Baron M (2002). Manic-depression genes and the new millennium: poised for discovery.

[Wise Young]

• Baron M (2002). Manic-depression genes and the new millennium: poised for discovery. Mol Psychiatry. 7 (4): 342-58. Summary: Manic-depressive illness is a common psychiatric disorder with complex etiology that likely involves multiple genes and non-genetic influences. The uncertain path to gene discovery has spurred considerable debate over genetic findings and gene-finding strategies. In this article, I review the main findings, with a focus on: (1) putative linked loci on chromosomes 1q31-32, 4p16, 6pter-p24, 10p14, 10q21-26, 12q23-24, 13q31-32, 18p11, 18q21-23, 21q22, 22q11-13, and Xq24-28; and (2) association studies with candidate genes, dynamic mutations, mitochondrial mutations, and chromosomal aberrations. Although no gene has been identified, promising findings are emerging. I then discuss the challenges and opportunities ahead, with special emphasis on gene-finding methods-in particular, questions pertaining to phenotype definition, linkage and association mapping, gene markers, sampling, study population, multigene systems, lessons from other disorders, animal models, and bioinformatics. The progress to date, together with rapid advances in genomics, analytical and computational methods, and bioinformatics, holds promise for new insights into the genetics of manic-depression, in the new millennium. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11986978> Department of Psychiatry, Columbia University College of Physicians and Surgeons and Department of Medical Genetics, New York State Psychiatric Institute, New York, USA.

[Wise Young]

• Shamir A, Sjoholt G, Ebstein RP, Agam G and Steen VM (2001). Characterization of two genes, Impa1 and Impa2 encoding mouse myo- inositol monophosphatases. Gene. 271 (2): 285-91. Summary: The enzyme myo-inositol monophosphatase (Impa) catalyzes the synthesis of free myo-inositol from various myo-inositol monophosphates in the phosphatidylinositol signaling system. Impa is a lithium-blockable enzyme that has been hypothesized to be the biological target for lithium-salts used as mood-stabilizing drugs in the treatment of manic- depressive (bipolar) illness. As an initial step to explore the functional consequences of reduced or absent Impa activity in an animal model we here report the isolation of two Impa-encoding mouse genes, Impa1 and Impa2. Impa1 spans approximately 17.5 kb and contains nine exons of 46--1354 bp encoding a protein of 277 amino acids. Impa2 spans at least 19.5 kb and contains eight exons of 46--444 bp size encoding a protein of 290 amino acids. The genomic structure including the positions of the exon-intron splice sites seems to be conserved among myo-inositol monophosphatase genes in mammalian species. One or more Impa-like genes do also exist in evolutionary more distant species like invertebrates, plants and bacteria. The proteins encoded by the non- vertebrate genes seem to be equally related to Impa1 and Impa2. We therefore suggest that the Impa1 and Impa2 genes duplicated from a common ancestral gene after the evolutionary divergence of vertebrates. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11418250> Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.

[Wise Young]

• Piccardi MP, Ardau R, Chillotti C, Deleuze JF, Mallet J, Meloni R, Oi A, Severino G, Congiu D, Bayorek M and Del Zompo M (2002). Manic-depressive illness: an association study with the inositol polyphosphate 1-phosphatase and serotonin transporter genes. Psychiatr Genet. 12 (1): 23-7. Summary: Association studies with candidate genes may contribute towards the understanding of the etiopathogenesis of bipolar disorder. Candidate genes in bipolar disorders are those related to aminergic neurotransmission, which is the target of the effects of antipsychotics and antidepressants, as well as genes related to signal transduction pathways, reporting the target for the mood-stabilizing effects of lithium. Association with such candidate genes may provide clues towards the understanding of the biological components of bipolar disorder. An association study was performed between the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), the inositol polyphosphate 1-phosphatase gene (INPP1) and bipolar disorder using our sample of proband/parent trios. A total of 101 bipolar probands were considered eligible for the study. Since both parents had to be available, mean age at onset of bipolar disorder in probands was relatively young. However, the mean duration of illness and the number of episodes were consistent with a stable diagnosis. In our trios sample, the transmission disequilibrium test revealed no preferential transmission of alleles of the 5-HTTLPR and INPP1 from heterozygous parents to probands. Therefore, additional family-based data are warranted, possibly with a more complete subdivision of 5-HTTLPR alleles, since short and long alleles have recently been divided into four and six kinds of allelic variant, respectively, with significant ethnic differences in allele and genotype distributions. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11901356> Center of Clinical Psychopharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, Cagliari, Italy.

[Wise Young]

• Radhakrishna U, Senol S, Herken H, Gucuyener K, Gehrig C, Blouin JL, Akarsu NA and Antonarakis SE (2001). An apparently dominant bipolar affective disorder (BPAD) locus on chromosome 20p11.2-q11.2 in a large Turkish pedigree. Eur J Hum Genet. 9 (1): 39-44. Summary: Bipolar affective disorder (BPAD), also known as manic-depressive illness, is a common complex, polygenic disorder characterised by recurrent cyclic episodes of mania and depression. Family, twin, and adoption studies strongly suggest a genetic predisposition/susceptibility to BPAD, but no genes have yet been identified. We studied a large Turkish pedigree, with an apparently autosomal dominant BPAD, which contained 13 affected individuals. The age of onset ranged from 15-40 with a mean of 25 years. The phenotypes consisted of recurrent manic and major depressive episodes, including suicidal attempts; there was usually full remission with lithium treatment. A genome-wide linkage analysis using a dominant mode of inheritance showed strong evidence for a BPAD susceptibility locus on chromosome 20p11.2-q11.2. The highest 2-point lod score of 4.34 at theta = 0 was obtained with markers D20S604, D20S470, D20S836 and D20S838 using a dominant model with full penetrance. Haplotype analysis enabled the mapping of the BPAD locus in this family between markers D20S186 and D20S109, to a region of approximately 42 cM. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11175298> Division of Medical Genetics, University of Geneva Medical School, Geneva, Switzerland.

[Acid]

"association studies with candidate genes, dynamic mutations, mitochondrial mutations,"

Not sure, if this at all meant also,
that mitochondrial mutations are supposed to be to do with one's own gene stuff,
but if so, I do not really get that,
as I thought they are symbionts,
and have their own genetics.


The "bipolar" ... I did not read into, as for me that is more some psycho-brancher expression of people not discerning one emotioal system from another in their own head&body systems.
As MBD I guess I regard a bunch differing.
(Including high activities and low,
with not much of a middle.
Also a lot of other aspects.)

I tend to regard the individual more relevant.


... And if there were a geneline tending more towards, for example, suicide, that geneline might terminate itself.

Someone with high emotional problems might then not get and disturb children with these,
nor others in the "herd" and the stability of the herd.


(Some people seem to never wish to regard that aspect.)



Though this seemed not the topic here,
what I find interesting, is how many in differing cultures kill themselves,
and how.

I find the numbers of suiciders (along with water quality) a statement about the quality of that culture,

and common ways there to do that, to be rather "speaking" about the culture.


Acid