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April 28, 2009

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Schizophrenia reassessed as fixation on self

Jan. 23, 2009
Courtesy Massachusetts 
Institute of Technology
and World Science staff

Schiz­o­phre­nia may blur the bound­a­ry be­tween in­ter­nal and ex­ter­nal real­i­ties by over­ac­ti­vat­ing a brain sys­tem in­volved in self-re­flec­tion, caus­ing an ex­ag­ger­at­ed fo­cus on self, a study has found.

The tra­di­tion­al view of schiz­o­phre­nia is that the dis­turbed thoughts, per­cep­tions and emo­tions char­ac­ter­iz­ing the men­tal ill­ness result from dis­con­nec­tions among the brain re­gions that con­trol these dif­fer­ent func­tions.

But the new stu­dy found that schiz­o­phre­nia al­so in­volves ex­cess con­nec­ti­vity be­tween brain re­gions in­volved in self-re­flec­tion which be­come ac­tive when we think of noth­ing in par­tic­u­lar, or of our­selves.

“Peo­ple nor­mally sup­press this ‘de­fault’ sys­tem when they per­form chal­leng­ing tasks. But we found that pa­tients with schiz­o­phre­nia don’t,” said John D. Ga­bri­e­li of the Mas­sa­chu­setts In­sti­tute of Tech­nol­o­gy, one of 13 au­thors of the study, published Jan. 19 in the ad­vance on­line is­sue of the research journal Pro­ceed­ings of the Na­tional Acad­e­my of Sci­ences.

The findings “may re­flect an in­abil­ity of peo­ple with schiz­o­phre­nia to di­rect men­tal re­sources away from in­ter­nal thoughts and feel­ings and to­ward the ex­ter­nal world,” said MIT’s Su­san Whitfield-Ga­bri­e­li, al­so a co-author.

John Ga­bri­e­li added that he hopes the re­search might lead to ways of pre­dict­ing or mon­i­tor­ing in­di­vid­ual pa­tients’ re­sponse to treat­ments for the ill­ness, which oc­curs in about one per­cent of peo­ple.

Schiz­o­phre­nia is largely ge­net­ic. First-degree rel­a­tives of pa­tients (their par­ents, broth­ers, sis­ters, or chil­dren) are 10 times more likely to de­vel­op the dis­ease than the gen­er­al popula­t­ion. Which genes are re­spon­si­ble are largely un­known. 

The re­search­ers stud­ied three matched groups of 13 sub­jects each: schiz­o­phre­nia pa­tients, non­psy­chot­ic first-degree rel­a­tives of pa­tients and healthy nonrel­a­tives. They chose re­cently di­ag­nosed pa­tients, so that dif­fer­ences in pri­or treat­ment or psy­chot­ic episodes would­n’t bi­as the re­sults. 

The par­ti­ci­pants were brain-scanned us­ing a widely used tech­nique known as func­tion­al mag­net­ic res­o­nance im­ag­ing, while rest­ing and while per­forming easy or hard mem­o­ry tasks.

The re­search­ers fo­cused on the “de­fault” sys­tem, a net­work of brain re­gions whose ac­ti­vity drops when peo­ple per­form hard men­tal tasks. This net­work in­cludes ar­eas of the out­er brain known as the me­di­al pre­fron­tal cor­tex and the pos­te­ri­or cin­gu­late cor­tex, as­so­ci­at­ed with self-re­flec­tion and mem­o­ries about the self. The net­work ap­pears to be­come linked to­geth­er and ac­tive when the mind wan­ders.

The sci­en­tists found that in the schiz­o­phre­nia pa­tients, the de­fault sys­tem was both hyperac­tive and hy­per­con­nected dur­ing rest, and it re­mained so as they per­formed the mem­o­ry tasks. In oth­er words, the pa­tients were less able than healthy sub­jects to sup­press the net­work’s ac­ti­vity dur­ing the task. Interest­ingly, the less the sup­pression and the great­er the con­nec­ti­vity, the worse they per­formed on the hard mem­o­ry task, and the worse their symp­toms.

