Differences in childhood stress between Neanderthals and early modern humans as reflected by dental enamel growth disruptions

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Limmer, Matteo Santon, Kate McGrath, Katerina Harvati, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3757968/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Neanderthals’ lives historically portrayed as highly stressful, shaped by constant pressures to survive in harsh ecological conditions, thus potentially contributing to their extinction. Recent work has challenged this interpretation, leaving the issue of stress among Paleolithic populations highly contested and warranting in-depth examination. Here, we analyze the frequency of dental enamel hypoplasia, a physiological stress induced pathology, in the largest sample of Neanderthal and Upper Paleolithic dentitions investigated to date. To track potential species-specific patterns in the ontogenetic distribution of childhood stress, we present the first comprehensive Bayesian modelling of the likelihood of occurrence of individual and matched enamel growth disruptions throughout ontogeny. Our findings support similar overall stress levels in both groups but reveal species-specific patterns in its ontogenetic distribution. While Neanderthal children faced increasing stress starting with the weaning process and culminating in intensity post-weaning, physiological stress in Upper Paleolithic children was found to be limited to the period of weaning and substantially dropping right after its completion. These results might, at least in part, reflect differences in childcare or other behavioral strategies between the two taxa, including those that were advantageous for modern humans’ long-term survival. Biological sciences/Evolution/Anthropology/Biological anthropology Biological sciences/Evolution/Archaeology Figures Figure 1 Figure 2 Figure 3 Introduction Neanderthals have been traditionally portrayed as having led exceptionally stressful lives including the pressure to survive in Eurasia’s Pleistocene harsh and widely fluctuating ecological conditions, which was thought to have contributed to their extinction [ 1 ]. Even though Upper Paleolithic modern humans (UPMH) also faced similar environmental conditions, particularly leading up to and during the Last Glacial Maximum [ 2 ], they are commonly believed to have been better able to mitigate such pressures through their behavioral repertoire. This included strategies such as greater flexibility and efficiency in resource exploitation and more complex social organization and networks. Their behavioral repertoire was thought to have provided UPMH with a competitive advantage over Neanderthals, allowing them to persist while Neanderthals perished [ 3 – 9 ]. Some recent studies, however, are casting doubt on this view, arguing instead that Neanderthals and UPMH led similarly stressful lives [ 10 – 12 ]. Here, we further explore the topic of stress in the Paleolithic. We track dental enamel hypoplasia, i.e., localized areas of reduced enamel thickness resulting from periods of growth disruptions during crown formation. [ 13 – 15 ]. Experimental and clinical research on recent humans and primates, as well as on other mammals, have extensively shown that physiologically demanding periods, such as times of illness, infections, malnutrition, deficiencies or trauma, can result in the manifestation of hypoplastic defects on dental enamel surfaces [ 13 , 16 – 20 ]. The examinations of dental enamel hypoplasia can thus be used to provide insights into these physiologically demanding periods, even if the defects themselves are non-specific in their etiology, particularly when associated behavioral records are lacking. Additionally, since enamel is deposited with known regularity and does not remodel in later life, assessments of the position of hypoplastic defects within tooth crowns also allows for the estimation of their timing in dental developmental terms [ 13 , 21 , 22 ]. Thus, enamel hypoplasia, especially in its linear form (LEH), is considered a well-established marker of non-specific physiological stress experienced during ontogeny [ 13 – 15 , 23 ]. The potential of using enamel growth disruptions to elucidate stress profiles of past populations has prompted many studies to track enamel hypoplasia occurrences in Paleolithic hominins [ 12 , 24 – 32 ]. However, these have provided contradictory results when it comes to reconstructions and comparisons of stress levels in Neanderthals and UPMH. While some concluded that Neanderthal children were subjected to severe levels of physiological stress [ 29 , 31 ], i.e., higher than those observed in UP or recent modern humans [ 24 ], others argued that the levels documented for Neanderthals were comparable to those seen in UPMH [ 11 ] and also fell within expected ranges of modern foraging populations [ 26 , 28 ]. The lack of agreement in the interpretations of previous studies stems mostly from two factors: the focus on different samples in different studies, and/or their use of different methodologies. The samples in previous studies have often been limited in the number of individuals or sites represented. Moreover, inconsistencies in the methodology and objectives of these studies, e.g., differences in the kinds of defect and tooth types included, are limiting the potential for direct comparisons. As a result, there is a lack of a comprehensive understanding of enamel hypoplasia occurrences in Paleolithic hominins and thus their implications for childhood stress. Additionally, only a few studies have focused on hypoplastic defects in the context of their ontogenetic distribution [ 27 , 29 , 30 , 33 ]. Thus, our understanding of the relationship between stress marker occurrence and life history and development is still limited. Here, we build upon previous work, overcoming these limitations. We assess the frequency and ontogenetic distribution of dental growth disruptions in the largest sample of Middle and Upper Paleolithic remains studied to date, i.e., a total of 867 teeth representing 177 individuals from a total of 57 sites (Fig. 1 ). As growth disruptions can be expressed in a different way in different tooth types [ 14 , 21 , 23 , 34 ], we document all enamel hypoplasia potentially related to demanding periods during crown formation (i.e., LEH/furrow form, pits/lines of pitting, localized hypoplasia of the primary canine) [ 13 , 15 ]. We thus employ a comprehensive approach to assess all hypoplastic defects and track their developmental timing across all tooth types. We aim to investigate: 1) whether Neanderthals and UPMH experienced different levels of enamel growth disruptions during development and 2) whether the ontogenetic distribution of enamel hypoplasia as a marker for potential physiological stress differed between the two taxa. Results To fulfill these aims, we implemented two generalized linear mixed models. We first evaluated the overall likelihood of enamel hypoplasia occurrence for Neanderthals and UPMH in Model 1. Within hominin groups, we assessed the likelihood for defect manifestation on any single tooth, regardless of its type. Then, we used this same Model 1 to assess the ontogenetic distribution of the likelihood of enamel defect manifestation in each tooth type of each taxon by referencing their known developmental schedules. We further explored the ontogenetic pattern of defect occurrence in Model 2, but here, instead of single teeth, we focused on multiple teeth of single individuals, where we tracked the likelihood of occurrence of systemic stress, i.e., single, or closely timed stress events, as manifested by hypoplastic defects on simultaneously forming regions of different tooth types of single individuals. Assessment of the likelihood of hypoplastic defect manifestation in single teeth within each taxon – Model 1 Our results for Model 1 reveal that, irrespective of tooth type or defect form, Neanderthal and UPMH teeth are comparably likely to be affected by hypoplastic defects (Fig. 2 a, Supplementary Tables S1-S2 ). When the likelihood of hypoplastic defect manifestation was calculated by tooth