Julia A. Sherman, (2001) Evolutionary Origin of Bipolar Disorder (eobd). Psycoloquy: 12(028) Evolution Bipolar Disorder (1)

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PSYCOLOQUY (ISSN 1055-0143) is sponsored by the American Psychological Association (APA).
Psycoloquy 12(028): Evolutionary Origin of Bipolar Disorder (eobd)

Target Article by Sherman on Evolution-Bipolar-Disorder

Julia A. Sherman,
6302 Mineral Pt. Rd., #303
Madison WI 53705



The hypothesis of the evolutionary origin of Bipolar Disorder (EOBD) attempts to make sense of BD by placing it in evolutionary perspective. The hypothesis emerges from ideas about the importance of the organism's biological clock and energy-regulating mechanism (Wehr, Goodwin, Rosenthal), and theorising that BD descends from a pyknic (compact, cold-adapted) group (Kretschmer). It suggests that BD behaviors evolved as highly derived adaptations to the selective pressures of extreme climatic conditions (long, severe winters and short summers). The EOBD hypothesis integrates existing observations, economically explains puzzling aspects of BD, yields testable predictions, and suggests new research directions.


Biological clock; Bipolar Disorder; depression; cold adaptation; environment; evolution; Kretschmer; mania; physique; seasonal.
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    evolutionary origin of Bipolar Disorder (EOBD) is relevant to many
    disciplines. (1) Scientists from the fields of psychiatry,
    psychology, genetics, and epidemiology are invited to test the
    hypothesis against knowledge from their fields. (2)
    Neurophysiologists may propose a model for the mechanisms
    underlying BD. (3) Sociologists and historians of science may
    comment on the fate of Kretschmer's ideas. (4) Clinicians may
    contribute thoughts about the implications of the EOBD hypothesis
    for treatment of BD. (5) Experts from paleoanthropology and
    molecular biology may suggest likely scenarios for BD evolution.
    For example, could BD have evolved between the time that peoples
    left Africa (200,000 BP?) and the end of the last Ice Age?


1. Bipolar Disorder (BD) has eluded scientific understanding for more than a century. This target article explores the possible evolutionary origin of the genes responsible for BD vulnerability (BD genes). The idea that BD evolved as an adaptation may have heuristic value and contribute to demystification of the disorder. Ideas from Kretschmer (1970, orig. 1921), Wehr and Rosenthal (1989), and Goodwin and Jamison (1990) are synthesised within the context of evolutionary theory. EOBD hypothesizes that BD behaviors evolved as adaptations to long, harsh winters and short summers. Reviews of the literature are limited to English-language publications.

2. BD is a puzzling and intriguing disorder. It encompasses the extremes of human behaviors; nonetheless, BD behaviors form stable, recognizable patterns described throughout recorded history (Jackson 1986; Jablensky et al. 1993). Despite the disorder's handicapping effects, BD is associated with leadership, creativity, high intelligence, and upper socioeconomic status (Andreasen 1987; Goodwin & Jamison 1990; Jamison 1995a; Ludwig 1995). The goal of this target article is to begin a dialogue that may eventually make sense of these disparate observations.

3. The incidence of BD is described as about 1% worldwide (Goodwin & Jamison 1990). Weissman and colleagues (1996) reported the results of population-based epidemiological studies in ten countries. The lifetime rate for BD ranged from 0.3/100 in Taiwan to 1.5/100 in New Zealand. The true incidence of BD may vary from group to group (Bebbington & Ramana 1995; Daly et al. 1995; Rasanen et al. 1998; Regier et al. 1993; Veijola et al. 1996), but our understanding is hampered by incomplete data. Epidemiological studies encounter many sources of error, such as problems of sampling, and consistent, valid diagnostic procedures. Cross-national and cross-cultural epidemiological studies experience additional problems. Groups resist association with a high incidence of a severe mental illness, which makes objective data difficult to obtain. Furthermore, mental illnesses are defined in a particular language and cultural context: Is "Lapp panic" a manifestation of BD (Collinder 1949)? Data about the incidence of BD in indigenous groups may have theoretical significance, but contemporary theoretical needs require more refined data. BD is found among the Inuit in North America (Aoun & Gregory 1998; Sampath 1974; Seltzer & Langford 1984), which suggests that BD genes were carried by peoples migrating across the land bridge from Asia before the end of the last Ice Age. However, this is true only if the source of BD genes proves to be indigenous. (See also 27, 56.) Because rapid advances in genetics research are expected, only the most relevant epidemiological and genetic studies are reviewed in this article.

4. In regard to the genetics of BD, consensual agreement of genetic researchers attributes BD vulnerability to a polygenic source, rather than a single mutant gene. Neither the polygenic source of the disorder nor its underlying mechanism has been identified (Barondes 1998; McGuffin et al. 2001; Morell 1996; Mynett-Johnson & McKeon 1996; Nurnberger & Gershon 1992; Nurnberger et al. 1997; Plomin et al. 2001; Segman & Lerer 2000).

5. In the United States, the current standard for psychiatric diagnosis is the Diagnostic and Statistical Manual-IV (DSM-IV 1994) published by the American Psychiatric Association. When formal diagnostic terms are used that are defined in this manual, they will be capitalized. BD typically has a periodic course of Major Depressive, and Hypomanic, or Manic Episodes, interspersed with periods of usual functioning. The BD I diagnosis requires one or more Manic Episodes, with or without Major Depressive Episodes; the BD II diagnosis requires both Major Depressive and Hypomanic Episodes. The older diagnostic category, manic-depressive illness (MDI), also included patients who experienced recurrent Major Depressive Episodes, but no Hypomanic or Manic Episodes (DSM III-R 1987). (For discussions of the change in the diagnostic nosology, see Goodwin & Jamison 1990; Winokur et al. 1995).

