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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Sam on January 31, 2000, at 2:43:01
Does anyone know if they have made any progress towards identifying genes or defective genes correlating to manic depression and schizophrenia etc.?
Posted by Cam W. on January 31, 2000, at 7:29:12
In reply to The Human Genome Project, posted by Sam on January 31, 2000, at 2:43:01
> Does anyone know if they have made any progress towards identifying genes or defective genes correlating to manic depression and schizophrenia etc.?
Sam - The answer to your question is "sort of". There are many studies coming out on certain types of bipolar disorder having a strong genetic component (eg classical bipolar disorder that responds well to lithium). You have to remember that environment (upbringing, traumas, stressors, etc. also play a large role). In utero viruses have been implicated in some schizophrenias, but then again, if we give very low doses of antipsychotic medication to first degree relatives of some schizophrenics their cogniton improves. Many sites on chromosomes have been "implicated" in these 2 disorders, but nothing has been proven. As always, give them a little more time. - Cam W.
Posted by Noa on January 31, 2000, at 7:57:54
In reply to Re: The Human Genome Project, posted by Cam W. on January 31, 2000, at 7:29:12
I think a study just came out by E. Fuller Torrey, which shows that an in utero virus is implicated in affecting those with a genetic predisposition to schizophrenia.
I believe it is this sort of finding that will be the norm---ie, multi-causal, complex relationships among genetic, environmental, and experiencial factors. Not the kind of explanation that America loves or that the popular media loves to tout. It is much easier to make a glitzy cover story out of a single causative factor.
Posted by Abby on January 31, 2000, at 13:13:10
In reply to Re: The Human Genome Project, posted by Noa on January 31, 2000, at 7:57:54
> I think a study just came out by E. Fuller Torrey, which shows that an in utero virus is implicated in affecting those with a genetic predisposition to schizophrenia.
>
> I believe it is this sort of finding that will be the norm---ie, multi-causal, complex relationships among genetic, environmental, and experiencial factors. Not the kind of explanation that America loves or that the popular media loves to tout. It is much easier to make a glitzy cover story out of a single causative factor.Of course it has multiple causes, but it would be nice to know what genes might put you at risk. That way, you might be able to control the environment better. Or, using the knowledge about which genes can make people vulnerable ---and remember genes code for proteins---people might be able to try designing treatments based on the alleles found in peole who never experience anything.
Diagnoses which were based on something other than *just* a clinical interview would be good too.Abby
Posted by Noa on January 31, 2000, at 13:40:07
In reply to Re: The Genes thing, posted by Abby on January 31, 2000, at 13:13:10
Agreed, as long as we can keep the money makers of the insurance world out of it--ie, not allow a person's genetic make-up to make him or her an insurance pariah or to negatively affect other opportunities in life.
Posted by Abby on January 31, 2000, at 14:29:00
In reply to Re: The Genes thing, posted by Noa on January 31, 2000, at 13:40:07
> Agreed, as long as we can keep the money makers of the insurance world out of it--ie, not allow a person's genetic make-up to make him or her an insurance pariah or to negatively affect other opportunities in life.
Goes without saying, at least in my book---Abby
Posted by Adam on January 31, 2000, at 17:36:01
In reply to The Human Genome Project, posted by Sam on January 31, 2000, at 2:43:01
> Does anyone know if they have made any progress towards identifying genes or defective genes correlating to manic depression and schizophrenia etc.?
Well, there's this...
Am J Hum Genet 2000 Jan;66(1):205-215
Full-Genome Scan for Linkage in 50 Families Segregating the Bipolar Affective Disease Phenotype.
Friddle C, Koskela R, Ranade K, Hebert J, Cargill M, Clark CD, McInnis M, Simpson S, McMahon F, Stine OC, Meyers D, Xu J, MacKinnon D, Swift-Scanlan T, Jamison K, Folstein S, Daly M, Kruglyak L, Marr T, DePaulo JR, Botstein DDepartment of Genetics, Stanford University, Stanford, CA, USA.
