• Shared genetic susceptibility between bipolar disorder and schizophrenia - the evidence
• Shared genetic susceptibility between bipolar disorder and ADHD - the evidence
• Shared genetic susceptibility between bipolar disorder and VCFS - the evidence
• Helpful actions - what can you do?

Numerous studies, particularly studies of identical twins and studies of adopted children who's biological parents have bipolar disorder, have shown that there is a large aspect of heritability to this disease. However, studies are also showing that bipolar disorder may share many of the same genes with other psychiatric diseases, such as schizophrenia or ADHD. If you have any of these diagnoses in your family, you may be at increased risk for developing bipolar disorder.

Interestingly, according to Samuel Barondes (a psychiatric researcher), "more than a dozen independent studies of first-degree relatives of hundreds of index cases with unipolar or bipolar disorder...show that these two forms of mood disorder generally run in different families" (quoted in Surviving Manic Depression, p. 53). This does not mean that there is never any overlap - relatives of someone with bipolar disorder can and do develop unipolar depression, or the other way around. The potential stress to many relatives of being a caretaker of someone with bipolar disorder probably plays a role in unipolar depression diagnoses, however.

Possible confounds of gene studies showing possible overlapping genes for bipolar disorder and schizophrenia or bipolar disorder and ADHD include: the possibility of subjects being misdiagnosed, the possibility that subjects may have two concurrent diagnoses, or loose inclusion criteria for subjects that might allow people with arguably different diagnoses to be labeled as having the same diagnosis. It is important to keep these confounds in mind when considering the results of these studies - although evidence shows that these particular psychiatric disorders tend to occur within the same families, the degree to which this is true (and the degree to which it might be due to genes rather than shared environment) is far from clear.

Shared susceptibility between bipolar disorder and schizophrenia - the evidence

Clinically, bipolar disorder and schizophrenia share many of the same symptoms. For example, some cases of bipolar disorder have psychotic episodes, while some cases of schizophrenia will have a strong affective mood component. This leads to the possibility that some of the shared symptoms may be caused by shared genes, which are passed down through families. Many scientific studies have now found a "familial co-aggregation of both schizophrenia and bipolar disorder" (Murray et al. 2004 - review article). One study of monozygotic (identical) twins - identical twins share 100% of their genes - showed the likelihood of overlapping genetic regions (Cardno et al, 2002). Of the subjects that had schizophrenia, the identical twin had about a 40% chance of also developing schizophrenia, but a 10% increased chance of developing mania (with psychotic features) instead. Of the twins that had mania, a similar picture emerged - the other twin had about a 36% chance of also having mania, and a 13.6% increased risk of having schizophrenia. Of the twins that had schizo-affective disorder, the other twin had identically increased incidences (26.1%) of developing either schizophrenia or mania.

Murray et al., (2004) in their review of the current data, state: "...it appears that a number of genes of relatively small individual effects are likely to be involved in the aetiology [cause] of schizophrenia and also of bipolar disorder."

Increased risk to relatives of either disorder seems to occur most often (according to the data) with histories of schizoaffective disorder (schizophrenia with a mood component) or bipolar disorder with psychotic symptoms. Thus, shared genetic regions would appear to contribute somehow to the biological mechanism of extreme moods and/or psychosis, given that these traits appear in both disorders.

Some of the candidate gene regions for shared susceptibility to schizophrenia and bipolar disorder that are currently being studied include: regions on chromosome 8, 10, 13, 18, and 22. Specifically, the COMT gene on chromosome 22 has been identified as possibly contributing to both schizophrenia and bipolar disorder (see more information about this connection). Other candidate genes within these large chromosomal areas include G72 and BDNF.

Supporting research (a sample):

• Schizophrenia and Bipolar Genetic Links Substantiated (News, May 2005)
• A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder (2004)
• Gene Variation Raises Risk Of Bipolar Disorder And Schizophrenia (News, April 2003)
• Evidence for shared susceptibility in bipolar disorder and schizophrenia (2003)
• A twin study of genetic relationships between psychotic symptoms (2002)
• Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders (1986)

Shared susceptibility between bipolar disorder and ADHD - the evidence

Only recently has psychiatry begun to diagnose cases of pediatric bipolar disorder - previously, children with manic tendencies were more likely to be given a diagnosis of ADHD (attention deficit hyperactivity disorder). Now, some studies are suggesting that ADHD and bipolar disorder tend to co-aggregate in families, and that what appears to be ADHD in children of a parent with bipolar disorder may actually be an early indication of pediatric onset bipolar disorder (Chang et al 2003).