type, the results show that, within Neanderthals, the deciduous teeth were overall less likely to show defects than all permanent tooth types, except for central incisors, first molars, and third molars, from which no considerable differences were detected ( Fig. 2 b, Supplementary Table S3) . Within the Neanderthal permanent dentition, the central incisors, and first and third molars were less likely to exhibit defects compared to the canines, premolars, and second molars. Additionally, the central incisors were also less likely to exhibit defects compared to the lateral incisors, while the latter were less likely to exhibit defects in comparison to fourth premolars. ( Fig. 2 b, Supplementary Table S3). In UPMH, deciduous teeth were less likely to show hypoplastic defects compared to the permanent central and lateral incisors, canines, and first molars ( Fig. 2 b, Supplementary Table S3) . Within the UPMH permanent dentition, lateral incisors were more likely to exhibit enamel hypoplasia compared to the premolars and second and third molars. The third molars were considerably less likely to show defects than all permanent tooth types except for premolars and second molars ( Fig. 2 b, Supplementary Table S3) . Finally, when we compared the likelihood of defect occurrence by tooth type between the two hominin groups, only premolars and second molars showed a higher likelihood of defect presence in Neanderthal teeth than in UPMH (Fig. 2 b, Supplementary Table S 2 ). Assessment of the likelihood of systemic stress marker occurrence throughout ontogeny – Model 2 In Model 2, we assessed and compared the likelihoods of Neanderthal and UPMH individuals experiencing systemic stress as manifested in hypoplastic defects at each of our predefined 11 dental developmental stages ( Supplementary Tables S4-S5 ). In the UPMH sample, the likelihood of occurrence of systemic stress episodes shows a marked increase starting between Stages 1 and 2 (as indicated by the black arrows in Fig. 3 ), which, after a peak shortly after Stage 3, is followed by a sharp and then gradual but steady decrease. In contrast, the Neanderthal curve shows the beginning of an increasing trend after Stage 2 that peaks at Stage 6, after which it drops sharply to culminate in a period with no traceable systemic stress marker occurrence after Stage 8. At the stages where the likelihood of hypoplasia occurrence peaks in each of the hominin groups, the recorded likelihood at the same ontogenetic stage for the other group remains significantly lower. Also, the recorded peak in the likelihood of hypoplasia occurrence in Neanderthals at dental developmental Stage 6 is significantly higher than that recorded in UPMH at its peak at Stage 3. Discussion The first question this study set out to answer was whether Neanderthal and Upper Paleolithic children faced different levels of physiological stress as gleaned through the analysis of enamel growth disruptions. Previous analyses provided contradictory results, mainly owing to sample size limitations and sample and methodological diversity across studies. Our results are derived from the most comprehensive sample and assessment used to date. They reveal that the probability for any single tooth to manifest a hypoplastic defect (of any form) is similar in Neanderthals and UPMH. These results support previous work arguing for the lack of substantial differences in overall childhood stress levels between the two hominin groups [ 12 , 20 , 21 , 35 ]. Our findings therefore counter arguments that Neanderthal lives were generally much more stressful compared to those of UPMH. Second, we addressed the question of whether Neanderthals and UPMH showed different patterns in the ontogenetic distribution of physiological stress as indicated by enamel hypoplasia. For this, we assessed the timing of defects occurrences by employing two approaches: for the first we referenced enamel hypoplasia occurrences on single teeth using the sequential development of crowns of different tooth types and for the second we matched systemic stress markers occurrence for individuals to one of 11 developmental stages. These stages were defined based on the combination of crown formation status of concurrently developing tooth types. When comparing tooth types, we found that deciduous teeth stand out in both hominin groups as being generally less likely to manifest enamel defects relative to the permanent dentition. This is consistent with previous reports of low defect prevalence in the primary dentition, not only in Paleolithic but also in recent modern human groups [ 13 , 29 , 32 , 36 – 38 ]. Yet, overall, compared to permanent dentition, enamel defects in deciduous teeth in human groups are not-well documented [ 23 , 32 ]. It is possible that different enamel properties and growth patterns of deciduous and permanent teeth could make the former relatively less prone to enamel defects; deciduous teeth generally have faster-forming enamel, resulting in shorter developmental windows and fewer perikymata manifested on the enamel surface [ 13 , 15 , 39 , 40 ]. However, it is also possible that such low prevalence might reflect a sheltered fetal environment during the formation of deciduous tooth crowns [ 13 ]. Our results also reveal that Neanderthals and Upper Paleolithic modern humans differ in their pattern of likelihood of defect occurrence among permanent tooth types. While in UPMH the central and lateral incisors are the most likely tooth types to show enamel defects, in Neanderthals, it is canines and premolars instead. In fact, the premolars (and second molars) are significantly more likely to show defects in Neanderthals compared to UPMH. As the crown formation times of permanent incisors do not generally overlap with those of premolars and second molars in either hominin group [ 23 , 35 , 41 ] (also see Supplementary Table S5) , our results allow us to distinguish a developmentally earlier peak in stress-related enamel defect prevalence in UPMH versus a developmentally later one in Neanderthals. However, single teeth are prone to individual and population specific variation in their enamel growth, microstructure, and crown geometry, all of which might affect their level of susceptibility to disruptions [ 13 , 15 , 22 , 42 ]. We thus cross-checked our results using a second approach in which we concentrated on linear defects matched across multiple tooth types with overlapping crown formation times in single individuals to track systemically stressful periods throughout ontogeny. Linear enamel hypoplasia in particular has been associated with non-specific stress [ 13 – 15 ]. Using this second approach, we also found distinctive patterns of ontogenetic defect distribution in Neanderthals and UPMH ( Fig. 3 ) . We observed that in the UPMH sample, the likelihood of systemic hypoplastic manifestations starts to increase between our dental developmental stages 1–2. This likelihood continues to sharply increase, to peak at a stage of dental development (our Stage 3–4) coinciding with the time of formation of the last third of the permanent incisors and first molar crowns ( Fig. 3 ; Supplementary Table S5) . Therefore, the initiation of the increase in likelihood of stressful periods and its peak, corresponds to the average biological ages at which two life history milestones related to the process of weaning are documented among non-industrial populations [ 43 ]: the average age of first introduction of solid foods around 6 months; and the average age of completion of the weaning process around 2.5 years (see Supplementary Table S5) . A number of studies have demonstrated a link between the stressful process of weaning in the first years of life and the formation of linear enamel hypoplasia particularly on the anterior teeth in nonhuman primates [ 44 – 46 ]. Such a relationship has also been hypothesized for hominins [ 13 , 21 , 29 , 30 , 33 , 37 , 47 – 51 ]. During the weaning process, the increasing energetic demands of a growing infant must be met by supplementing breastmilk with foods that provide the needed nutrition; otherwise, insufficient nourishment can lead to malnutrition, chronic digestive