The synchronies between lunar orbital cycles and bipolar mood cycles raise the possibility that the lunar cycles entrained or even generated the mood cycles. Although the present study did not address causality, several observations suggest that the hypothesis of a causal relationship between lunar cycles and mood cycles is plausible:

1 Diverse patients exhibited similar periodicities in their mood cycles, as if they arose from a common external source (Figures 1, 2, 3, 5 and 6). 2 These periodicities were synchronous with multiples of bi-weekly lunar tidal cycles. 3 Changes in the mood cycles’ frequency were not gradual, but rather were quantal or modular, as though the mood cycles were constrained to remain synchronous with integer multiples of the bi-weekly lunar cycles, with resonances of 1:2, 1:3 and 2:3 in most cases (Figures 5 and 6). Interestingly, such resonances are ubiquitous among the gravitational interactions between orbiting bodies in the solar system. For example, for every two orbits of Pluto, Neptune completes three—a 2:3 resonance. For every orbit of Jupiter’s moon Europa, its moon Io completes two—a 1:2 resonance. For every orbit of the trans-Neptune object, 2003 LG7, Neptune completes three—a 1:3 resonance. 4 After such frequency changes, when onsets of mania shifted back to their initial mode of synchrony with lunar tidal cycles, they re-established the same phase-relationships to those cycles that they had previously exhibited, as would occur if they were entrained to, or were generated by those cycles (Figure 4 and Supplementary Figure S4). 5 Major shifts in frequency from shorter mood cycles to longer mood cycles repeatedly coincided with 206-day recurrences of perigee-syzygies in six cases (Figure 4, 5 and Supplementary Figure S4).

With regard to causality, the case of index Patient 17 seems particularly compelling. Frequency shifts from shorter to longer mood cycles consistently coincided with 206-day recurrences of perigee-syzygies through five iterations (Figure 4). After such shifts, a stereotypic sequence of alternating advances and delays in the onsets of mania recurred repeatedly (Supplementary Figures S5a and S6). Furthermore, in each iteration, the sequences of alternating advances and delays could be mapped onto alternating recurrences of every second and every third spring–neap cycle and onto combinations of multiples of declination cycles and spring–neap cycles (Supplementary Figures S5b and S6). Finally, transits of full-moon and new-moon peaks of every second spring–neap cycle exhibited temporal relationships with onsets of mania in one sequence of mood cycles that were repeated exactly in the sequence of mood cycles that followed, one-half lunar year later (Supplementary Figure S5c). The co-occurrence of so many coincidences spanning so many iterations seems highly improbable.

Patient 8’s data suggest a causal explanation for the prevalence in the patient group of shifts among 1:2, 1:3, 2:3 and other modes of resonance of mood cycles with lunar cycles. In Patient 8, the shifts appear to have facilitated the mood cycles’ being simultaneously entrained to both the spring–neap cycle and the declination cycle, in spite of the two lunar cycles’ having slightly different periods (Figure 7 and Supplementary Figure S6). Simultaneous entrainment to both the spring–neap cycle and the declincation cycle is not surprising, because the two cycles are inextricably linked. Both emanate from a single body’s orbit around the earth, and their oscillations are expressed additively in a single gravimetric variable.

If lunar orbital cycles controlled the mood cycles in these patients, how might they have done so? The fact that the period of the declination cycle differs slightly from the period of the spring–neap cycle, whose every second peak coincides with the full moon, would seem to indicate that the declination cycle acts through a medium other than moonlight, such as, for example, gravitational forces, or more likely, perhaps, gravitational forces’ effects on other media, such as the earth’s magnetic field or its atmosphere.21, 22, 23, 24

Longitudinal recordings of body temperature in Patients 5, 9, 12, and 17 and in other patients suggest a possible biological mechanism through which lunar gravimetric cycles might control mood cycles (Supplementary Figures S13-15).18 The recordings show that that the timing of circadian rhythms in temperature consistently shifted progressively later during periods that led up to switches from depression to mania, and that these changes coincided with every second or every third transit of a lunar semi-diurnal tide (Supplementary Figure S13). These observations raise the possibility that transits of the tide intermittently entrained a component of the human circadian (or circalunar) timing system to its 24.84-h rhythm during phases of the bi-weekly cycles when the tide’s amplitude was highest and its strength as a forcing cycle would be greatest. This type of shift in the timing of circadian rhythms relative to the timing of sleep has been shown to cause switches from depression to mania and might therefore be a mechanism through which a semi-diurnal tide could drive the mood cycles (Supplementary Figure S16).13, 25, 26, 27, 28, 29