6. To facilitate precise communication, the current diagnostic criteria for BD episodes are detailed (DSM-IV 1994). The symptoms that are accounted for by the ideas presented in this article are noted at the end of each diagnostic description. The criteria for diagnosis of a Major Depressive Episode require the presence of at least five of the following symptoms and must include either (1) or (2): (1) depressed mood; (2) loss of interest or pleasure; (3) significant unaccounted for increased or decreased appetite or weight; (4) insomnia or hypersomnia; (5) psychomotor retardation or agitation; (6) fatigue or loss of energy; (7) feelings of worthlessness or guilt; (8) poor concentration; (9) recurrent thoughts of death or suicide. (The ideas presented in this article purport to account for criteria (2), (3), (6), (8), and for hypersomnia and psychomotor retardation in criteria (4) and (5), which meets six of the criteria.)

7. The criteria for a Hypomanic Episode require a distinct period of elevated, expansive, or irritable mood with three (or more) of the following symptoms (four if the mood is only irritable): (1) inflated self-esteem or grandiosity; (2) decreased need for sleep; (3) more talkative than usual; (4) flight of ideas or subjective feeling that thoughts are racing; (5) distractibility; (6) increase in goal-directed activity (either socially, at work, at school, or sexually) or psychomotor agitation; (7) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., buying sprees, sexual indiscretions, or foolish business investments). (Criteria (1), (2), (3), and increased goal-directed activity and sexual indiscretions in criteria (6) and (7) are accounted for, which meets five of the criteria.)

8. The criteria for a Manic Episode are the same as for a Hypomanic Episode, but in mania, the behaviors are extreme. For example, the individual may talk nonstop, jumping from subject to subject; go for days without feeling the need to sleep; engage in uncharacteristic inappropriate behavior. The diagnosis of a Manic Episode requires a disturbance sufficiently severe to cause marked impairment in social or occupational functioning. (The same symptoms are accounted for as in the case of a Hypomanic Episode.)

9. Psychosis is not a listed symptom of BD, but it may be associated with either a Major Depressive Episode or a Manic Episode, as it is with many disorders (e. g. porphyria, hyperthyroidism, and multiple sclerosis). The severe disturbances associated with BD raise the question: how could a disorder so apparently maladaptive as BD evolve as an adaptation? First, as described in section III, it is hypothesized that BD was adaptive at the time(s) and place(s) of its evolution. Second, some might argue that aspects of BD are adaptive even today ( 2; Whybrow 1997). Third, the alleles responsible for sickle cell anaemia, two of which cause early death, nonetheless evolved as an adaptation. If sickle cell anaemia evolved as an adaptation, is it not possible that BD also evolved as an adaptation?

10. While this article was under editorial review, Wilson (1998) published an article with the conclusion that the medical genetics of MDI are those of an adaptive polymorphism in the human genome. Wilson developed his argument within the framework of evolutionary epidemiology, and his ideas may provide independent support for the EOBD hypothesis. On the other hand, unless the medical genetics of BD are shown to be incompatible with an adaptive polymorphism, criticisms of Wilson's argument do not affect the EOBD hypothesis since the two hypotheses are argued on different grounds.

11. Nesse (2000) discussed the evolutionary origin of milder depressions while the ideas presented in this target article account for more severe depressions found in BD. The presence of a BD Major Depressive Episode (BDD) does not rule out other types of depression, which may occur concurrently. Indeed, the many negative consequences that flow from a BD illness would be expected to precipitate ordinary depressions (Coryell et al. 1990; Goldberg et al. 1995; Malkoff-Schwartz et al. 1998). For personal accounts of survivors of the illness see Beers (1953); Berger & Berger (1991); Duke & Hochman (1992), and Jamison (1995b).

12. For several reasons, the EOBD hypothesis de-emphasizes BD as an emotional disorder. (1) An emphasis on moods and emotions overlooks important shifts in levels of activity that occur from the depressive state to hypomanic and mania states (Widlocker 1983). (2) Common meanings of the word "depression" do not envisage the physiological symptoms of severe depression, which was dubbed "chemical depression" to differentiate it from milder depressions. Instead of reporting feelings of sadness or guilt, individuals with "chemical depressions" often report that they feel "Nothing." (3) The ways in which various physiological reactions are interpreted and labelled as emotions are affected by the social and cognitive context in which they occur. For discussions of this point, see DSM-IV (1994) and Whybrow (1997). Lack of emphasis on BD emotional symptoms (sadness, excessive guilt) creates a more culture-free context for understanding BD. In any case, the criteria for the diagnoses of a Major Depressive, Hypomanic, or Manic Episode may be met without inclusion of the emotional symptoms ( 5-8).

13. Among the bipolar group of illnesses is Cyclothymic Disorder, which is characterized by numerous periods of mild hypomanic and mild depressive symptoms. Of individuals diagnosed with Cyclothymic Disorder, 15-50% are subsequently diagnosed with BD (DSM-IV 1994). Since cyclothymia is less severe than BD, is it more reasonable to suppose that cyclothymia, not BD, evolved as an adaptation? In this view, unknown factor(s) make cyclothymic behaviors more severe, resulting in a BD episode. The most cogent reason to focus on BD rather than cyclothymia is this: Diminution of extreme characteristics that are no longer adaptive is a common observation in evolutionary biology. Therefore, it is more parsimonious to focus on BD since an explanation of BD serves for cyclothymia while the converse is not true. (In addition, BD is more clearly defined and more thoroughly researched.)