problems, and an increased risk of disease, all potentially causing high metabolic stress, growth disruptions, and thus peaks in enamel hypoplasia occurrences [ 29 , 37 , 49 , 52 ]. In UPMH children, the period coinciding with the process of weaning (from its initiation to its completion) apears to have been the most stressful time, after which we document a gradual continuous decrease in defect occurrence likelihood. In Neanderthals, the pattern is significantly different. First, compared to UPMH, the initiation of the trend of increased stress seems to be delayed by around a stage and a half of dental development ( Fig. 3 ) . Similarly, at dental developmental Stages 3–4, when the hypoplastic manifestation of stress peaks in UPMH, such manifestations are still significantly lower in Neanderthals. For the latter, the likelihood of hypoplastic manifestations of stressful periods increases to the peak level seen in UPMH midway between dental developmental Stages 4–5 ( Fig. 3 ) . Additionally, beyond this point in ontogeny, Neanderthals continue to increasingly be at risk of experiencing further systemic stress events, with likelihoods ultimately surpassing the highest levels we observe for the UPMH, and peaking at a later stage of dental development, i.e., at Stage 6 (after the completion of the incisor and first molar crowns, when the second molar crowns are starting to form). At this point, the likelihood of stress manifestation occurrences in UPMH has already significantly dropped. This ontogenetically delayed initiation and peak in stress events in Neanderthals might initially be interpreted as reflecting delayed initiation and completion of the weaning process in comparison to UPMH. However, dental development could potentially be accelerated in Neanderthals compared to modern humans [ 53 – 55 ]. In such a case, and following dental crown developmental charts established for Neanderthals [ 27 ], the initiation of a trend of increasing likelihood of manifestation of stressful episodes can be aged at between 6–9 months (see Supplementary Table S5 ). This also coincides with the age at introduction of solid foods evidenced in several Neanderthal individuals [ 29 , 48 , 56 – 58 ]. Similarly, also following the age estimates from Neanderthal dental crown developmental charts [ 27 ], as well as more accurate age determinations for relevant specimens (i.e., Engis) based on dental histology [ 54 ], the peak stress we observe in Neanderthals at our Stage 6 corresponds to a chronological age of around 3 years, thus younger than the corresponding estimate of 4.5 years of age for Northern European modern humans at this dental developmental stage [ 59 ]. Even though this biological age of 3 years is broadly within the average age range of 2.5 years ± 10 months for cessation of breastfeeding reported in non-industrial human populations [ 43 , 60 , 61 ], available determinations of ages at cessation of breastfeeding for Neanderthal specimens show that the completion of weaning occurred at around 1.2 and 2.5 years [ 56 , 58 ]. With these estimations, we would then expect a stress peak related to the weaning process to manifest in Neanderthals at our dental developmental stages 4–5, which is not the case (see Supplementary Table S5) . Thus, unless the weaning ages reported for these Neanderthal individuals significantly divert from the population average, the later peak we observe in this group (at our Stage 6) can be interpreted as a post-weaning signal of systemic physiological stress. The early post-weaning phase would potentially continue to be a stressful stage as a child’s growing energetic demands, the developing immune system, and the increased independence, pose an increased risk of malnutrition and disease [ 49 , 52 , 62 – 64 ] which would translate into an increased likelihood of hypoplastic defect manifestation [ 13 , 49 ]. The observation of a reduction of physiological stress post-weaning in UPMH might thus indicate the presence of social and behavioral strategies and/or life history traits that would ensure sufficient high energy nutrition for newly weaned children [ 52 , 62 ]. Some such strategies that play a role in reducing early childhood physiological stress, like prolonged post-weaning dependency, optimized resource exploitation [ 4 , 5 , 7 , 9 , 57 , 65 ], support in provisioning [ 52 , 60 , 64 , 66 ] are believed to have been in place in the Upper Paleolithic Period, and could have contributed in turn to long-term advantages for the population [ 52 , 60 , 66 ]. In summary, even though we detect a similar overall signal in hypoplasia occurrence likelihood on a population level between Neanderthals and UPMH, our findings suggest differences in the likelihood of occurrence of these defects throughout ontogeny between these two Paleolithic hominin groups. We interpret the latter as reflecting a better ability of UPMH in mitigating stress in newly weaned children, in contrast to Neanderthals where the period shortly after the presumed completion of the weaning process coincides with the most stressful childhood phase. Our results could thus be taken as implications for the practice of advantageous survival strategies by UPMH. Methods This study is based on the examination of high-resolution epoxy replicas of 1048 Paleolithic deciduous and permanent dental remains of the Paleoanthropological collection, University of Tuebingen (Germany). Out of these, a total of 867 teeth of which 423 belonged to Neanderthals (n = 75 individuals) and 444 to UPMH (n = 102 individuals) were judged to be sufficiently preserved (with at least 50% of their crown height in good condition) to be included in the analyses. These originated from a total of 57 western Eurasia sites (Fig. 1 ). Following established methodologies [ 13 , 14 , 27 ], lingual and buccal/labial crown enamel surfaces of all selected teeth were inspected by one of the authors (L.S.L.) for the presence of hypoplastic defects under oblique light conditions, first with the naked eye and then with a 20x magnification lamp. Every single hypoplasia incidence identified, (i.e., LEH/furrow form, pits/lines of pitting, localized hypoplasia of the primary canine)[ 13 , 15 ], was recorded; with the tooth type it affected also noted. In the cases when linear defects were identified on multiple teeth of single individuals, their horizontal locations within crown vertical thirds were additionally documented. These locations were then used to estimate ontogenetic timing of defect formation in terms of the 11 dental developmental stages we defined using the concurrency of formation of dental crown thirds of different teeth in northern European populations as reported by Reid and Dean [ 59 ] and Holt et al. [ 67 ] as a reference (see Supplementary Table S5) . Any defects reported on multiple (2 or more) teeth of single individuals and assigned to the same developmental stage were considered as broadly contemporaneous and taken to represent a stressful period, whether a single event or a series of closely timed events. Developmental stages, rather than biological ages, were used in this study to mitigate any potential effects of differences in dental growth patterns between Neanderthals and modern humans. Even if it is argued that Neanderthals had accelerated growth rates compared to modern humans [ 53 – 55 ], they seem to follow a sequence of crown formation comparable to those of modern humans [ 27 , 54 , 57 , 68 , 69 ]. Statistical Analysis Data analysis focused on assessing differences in the rate and timing of defect manifestations in the hominin groups using generalized linear mixed models (GLMMs). Models were implemented in R (version 4.2.1) with the brms package, which fits Bayesian models using Stan [ 70 – 72 ]. Two GLMMs were generated based on a Bernoulli distribution with logit-link to compare, between Neanderthals and UPMH, the likelihood of: 1) a tooth manifesting at least one hypoplastic defect of any form for each tooth type and for an average of all tooth types combined, and 2) an individual experiencing a stressful period at each of the predefined 11 developmental stages. Both models included taxon (NEA, UPMH) as the main factor predictor and individual and site ID as random components to account for the repeated measurements of single individuals and/or sites [ 73 ]. Model 1 further included the factor predictor tooth type and the interaction between tooth type and the main factor predictor taxon . Permanent teeth were divided by tooth type (I1, I2, C, P3, P4, M1, M2, M3) albeit without regard to side or jaw, while deciduous teeth were combined into a single category due to low sample sizes when split by type. This approach allowed for the inclusion of all teeth within our sample (N = 867 teeth of which 423 belong to 75 Neanderthals and 444 to 102 UPMH), including those that were found in isolation. Model 2 included, as a covariate, a smooth interaction term based on the standardized continuous predictor developmental stage (Stages 1–11) grouped by the factor predictor taxon . Additionally, it should be noted that since this second model assessed the likelihood of individuals manifesting a systemic stress period, it was run based on a more restricted sample of the 35 NEA and 37 UPMH individuals manifesting linear defects whose timing of occurrence was assigned to the same developmental stage, i.e., whose vertical locations within crown thirds were broadly matched on at least two concurrently forming tooth crowns in single individuals. Both models were fit using weakly informative prior distributions (normal with mean = 0 and s.d. =1 for intercept and coefficients, exponential (1) for standard deviations) and their performance evaluated with posterior predictive model checking, which compares model predictions with observed data. We ran 4 Markov-Chain-Monte-Carlo (MCMC) chains for each model and obtained coefficient estimates from a total of 16000 postwarmup samples. All model parameters reached reliable conversion indicators [ 74 ]: A Monte Carlo standard error smaller than 5% of the posterior s.d., an effective posterior sample size greater than 10% of the total sample size, and an \(\widehat{R}\) statistic value smaller than 1.01 [ 75 ]. Using customized code based on Santon et. al. [ 76 ], we graphically display the results as the medians of response values across or within the predictors’ and their 95% credible intervals (CIs) of the posterior distributions of fitted values for the population average obtained from the joint posterior distributions of the model parameters [84]. We further used the package emmeans [ 77 ] to compute from Model 1 the pairwise contrast odds ratios and their CIs between Neanderthals and UPMH for each tooth type. Effect size strength increases with increasing deviation of ratios from 1, and the robustness of the result increases with decreasing degree of overlap of the 95% compatibility intervals (CIs) with one. Finally, using the method of finite differences, we estimated the first derivatives of the non-linear trends of Model 2 to identify periods of marked increase or decrease in systemic stress manifestation for each taxon [ 78 ]. Such periods are identified as developmental stages where the credible intervals of the first derivatives do not include zero and are highlighted by arrows in the graphical display ( Fig. 3 ) . Declarations Acknowledgments German Research Foundation Project number 353106138 (SEZ, KH) Baden-Württemberg Ministry for Science, Research and Art (Baden-Württemberg State Research Award 2014, KH) KH is further supported by the German Research Foundation (DFG FOR 2237) and the European Research Council (ERC-AdG-101019659). Open Access Publishing Fund of University of Tübingen. Additional information: Authors declare that they have no competing interests. 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The relationship of accentuated lines in enamel to weaning stress in juvenile baboons (Papio hamadryas anubis). Folia primatologica; international journal of primatology 81, 207–223 (2010). Dirks, W., Reid, D. J., Jolly, C. J., Phillips-Conroy, J. E. & Brett, F. L. Out of the mouths of baboons: stress, life history, and dental development in the Awash National Park hybrid zone, Ethiopia. American Journal of Physical Anthropology 118, 239–252 (2002). Berbesque, J. C. & Doran, G. H. Brief communication: physiological stress in the Florida Archaic-enamel hypoplasia and patterns of developmental insult in early North American hunter-gatherers. American Journal of Physical Anthropology 136, 351–356 (2008). Bermúdez de Castro, J. M. & Pérez, P. J. Enamel hypoplasia in the middle pleistocene hominids from Atapuerca (Spain). American Journal of Physical Anthropology 96, 301–314 (1995). Sandberg, P. A., Sponheimer, M., Lee-Thorp, J. & van Gerven, D. Intra-tooth stable isotope analysis of dentine: a step toward addressing selective mortality in the reconstruction of life history in the archaeological record. American Journal of Physical Anthropology 155, 281–293 (2014). Skinner, M. F., Skinner, M. M. & Boesch, C. Developmental defects of the dental crown in chimpanzees from the Taï National Park, Côte D’Ivoire: coronal waisting. American Journal of Physical Anthropology 149, 272–282 (2012). Infante, P. F. & Gillespie, G. M. An epidemiologic study of linear enamel hypoplasia of deciduous anterior teeth in Guatemalan children. Archives of Oral Biology 19, 1055–1061 (1974). Humphrey, L. T. Weaning behaviour in human evolution. Seminars in cell & developmental biology 21 (2010). Ramirez Rozzi, F. V. & Bermudez, D. C. J. Surprisingly rapid growth in Neanderthals. Nature 428 (2004). Smith, T. M. et al. Dental evidence for ontogenetic differences between modern humans and Neanderthals. Proceedings of the National Academy of Sciences of the United States of America 107, 20923–20928 (2010). Smith, T. M., Toussaint, M., Reid, D. J., Olejniczak, A. J. & Hublin, J.-J. Rapid dental development in a Middle Paleolithic Belgian Neanderthal. Proceedings of the National Academy of Sciences of the United States of America 104, 20220–20225 (2007). Austin, C. et al. Barium distributions in teeth reveal early-life dietary transitions in primates. Nature 498, 216–219 (2013). Nava, A. et al. Early life of Neanderthals. Proceedings of the National Academy of Sciences of the United States of America; 10.1073/pnas.2011765117 (2020). Smith, T. M. et al. Wintertime stress, nursing, and lead exposure in Neanderthal children. Science advances 4, eaau9483 (2018). Reid, D. J. & Dean, M. C. Variation in modern human enamel formation times. Journal of Human Evolution 50, 329–346 (2006). Robson, S. L. & Wood, B. Hominin life history: reconstruction and evolution. Journal of Anatomy 212, 394–425 (2008). Sellen, D. W. Comparison of Infant Feeding Patterns Reported for Nonindustrial Populations with Current Recommendations. The Journal of Nutrition 131, 2707–2715 (2001). Hillson, S. Tooth Development in Human Evolution and Bioarchaeology (Cambridge Univ. Press, 2014). Pettitt, P. B. Neanderthal lifecycles: developmental and social phases in the lives of the last archaics. World archaeology 31, 351–366 (2000). Bogin, B. Childhood, adolescence, and longevity: A multilevel model of the evolution of reserve capacity in human life history. American Journal of Human Biology 21, 567–577 (2009). Timmermann, A. Quantifying the potential causes of Neanderthal extinction: Abrupt climate change versus competition and interbreeding. Quaternary Science Reviews 238, 106331 (2020). Caspari, R. & Lee, S.-H. Is human longevity a consequence of cultural change or modern biology? American Journal of Physical Anthropology 129, 512–517 (2006). Holt, S. A., Reid, D. J. & Guatelli-Steinberg, D. Brief Communication: Premolar Enamel Formation: Completion of Figures for Aging LEH Defects in Permanent Dentition. Dental Anthropology Journal 25, 4–7 (2018). Guatelli-Steinberg, D., Reid, D. J., Bishop, T. A. & Larsen, C. S. Anterior tooth growth periods in Neandertals were comparable to those of modern humans. Proceedings of the National Academy of Sciences of the United States of America 102, 14197–14202 (2005). Tompkins, R. L. Relative dental development of Upper Pleistocene hominids compared to human population variation. American Journal of Physical Anthropology 99, 103–118 (1996). R Core Team. R: A Language and Environment for Statistical Computing (2017). Bürkner, P.