The complexity and variety of the associations reported here between mood cycles and lunar orbital cycles might be non-physiological artifacts of modern lighting technology, which has greatly diminished the impact of the moon’s luminance cycle.30 In a natural lighting environment, the 29.5-day cycle of waxing and waning moonlight might once have reinforced entrainment of bio-behavioral cycles to 29.5-day recurrences of every second spring–neap gravimetric cycle and suppressed their entrainment to non-synchronous 27.3-day recurrences of every second declination gravimetric cycle, as well as to every third, fourth or sixth oscillation of either the spring–neap or the declination gravimetric cycles. The brightness of the full moon might also have reinforced the mood cycles’ entrainment to the full-moon phase of every second spring–neap gravimetric cycle and suppressed their entrainment to its new-moon phase. In these circumstances, the bio-behavioral cycles might once have exhibited the simple, one-to-one relationship with recurrences of the full moon that has been sought, but not found, in modern epidemiological studies.3

Implicit in the foregoing discussion is a hypothesis that the putative biological system that responds to lunar cycles has two separate, but mutually reinforcing entrainment mechanisms—one that responds to the moon’s luminance cycles and one that responds to the moon’s gravimetric tidal cycles. If humans possess such a system, its function remains to be elucidated. In other animals, such systems most often serve to facilitate reproduction and avoidance of predation.6 Whatever its function in humans, light pollution has made the operation of this system dysfunctional, in the scenario proposed above.

In the eight menstruating women, it is unclear whether lunar influences, if present, act directly on the mood cycles or—as Patient 12’s data might suggest—indirectly through the menstrual cycle (Supplementary Figure S11). The occurrence of hypersexuality in mania and loss of libido in depression does indicate that mood cycles and cycles in the reproductive neuroendocrine system are linked.

Antidepressant medications sometimes induce, or accelerate the frequency of, rapid mood cycling.12 These types of responses seem to have occurred in nine patients (Patients 3, 4, 6, 8, 9, 11, 14, 15 and 17), in as much as withdrawal of these agents was associated with slowing of cycling or onset of unremitting depression (see, for example, Supplementary Figure S7).10, 13, 19, 20 If the relationship of mood cycles to lunar cycles is causal, this observation raises the possibility that antidepressant medications somehow sensitized the individuals to the influence of lunar cycles. This effect might result from the demonstrated capacity of some antidepressants to slow the intrinsic rhythm of the circadian pacemaker, thereby making it susceptible to capture by the slower-than-24-h rhythm of the lunar tidal day.31, 32

If bi-weekly lunar cycles drive rapid mood cycles by entraining the circadian pacemaker to the 24.8-h lunar tidal day, how might one interfere with their influence? One approach would be to refrain from prescribing antidepressant medications while continuing maintenance treatment with lithium carbonate.12 Another approach would be to strengthen the pacemaker’s entrainment to the 24.0-h solar day. This could be accomplished by exposing patients to longer periods of darkness at night, which have been shown to increase the amplitude of the pacemaker’s phase-responses to light and strengthen its coupling to the light–dark cycle.33 Consistent with this prediction, Patient 9 achieved a complete remission when he stayed in total darkness from 1800 hours to 0800 hours every night.10 Recently reported modifications of this procedure might make it more practical and convenient.34

In summary, rapid bipolar mood cycles exhibited synchronies with three different lunar cycles that modulate the amplitude of the moon’s semi-diurnal tides. Future research would be necessary to determine whether the findings can be replicated, and whether they can be extended more broadly to other biological phenomena. In this regard, recent reports of lunar month variation of total sleep time in healthy individuals seem consistent with the finding of lunar month variation in onsets of mania, which are associated with marked changes in total sleep time (Supplementary Figure S16).35, 36, 37, 38, 39, 40, 41

The force that emanates from the moon whose variation is subject to all three types of lunar cycles is gravity. If the associations between lunar cycles and mood cycles are causal in nature, they would indicate that: (1) cycles in the moon’s gravimetric tides govern the course of a type of bipolar illness; (2) humans possess a biological system that can detect and respond to lunar gravimetric cycles directly, or indirectly through an intervening variable; and (3) operations of this system are part of the mechanism that underlies the illness. The findings would also raise the possibility that modern light pollution has substantially altered the operations of this system. More broadly, the findings would open a new perspective on humans’ place in their cosmic neighborhood.