Schizophrenia and Bipolar Disorder

Part 1: Etiology and Diagnosis

First published in Psychiatry Weekly, November 26, 2007 

This is the first of a three-part series covering recent advances in diagnosis and treatment of schizophrenia and bipolar disorder. This first feature focuses on etiology and diagnosis—the following two features will address current best practice for schizophrenia and bipolar disorder respectively.

Accreditation Statement

This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation

The Mount Sinai School of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty Disclosure Policy Statement

It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices.

This activity has been peer reviewed and approved by Eric Hollander, MD, Professor of Psychiatry and Chair at Mount Sinai School of Medicine. Review Date: November 9, 2007

Statement of Need

Schizophrenia and bipolar disorder, with prevalence rates of 1% and 3.5% respectively, are two of the most common and debilitating psychiatric disorders. Both have a strong association with suicidality, and medical and psychiatric comorbidities, particularly substance abuse, are common in both disorders, complicating diagnosis and treatment. The need for physical health care, the need for prolonged psychiatric care, the impact of crisis management and perhaps even legal management, and the burden of care on families and society, including the loss of human potential and productivity, all contribute to the difficulty and importance of addressing these two disorders.

Both disorders evince strong familiality, and new evidence points toward a partial overlap of implicated genes. Environment is also a factor, with indications that parents’ age at conception and birth month have an impact. Drug use has also been linked with disease onset. The etiology of these disorders is multifactorial and not yet fully understood.

An important educational need exists to clarify the overlapping contribution of genetics to these two disorders. In addition, diagnostic strategies must be refined so as to detect these disorders in their prodromal phases, shortening the period before onset and treatment.

Learning Objectives

• Describe the impact of schizophrenia and bipolar disorder on patient morbidity and mortality.
• Assess diagnostic strategies that address impediments to diagnosis in these patient populations.
• Explain the contribution of genetics in schizophrenia and bipolar disorder.

Target Audience

This activity will benefit psychiatrists, hospital staff physicians, and office-based “attending” physicians from the community.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Eli Lilly and Company.

Faculty Disclosure

Peter Buckley, MD, is a consultant to Abbott, Alamo, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Merck, Roche, Solvay, and Wyeth; receives grant/research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, the National Institute of Mental Health, Pfizer, Solvay, and Wyeth; and receives honorarium/expenses from Abbott, Alamo, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, and Pfizer.

Peer Reviewers

Eric Hollander, MD, reports no affiliation with or financial interest in any organization that may pose a conflict of interest.

To Receive Credit for this Activity

Read this poster, reflect on the information presented, and then complete the CME quiz found in the accompanying brochure or online (www.mssmtv.org/psychweekly). To obtain credit you should score 70% or better. The estimated time to complete this activity is 1 hour.

Release Date: November 26, 2007

Termination Date: November 26, 2009

Impact on the Affected Populations

Schizophrenia and bipolar disorder are two of the most common and most debilitating psychiatric disorders, both listed among the most debilitating illnesses in the developed world by the WHO.¹ Both disorders tend to manifest early in adulthood, contributing to their profound impact, and both illnesses have a particularly high mortality associated with them. Rates of suicide in patients with bipolar disorder are roughly 1% annually, 60 times higher than in the general population. Suicide attempts in bipolar patients are far more likely to be lethal, as well.² 25%–60% of bipolar patients will attempt suicide at least once, and up to 18.9% of deaths in this patient population are attributed to suicide,³ a rate three times higher than that in patients with other mood disorders.⁴ Studies also indicate that substance use also appears to play a role. 39.5% of bipolar patients with a substance use disorder attempt suicide as opposed to only 23.8% of bipolar patients without a substance use disorder.⁵

The numbers for schizophrenia are similarly grim. The conventional wisdom long held that 10% of patients with schizophrenia would commit suicide, but this was found to overestimate the likelihood of suicide in older patients. The actual number is now thought to be closer to 5%.⁶