-C. Advanced Bayesian Multilevel Modelling with the R Package brms. The R Journal 10, 395 (2018). Bürkner, P.-C. brms: An R Package for Bayesian Multilevel Models Using Stan. Journal of Statistical Software 80 (2017). Schielzeth, H. & Forstmeier, W. Conclusions beyond support: overconfident estimates in mixed models. Behavioral ecology: official journal of the International Society for Behavioral Ecology 20, 416–420 (2009). Korner-Nievergelt, F. et al. Bayesian data analysis in ecology using linear models with R, BUGS, and Stan (Elsevier AP, 2015). Brooks, S. P. & Gelman, A. General Methods for Monitoring Convergence of Iterative Simulations. Journal of Computational and Graphical Statistics 7, 434–455 (1998). Santon, M., Korner-Nievergelt, F., Michiels, N. & Anthes, N. A versatile workflow for linear modelling in R. Frontiers in Ecology and Evolution 11 (2023). Lenth, R. Emmeans: Estimated marginal means, aka least-squares means. R package version 1.8.4–1. Simpson, G. L. Modelling Palaeoecological Time Series Using Generalised Additive Models. Frontiers in Ecology and Evolution 6, 149 (2018). Additional Declarations No competing interests reported. Supplementary Files LimmerSupplementaryMaterialSR.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 25 Jan, 2024 Reviews received at journal 05 Jan, 2024 Reviewers agreed at journal 04 Jan, 2024 Reviewers invited by journal 04 Jan, 2024 Editor assigned by journal 04 Jan, 2024 Editor invited by journal 04 Jan, 2024 Submission checks completed at journal 04 Jan, 2024 First submitted to journal 15 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3757968","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":265501771,"identity":"7edd8cc1-986f-479a-bbf1-a6ced4991cf2","order_by":0,"name":"Laura S. Limmer","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"S.","lastName":"Limmer","suffix":""},{"id":265501772,"identity":"8dc05d28-3235-4567-a0bc-d6de3aa254da","order_by":1,"name":"Matteo Santon","email":"","orcid":"","institution":"University of Bristol","correspondingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Santon","suffix":""},{"id":265501773,"identity":"a9dc61d3-c9ba-43ec-a991-f410058888db","order_by":2,"name":"Kate McGrath","email":"","orcid":"","institution":"George Washington University","correspondingAuthor":false,"prefix":"","firstName":"Kate","middleName":"","lastName":"McGrath","suffix":""},{"id":265501774,"identity":"81c44453-4d48-4a06-9c84-787096188d34","order_by":3,"name":"Katerina Harvati","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Katerina","middleName":"","lastName":"Harvati","suffix":""},{"id":265501775,"identity":"20378d21-ada4-44a0-9f4c-4dba9f20ea9f","order_by":4,"name":"Sireen El Zaatari","email":"data:image/png;base64,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","orcid":"","institution":"University of Tübingen","correspondingAuthor":true,"prefix":"","firstName":"Sireen","middleName":"El","lastName":"Zaatari","suffix":""}],"badges":[],"createdAt":"2023-12-15 09:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3757968/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3757968/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49292073,"identity":"03c65d9c-6e93-443d-a13b-dc0c8521f532","added_by":"auto","created_at":"2024-01-08 05:21:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":186935,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSITES INCLUDED IN THIS STUDY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Map was created in QGIS v.3.18 using Natural Earth vector map data.\u003c/p\u003e\n\u003cp\u003e1 Abri Pataud; 2 Amud; 3 Archi; 4 Arcy-Sur-Cure Grotte Bison; 5 Arcy-Sur-Cure Grotte De L'hyène; 6 Arcy-Sur-Cure Grotte Des Fées; 7 Arcy-Sur-Cure Grotte Du Renne; 8 Biache-St-Vaast; 9 Blanchard (Castelmerle); 10 Brno; 11 Combe Grenal; 12 Couvin; 13 Cro-Magnon; 14 Dolní Věstonice; 15 Engis; 16 Estelas; 17 Farincourt; 18 Fontéchevade; 19 Grimaldi - Barma Grande; 20 Grotta Breuil; 21 Guattari; 22 Isturitz; 23 Kebara; 24 Kulna; 25 La Chaise - Abri Bourgois-Delaunay; 26 La Chaise - Suard; 27 La Ferrassie; 28 La Madeleine; 29 La Quina; 30 Labatut (Castelmerle); 31 Lachaud; 32 Laugerie-Basse; 33 Le Moustier; 34 Le Petit Puymoyen; 35 Les Rois; 36 Malarnaud; 37 Masd'Azil; 38 Mladeč; 39 Monsempron; 40 Montmaurin; 41 Ochoz; 42 Pavlov; 43 Pech De L'Aze; 44 Predmostí; 45 Roc De Marsal; 46 Rochelot; 47 Saccopastore; 48 Saint Césaire; 49 Saint-Germain-La -Rivière; 50 Scladina; 51 Solutré; 52 Spy; 54 Subalyuk; 55 Tabun; 56 Vindija; 57 Zafarraya\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3757968/v1/831cdcafe112dcfb3d2aaf73.png"},{"id":49292070,"identity":"c9e72c70-3042-4849-97db-acece3a29a8b","added_by":"auto","created_at":"2024-01-08 05:21:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25494,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLIKELIHOOD OF NEANDERTHAL AND UPMH TEETH BEING AFFECTED BY ENAMEL HYPOPLASIA (a) \u003c/strong\u003ewhen considering all tooth types in combination, and \u003cstrong\u003e(b)\u003c/strong\u003e when considering different tooth types separately (deciduous teeth: dd with different tooth types combined due to small sample sizes; permanent teeth: I=incisors, C=canines, P=premolars, M=molars). Colored points in (a) represent the likelihood of defect presence averaged for tooth types. Colored points in (b) represent the density of observations for each combination of hominin and tooth type. Diamonds in (a) and (b) represent model predicted medians with error bars showing their 95% credible intervals.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3757968/v1/41b2d68d088bd36805d748f4.png"},{"id":49292072,"identity":"624f1007-d370-4740-9157-841ffd9ec858","added_by":"auto","created_at":"2024-01-08 05:21:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57980,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLIKELIHOODS OF NEANDERTHAL AND UPMH INDIVIDUALS EXPERIENCING SYSTEMIC STRESS OCCURRENCES THROUGHOUT PREDEFINED DEVELOPMENTAL STAGES\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLines represent model predicted medians of stress event occurrences likelihoods across 11 developmental stages and shaded areas represent their 95% credible intervals. Black arrows represent periods of marked increase or decrease in the likelihood of stress event occurrence. Colored points represent the density of observations for each combination of hominin and developmental stage. A description of the developmental stages, distribution of stress events and the equivalent biological age ranges in modern humans and Neanderthals are given in \u003cstrong\u003eSupplementary Table S5\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3757968/v1/9324513e20248c0791cdce0b.png"},{"id":49292380,"identity":"1efcd828-e754-471c-8a0a-255997b460bb","added_by":"auto","created_at":"2024-01-08 05:37:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":632370,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3757968/v1/4163bf95-a48d-4019-8a2b-34a36fa99e49.pdf"},{"id":49292238,"identity":"3aea3579-b0c2-4509-831a-692d47bf113a","added_by":"auto","created_at":"2024-01-08 05:29:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":128693,"visible":true,"origin":"","legend":"","description":"","filename":"LimmerSupplementaryMaterialSR.