Bipolar Disorder Sarah Brown

Transcription

1 Bipolar Disorder Sarah Brown Introduction Bipolar disorder, also referred to as Manic Depressive Illness, is an affective disorder characterized by alternating periods of mania and depression. A person s mood may be extremely irritable and impulsive during the manic phase, and extremely sad and lethargic during the depressive phase. Normal moods may or may not occur in between the high and low moods. Bipolar disorder exists on a spectrum, combining hypomanic or manic phases with subthreshold to major depressive phases. According to the Diagnostic and Statistical Manual of Mental Disorders-4 th edition (DSM-IV), a diagnosis of bipolar I disorder requires at least one manic or hypomanic episode, with or without a current or previous depressive episode (American Psychiatric Association [APA], 1994). A manic episode requires a period of abnormally and persistently elevated, expansive, or irritable mood lasting at least 1 week in addition to at least 3 of the following symptoms (4 symptoms are required if mood is only irritable): 1. inflated self esteem or grandiosity 2. decreased need for sleep 3. more talkative than usual or pressure to keep talking 4. flight of ideas or subjective experience that thoughts are racing 5. distractibility 6. increase in goal-directed activity or psychomotor agitation 7. excessive involvement in pleasurable activities that have a high potential for painful consequences In addition, the symptoms must cause significant impairment in daily or occupational functioning and not be due to another disorder or physiological effects of a substance. A DSM-IV diagnosis of bipolar II disorder requires at least one or more Major Depressive episodes accompanied by at least one hypomanic episode. The criteria for a hypomanic episode is similar to that for a manic episode, except the elevated, expansive, or irritable mood only needs to last 4 days, and the mood disturbance does not cause marked impairment in social or occupational functioning. A person with hypomania, however, does exhibit a change in functioning that is observable as different than their normal mood by other people. Lifetime prevalence rates for bipolar I disorder range from %, and for bipolar II disorder, % (Angst, 1998). When including subthreshold disorders, the rates range from % (Angst et al., 2003). A gender difference in rates has not been definitively proven, although women are at highest risk in the postpartum period. Women also are more likely to have a major depressive episode prior to mania, while men are more likely to exhibit symptoms of mania prior to depression. Most persons who develop bipolar disorder do so during adolescence or early adulthood (NIMH, 2001).

2 People with bipolar disorder are more likely to have comorbid panic disorder, social phobia and substance abuse/dependence, somatization disorder, personality disorders, suicidality and delinquency. Clinical studies raise the question of associations with GAD, OCD, Tourette syndrome, impulse control and eating disorders, ADHD and conduct disorder (NIMH, 2001). Literature Search The literature on potentially modifiable risk factors for bipolar disorder was obtained through searching keywords in Medline and PsychInfo from 1980 through January Searches were conducted using the following keywords: bipolar disorder, community samples, longitudinal studies, risk factors, family characteristics, modifiable causes, non-genetic causes, and prevention. In addition, bibliographies of articles on antecedents of bipolar disorder were obtained and searched for relevant literature. Inclusion criteria included: published in English, longitudinal assessment (defined as assessment at 2 or more consecutive time points), community samples, non-genetic risk factors, and bipolar disorder as the outcome. Broader classifications of affective disorders and mood disorders were not included. This search yielded 363 studies, of which 306 were discarded for not meeting inclusion criteria. The remaining 57 studies were reviewed. Of these studies, 5 articles were excluded because they were review articles, 11 articles were excluded for not meeting inclusion criteria once reviewed (e.g. study examining life stressors predicting severity of bipolar symptoms as opposed to a bipolar diagnosis), and ten studies were excluded for examining broad diagnoses of psychopathology including affective disorders, generalized psychosis, and schizophreniform disorders. While bipolar disorder often falls within the broader diagnostic rubric of affective disorders, it was impossible to make diagnostic distinctions based on this broader classification. Moreover, because bipolar disorder is so rare, it is unlikely that large analytic samples of affective disordered subjects (van Os et al., 1997; Wicki & Angst, 1991) are comprised primarily of bipolar, and not major depressive disordered, subjects. Twenty-eight studies were also excluded based on sampling. These studies examined inpatient or outpatient psychiatry patients or children of former or current patients. Clinic samples were excluded because they may have identified a particular subset of bipolar disordered individuals, perhaps individuals with more severe symptoms. Table 2 reports on potentially modifiable risk factors for bipolar disorder presented in the one study meeting inclusion criteria (Johnson et al., 2000). However, two additional studies that highlight precursors to adult affective disorder (van Os et al., 1997) and hypomania (Wicki et al., 1991), respectively, also are summarized. Although these studies fail to meet our inclusion criteria, they are included in our tables and results section because they may guide future investigation by identifying potential risk factors for bipolar disorder. These studies are summarized by: publication date, study design, sample description, analytic sample and number of cases, measures and mode of reporting the outcome, measures and modes of reporting risk factors, and adjusted odds ratios/risk ratios. Confidence intervals are reported from the published papers where