Suicide aside, both bipolar disorder and schizophrenia are life-shortening conditions, and patients who suffer from either condition have a high rate of medical comorbidity, developing health problems at a significantly younger age than members of the general population.^7-9

There’s also a very high rate of substance abuse among people with schizophrenia, and an even higher rate in bipolar disorder, upward of 60%.¹⁰ Many theorize that the frequency of substance abuse in these populations may be in part an effort at self medication. Additionally, some very recent information suggests that there may even be a genetic vulnerability that could explain in part why some people with schizophrenia abuse drugs.¹¹

The need for physical healthcare and prolonged psychiatric care, the impact of crisis management and perhaps even legal management, comorbidity, substance abuse, and the burden of care on families and society, including the loss of human potential and productivity, all contribute to the difficulty and importance of addressing these two disorders.

Prevalence

The prevalence of bipolar disorder was traditionally been held to be in the range of 1%, but more recent
evidence suggests that subtypes of the disease have been underrepresented, and the actual prevalence rate may be closer to 3.5%.^12,13 Schizophrenia is believed to be somewhat less common, with a prevalence of roughly 1%.¹⁴

There is currently no conclusive evidence that either condition is increasing or decreasing in prevalence. There are noted regional variations in prevalence, and both conditions appear to be overrepresented in immigrants (although there is some conflicting evidence on that count).^15,16

Exploring Multifactorial Etiology

Both schizophrenia and bipolar disorder are highly familial, with heritability estimates ranging from 59% to as high as 87%.^17,18

This suggests that genes are overwhelmingly important in both disorders, suggesting that these disorders may be more similar in etiology than has been previously suspected. The genetics of both schizophrenia and bipolar disorder are common and complex. There is some overlap in areas of chromosome linkage in chromosome 13 and 15, suggesting that dichotomy between these two disorders may be less strong than suspected.²⁰

Environmental contributions to the disorders may be quite broad. The mothers of 1 in 5 people with schizophrenia underwent obstetric complications, with no particular complication specifically indicated.²¹

Additionally, there is the curious finding that people with schizophrenia are more likely to have been born during the first 3 months of the year, during the so-called “season of birth defects.”²²

There is also growing interest in the age of parents when they conceive, with several studies suggesting there’s a higher risk of schizophrenia when fathers are older.²³

There is no clear single factor that accounts for either of these diseases. There are multiple contributing factors, and some have suggested that neither disease is one single condition. Perhaps one set of symptoms is more determined by genetic factors and another by environmental factors. These are complex disorders, and a great deal more research is needed before they are fully understood.

Diagnosis with an Emphasis on Timing

The pathways by which people suffering from bipolar disorder and/or schizophrenia get diagnosed and come into care are highly variable.

Both of these disorders are stigmatizing conditions that often occur in youth or early adulthood and often have a prodrome phase during which the symptoms are not as florid or obvious as in the full-blown disorders.²⁵ The symptoms of these disorders can be mistaken for physical illness, for moodiness, for substance abuse, and it may not be obvious to the person or their family that bipolar disorder or schizophrenia is at the heart of the matter.

There appears to be a period during which people develop more florid illness and before they’re able to connect with treatment services; this period is referred to as the “duration of untreated illness.”²⁶ The hope is that if we can shorten that duration than we may be able to be more effective in our treatment, particularly in regard to prevention of secondary disability related to serious mental illness. Addressing this treatment gap is going to require public health assistance.

Diagnosis is also impeded by the high rate of use of alcohol and drugs in these patient populations. When substance abuse is part of the clinical picture, it can be very difficult to piece together the pathway to deterioration. Availability of good collaborative information from family or friends is a very important element to diagnosis.

Schizophrenia and bipolar disorder are serious, frequently occurring, and multi-factorial. Emerging genetic evidence is elaborating understanding of their etiology, and there are suggestions that the two disorders may share some common genetic basis. Accurate and early diagnosis is the first step to managing these disorders.