14. Ernst Kretschmer's book, Physique and Character (1970, orig. 1921), was revised through twenty editions by the time of his death (Anon. 1968); a simplified version of his later views is presented here. Kretschmer was a German psychiatrist steeped in classical learning. He reviewed the literature since antiquity and concluded that descriptions of humanity centre about two basic constitutional types. (Constitution means a group of intercorrelated inherited characteristics; a constitutional type exemplifies characteristics of a genetically homogeneous group [Sheldon et al. 1940].) Kretschmer suggested that the two major mental illnesses, MDI and schizophrenia, descend from these two constitutional types, and that they differ in physique. He observed that individuals with MDI tended to have a pyknic (compact) somatotype, in contrast to the leptosomic (long, slender) body build characteristic of individuals with schizophrenia. (For more information, see Kretschmer [1970]; see Sheldon et al. [1940] for corrections of Kretschmer's text. Caveat: Discussion necessarily centers on BD, to the neglect of schizophrenia. Because relevant literature is old and difficult to access, it is cited in some detail.)

15. Descriptions of the pyknic somatotype emphasized the more distinctive male form; females are similar, but smaller, with broad hips. A summary of Kretschmer's descriptions of the pyknic somotype follows: The pyknic head is large (broad, deep, rounded in back) and set on a short, thick neck. The cheekbones are "massive and prominent," accompanied by a "characteristic underjaw," presumably meaning weak chin. The body of the male pyknic has a broad, deep trunk that is relatively long compared to the length of the arms and legs. The shoulders, not unusually broad, tend to align with the broad pelvis. The distribution of fat is distinctive: a moderate layer of subcutaneous fat covers the entire body; between ages 30-40, fat begins to collect in a pronounced fashion in the abdomen and neck, while the lower limbs are conspicuously free of excessive fat. The face is unusually red. Among females, the breasts and hips concentrate proportionately more fat.

16. Kretschmer's empirical work, using "circulars" (equivalent to BD) as subjects, confirmed his hypothesis. Many subsequent studies tested his ideas with improved methodologies, mostly using subjects from the broader MDI diagnosis (5). Although cold adaptation was not part of Kretschmer's hypothesis, his description of the pyknic somatotype corresponds to that of a cold adapted physique. The idea that environmental cold and heat affect body shape and size is a well-accepted tenet in physical anthropology (Jurmain et al. 1997). A thick body core, with the trunk relatively large compared to the length of the arms and legs, favors conservation of heat. Thus, the association between BD and a pyknic physique suggests that the ancestral BD group was subjected to the selective pressures of cold. Cold adaptations documented in fossil remains include the following: compact, stocky build; bigger brain; expanded cheek area for the maxillary sinuses; larger foramen in the face (to increase blood circulation), and large nose with apomorphic (uniquely derived) internal features (Holliday 1997; Laitman et al. 1996; Schwartz & Tattersall 1996; Stringer 1995; Wolpoff 1999). Some similar adaptations are found among the contemporary Saami (Lapps) and Inuit who, nonetheless, are not closely related to each other (Cavalli-Sforza et al. 1994; Jurmain et al. 1997).

17. To test Kretschmer's hypothesis of an association between mental illness and somatotype, most early studies used the observational method: experts classified patients as pyknic or leptosomic according to descriptive criteria for their age and sex (no forced choice). Westphal (1931, cited in Eysenck 1953) summarized the results of many, independent German studies that used the observational method. Of the total number of subjects with MDI (n=1361), 64.6% were judged to have a pyknic build, 19.2%, leptosomic. Among the subjects with schizophrenia (n=5233), 50.3% were judged to have a leptosomic build, 13.7% pyknic. Two non-German researchers also obtained similar, statistically significant results using the observational method (Burchard 1936; Garvey 1933).

18. Anglo-American empirical psychologists at first enthusiastically received Kretschmer's ideas. For example, although unsympathetic to "type thinking" and preferring quantification to verbal description, Donald G. Paterson (1930) characterized Kretschmer's hypothesis as "bold" and "ingenious," "arising from wide clinical practice and shrewd observation" (238).

19. Empiricists attempted to test Kretschmer's hypothesis using quantitative techniques based on anthropometric measurements, but problems developed, some of which are discussed here. Kretschmer was interested in the genetics of BD and MDI, but research designs examined physique differences as a means of objective diagnosis. A reductionism error occurred in which a complex of ideas was reduced to a narrow focus, unrepresentative of the original whole. Even within this narrow focus, most of the fifteen relevant studies suffered from methodological problems, especially failure to control for age, and/or factors correlated with age, notably fat accumulation.

20. The early literature that Kretschmer's hypothesis inspired was evaluated in ten publications (Anastasi 1937, 1958; Anastasi & Foley 1949; Eysenck 1947, 1953; Hafner 1990; Paterson 1930; Rees 1973; Sheldon et al. 1940; von Zerssen 1976). (See these reviews for relevant references.) In 1937, Anne Anastasi, an outstanding, influential statistician, published the first of three critical reviews. She concluded, "The association reported is too slight to permit body type to be regarded as diagnostic of psychosis (sic)" (Anastasi 1937, 236). In 1949, Anastasi and Foley dismissed small, but statistically significant findings, as of "theoretical interest only." In 1958, much the same opinion was repeated.