3 possible. Odds ratios that appear in bold indicate data from the one study meeting our inclusion criteria (Johnson et al., 2000). Results (a) To our knowledge, Johnson et al. (2000) conducted the only prospective, longitudinal study assessing non-genetic risk factors for bipolar disorder in a community sample. This study reports on the relationship between a) DSM-IV diagnoses in adolescence of anxiety disorder, depressive disorder, personality disorder or substance use disorder and b) bipolar disorder in early adulthood. Researchers followed a random sample of youth and their mothers from upstate New York for 10 years. Johnson et al. (2000) found the following disorders to be associated with bipolar disorder in adolescence: anxiety disorder in adolescence (OR=4.69, CI: ), depressive disorder (OR=3.54, CI: ), disruptive disorder (OR=2.75, CI: ), personality disorder (OR=2.23, CI: ) and substance use disorder (OR=2.33, CI: ). While many studies on child and adolescent psychopathology indicate high rates of psychiatric comorbidity (Wilens, et al., 2002), few studies identify a temporal sequence whereby one disorder clearly precedes another. Johnson et al. (2000) suggested that disorders such as anxiety, depression, disruptive behavior, personality and substance abuse, significantly and independently, predicted or heightened the risk for bipolar disorder. These results implicate the need for better identification and treatment of anxiety, depressive, disruptive, and substance use disorders in young adulthood, as these forms of psychopathology may lead to more severe disorders such as bipolar disorder. Results (b) Two studies that examined as their outcome adult affective disorder (AD) and hypomania, respectively warrant review despite not meeting our inclusion criteria. van Os et al. (1997) conducted the most comprehensive study of developmental risk factors for AD. Examining precursors of affective illness in a British birth cohort born between March 3-9, 1946, van Os et al. (1997) prospectively assessed the relationship between cognitive ability, sociobehavioral, neurodevelopmental and physical development, and AD. Qualifying AD as depressive states, not including schizophrenia or schizoaffective disorders, the work of van Os et al. (1997) may contribute to our understanding of potential precursors to bipolar disorder. However, due to the rarity of bipolar disorder and the large analytic sample, it is likely that small numbers of participants meeting criteria for AD met diagnostic qualifications for bipolar disorder. Cognitive ability was quantified by scores on nonverbal, verbal and reading ability tests, and sociodevelopment by physician ratings of alertness and maternal descriptions of solitary play versus group play preferences at age 4. Neurodevelopmental and physical development were characterized by the age of obtaining motor and linguistic milestones (e.g. sitting, walking, babbling mumma, etc.). In addition to these developmental variables, van Os et al. (1997) examined levels of depression and anxiety in childhood, a measure they termed childhood affective disturbance (CAD), defined by total scores on a 3 measure index of teacher rated anxiety-depression at 13 and 15 years of age.

