectrum of them. A large number of diverse genes have been identified as contributing to autism, but with each responsible for only a sliver of cases. Fragile X syndrome patients often manifest discomfort with eye contact, hypersensitivity to sound or touch, abnormalities of language and movement, and varying levels of developmental delay.

In the study, the Stanford and UNC investigators used high-resolution magnetic resonance imaging (MRI) to obtain detailed images of one- to three-year-old boys' brains, and followed-up two years later with a second imaging session. The MRI findings were analyzed at Stanford, chiefly by Dr. Reiss and the study's lead authors: Fumiko Hoeft, M.D., Ph.D., an imaging expert, and instructor at the Center for Interdisciplinary Brain Sciences Research (CIBSR), and medical student John Carter. MR brain images from 41 fragile X syndrome boys were compared with those from age- and developmentally-matched control subjects: 21 boys who were developing typically, and 7 others who were experiencing nonfragile-X-related developmental delay.

Whereas many features of brain anatomy were similar from one group to the next, the fragile X brains evidenced at an early age (that is, during their first imaging session at one to three years of age) an overabundance of gray matter in such regions as the caudate and thalamus, and a diminished presence in a part of the cerebellum called the vermis. This suggests that the fragile X syndrome mutation had already begun to cause identifiable, consistent changes in brain development, perhaps even before birth. However, the basal forebrain as well as a different part of the thalamus and many areas of the cerebral cortex of fragile X patients, while interchangeable from those of control subjects during the first imaging session, diverged from their counterparts two years later. These findings suggest that specific downstream effects of the mutation become evident only later in brain development.

Knowing the locations of fragile X syndrome brain-structure abnormalities and the developmental time course over which they occur--and being able to noninvasively detect those changes in young patients--will make it possible to monitor new therapies' effectiveness in (it is hoped) restoring patients' brain structure and function to normality.

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Stanford University School of Medicine
University of North Carolina-Chapel Hill


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87 (46.014785766602): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (29.087066650391): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (32.901763916016): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (51.021575927734): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
105 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
106 (52.928924560547): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (48.160552978516): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (118.97087097168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
109 (51.021575927734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
110 (45.7763671875): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (524.04403686523): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (556.94580078125): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (318.05038452148): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
115 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
116 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
117 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
118 (45.061111450195): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
119 (36.001205444336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
120 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
121 (47.922134399414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
122 (272.03559875488): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 18804.07333374): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (476.83715820312): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729705 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729705 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 7375.0019073486): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (125.16975402832): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (36.954879760742): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (29.802322387695): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (41.961669921875): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (40.054321289062): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (355.95893859863): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (41.007995605469): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (33.140182495117): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (28.133392333984): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (542.87910461426): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (423.19297790527): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (218.86825561523): SELECT name FROM jos_deeppockets WHERE id=212
138 (32.901763916016): SELECT name FROM jos_deeppockets WHERE id=212
139 (555.03845214844): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (524.99771118164): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
142 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
143 (!!!!! 8116.9605255127): TRUNCATE TABLE jos_trademed_module
144 (84.877014160156): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (56.028366088867): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729705 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (780.10559082031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (58.174133300781): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
149 (48.160552978516): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
150 (!!!!! 1270.055770874): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (84.877014160156): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
152 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
153 (56.982040405273): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729705 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729705 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (46.014785766602): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
155 (43.153762817383): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
156 (45.061111450195): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (146.86584472656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
158 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729705 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729705 AND published='1' LIMIT 1
159 (50.067901611328): select jos_twitters.link from jos_twitters where cat=10
160 (39.100646972656): select jos_facebook.link from jos_facebook where cat=10
161 (36.001205444336): select jos_google_plus.link from jos_google_plus where cat=10
162 (61.03515625): select jos_linkedin.link from jos_linkedin where cat=10
163 (533.10394287109): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 1481.0562133789): insert into jos_banners_delta values (14615,'2025-06-28 04:51:19','216.73.216.249','view'),(14202,'2025-06-28 04:51:19','216.73.216.249','view'),(14203,'2025-06-28 04:51:19','216.73.216.249','view')