21. Other contemporary scientists were more favorable. Sheldon and his colleagues wrote, "Quite a large number of other investigators have repeated Kretschmer's work, and fairly definite general agreement with Kretschmer's main finding has been reported" (26). "(He) may have been closer to matters of greater importance than appears on the surface" (Sheldon et al. 1940, 243). Hans Eysenck (1953, 167), a pioneer in the advancement of psychology as an empirical science, reviewed the literature concerning Kretschmer's work and concluded, "Kretschmer's hypotheses and his methods have been very much misrepresented in the non-German literature." In reference to the results of German researchers summarized by Westphal (1931), Eysenck gave this opinion: "While these figures are subject to much criticism, they nevertheless illustrate a conclusion which is forced on the reader after a careful survey of the whole literature (Eysenck 1947), namely that there is a genuine difference in body build between schizophrenics (sic) and manic-depressives (sic)" (Eysenck 1953, 166). Some idea of the results of these studies may be gained from accounts of the four studies that controlled for what was called the "age factor."

22. With the use of factor analytic techniques, Cohen (1940) obtained a correlation of .41 (p<. 01) between a combined weighted measure (chest depth and pelvic breadth) and psychiatric disorder (MDI versus schizophrenia) in a sample of 47 male patients. In a sample of 51 female patients, a correlation of .56 (p<. 01) was obtained between the combined weighted measure and psychiatric disorder.

23. Pivicki and Christie (1968) studied 231 male patients with schizophrenia and 31 male patients with MDI, covarying out age. They concluded, "Our findings are in agreement in their main points with the majority of similar previous studies. They show once more that the manic-depressives (sic) tend to have a body build which is entirely opposite to that seen in schizophrenics (sic) as a whole" (p.580). (The largest difference was in chest depth [p < .01]).

24. Two studies tested the hypothesis among the southern Chinese. The first used male subjects: 411 with schizophrenia, 42 with affective disorder, and 180 normal controls (Singer et al. 1972). The affective group lacked clear definition, but was described as 25% manic. All groups were matched for mean age and socioeconomic status. Several statistically significant results were obtained. The group with affective disorder was broader (bi-acromial diameter and bi-iliac diameter) than the control group, and the group with schizophrenia (bi-acromial diameter, bi-iliac diameter, and transverse chest diameter); however, affective disorder was not negatively correlated with linearity. The authors concluded, "On balance there was probably insufficient evidence that affectives (sic) were more pyknic"(p. 316). A parallel study with female subjects (317 with schizophrenia, 44 with affective disorder, 115 normal controls) concluded that the correlation between body build and type of mental illness was similar to that reported by Kretschmer (Singer et al. 1976).

25. The last major review of this research was by von Zerssen (1976) in, Human Behavior Genetics, edited by Arnold Kaplan. Von Zerssen wrote, "(Kretschmer's) system received much empirical support until proper scientific criteria were applied to the problem" (249). "Correlations between physique and type or subtype of psychosis (sic) tend to be negligibly low when samples of equal age are compared with each other, and of no practical value for diagnostic purpose" (259). Ironically, however, von Zerssen (1969) made a statistical error, which was apparently unnoticed until this review. Von Zerssen compared several anthropometric measures of patients with MDI and schizophrenia, matching the subjects for age, sex, and verbal intelligence (N=48). He tested the statistical significance of these differences with the Mann-Whitney U-test (Siegel 1956). This test assumes that samples are randomly drawn, which was not the case since the samples were matched for three variables. The effect of this error in research design was to underestimate the size of the effect. Von Zerssen's mistake may have contributed to the demise of interest in Kretschmer's hypothesis. Subsequent to 1976, no studies were found relating physique to BD.

26. Evidence in favor of the hypothesized relationship between MDI and a pyknic build is of three kinds. First, a high percentage of pyknic builds was found among individuals with MDI. Second, individuals with MDI and schizophrenia tended to have contrasting somatotypes. Third, the expected differences were found in comparison of MDI and normal control samples. The weight of evidence favors the hypothesis because of repeated, independent replications, confirmation of specific details, and the absence of studies yielding results contrary to prediction. The significance of the BD-pyknic correlation lies not in its size, but in the demonstration that the relationship is not zero, which even Kretschmer's harshest critics admitted (Anastasi, 1937, 1958; Anastasi & Foley 1949; von Zerssen 1969, 1976). Correlated traits do not always segregate together, and after thousands of years of gene flow, contemporary individuals cannot be expected to exemplify a pure constitutional type. This modest but statistically significant association is consistent with the inference that BD descends from a constitutional type, which had a pyknic build as one of its features. The body of research testing Kretschmer's hypothesis suffers from limitations. The data are old and most of the studies concern MDI, rather than BD samples. A review of the literature does suggest, however, that Kretschmer's intriguing hypothesis was incorrectly discarded (Type II error).


27. The cold adapted physique associated with BD is a clue suggesting that the BD ancestral group was subjected to the selective pressures of cold. In the case of BD behaviors, however, the adaptation was not simply to cold, but to climatic conditions involving "long, severe winters" and "short summers." (These terms are descriptive; they correspond neither to social nor astronomic definitions of seasons. Under severe conditions, cold, snowy, overcast weather may extend beyond the three months of winter, as usually defined, while fair weather may last only two months.) Conditions such as these occurred at various times and places during the Pleistocene. For example, long, severe winters and short summers occurred near the glaciated areas as far south as London and Italy during the Pleistocene; otherwise, such conditions occur only at more extreme latitudes. Of these two possibilities, evolution during the Pleistocene or at extreme latitude, the latter may be ruled out on the grounds that neither data nor theorizing suggest that any group evolved at extreme latitude (Stringer & McKie 1996; Wolpoff 1999). Contemporary groups living at extreme latitude migrated there as the last Ice Age ended (Vrba et al. 1995). Because cold adapted builds may evolve independently, the EOBD hypothesis does not necessarily predict increased incidence of BD among cold adapted peoples, such as the Saami and Inuit. Some data suggest an increased incidence among the Inuit (Sampath 1974; Seltzer & Langford 1984), but a more recent study suggests otherwise (Aoun & Gregory 1998). No relevant epidemiological study of the Saami was found.