Aggregation studies of ADHD and bipolar indicate that a co-diagnosis of both disorders in an individual confers greater risk of a co-diagnosis for relatives, but that co-diagnosis does not increase the risk for single diagnoses for either disorder. That is, the prevalence of ADHD/bipolar is increased (12%) among relatives of ADHD/bipolar subjects, as compared to the relatives of healthy control subjects and the relatives of subjects with a single diagnosis of ADHD or bipolar disorder. This led researchers to believe that ADHD and bipolar disorder tend to co-segregate in families.

Other researchers, however, strongly disagree with this hypothesis. It is difficult to make a conclusion one way or the other, due to the extreme challenge of correctly diagnosing either ADHD, bipolar disorder, or both in a child. It is logical, however, to imagine that a gene or set of genes that contributes to the prevalence of extreme hyperactivity in response to certain situations could be inherited and, in certain individuals with certain life situations, manifest as either ADHD or (in combination with other genes, perhaps, or other environmental factors) pediatric bipolar disorder.

Supporting research (a sample):

• The genetics of pediatric-onset bipolar disorder (2003)
• Studies of parents and offspring with bipolar disorder (2003)
• A pilot family study of childhood-onset mania (1995)

Shared susceptibility between bipolar and velo-cardio-facial-syndrome (VCFS)

VCFS is a somewhat common congenital disorder characterized by nasal speech, cardiac problems, learning disabilities, and certain facial abnormalities (for example, a longish vertical face, long nose with wide bridge, small ears, long tapered fingers,squinting eyes, and flat facial expression). The genetic defect for most patients is a deletion of a section of genes on chromosome 22.

Interestingly, studies by Dr. Demitri Papolos and others have found that "more than 90% of VCFS children over the age of 12 have some form of bipolar disorder" ("The Bipolar Child", p. 172). Papolos hypothesizes that this significant incidence of psychopathology in VCFS children occurs because one of the commonly deleted genes on chromosome 22 is the COMT gene. Variations in the COMT gene have been implicated in both schizophrenia and bipolar disorder. The gene normally codes for an enzyme that breaks down neurotransmitters important to mood regulation - norepinephrine, dopamine, and epinephrine. The children with VCFS that had ultra- ultra-rapid cycling form of bipolar disorder all had one deleted copy of the COMT gene (from the mutated chromosome 22 causing VCFS), and one COMT variant known as a "low-activity allele" (inherited from the other parent), coding for a COMT enzyme that has low activity.

Because children with VCFS must depend on only one COMT allele (the other has been deleted), they seem to be at signficantly higher risk for developing bipolar spectrum disorders, particularly the ultra-rapid cycling variety, if they happen to inherit the short-allele variety. If your child has VCFS, be particularly vigilant for the appearance of psychiatric symptoms related to bipolar disorder or schizophrenia.

For more details on the studies linking VCFS and bipolar disorder, see "The Bipolar Child" pp. 171-174, or the following study abstract from Am J Med Genet., 1997 Apr 18;74(2):121-8.

Scientific Studies:

• Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders. Am J Med Genet. 2001 May 8;105(4):354-62.
• Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and language phenotypes. Eur Child Adolesc Psychiatry. 2000 Jun;9(2):109-14.
• The behavioural phenotype in velo-cardio-facial syndrome (VCFS): from infancy to adolescence. Genet Couns. 1999;10(1):79-88. Review.
• Brain Scans May Predict Mental Illness in Children with VCFS (Moodswing Newsblog Entry, July 2005)

Helpful Actions:

Know your family's health history, including any psychiatric diagnoses. Knowing whether (and to what degree) these diseases run in your family will help you know whether you are at increased risk. If you are, you can hopefully take extra precautions to help prevent the onset (see other environmental factors that may contribute to bipolar disorder).

• See a heritability chart, with estimates of the risk for various relatives of someone with bipolar disorder

A family health tree is a great way to help organize what you know about your family health history, and is also an excellent tool for a doctor if you ever want to discuss your risks and/or your options. The U.S. government is offering a free, web-based software designed to create a visual, easily-readable family health tree. The program incorporates information (entered by the user) about the occurence of several genetically-based conditions in grandparents, parents, siblings, children, aunts, uncles, and cousins. The outcome is a family tree that shows kin relationships as well as the existence of medical conditions such as heart disease, diabetes, and cancer (indicated by shaded symbols). In addition to these diseases, the user can choose to enter additional information about general patterns of health, psychiatric problems (such as depression or schizophrenia), birth defects, allergies, dental problems, health-related habits such as smoking or substance abuse, and vision/hearing problems. All this information is incorporated into the final family tree.