The hyperac­tive de­fault sys­tem could al­so help to ex­plain hal­lu­cina­t­ions and par­a­noia by mak­ing neu­tral ex­ter­nal stim­u­li seem in­ap­pro­pri­ately self-relevant, the in­ves­ti­ga­tors said. For in­stance, if brain re­gions whose ac­ti­vity nor­mally sig­ni­fies self-fo­cus are ac­tive while lis­ten­ing to a voice on tel­e­vi­sion, the per­son may per­ceive that the voice is speak­ing di­rectly to them. 

The de­fault sys­tem was al­so overac­tive, though less so, in first-degree rel­a­tives of schiz­o­phre­nia pa­tients who did­n’t them­selves have the dis­ease, the re­search­ers said. This sug­gests overac­tiva­t­ion of the de­fault sys­tem may be linked to the ge­net­ic cause of the dis­ease rath­er than to its con­se­quenc­es, they added. The de­fault sys­tem is a hot top­ic in brain im­ag­ing, said John Ga­bri­e­li, partly be­cause it’s easy to meas­ure and is af­fect­ed in dif­fer­ent ways by dif­fer­ent dis­or­ders.

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Schizophrenia may blur the boundary between internal and external realities by overactivating a brain system involved in self-reflection, causing an exaggerated focus on self, a brain imaging study has found. The traditional view of schizophrenia is that the disturbed thoughts, perceptions and emotions characterizing the mental illness are caused by disconnections among the brain regions that control these different functions. But the new study, appearing Jan. 19 in the advance online issue of the Proceedings of the National Academy of Sciences, found that schizophrenia also involves excess connectivity between brain regions that are involved in self-reflection and become active when we are thinking about nothing in particular, or about ourselves. “People normally suppress this ‘default’ system when they perform challenging tasks, but we found that patients with schizophrenia don’t,” said John D. Gabrieli of the Massachusetts Institute of Technology, one of the study’s 13 authors. “This may reflect an inability of people with schizophrenia to direct mental resources away from internal thoughts and feelings and toward the external world,” said MIT’s Susan Whitfield-Gabrieli, also a co-author. John Gabrieli added that he hopes the research might lead to ways of predicting or monitoring individual patients’ response to treatments for the illness, which occurs in about one percent of people. Schizophrenia is largely genetic. First-degree relatives of patients (their parents, brothers, sisters, or children) are 10 times more likely to develop the disease than the general population. Which genes are responsible are largely unknown. The researchers studied three matched groups of 13 subjects each: schizophrenia patients, nonpsychotic first-degree relatives of patients and healthy nonrelatives. They chose recently diagnosed patients, so that differences in prior treatment or psychotic episodes wouldn’t bias the results. The participants were brain-scanned using a widely used technique known as functional magnetic resonance imaging, while resting and while performing easy or hard memory tasks. The researchers focused on the “default” system, a network of brain regions whose activity drops when people perform hard mental tasks. This network includes areas of the outer brain known as the medial prefrontal cortex and the posterior cingulate cortex, associated with self-reflection and memories about the self. The network appears to become linked together and active when the mind wanders. The scientists found that in the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. In other words, the patients were less able than healthy control subjects to suppress the network’s activity during the task. Interestingly, the less the suppression and the greater the connectivity, the worse they performed on the hard memory task, and the worse their symptoms. The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant, the investigators said. For instance, if brain regions whose activity normally signifies self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them. The default system is also overactive, though less so, in first-degree relatives of schizophrenia patients who didn’t themselves have the disease, the researchers said. This suggests overactivation of the default system may be linked to the genetic cause of the disease rather than to its consequences, they added. The default system is a hot topic in brain imaging, said John Gabrieli, partly because it is easy to measure and because it is affected in different ways by different disorders.