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3757968/v1/8a56b806697f8293cf3b802b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Differences in childhood stress between Neanderthals and early modern humans as reflected by dental enamel growth disruptions","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNeanderthals have been traditionally portrayed as having led exceptionally stressful lives including the pressure to survive in Eurasia\u0026rsquo;s Pleistocene harsh and widely fluctuating ecological conditions, which was thought to have contributed to their extinction [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Even though Upper Paleolithic modern humans (UPMH) also faced similar environmental conditions, particularly leading up to and during the Last Glacial Maximum [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], they are commonly believed to have been better able to mitigate such pressures through their behavioral repertoire. This included strategies such as greater flexibility and efficiency in resource exploitation and more complex social organization and networks. Their behavioral repertoire was thought to have provided UPMH with a competitive advantage over Neanderthals, allowing them to persist while Neanderthals perished [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Some recent studies, however, are casting doubt on this view, arguing instead that Neanderthals and UPMH led similarly stressful lives [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we further explore the topic of stress in the Paleolithic. We track dental enamel hypoplasia, i.e., localized areas of reduced enamel thickness resulting from periods of growth disruptions during crown formation. [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExperimental and clinical research on recent humans and primates, as well as on other mammals, have extensively shown that physiologically demanding periods, such as times of illness, infections, malnutrition, deficiencies or trauma, can result in the manifestation of hypoplastic defects on dental enamel surfaces [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The examinations of dental enamel hypoplasia can thus be used to provide insights into these physiologically demanding periods, even if the defects themselves are non-specific in their etiology, particularly when associated behavioral records are lacking.\u003c/p\u003e \u003cp\u003eAdditionally, since enamel is deposited with known regularity and does not remodel in later life, assessments of the position of hypoplastic defects within tooth crowns also allows for the estimation of their timing in dental developmental terms [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThus, enamel hypoplasia, especially in its linear form (LEH), is considered a well-established marker of non-specific physiological stress experienced during ontogeny [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The potential of using enamel growth disruptions to elucidate stress profiles of past populations has prompted many studies to track enamel hypoplasia occurrences in Paleolithic hominins [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, these have provided contradictory results when it comes to reconstructions and comparisons of stress levels in Neanderthals and UPMH. While some concluded that Neanderthal children were subjected to severe levels of physiological stress [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], i.e., higher than those observed in UP or recent modern humans [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], others argued that the levels documented for Neanderthals were comparable to those seen in UPMH [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and also fell within expected ranges of modern foraging populations [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The lack of agreement in the interpretations of previous studies stems mostly from two factors: the focus on different samples in different studies, and/or their use of different methodologies. The samples in previous studies have often been limited in the number of individuals or sites represented. Moreover, inconsistencies in the methodology and objectives of these studies, e.g., differences in the kinds of defect and tooth types included, are limiting the potential for direct comparisons. As a result, there is a lack of a comprehensive understanding of enamel hypoplasia occurrences in Paleolithic hominins and thus their implications for childhood stress. Additionally, only a few studies have focused on hypoplastic defects in the context of their ontogenetic distribution [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Thus, our understanding of the relationship between stress marker occurrence and life history and development is still limited.\u003c/p\u003e \u003cp\u003eHere, we build upon previous work, overcoming these limitations. We assess the frequency and ontogenetic distribution of dental growth disruptions in the largest sample of Middle and Upper Paleolithic remains studied to date, i.e., a total of 867 teeth representing 177 individuals from a total of 57 sites (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). As growth disruptions can be expressed in a different way in different tooth types [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], we document all enamel hypoplasia potentially related to demanding periods during crown formation (i.e., LEH/furrow form, pits/lines of pitting, localized hypoplasia of the primary canine) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe thus employ a comprehensive approach to assess all hypoplastic defects and track their developmental timing across all tooth types. We aim to investigate: 1) whether Neanderthals and UPMH experienced different levels of enamel growth disruptions during development and 2) whether the ontogenetic distribution of enamel hypoplasia as a marker for potential physiological stress differed between the two taxa.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTo fulfill these aims, we implemented two generalized linear mixed models. We first evaluated the overall likelihood of enamel hypoplasia occurrence for Neanderthals and UPMH in Model 1. Within hominin groups, we assessed the likelihood for defect manifestation on any single tooth, regardless of its type. Then, we used this same Model 1 to assess the ontogenetic distribution of the likelihood of enamel defect manifestation in each tooth type of each taxon by referencing their known developmental schedules.\u003c/p\u003e \u003cp\u003eWe further explored the ontogenetic pattern of defect occurrence in Model 2, but here, instead of single teeth, we focused on multiple teeth of single individuals, where we tracked the likelihood of occurrence of systemic stress, i.e., single, or closely timed stress events, as manifested by hypoplastic defects on simultaneously forming regions of different tooth types of single individuals.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAssessment of the likelihood of hypoplastic defect manifestation in single teeth within each taxon \u0026ndash; Model 1\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOur results for Model 1 reveal that, irrespective of tooth type or defect form, Neanderthal and UPMH teeth are comparably likely to be affected by hypoplastic defects (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, \u003cb\u003eSupplementary Tables S1-S2\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWhen the likelihood of hypoplastic defect manifestation was calculated by tooth type, the results show that, within Neanderthals, the deciduous teeth were overall less likely to show defects than all permanent tooth types, except for central incisors, first molars, and third molars, from which no considerable differences were detected \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, \u003cb\u003eSupplementary Table S3)\u003c/b\u003e. Within the Neanderthal permanent dentition, the central incisors, and first and third molars were less likely to exhibit defects compared to the canines, premolars, and second molars. Additionally, the central incisors were also less likely to exhibit defects compared to the lateral incisors, while the latter were less likely to exhibit defects in comparison to fourth premolars. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, \u003cb\u003eSupplementary Table S3).