Research has shown that thousands of new cells are produced in the hippocampus each day, although many die within weeks of their birth.
Recent animal studies have shown a correlation between learning and new neurons surviving in the hippocampus.
After teaching rodents a variety of tasks that engaged a range of brain areas, scientists found that, generally,
the more the animal learned, the more neurons survived in the hippocampus.
Cells that were born before the learning experience were more likely to survive to become neurons, but only if the animals actually learned.
The increase in survival occurred with tasks that depended on the hippocampus as well as those that required significant effort to learn.Hippocampus holds information coming in temporarily
so that it can be looked at through the light of held experience,
in that it might be significant to him in the frontal lobes of the brainIn the September Archives of General Psychiatry,
the researchers report that the hippocampal CA1 sub-field becomes overactive in schizophrenia
and that this dysfunction foretells which high-risk subjects will develop psychosisThe baseline activity of dopaminergic neurons in the VTA are regulated by the ventral hippocampus,
and that the disruptions in dopamine signalling associated with schizophrenia
may be caused by the hippocampal abnormalities reported in the disease.one stood out: the CA1 subfield of the hippocampus.The findings suggest that, in schizophrenia, oxygen use increases in the hippocampal CA1 subfield and the orbitofrontal cortex.
In contrast, it seems to decrease in the dorsolateral prefrontal cortex.Studied 18 prodromal subjects who met clinical criteria for being at ultra high risk of developing psychosis.
These subjects presented symptoms that did not quite rise to the level seen in psychosis.
For example, prodromal subjects might profess unusual ideas that seem less compelling than delusions.During the two years of follow-up, seven of the prodromal subjects became psychotic.Of the three dysfunctional areas seen in subjects with more established disease, only the CA1 subfield appeared awry in these subjects.
Notably, high activity in this area predicted the eventual emergence of psychosis.
In fact, it did so with a positive predictive value of 71 percent and a negative predictive value of 82 percent.
Not only do these findings yield insight into the earliest stages of psychosis, they raise hopes for a marker to flag those at greatest risk with the idea of someday preventing the disease from taking its toll.
Anatomical studies of prosepective memory
Experimental study prospective memory
This study is published in the August 15 printed issue of Proceedings of National Academy of Sciences.
Earlier research [at Mount Sinai and elsewhere] suggests that schizophrenia is associated with changes in myelin,
the fatty substance or white matter in the brain that coats nerve fibers and is critical for the brain to function properly.
Myelin is formed by a group of central nervous cells called oligodendrocytes,
which are regulated by the gene oligodendrocyte lineage transcription factor 2 (OLIG2).
Patients with schizophrenia are known to have insufficient levels of oligodendrocytes, however the source of this [deficiency] has not been identified,
explains study co-author Joseph D. Buxbaum,
The study showed that genetic variation in OLIG2 was strongly associated with schizophrenia.
In addition, OLIG2 also showed a genetic association with schizophrenia
when examined together with two other genes previously associated with schizophrenia-
-CNP and ERBB4--which are also active in the development of myelin.
The expression of these three genes was also coordinated. Taken together the data support an etiological role for oligodendrocyte abnormalities in the development of schizophrenia.
Dr. Buxbaum and a team of Mount Sinai researchers collaborated with researchers from the Cardiff University School of Medicine in the United Kingdom
to analyze DNA in blood samples taken from 673 unrelated patients with schizophrenia
and compared their genetic information to 716 patients who did not have the disease.
The controls were matched for age, sex, and ethnicity; none were taking medications at the time of the study.
The study showed that genetic variation in OLIG2 was strongly associated with schizophrenia. In addition, OLIG2 also showed a genetic association with schizophrenia when examined together with two other genes previously associated with schizophrenia--CNP and ERBB4--which are also active in the development of myelin. The expression of these three genes was also coordinated. Taken together the data support an etiological role for oligodendrocyte abnormalities in the development of schizophrenia.
The study showed that genetic variation in OLIG2 was strongly associated with schizophrenia.
In addition, OLIG2 also showed a genetic association with schizophrenia
when examined together with two other genes previously associated with schizophrenia--CNP and ERBB4-
-which are also active in the development of myelin.
The expression of these three genes was also coordinated.
Taken together the data support an etiological role for oligodendrocyte abnormalities in the development of schizophrenia.
"Multiple genes likely have a role in schizophrenia and there are probably many things happening in the brain of a schizophrenia patient," Dr. Buxbaum says.
"The findings from this study help us tease out a potential biological cause that may be contributing to this debilitating illness.
This study showed that OLIG2 has a causal etiological effect
and these findings give us a stronger sense of where to look so we can develop more therapeutic targets for this very complex disease."
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