28. In thinking about the most likely time and place for the evolution of BD genes, it is important to consider level of cultural adaptation. Improvements in clothing, shelter, food storage, and knowledge of the controlled use of fire weakened the selective pressures of long, severe winters and made biological adaptation less necessary. For this reason, evolution of BD genes more probably occurred earlier rather than later; however, the evolution of these genes has undoubtedly been influenced by factors in many different times and places. One suitable place for the evolution of highly derived characteristics adaptive to long, severe winters and short summers was the northern Temperate Zone of the Old World during the Pleistocene. Small groups were isolated by ice barriers and environmental pressures were extreme, the harshest conditions that humans have ever been known to survive (Boaz 1997; Erickson 1996; Vrba et al. 1995).

29. Scientists working to unravel the BD mystery have started with different threads, but converged on a common path. The salient clue for the present author was the association between BD and a cold adapted build. In contrast, Wehr and Rosenthal (1989, 836) wrote, "The seasonality of some forms of affective illness and their sensitivity to environmental factors may be clues to the nature of affective illness: it might be a disorder of systems that mediate the organism's adaptations to changes in the physical environment." Their ideas confirmed the plausibility that BD evolved as an adaptation to severe climatic conditions.

30. The similarities between BD and the cycle of hibernation behaviors suggest that both sets of behaviors evolved in response to environmental adversity. Two types of depressive behaviors that are more common in BD (Bowden 2000; DSM-IV 1994; Parker et al. 2000) illustrate these similarities. One of these is atypical depression, also called "winter" depression, which involves lethargy, hypersomnia, and marked overeating; it resembles the behavior of hibernating animals that gorge before winter hibernation. For contemporary humans, however, winter conditions of food scarcity never begin; excessive eating often continues, and stored fat is unused. The second type of depression is called Melancholia (DSM-IV 1994), and it is unlike depressions familiar to laypersons. Melancholic individuals are slowed in thought, speech, movement, and physiological functioning. Unresponsive to stimuli ordinarily considered pleasurable, they may even be stuporous. They lose their appetite; weight losses may be significant, and sleep patterns are disturbed. They typically awaken during the early hours of morning; Wehr and Goodwin (1983) showed that the circadian rhythm of energy regulation, as measured by body temperature, was significantly different in a sample of patients with Major Depression compared to a normal control group. This pattern of arousal time may have adaptive significance. The extreme torpor and lack of reactivity of Melancholia resemble hibernation behavior. For further analogies between hibernation and depression, see Wehr (1990).

31. The increased social, sexual, and goal-directed activities typical of hypomania are mirrored in the greatly accelerated fair-weather behaviors of hibernating animals. The irritability, or agitation, of mood disorders may find their counterpart during changeover times, or when biologically influenced behavior sequences are disrupted. (For descriptions of hibernation behaviors, see Kilduff et al. 1993; Rusak 1981; Wehr & Rosenthal 1989.)

32. The potential adaptive significance of BD behaviors is more easily understood when placed in an evolutionary scenario. The picture of a human group holed up together for a long winter lends credence to the adaptive value of BD depressive behaviors. Lack of interest in food, sex, social, or other activity would facilitate group tranquility and survival. Inactivity would conserve energy. Energy conservation was important since humans, compared to other species, are small, slow, weak, and relatively hairless; their young are unusually dependent, and they uniquely rely on their large brains, which have high energy requirements (Aiello & Wheeler 1995). Evidence supports the view that a Major Depressive Episode is characterized by less motor activity than a Manic Episode, or a euthymic state (agitated depression, an exception) (Nofzinger 2000; Wolff et al. 1985).

33. Ways and reasons to conserve energy, hibernation, and hibernation-like behaviors vary widely, and a broader view of these behaviors may be helpful. For example, the conceptual validity of the seasonal occurrence of affective episodes has been questioned because of lack of homogeneity, but known hibernation behaviors are heterogeneous (Kilduff et al. 1993; Rusak 1981). Behavior of the only primate hibernator, the lemur, varies among lemur species, and behavior of the same species varies by sex, and from one part of Madagascar to another. In the case of the lemur, hibernation is an adaptation to drought, not cold (Kappeler & Dill 2000). Other animals hibernate under conditions of high environmental heat (Berger & Phillips 1995; Cossins & Barnes 1996). It is expected that depressive behaviors vary depending upon environmental conditions, and the health and reproductive status of the individual, i.e. each individual's need to conserve energy.

34. Prior theoretical work focused on depression more than hypomania, or mania, but the EOBD hypothesis encompasses both poles of behavior. During the short summer, hypomania would be adaptive since many tasks necessary for survival needed to be accomplished in a short time. Increased activity and heightened interest in sex, social, and goal-directed activities permitted maximal accomplishment of tasks necessary for survival. Elevated self-esteem would facilitate wooing and initiation of new activities.