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn UPMH, deciduous teeth were less likely to show hypoplastic defects compared to the permanent central and lateral incisors, canines, and first molars \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, \u003cb\u003eSupplementary Table S3)\u003c/b\u003e. Within the UPMH permanent dentition, lateral incisors were more likely to exhibit enamel hypoplasia compared to the premolars and second and third molars. The third molars were considerably less likely to show defects than all permanent tooth types except for premolars and second molars \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, \u003cb\u003eSupplementary Table S3)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eFinally, when we compared the likelihood of defect occurrence by tooth type between the two hominin groups, only premolars and second molars showed a higher likelihood of defect presence in Neanderthal teeth than in UPMH (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, \u003cb\u003eSupplementary Table S 2\u003c/b\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of the likelihood of systemic stress marker occurrence throughout ontogeny \u0026ndash; Model 2\u003c/h2\u003e \u003cp\u003eIn Model 2, we assessed and compared the likelihoods of Neanderthal and UPMH individuals experiencing systemic stress as manifested in hypoplastic defects at each of our predefined 11 dental developmental stages (\u003cb\u003eSupplementary Tables S4-S5\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eIn the UPMH sample, the likelihood of occurrence of systemic stress episodes shows a marked increase starting between Stages 1 and 2 (as indicated by the black arrows in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), which, after a peak shortly after Stage 3, is followed by a sharp and then gradual but steady decrease. In contrast, the Neanderthal curve shows the beginning of an increasing trend after Stage 2 that peaks at Stage 6, after which it drops sharply to culminate in a period with no traceable systemic stress marker occurrence after Stage 8. At the stages where the likelihood of hypoplasia occurrence peaks in each of the hominin groups, the recorded likelihood at the same ontogenetic stage for the other group remains significantly lower. Also, the recorded peak in the likelihood of hypoplasia occurrence in Neanderthals at dental developmental Stage 6 is significantly higher than that recorded in UPMH at its peak at Stage 3.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe first question this study set out to answer was whether Neanderthal and Upper Paleolithic children faced different levels of physiological stress as gleaned through the analysis of enamel growth disruptions. Previous analyses provided contradictory results, mainly owing to sample size limitations and sample and methodological diversity across studies. Our results are derived from the most comprehensive sample and assessment used to date. They reveal that the probability for any single tooth to manifest a hypoplastic defect (of any form) is similar in Neanderthals and UPMH. These results support previous work arguing for the lack of substantial differences in overall childhood stress levels between the two hominin groups [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Our findings therefore counter arguments that Neanderthal lives were generally much more stressful compared to those of UPMH.\u003c/p\u003e \u003cp\u003eSecond, we addressed the question of whether Neanderthals and UPMH showed different patterns in the ontogenetic distribution of physiological stress as indicated by enamel hypoplasia. For this, we assessed the timing of defects occurrences by employing two approaches: for the first we referenced enamel hypoplasia occurrences on single teeth using the sequential development of crowns of different tooth types and for the second we matched systemic stress markers occurrence for individuals to one of 11 developmental stages. These stages were defined based on the combination of crown formation status of concurrently developing tooth types.\u003c/p\u003e \u003cp\u003eWhen comparing tooth types, we found that deciduous teeth stand out in both hominin groups as being generally less likely to manifest enamel defects relative to the permanent dentition. This is consistent with previous reports of low defect prevalence in the primary dentition, not only in Paleolithic but also in recent modern human groups [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYet, overall, compared to permanent dentition, enamel defects in deciduous teeth in human groups are not-well documented [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. It is possible that different enamel properties and growth patterns of deciduous and permanent teeth could make the former relatively less prone to enamel defects; deciduous teeth generally have faster-forming enamel, resulting in shorter developmental windows and fewer perikymata manifested on the enamel surface [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, it is also possible that such low prevalence might reflect a sheltered fetal environment during the formation of deciduous tooth crowns [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur results also reveal that Neanderthals and Upper Paleolithic modern humans differ in their pattern of likelihood of defect occurrence among permanent tooth types. While in UPMH the central and lateral incisors are the most likely tooth types to show enamel defects, in Neanderthals, it is canines and premolars instead. In fact, the premolars (and second molars) are significantly more likely to show defects in Neanderthals compared to UPMH. As the crown formation times of permanent incisors do not generally overlap with those of premolars and second molars in either hominin group [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] \u003cb\u003e(also see Supplementary Table S5)\u003c/b\u003e, our results allow us to distinguish a developmentally earlier peak in stress-related enamel defect prevalence in UPMH versus a developmentally later one in Neanderthals.\u003c/p\u003e \u003cp\u003eHowever, single teeth are prone to individual and population specific variation in their enamel growth, microstructure, and crown geometry, all of which might affect their level of susceptibility to disruptions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. We thus cross-checked our results using a second approach in which we concentrated on linear defects matched across multiple tooth types with overlapping crown formation times in single individuals to track systemically stressful periods throughout ontogeny. Linear enamel hypoplasia in particular has been associated with non-specific stress [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Using this second approach, we also found distinctive patterns of ontogenetic defect distribution in Neanderthals and UPMH \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eWe observed that in the UPMH sample, the likelihood of systemic hypoplastic manifestations starts to increase between our dental developmental stages 1\u0026ndash;2. This likelihood continues to sharply increase, to peak at a stage of dental development (our Stage 3\u0026ndash;4) coinciding with the time of formation of the last third of the permanent incisors and first molar crowns \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; \u003cb\u003eSupplementary Table S5)\u003c/b\u003e. Therefore, the initiation of the increase in likelihood of stressful periods and its peak, corresponds to the average biological ages at which two life history milestones related to the process of weaning are documented among non-industrial populations [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]: the average age of first introduction of solid foods around 6 months; and the average age of completion of the weaning process around 2.5 years \u003cb\u003e(see Supplementary Table S5)\u003c/b\u003e. A number of studies have demonstrated a link between the stressful process of weaning in the first years of life and the formation of linear enamel hypoplasia particularly on the anterior teeth in nonhuman primates [\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Such a relationship has also been hypothesized for hominins [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan additionalcitationids=\"CR48 CR49 CR50\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. During the weaning process, the increasing energetic demands of a growing infant must be met by supplementing breastmilk with foods that provide the needed nutrition; otherwise, insufficient nourishment can lead to malnutrition, chronic