I'm not sure what to make of the findings with lithium, definitely complicated. Appreciate you drawing attention to that complexity.
The discussion section of one of the papers linked from the post you shared stuck out to me.
From: Helbich, M., Blüml, V., Leitner, M., & Kapusta, N. D. (2013). Does altitude moderate the impact of lithium on suicide? A spatial analysis of Austria. Geospatial Health, 7(2), 209–218. https://doi.org/10.4081/gh.2013.81
(Unindented:)
The present research statistically investigated the impact of lithium in drinking water on suicide rates in response to altitude across 99 districts in Austria from a spatial perspective. Simple correlation analysis showed a distinct positive association between altitude and SMR, corroborating previous studies (Brenner et al., 2011; Kim et al., 2011) that speculated the influence of altitude on brain oxygen supply might explain higher suicide rates in high-altitude areas. Supporting Shvartsev’s findings (2008), which demonstrated that the general salinity of groundwater increases with decreasing altitude—an association that holds true for lithium—our results also showed a negative association between lithium concentrations and altitude.
Considering the previously reported negative association between lithium levels in drinking water and SMR by Kapusta et al. (2011) and Helbich et al. (2012), these findings offer a novel explanation for the reported association between altitude and SMR: lower lithium concentrations in the ground and drinking water might be responsible for higher suicide rates in high-altitude areas. Of course, this hypothesis needs further meticulous examination.
Subsequently, our study expands previous simple main effects models, which tested only the effect of lithium on suicide in addition to other control variables, by including the predictor altitude as well as its interaction effect with lithium. The significant negative association of lithium and suicide rates in Austria still held true. More importantly, this study demonstrates that this effect is moderated by altitude. While lithium is negatively associated with suicide rates in lower-altitude regions, this association changes to a positive correlation in high-altitude regions. The modeling results show that assuming additivity in the parameters, as in Helbich et al. (2012) and others, hides essential relationships, indicating that more complex associations can be expected.
The possible mechanism of action for this moderating effect of altitude on lithium activity is uncertain. It has been reported that altitude influences the pharmacokinetics of lithium and that these changes might be clinically significant (Arancibia et al., 2003; Brahm and Puls, 2011). Yet, more research using experimental designs is needed to investigate the interaction between lithium and altitude in more detail. Finally, the results highlight the requirement for explicit consideration of spatial effects in this type of medical research. To our knowledge, this paper successfully uses SEF for the first time in medicine to correct for spatial effects in linear models.
Woodard's American Nations "Far West" cultural grouping roughly corresponds to this map. Woodard divides states into smaller units (I think counties) so the eastern chunk of California, Oregon and Washington are different from the western portions. The "Far West" also generally correlates with the elevation factor. You would expect his "Appalachian" culture to be somewhat similar, but that does not play out here. Since Woodard is going specifically to the organizing cultural assumptions, it would probably relate to the gun culture adopted in those regions.
Thank you for reading, David. I see what you mean with the contrast between the part of the map Woodward grouped and described as "Far West" vs "Left Coast".
There is a theory about lithium accumulation in drinking water along the water shed that tracks with the suicide–altitude correlation (https://slimemoldtimemold.com/2021/08/02/a-chemical-hunger-part-vii-lithium/).
I'm not sure what to make of the findings with lithium, definitely complicated. Appreciate you drawing attention to that complexity.
The discussion section of one of the papers linked from the post you shared stuck out to me.
From: Helbich, M., Blüml, V., Leitner, M., & Kapusta, N. D. (2013). Does altitude moderate the impact of lithium on suicide? A spatial analysis of Austria. Geospatial Health, 7(2), 209–218. https://doi.org/10.4081/gh.2013.81
(Unindented:)
The present research statistically investigated the impact of lithium in drinking water on suicide rates in response to altitude across 99 districts in Austria from a spatial perspective. Simple correlation analysis showed a distinct positive association between altitude and SMR, corroborating previous studies (Brenner et al., 2011; Kim et al., 2011) that speculated the influence of altitude on brain oxygen supply might explain higher suicide rates in high-altitude areas. Supporting Shvartsev’s findings (2008), which demonstrated that the general salinity of groundwater increases with decreasing altitude—an association that holds true for lithium—our results also showed a negative association between lithium concentrations and altitude.
Considering the previously reported negative association between lithium levels in drinking water and SMR by Kapusta et al. (2011) and Helbich et al. (2012), these findings offer a novel explanation for the reported association between altitude and SMR: lower lithium concentrations in the ground and drinking water might be responsible for higher suicide rates in high-altitude areas. Of course, this hypothesis needs further meticulous examination.
Subsequently, our study expands previous simple main effects models, which tested only the effect of lithium on suicide in addition to other control variables, by including the predictor altitude as well as its interaction effect with lithium. The significant negative association of lithium and suicide rates in Austria still held true. More importantly, this study demonstrates that this effect is moderated by altitude. While lithium is negatively associated with suicide rates in lower-altitude regions, this association changes to a positive correlation in high-altitude regions. The modeling results show that assuming additivity in the parameters, as in Helbich et al. (2012) and others, hides essential relationships, indicating that more complex associations can be expected.
The possible mechanism of action for this moderating effect of altitude on lithium activity is uncertain. It has been reported that altitude influences the pharmacokinetics of lithium and that these changes might be clinically significant (Arancibia et al., 2003; Brahm and Puls, 2011). Yet, more research using experimental designs is needed to investigate the interaction between lithium and altitude in more detail. Finally, the results highlight the requirement for explicit consideration of spatial effects in this type of medical research. To our knowledge, this paper successfully uses SEF for the first time in medicine to correct for spatial effects in linear models.
Woodard's American Nations "Far West" cultural grouping roughly corresponds to this map. Woodard divides states into smaller units (I think counties) so the eastern chunk of California, Oregon and Washington are different from the western portions. The "Far West" also generally correlates with the elevation factor. You would expect his "Appalachian" culture to be somewhat similar, but that does not play out here. Since Woodard is going specifically to the organizing cultural assumptions, it would probably relate to the gun culture adopted in those regions.
Thank you for reading, David. I see what you mean with the contrast between the part of the map Woodward grouped and described as "Far West" vs "Left Coast".