35. At the extreme end of the continuum, mania would have adaptive potential for emergencies and circumstances of physical challenge. In these situations, superhuman strength and the ability to continue without feeling the need for food and sleep would be advantageous even in modern times (Whybrow 1997). Remarkable "switches" from a severely depressed state to a manic state have been observed to occur within hours (Bunney et al. 1972 a,b,c). This "switch mechanism" may be an emergency reaction that evolved in response to the vulnerability of the depressed state. See Wehr (1990) for a discussion of the evolutionary origin of the connection between depression and sleep, and between mania and sleep-deprivation.


36. The behavior of living organisms is organized by a biological clock that adjusts to environmental variables and regulates circadian and seasonal rhythms. (For recent research on this topic, see Stokkan et al. 2001; for general references, see Klein et al. 1991; Takahashi et al. In Press.) Previous theoretical work examinined BD symptoms as a reflection of energy regulation by the biological clock, especially as influenced by light (Goodwin & Jamison 1990; Healy & Waterhouse 1995; Lewy & Sack 1986; Rosenthal & Wehr 1987; Wehr 1989; Wehr 1990; Wehr & Goodwin 1983; Wehr & Rosenthal 1989; Wehr et al. 1986; Wehr et al. 1993; Wirz-Justice 1995).

37. In a little known article in, Chronobiology International, Wehr (1990) makes some important points relevant to these theoretical ideas: (1) "A principal function of circadian rhythms might be to organize the organism's energy economy in such a way that expenditures of energy occur during intervals of the day-night cycle, and at locations, in which the probability of success in meeting the goals of those expenditures is high, and that conservation of energy occurs when probability of success is low. This is essentially the same function that has been ascribed to seasonal biological rhythms, particularly those of hibernation and reproduction" (12). (2) Two genetically programmed strategies of dealing with threats to energy homeostasis or survival are engagement and withdrawal, which may be reflected in manic and depressive behaviors. These strategies may be evoked by unpredictable stresses, such as social defeats ("reactive homeostasis"), or they can be triggered by endogenous processes in anticipation of regularly recurring stresses, such as seasonal shortages of food, "predictive homeostasis." "The first type of response might correspond to psychogenic affective episodes, the latter to seasonal ones" (13). (3) "It seems likely that interactions between clocks and symptoms would always be bidirectional" (11).

38. The EOBD hypothesis suggests that the BD biological clock is a highly derived adaptation to long, harsh winters and short summers. The problem is not primarily that the biological clock is dysregulated, but that it is regulated differently. For various reasons, however, the BD biological clock may become more frequently and severely dyregulated than is the case in the general population, which may explain some psychotic reactions associated with BD (Goodwin & Jamison 1990). Detailed discussions of neurophysiological mechanisms and the role of various neurotransmitters lie at a different level of analysis, outside the scope of this paper.

39. In contemporary society, the hypothesized, patterned sequences of behavior, as described (30-35) are not regularly observed among persons with BD. Does this mean that the EOBD hypothesis is disconfirmed? Several points merit consideration. (1) Human behavior is flexible and not strongly stimulus bound. (2) Changes have occurred between the hypothesized evolution of BD genes and life now. BD genes may have changed over time and/or combined in novel ways with genes from other groups. (3) The hypothesized environmental niche to which the BD ancestral group adapted no longer exists. (4) Individuals with BD no longer live in a homogeneous group that is supportive of their behaviors. Their genes have been dispersed worldwide, and the rhythm of their lives disrupted. Because of these factors, the cues that elicited BD behaviors are now less reliably compelling. (5) Many BD behaviors are maladaptive and rejected by modern society; individuals with BD often seek to prevent and/or hide BD behaviors. (6) Exogenous factors (psychoactive substances, rapid travel, and unnatural heat and lighting conditions) affect the occurrence of affective episodes. These factors may blunt the occurrence of episodes (e.g. lithium), or precipitate an episode out of time (e.g. cocaine) (Antelman et al. 2000; Goodwin & Jamison 1990; Himmelhoch 2000; Wehr & Goodwin 1987; Wehr et al. 1987).


40. Unlike other creatures, humans were thought unresponsive to environmental influences such as light (Weaver 1979), but recent evidence suggests that light affects humans not only through the eyes, but possibly also through skin exposure (Campbell & Murphy 1998). Data show that humans adapt to changes in environmental light; after switching latitudes, members of successive generations showed altered skin absorption of light (Loomis 1967). Individuals with BD, or a subset of them, may be especially sensitive to light. Compared to normal controls, persons with BD and their offspring were supersensitive to light, as reflected by a lower threshold required to reduce nighttime plasma melatonin levels. This supersensitivity to light was state independent and may be a trait marker for BD, underlying periodic expressions of affective illness (Lewy et al. 1981, 1985; Nurnberger et al. 1988; Nurnberger et al. 2000). It has also been reported that sensitivity to light was reduced by certain medications used to treat BD (Seggie et al. 1989 a,b). Supersensitivity to light supports the view that BD environmental physiology is more highly derived. Also, individuals with BD show greater exaggeration of periodicities found in the general population (Eastwood et al. 1985; Lacoste & Wirz-Justice 1989).

41. Evidence from disparate research findings provides support for the behavioral effects of light. (1) Experimental conditions of light deprivation inadvertently produced severe depression in 1 of 16 previously well subjects. The affected subject had a family history of depression in a second-degree relative (Wehr et al. 1993). (2) On the other hand, hypomanic symptoms emerged following phototherapy (Pande 1985). (3) Exposure to intense light is an effective treatment for depression, and possibly even more effective for BDD (Bauer 1993; Beauchemin & Hays 1997; Bower 1998; Deltito et al. 1991; Kripke et al. 1992; Rosenthal & Blehar 1989). (4) Consistent with the hypothesized effects of light, depressive episodes tend to begin during nighttime sleep, manias during daytime wakefulness (Feldman-Naim et al. 1997). These data are suggestive, but more verification is needed.