To take the free, online CME post-test, go to www.mssmtv.org/psychweekly

References

1. Murray CJL, Lopez AD, eds. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. 1st ed. Cambridge: Harvard School of Public Health on behalf of the World Health Organization and the World Bank; 1996.

2. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: Risks and management. CNS Spectr. 2006;11(6):465-471.

3. Goodwin FK, Jamison KR. Manic-Depressive Illness. New York, NY: Oxford University Press; 1990.

4. Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry. 2000;61 Suppl 9:47–51.

5. Dalton EJ, Cate-Carter TD, Mundo E, Parikh SV, Kennedy JL. Suicide risk in bipolar patients: the role of co-morbid substance use disorders. Bipolar Disord. 2003;5(1):58-61.

6. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62(3):247-253.

7. Buckley P. Considerations of Medical Comorbidity in Schizophrenia. Available at: http://www.medscape.com/infosite/schizophrenia-management/article-4. Accessed October 30, 2007.

8. Newcomer JW. Medical risk in patients with bipolar disorder and schizophrenia. J Clin Psychiatry. 2006;67 Suppl 9:25-30.

9. Krishnan KR. Psychiatric and Medical Comorbidities of Bipolar Disorder. Psychosom Med. 2005;67(1)1-8.

10. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511-2518.

11. Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychsosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;15(10)57:1117-1127.

12. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2007;64(5)543-552.

13. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Arch Gen Psychiatry. 2005;62(6):617-627.

14. Regier DA, Narrow WE, Rae DS, et al. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50(2):85-94.

15. Selten JP, Sijben N. First admission rates for schizophrenia in immigrants to the Netherlands: The Dutch National Register. Soc Psychiatry Psychiatr Epidemiol. 1994;29(2):71-77.

16. Grove W, Clayton PJ, Endicott J, et al. Immigration and major affective disorder. Acta Psychiatr Scand. 1986;74(6):548–552.

17. Kendler KS. Twin studies of psychiatric illness. Current status and future directions. Arch Gen Psychiatry. 1993;50(11):905-915.

18. Kendler KS. Genetic epidemiology in psychiatry. Taking both genes and environment seriously. Arch Gen Psychiatry. 1995;52(11):895-899.

19. Hawton K, Sutton L, Haw C, et al. Suicide and attempted suicide in bipolar disorder: a systematic review of risk factors. J Clin Psychiatry. 2005;66(6):693–704.

20. Craddock N, O’Donovan MC, Owen MJ. The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet. 2005;42(3):193-204

21. Cannon M, Jones PB, Murray RM. Obstetric Complications and Schizophrenia: Historical and Meta-Analytic Review. Am J Psychiatry. 2002;159(7):1080-1092.

22. Pulver AE, Liang KY, Brown CH, et al. Risk factors in schizophrenia. Season of birth, gender, and familial risk. Br J Psychiatry. 1992;160:65-71.

23. Zammit S, Allebeck P, Dalman C. Paternal age and risk for schizophrenia. Br J Psychiatry. 2003;183:405-408.

24. Gorwood P, Leboyer M, Jay M, et al. Gender and age at onset in schizophrenia: impact of family history. Am J Psychiatry. 1995;152(2):208–212.

25. Correll CU, Penzner JB, Frederickson AM, et al. Differentiation in the preonset phases of schizophrenia and mood disorders: evidence in support of a bipolar mania prodrome. Schizophr Bull. 2007;33(3):703-714.

26. Peralta V, Cuesta MJ, Martinez-Larrea A, et al. Duration of untreated psychotic illness: the role of premorbid social support networks. Soc Psychiatry Psychiatr Epidemiol. 2005;40(5):345-349.

27. Addington J. The diagnosis and assessment of individuals prodromal for schizophrenia psychosis. CNS Spectr. 2004;9(8):588-594.

To take the free, online CME post-test, go to www.mssmtv.org/psychweekly