[Record supplied by publisher]A genome scan of approximately 12-cM initial resolution was done on 50 of a set of 51 carefully ascertained unilineal multiplex families segregating the bipolar affective disorder phenotype. In addition to standard multipoint linkage analysis methods, a simultaneous-search algorithm was applied in an attempt to surmount the problem of genetic heterogeneity. The results revealed no linkage across the genome. The results exclude monogenic models and make it unlikely that two genes account for the disease in this sample. These results support the conclusion that at least several hundred kindreds will be required in order to establish linkage of susceptibility loci to bipolar disorder in heterogeneous populations.
Not very satisfying, is it? That's why I think I got so worked up about the 5-HT2A/suicide link (which still needs to be proven). It seems to be awfully rare to find such strong correlations in the realm of mental illness. But people have been saying for years that there's a genetic component to bipolar illness, and the various pedigrees that have been done in the past clearly support this. Exogenous factors like, say, a viral infection can hugely complicate the issue, especially if the infection is temporary and the virus is of a type that leaves no genetic trace of its presence (i.e., it doesn't incorporate its genome into that of the host, such as a virus with a lytic and lysogenic cycle that can remain dormant for years or forever). However, the fact remains that bipolar illness has shown a strong familial link. Knowing the genetically predisposing factors can only help.
I think things will start to take off when the relationship between gene regulation and pathology starts to get worked out. That's one of the next big steps. Once the human genome has been sequenced and mapped completely (we're maybe two or three years away from that), of course people will look for mutations in the coding sequences of genes, and the enormous work of structure-function analysis of the protein products will assuredly illuminate the role of mutations, as well as the rational design of new drugs. But there's also the question of differential expression, which is an important factor that can confound standard genetic analysis. Gene regulation (signal transduction cascades, the importance of regulatory elements such as promotors or enhancers, sequences that affect mRNA stability, etc., etc.) present us with so many possible permutations that it's nearly impossible sometimes to tease out what the source of the difference is (a mutation someplace, most likely, maybe in a sequence not clearly associated with the "gene"). But you can at least identify resultant differences, and that will also allow one to build strategies for counteracting the effects of, say, the excessive production of an enzyme or the insufficient expression of a receptor. Massively parallel differential expression screening techniques have been developed and are being perfected. Once we have a good database of differential display and SAGE libraries, for instance, the nature of disease will be greatly elucidated.
Posted by Sam on January 31, 2000, at 19:27:23
In reply to Re: The Human Genome Project, posted by Adam on January 31, 2000, at 17:36:01
If the genetic makeup causes a complex structural abnormality in the brain this would be next to impossible to correct. If its just an imbalance in the neurotransmitters or enzyme abnormalities this might be fairly easy to correct.
Posted by Eric on January 31, 2000, at 22:45:31
In reply to The Human Genome Project, posted by Sam on January 31, 2000, at 2:43:01
> Does anyone know if they have made any progress towards identifying genes or defective genes correlating to manic depression and schizophrenia etc.?
Yes Sam, they have found some of the genes for bipolar and schizophrenia. They found them several years ago. They still have a long way to go though. Genetic engineering treatments for mental illness are still another 20 or more years away. Too far to factor into consideration anytime soon. But yes, that is the future and the scientists are working on it.
Posted by Sam on February 1, 2000, at 1:30:43
In reply to Re: The Human Genome Project, posted by Eric on January 31, 2000, at 22:45:31
I suppose a bioengineered virus might be designed to change the DNA at the site of a defective gene. No doubt this would be immensely complicated, and the same technology could be used to develop horrible weapons.
Posted by Francis McMahon on February 1, 2000, at 10:18:53
In reply to The Human Genome Project, posted by Sam on January 31, 2000, at 2:43:01
> Does anyone know if they have made any progress towards identifying genes or defective genes correlating to manic depression and schizophrenia etc.?
As a researcher in the field, I can say YES, we are making progress. But we do still have a long way to go. To help find the genes, the Univ of Chicago is looking for volunteer families with at least 2 siblings (brothers or sisters) who have manic-depression. If you are interested in helping out, please give Gail King a call at 773-834-3493; or simply respond to this email. Thanks!
This is the end of the thread.
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