Cosegregation of Bipolar Disorder and Autosomal-Dominant Medullary Cystic Kidney Disease in a Large Family

Department of Psychiatry, 0603, University of California-San Diego, La Jolla, CA 92093-0603, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 11/2005; 162(10):1972-4. DOI: 10.1176/appi.ajp.162.10.1972
Source: PubMed


The authors report a large family in which bipolar disorder appears to cosegregate with autosomal-dominant medullary cystic kidney disease.
Information regarding diagnostic criteria for bipolar disorder and medullary cystic kidney disease were gathered from family members through formal research interviews, hospital admission records, imaging reports, and laboratory data.
Of the seven members with medullary cystic kidney disease, five had bipolar I disorder, one had unipolar depression, and one had a hyperthymic phenotype. Information was not available on two members.
The cosegregation in this family suggests a close proximity between genes for the two disorders. The two known loci of medullary cystic kidney disease are in regions of chromosomes 1 and 16 that have been previously linked to bipolar disorder and schizophrenia. This family may be a useful resource for positional cloning of bipolar candidate genes.

Download full-text


Available from: Martin Schalling
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this review, all papers relevant to the molecular genetics of bipolar disorder published from 2004 to the present (mid 2006) are reviewed, and major results on depression are summarized. Several candidate genes for schizophrenia may also be associated with bipolar disorder: G72, DISC1, NRG1, RGS4, NCAM1, DAO, GRM3, GRM4, GRIN2B, MLC1, SYNGR1, and SLC12A6. Of these, association with G72 may be most robust. However, G72 haplotypes and polymorphisms associated with bipolar disorder are not consistent with each other. The positional candidate approach showed an association between bipolar disorder and TRPM2 (21q22.3), GPR50 (Xq28), Citron (12q24), CHMP1.5 (18p11.2), GCHI (14q22-24), MLC1 (22q13), GABRA5 (15q11-q13), BCR (22q11), CUX2, FLJ32356 (12q23-q24), and NAPG (18p11). Studies that focused on mood disorder comorbid with somatic symptoms, suggested roles for the mitochondrial DNA (mtDNA) 3644 mutation and the POLG mutation. From gene expression analysis, PDLIM5, somatostatin, and the mtDNA 3243 mutation were found to be related to bipolar disorder. Whereas most previous positive findings were not supported by subsequent studies, DRD1 and IMPA2 have been implicated in follow-up studies. Several candidate genes in the circadian rhythm pathway, BmaL1, TIMELESS, and PERIOD3, are reported to be associated with bipolar disorder. Linkage studies show many new linkage loci. In depression, the previously reported positive finding of a gene-environmental interaction between HTTLPR (insertion/deletion polymorphism in the promoter of a serotonin transporter) and stress was not replicated. Although the role of the TPH2 mutation in depression had drawn attention previously, this has not been replicated either. Pharmacogenetic studies show a relationship between antidepressant response and HTR2A or FKBP5. New technologies for comprehensive genomic analysis have already been applied. HTTLPR and BDNF promoter polymorphisms are now found to be more complex than previously thought, and previous papers on these polymorphisms should be treated with caution. Finally, this report addresses some possible causes for the lack of replication in this field.
    Full-text · Article · Mar 2007 · Psychiatry and Clinical Neurosciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric bipolar disorder is a serious mental illness with significant morbidity and mortality. A variety of medical and psychiatric conditions occur concurrently with bipolar disorder. These conditions have been more frequently reported in adults. There prevalence in pediatric bipolar disorder is less known. This report is particularly relevant and timely due to the chronic nature of bipolar disorder and the profound impact on health that its treatments can bring. This evolving area needs to be understood to maximize clinical outcomes. While little has been published about pediatric bipolar disorder and its concurrent medical conditions specifically, many reports that focused on adults included pediatric subjects. Concurrent medical conditions fall into a small number of groupings. (1) Those that are related to bipolar disorder or its treatment. (2) Medical conditions that mimic mania. (3) Conditions that occur more commonly in patients with bipolar disorder, but do not appear to be related to its treatment. (4) Those that may be related to risk behaviors associated with bipolar disorder. Many medical conditions that occur concurrently with bipolar disorder in adults are also present in youth. The premature (iatrogenic) initiation of some conditions related to its treatment may pose specific ethical dilemmas for those treating psychiatric conditions.
    Full-text · Article · Aug 2007 · Current Opinion in Psychiatry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An imbalanced immune system has long been known to influence a variety of mood disorders including anxiety, obsessive-compulsive disorders and depression. In this study, we sought to model the impact of an immunocompromised state on these emotional behaviors using RAG-1(-/-) mice, which lack T and B cells. We also investigated the relative contribution of CD4(+) or CD8(+) T cells to these manifestations using RAG-1(-/-)/OT-II and RAG-1(-/-)/OT-I transgenic mice, respectively. Our results show that RAG-1(-/-) mice present a significant increase in digging and marble-burying activities compared with wild-type mice. Surprisingly, these anxiety-like behaviors were significantly reverted in RAG-1(-/-)/OT-II but not RAG-1(-/-)/OT-I transgenic mice. Immunodepletion experiments with anti-CD4 or anti-CD8 in C57/BL6 mice or repopulation studies in RAG-1(-/-) mice did not reproduce these findings. Microarray analysis of the brain of RAG-1(-/-) and RAG-1(-/-)/OT-II mice revealed a significantly different gene fingerprint, with the latter being more similar to wild-type mice than the former. Further analysis revealed nine main signaling pathways as being significantly modulated in RAG-1(-/-) compared with wild-type mice. Taken together, these results suggest that life-long rather than transient immunodeficient conditions influence the emotional behaviors in mice. Most interestingly, these effects seem to correlate with a specific absence of CD4(+) rather than CD8(+) T cells. Validation of these findings in man might provide new clues on the mechanism by which early life immune modulation might impact mood response in adults and provide a further link between immune and emotional well-being.
    Full-text · Article · Jul 2013 · Translational Psychiatry
Show more