42. An association between the seasons and affective episodes is formally recognized in the psychiatric nomenclature, but the diagnostic criteria have varied over time and are in flux (Bauer & Dunner 1996; DSM III-R 1987; DSM-IV 1994; Faedda et al. 1993; Rosenthal et al. 1984; Wirz-Justice 1995).

43. Research about seasonal variation in affective episodes encounters many sources of error. These include: failure to use standard diagnostic procedures; groups of mixed diagnosis; unspecified polarity of the incident; data reflecting hospital admission rather than onset of illness; problems defining an episode; differing definitions of season. Studies lack controls for unadmitted drug abuse, prescribed medications, and for unusual exposure to light, or change in light exposure. The onset of depression is less accurately dated than the onset of mania (Winokur 1976), and hospitalizations for depressions are more likely to reflect the severity of the illness than the date of onset (Goodwin & Jamison 1990). Perhaps for this reason, more recent studies focused on manic rather than depressive episodes. The review of the literature is limited to seasonal variation of BD episodes.

44. Data suggest that a seasonal pattern is more common for Hypomanic than Manic Episodes (Bauer & Dunner 1999; Rosenthal et al. 1984; Thompson & Isaacs 1998; Wirz-Justice et al. 1986). The largest number of comparable studies concerns seasonal variation in hospital admissions for Manic Episodes. Most of these studies involve retrospective analysis of hospital admissions records, often over a period of many years. In keeping with previous findings (DSM-IV 1994; Leibenluft 1996), more women than men were hospitalized. Also, women sometimes showed a statistically significant seasonal pattern when men did not; the statistical significance of these gender differences was usually unreported. (Caveat: Gender differences in BD behaviors are beyond the scope of this paper; see Arnold et al. 2000; Hendrick et al. 2000; Leibenluft 1996; Weissman et al. 1996.) Table 1 displays the results of studies examining the peak season of hospital admissions for Manic Episode.

 TABLE I: Studies Examining Season of Peak Hospital Admissions for
 Manic Episodes.

     Study          Location         Years    No Subj.  No Admi.  Results

  1. Symond &       England & Wales  1970-73  M=7,196             Summer
     Williams 1976  52oN                      F=11,152            (Women)

  2. Walter         Reanalysis                                    Summer
     1977           See above.                                    (Men also)

  3. Myers &        England & Wales  1967-74  Not                 Summer
     Davies 1978    Scotland         1964-74  available           Summer

  4. Frangos        Greece           1928-79  M=107               Spring &
     et al. 1980    38oN                      F=133               Summer

  5. Carney         Ireland          1980-84  M=27                Summer
     et al. 1988    53oN                      F=39

  6. Mulder         New Zealand      1980-84  M=1,528             Spring &
     et al. 1990    42oS                      F=2,388             Summer

  7. Sayer          New Zealand      1979-87            N=5,160   Spring &
     et al. 1991                                                  Summer

  8. Jain           India            1980-88  N=270/yr            No peak
     et al. 1992    12oN (Bangalore)          M=63%

  9. Takei          England & Wales  1976-86  M=1,948             Summer
     et al. 1992                              F=2,475

  10. Jones         Tasmania         1983-89            M=485     Summer
     et al. 1995    41oS                                F=795

  11. Kerr-Correa   Brazil           1982-91  M=49      M=100     Spring &
     et al. 1998    21oS (Sao Paulo)          F=64      F=180     Summer

  12. Suhail &      England          1995     M=50                Summer
     Cochrane 1998  52oN (Birmingham)         F=65                (Women)

  13. Clarke        Ireland          1989-94  N=2,654             Summer
     et al. 1998

  14. Partonen &    Finland          1969-91  N=295               No peak
     Lonnqvist 1999 62oN

  15. Whitney       Canada           1920-95            N=2,533   No peak
     et al. 1999    50oN (Ontario)

45. None of the studies in Table 1 showed peak hospital admissions for Manic Episode during autumn or winter. In 13 of the 15 samples, hospital admissions for Manic Episode peaked in spring, summer, or during both periods. Seasonality was demonstrated in the Temperate Zones of both hemispheres. Failure to find a seasonal effect in Ontario, Canada is surprising, but data may be flawed. Whitney and colleagues (1999) acknowledged limitations of their study, which included changes in diagnostic criteria over time, and coding of diagnosis by clerical staff, rather than attending psychiatrists. Both of the remaining studies were conducted at latitudes outside the hypothesized environmental niche for BD's evolution: one (Jain et al. 1992) was conducted in a tropical area, which lacks seasons; the other (Partonen & Lonnqvist 1999) took place at extreme northern latitude. Overall, these findings are consistent with the EOBD hypothesis.

46. Data from the three large-scale studies of seasonal variation in BDD hospital admissions showed no peak season (Frangos et al. 1980; Suhail & Cochrane 1998), but Partonen and Lonnqvist (1996) found that the first episode of BDD occurred significantly more often during the week following the autumnal equinox. In South Africa, which has a latitude of 26 degrees south, Szabo and Blanche (1995) found a seasonal effect of hospital admissions for BDD, but not for Manic Episode in a small sample of white patients.