4 Childhood affective disorder (CAD) was the strongest predictor of AD. Controlling for gender and social class for all analyses, van Os et al. (1997) report an Odds Ratio (OR) of 2.6 (95% Confidence Interval (CI): ) for CAD predicting AD. Adjusting further for household crowding and, separately, for teachers impressions of parental interest in school progress as well a as family history of nervous trouble, the OR of CAD predicting AD dropped to 1.7 (no CI reported). and cognitive ability independently and significantly predicted AD. Female gender independently predicted CAD (OR=2.4, CI: ), followed by cognitive ability at age 15 (OR=1.5, CI: ), at age 11 (OR=1.3, CI: ), and at age 8 (OR=1.4, CI: ). Psychomotor agitation including twitching and grimacing at 15 years of age were at increased risk of AD (OR=1.7, CI: ). Children with decreased psychomotor alertness on medical examinations between 4 and 11 years of age were also at increased risk (OR=1.6, CI: ). Finally, speech defects between the ages of 6 and 15 years predicted AD (OR=1.5, CI: ). In addition to the developmental precursors of Affective Disorder reported by van Os et al. (1997), childhood psychopathology has been examined as a risk factor for hypomania in adulthood (Wicki & Angst, 1991). Conducting a prospective cohort design of year old men and women from Zurich, Switzerland, Wicki et al. (1997) examined the association between hypomania and other psychiatric disorders, including the predictive validity of life event stressors, neuroticism, and increased activity levels prior to the development of hypomania in adulthood (assessed at ages 28 or 30). A diagnosis of major depressive disorder (MDD) or dysthymia between the ages of 20 and 30 were risk factors for hypomania (OR: 1.98, CI: ) at ages 28 or 30. Further, seven years prior to the onset of hypomania, participants who later developed the disorder demonstrated increased neuroticism and high levels of stress in their interpersonal relationships. Hypomania was characterized by authors as mania without the social impairment that accompanies bipolar disorder. This study was thus excluded from our analysis. However, due to the potential association between symptoms among hypomania and mania, we included this study in our write up. Hypomania may represent a more mild form of bipolar disorder but the variation in severity may not preclude the associations between psychiatric precursors for both disorders. Summary The scarcity of literature on non-genetic risk factors for bipolar disorder matching our inclusion criteria limits the conclusions that can be drawn from this review. As noted, while many studies examine risk factors for bipolar disorder longitudinally, researchers typically subscribe to clinic sampling, an exclusion for this review piece. Secondly, many studies that matched our inclusion criteria in every other way did not assess bipolar disorder specifically as their outcome. We describe two articles that report on affective disorder and hypomania because these articles match all other inclusion criteria including a longitudinal study design, a non-clinic population, and community based sampling. However, few conclusions can be drawn about the risks conferred by psychopathology in adolescence, as well as psychosocial, physical, and neurodevelopmental lags in childhood and early adolescence.

5 The one article that matches our inclusion criteria allows us to speculate that Bipolar Disorder in adulthood may be related to psychiatric disturbance in childhood and adolescence. Specifically, it appears as though anxiety and major depressive disorders, and less significantly, disruptive disorders, personality disorder, and substance use disorders, may predispose young adults to later bipolar disorder (Johnson et al., 2000). As previously indicated, these results not only implicate high rates of psychiatric comorbidity among bipolar-disordered populations, but also support a temporal sequence in which specific disorders precede bipolar disorder. Public health implications for these results include the need for heightened screening and identification of psychopathology and its early manifestations in childhood and young adulthood as well as improved treatment strategies for children with psychopathology. While other reviewed articles failed to meet our inclusion criteria, several risk factors for bipolar disorder reported in these studies deserve mention. As with schizophrenia, twitches, lack of psychomotor alertness in childhood, and delays in motor and language development may confer a risk for the later development of bipolar disorder (Jones & Tarrant, 1999). The causal pathways between developmental delays and psychopathology, however, is complex and inconclusive (Jones & Tarrant, 1999). Epidemiologic data over the past 10 years on mania suggest that disorders more commonly associated with childhood, such as conduct disorder and attention deficit hyperactivity disorder, may not only confer a risk for bipolar disorder in adolescence and adulthood, but actually represent a manifestation of early-onset mania (Geller & Luby, 1997). This theory, while contentious, is purported by researchers who investigate the naturalistic course of bipolar disorder (Geller & Luby, 1997). Likewise, there exists a breadth of literature on the developmental path from unipolar depression to mania (Akiskal, 1995). Research on this phenomenon, while prospective and longitudinal in scope, is often conducted on young inpatients who admit to psychiatric hospitals with juvenile-onset unipolar depression and was therefore excluded from this review (Akiskal, 1995). In addition to psychomotor and language delays as well as psychological precursors, social influences may precipitate a switch from unipolar to bipolar depression (Ramana & Bebbington, 1995). Antecedent, stressful life events have been reported retrospectively by bipolar inpatients in several studies (Ramana & Bebbington, 1995). While retrospective recall may limit the reliability of such reports, social influences should be considered by future researchers conducting prospective community based studies of risk factors for bipolar disorder. Finally, it is important to consider the cyclical quality of bipolar disorder when investigating probable antecedents of the disorder. Characterized by periods of depression and mania, bipolar disorder may in fact be linked to unipolar depression both in syndromatic criteria and in potential precursors and developmental antecedents. Thus, when evaluating risks for bipolar disorder it may be important to simultaneously investigate risks for unipolar depression.