47. Other studies help round out the picture. (1) Instead of dating episodes by hospital admission, Silverstone and colleagues (1995) used the month of first symptoms. They found no seasonal effect for Manic Episodes in either London or New Zealand; first symptoms of BDD occurred significantly more often during autumn in both samples. (2) Initial outpatient visits for Manic Episodes peaked in spring in Tokyo (Kamo et al. 1993). (3) Manic, aggressive behavior was statistically more frequent during springtime (D'Mello et al. 1995). (Other results from this study are unreported because polarity of the episode was unspecified.) (4) Seasonal mania was identified in 15% of 86 patients from the London area, but there was no single pattern (Hunt et al. 1992). (5) The Seasonal Pattern Assessment Questionnaire did not differentiate 28 BD patients from controls (Hardin et al. 1991).

48. Several studies related environmental variables to hospital admissions. Myers and Davies (1978) reported moderate, positive relationships between admissions for Manic Episode and temperature, day-length, and daily hours of sunshine. Peck (1990), reanalyzing data from a previous study (Carney et al. 1988), found a strong relationship between amount of sunshine and admissions for mania one month later. In Israel, admissions for BDD were negatively correlated with monthly photoperiod (i.e., highest during winter) (Modai et al. 1994). Suhail and Cochrane (1998) reported that temperature explained 46% (R=0.68) of the variance in BDD admissions. Hours of daylight and hours of sunshine accounted for 68% (R=0.82) of the variance for admissions for Manic Episodes. Similar, but weaker associations were reported by Sayer and colleagues (1991). Eagles (1994) reported covariance (0.55) of mood and hours of sunshine in a single BD patient. All of these studies, which involve more carefully controlled measurement of some of the important variables, show the relationship between BD episodes and environmental variables expected by the EOBD hypothesis.

49. In summary, the EOBD hypothesis conceptualizes BD behaviors as highly derived adaptations to the selective pressures of exceptionally long, severe winters, and short summers. This hypothesis developed from two disparate sources synthesized in the context of evolutionary theory. The first source is Ernst Kretschmer (1970) who observed that BD is associated with a pyknic (thick, compact) physique, which is cold adapted. A review of the literature showed empirical support for the association between BD and a pyknic build, which in turn suggested that BD evolved as an adaptation to severe climatic conditions. This line of thinking dovetailed well with theorizing by Wehr and Rosenthal (1989), and Goodwin and Jamison (1990). They observed the seasonality of BD episodes, their relationship to environmental variables, especially light, and the resemblance between BD behaviors and hibernation behaviors. A review of the literature suggests that environmental factors affect BD behaviors in the expected ways. The EOBD hypothesis may gain independent support from Wilson (1998) who arrived at the conclusion that MDI evolved as an adaptation using a different process of reasoning. No known facts contradict the EOBD hypothesis, but its ideas need further empirical support and testing. The strength of the hypothesis lies in its explanatory power and its fit to known facts. The EOBD hypothesis raises questions about where, when, and among whom BD genes evolved. Our growing knowledge of the human genome may soon permit us to answer these questions.


50. The EOBD hypothesis is not primarily concerned with proximate causes of BD episodes. It does not account for rapid cycling, mixed states, kindling, or neuroanatomical differences between individuals with BD and others. (For reviews and information on these topics, see DSM IV 1994; Ghaemi et al. 1999; Hauser et al. 2000; Pearlson 1999; Post & Weiss 1996; Soares & Gershon 2000; Wehr & Goodwin 1987. The EOBD hypothesis does predict many differences between individuals with BD and the general population; see 55.)

51. BD in children is postdicted by the EOBD hypothesis since their adaptations must necessarily be congruent with those of their parents. Discrepancies between the symptoms and course of the disorder in children and adults are not accounted for by the EOBD hypothesis (Biederman et al. 1998; Geller et al. 1996; Geller & Luby 1997). BD behaviors in children may be seen differently in light of the possible role of the biological clock and energy-regulating mechanism.

52. The EOBD hypothesis does not exclude a viral contribution to the etiology of BD (Yolken & Torrey 2000).

53. Discussion of suicidal behaviors is beyond the scope of this paper; see Jamison (1999; 2000).

54. The designator, EOBD, may to used to differentiate this hypothesis from other hypotheses about the evolutionary origin of BD.


55. Kretschmer (1970) suggested that BD descends from an outlier constitutional type (14) that is different from the general population in many more respects than have been investigated. Compared to a control group, individuals with BD may share low frequency (derived) characteristics. However, research designs of adequate power are needed to demonstrate relationships between low frequency traits. For example, the association between BD and the O Rh-negative blood type can be validly tested only by use of a large number of subjects. Knowledge of the correlates of BD may improve diagnostic accuracy since the more correlates, the more likely that the individual carries BD genes. (If each of two traits has an incidence of 1/100, the probability of their occurring together is 1/1000.) This approach may facilitate identification of phenotypes useful in genetic research.

56. If BD is an adaptation to severe long, cold winters, and short summers, it could not have evolved in tropical Africa, and no existing data or theory suggests that prehistoric peoples returned to tropical Africa after a long sojourn in the northern Temperate Zone (Stringer & McKie 1996; Wolpoff 1999). Severe depression could evolve in tropical Africa as an adaptation to extreme, adverse environmental conditions. Mania could evolve as an emergency reaction, but it seems unlikely that the full spectrum of bipolar behaviors would independently evolve among indigenous peoples of tropical Africa. For example, one would not expect an indigenous person, free of European and other nonindigenous genes, to manifest both BDD and Manic Episodes. Szabo (1994) reported seasonality in a group of black South African patients with affective disorders; some data suggest ethnic differences in the incidence of BD (e.g., Kirov & Murray 1999), but answers to crucial questions await more refined research approaches.


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