6 While limited, our review of potentially modifiable risk factors for bipolar disorder suggests vulnerabilities to mania including physical and language delays in childhood, comorbid psychopathology, and depressive and anxious states. Longitudinal research on risk factors for a DSM-IV based diagnosis of bipolar disorder is lacking. Prevalence data on bipolar disorder substantiates the notion that literature on the prediction and prevention of mania is imperative. Compounded with personal, familial, and work related costs, monetary setbacks associated with bipolar disorder are astronomical. One recent study reported that the cost of the persons with a lifetime diagnoses of bipolar disorder totaled 24 billion US dollars (Begley et al., 2001). Such statistics emphasize the need for prevention strategies associated with well-designed longitudinal community-based studies.

7 363 studies matching the keywords Risk Factor Project: Bipolar Disorder 306 excluded for not meeting criteria 57 studies reviewed for inclusion criteria 5 Reviews excluded 11 excluded for not meeting criteria 10 excluded: Affective Disorder (unspecified), Generalized Psychosis, or Schizophrenia Outcome 28 excluded: Clinic Sample 2 Prevalence studies excluded 1 Study for inclusion

8 Table 2b: Risk Factors for Bipolar Disorder and Related Disorders organized by Risk Factor Risk Factor: Psychopathology in Childhood and Adolescence: Risk Factor Author Pub. Date Childhood Affective Disorder (CAD) Study Design van Os et al 1997 Prospective Cohort Sample Description British birth cohort (NSHD study) born between March 3 and March 9, 1946 Analytic Sample Size Number of Cases Outcome Criteria DSM-III-R Adult Affective Disorder (not including Schizophrenia or Schizoaffective disorder) Measure/ Outcome Mode of Reporting PSE, PSF, Self report Risk Factor Criteria/ Measure Depression & anxiety scores on Teacher questionnair es at ages 13 and 15 years Risk Factor Mode of Reporting Teacher report (presence of twitching and grimaces) and medical examinations (age of developmental milestones; observations of speech abnormalities) Adjusted OR/RR (95% CI) 2.6 ( ) OR/RR Adjustment household crowding Social Class Teacher s opinions on whether schoolwork affected by factors outside the school Social Class 1.7 Teacher s impression of parental interest in school progress, and family history of nervous trouble Social Class

9 Adolescent Anxiety Disorder Adolescent Depressive Disorder Johnson et al 2000 Prospective cohort Random sample of youth and their mothers from upstate New York DSM-IV DISC Self report and mother report Mother:child diads interviewed in their homes (1975, 1983, 1986, 1992) 4.69 ( ) 3.54 ( ) Manic symptoms during adolescence Adolescent Disruptive Disorder 2.75 ( ) Adolescent Personality Disorder 2.23 ( ) Adolescent Substance use disorder 2.33 ( ) Diagnosis of MDD or dysthymia between age 20 and 30 Wicki et al 1991 Prospective cohort Random sample of year old men and women from Zurich, Switzerland DSM-III-R SPIKE, SCL-90-R, FPI, SSIAM, SAS Self report Semistructured interviews administed to probands 1.98 ( ) unspecified

10 Risk Factor: Cognitive Ability, Language Development and Motor Milestone Attainment Risk Factor Author Pub. Date Cognitive ability Age 8 Age 11 Age 15 Study Design van Os et al Prospective cohort Sample Description British birth cohort (NSHD study) born between March 3 and March 9, 1946 Analytic Sample Size Number of Cases Outcome Criteria DSM-III-R Adult Affective Disorder (not including Schizophrenia or Schizoaffective disorder) Measure/ Outcome Mode of Reporting PSE, PSF, Self report Risk Factor Criteria/ Measure Nonverbal, verbal, and reading ability tests; vocabulary tests age 8 & 11 years; arithmetic tests 11 & 15 years Risk Factor Mode of Reporting Self Adjusted OR/RR (95% CI) 1.4 ( ) 1.3 ( ) 1.5 ( ) OR/RR Adjustment Age at first speech unspecified Maternal report (recall of child age 2) 1.0 ( ) Motor milestone attainment Medical examination alertness ratings ages 6 to 11 years Physician report 1.0 ( ) Speech defects between ages of 6 and 15 years Medical examinations Physician report 1.5 ( ) Decreased psychomotor alertness on medical examinations between 4 and 11 years 3 point scale of apathy Physician report 1.6 ( ) Twitching and grimacing at 15 years Teacher questionnaire at 15 years Teacher report 1.7 ( )

11 RISK FACTORS FOR AFFECTIVE / BIPOLAR DISORDERS FOREST PLOTS

12 Cognitive Ability, Language Development, and Motor Milestone Attainment Age 1st Speech Cog. Ability: Age 11 Cog. Ability: Age 15 Risk Factors Cog. Ability: Age 8 Decreased Psychomotor Alterness Motor Milestone CI Speech Defects UL Twitching, Grimacing LL EST Odds Ratio/Relative Risk Van Os et al., DSM-III-R Adult Affective Disorder (not including Schizophrenia or Schizoaffective disorder) for British birth cohort (NSHD study) born between March 3 and March 9, 1946

13 Psychopathology in Childhood + Adolescence Adol. Anxiety Dis. 2 Risk factors by Study Adol. Depressive Dis. 2 Adol. Disruptive Dis. 2 Adol. Personality Dis. 2 Adol. Substance Use 2 Child Affective Dis. 1 MDD, Dysthemia (age 20-30) 3 CI UL LL RR Odds Ratio/Relative Risk 1. Van Os et al., DSM-III-R Adult Affective Disorder (not including Schizophrenia or Schizoaffective disorder) for British birth cohort (NSHD study) born between March 3 and March 9, Johnson, J. G., Cohen, P., & Brook, J. S., Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: A community-based longitudinal investigation. American Journal of Psychiatry, 157(10), Wicki et al., DSM-III-R for Random sample of year old men and women from Zurich, Switzerland

14 References Akiskal, H. S. (1995). Developmental pathways to bipolarity: Are juvenile-onset depressions pre-bipolar? Journal of the American Academy of Child and Adolescent Psychiatry, 34(6), Angst J. (1998). The emerging epidemiology of hypomania and bipolar II disorder. Journal of Affective Disorders, 50(2-3), Angst, J., Gamma, A., Benazzi, F., Ajdacic, V., Eich, D., & Rossler, W. (2003). Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-ii, minor bipolar disorders and hypomania. Journal of Affective Disorders, 73(1-2), Begley, C. E., Annegers, J. F., Swann, A. C., Lewis, C., Coan, S., Schnapp, W. B., & Bryant-Comstock, L. (2001). The lifetime cost of bipolar disorder in the US: an estimate for new cases in Pharmacoeconomics, 19(5), Geller, B., & Luby, J. (1997). Child and adolescent bipolar disorder: A review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 36(9), Johnson, J. G., Cohen, P., & Brook, J. S. (2000). Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: A community-based longitudinal investigation. American Journal of Psychiatry, 157(10), Jones, P. B., & Tarrant, C. J. (1999). Specificity of developmental precursors to schizophrenia and affective disorders. Schizophrenia Research, 39(2), National Institute of Mental Health (2001). Bipolar Disorder. NIMH Publication: Ramana, R., & Bebbington, P. (1995). Social influences on bipolar affective disorders. Social Psychiatry & Psychiatric Epidemiology, 30( ). Regier, D. A., Farmer, M. E., Rae, D. S., Locke, B. Z., Keith, S. J., Judd, L., & Goodwin, F. K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Journal of the American Medical Association, 264(19), van Os, J., Jones, P., Lewis, L., Wadsworth, M., & Murray, R. (1997). Developmental precursors of Affective Illness in a general population birth cohort. Archives of General Psychiatry, 54, Wicki, W., & Angst, J. (1991). The Zurich study: X. Hypomania in a 28- to 30- year-old cohort. European Archives of Psychiatry and Clinical Neuroscience, 240, Wilens, T.E., Biederman, J., Brown, S., Tanguay, S., Monuteaux, M., Blake, C., & Spencer, T.J. (2002). Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 41(3),