digestive problems, and an increased risk of disease, all potentially causing high metabolic stress, growth disruptions, and thus peaks in enamel hypoplasia occurrences [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn UPMH children, the period coinciding with the process of weaning (from its initiation to its completion) apears to have been the most stressful time, after which we document a gradual continuous decrease in defect occurrence likelihood. In Neanderthals, the pattern is significantly different. First, compared to UPMH, the initiation of the trend of increased stress seems to be delayed by around a stage and a half of dental development \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Similarly, at dental developmental Stages 3\u0026ndash;4, when the hypoplastic manifestation of stress peaks in UPMH, such manifestations are still significantly lower in Neanderthals. For the latter, the likelihood of hypoplastic manifestations of stressful periods increases to the peak level seen in UPMH midway between dental developmental Stages 4\u0026ndash;5 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Additionally, beyond this point in ontogeny, Neanderthals continue to increasingly be at risk of experiencing further systemic stress events, with likelihoods ultimately surpassing the highest levels we observe for the UPMH, and peaking at a later stage of dental development, i.e., at Stage 6 (after the completion of the incisor and first molar crowns, when the second molar crowns are starting to form). At this point, the likelihood of stress manifestation occurrences in UPMH has already significantly dropped.\u003c/p\u003e \u003cp\u003eThis ontogenetically delayed initiation and peak in stress events in Neanderthals might initially be interpreted as reflecting delayed initiation and completion of the weaning process in comparison to UPMH. However, dental development could potentially be accelerated in Neanderthals compared to modern humans [\u003cspan additionalcitationids=\"CR54\" citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. In such a case, and following dental crown developmental charts established for Neanderthals [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], the initiation of a trend of increasing likelihood of manifestation of stressful episodes can be aged at between 6\u0026ndash;9 months \u003cb\u003e(see Supplementary Table S5\u003c/b\u003e). This also coincides with the age at introduction of solid foods evidenced in several Neanderthal individuals [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan additionalcitationids=\"CR57\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Similarly, also following the age estimates from Neanderthal dental crown developmental charts [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], as well as more accurate age determinations for relevant specimens (i.e., Engis) based on dental histology [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], the peak stress we observe in Neanderthals at our Stage 6 corresponds to a chronological age of around 3 years, thus younger than the corresponding estimate of 4.5 years of age for Northern European modern humans at this dental developmental stage [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Even though this biological age of 3 years is broadly within the average age range of 2.5 years\u0026thinsp;\u0026plusmn;\u0026thinsp;10 months for cessation of breastfeeding reported in non-industrial human populations [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e], available determinations of ages at cessation of breastfeeding for Neanderthal specimens show that the completion of weaning occurred at around 1.2 and 2.5 years [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. With these estimations, we would then expect a stress peak related to the weaning process to manifest in Neanderthals at our dental developmental stages 4\u0026ndash;5, which is not the case \u003cb\u003e(see Supplementary Table S5)\u003c/b\u003e. Thus, unless the weaning ages reported for these Neanderthal individuals significantly divert from the population average, the later peak we observe in this group (at our Stage 6) can be interpreted as a post-weaning signal of systemic physiological stress.\u003c/p\u003e \u003cp\u003eThe early post-weaning phase would potentially continue to be a stressful stage as a child\u0026rsquo;s growing energetic demands, the developing immune system, and the increased independence, pose an increased risk of malnutrition and disease [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan additionalcitationids=\"CR63\" citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e] which would translate into an increased likelihood of hypoplastic defect manifestation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. The observation of a reduction of physiological stress post-weaning in UPMH might thus indicate the presence of social and behavioral strategies and/or life history traits that would ensure sufficient high energy nutrition for newly weaned children [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. Some such strategies that play a role in reducing early childhood physiological stress, like prolonged post-weaning dependency, optimized resource exploitation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e], support in provisioning [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e] are believed to have been in place in the Upper Paleolithic Period, and could have contributed in turn to long-term advantages for the population [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn summary, even though we detect a similar overall signal in hypoplasia occurrence likelihood on a population level between Neanderthals and UPMH, our findings suggest differences in the likelihood of occurrence of these defects throughout ontogeny between these two Paleolithic hominin groups. We interpret the latter as reflecting a better ability of UPMH in mitigating stress in newly weaned children, in contrast to Neanderthals where the period shortly after the presumed completion of the weaning process coincides with the most stressful childhood phase. Our results could thus be taken as implications for the practice of advantageous survival strategies by UPMH.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study is based on the examination of high-resolution epoxy replicas of 1048 Paleolithic deciduous and permanent dental remains of the Paleoanthropological collection, University of Tuebingen (Germany). Out of these, a total of 867 teeth of which 423 belonged to Neanderthals (n\u0026thinsp;=\u0026thinsp;75 individuals) and 444 to UPMH (n\u0026thinsp;=\u0026thinsp;102 individuals) were judged to be sufficiently preserved (with at least 50% of their crown height in good condition) to be included in the analyses. These originated from a total of 57 western Eurasia sites (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFollowing established methodologies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], lingual and buccal/labial crown enamel surfaces of all selected teeth were inspected by one of the authors (L.S.L.) for the presence of hypoplastic defects under oblique light conditions, first with the naked eye and then with a 20x magnification lamp. Every single hypoplasia incidence identified, (i.e., LEH/furrow form, pits/lines of pitting, localized hypoplasia of the primary canine)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], was recorded; with the tooth type it affected also noted. In the cases when linear defects were identified on multiple teeth of single individuals, their horizontal locations within crown vertical thirds were additionally documented. These locations were then used to estimate ontogenetic timing of defect formation in terms of the 11 dental developmental stages we defined using the concurrency of formation of dental crown thirds of different teeth in northern European populations as reported by Reid and Dean [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e] and Holt et al. [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e] as a reference \u003cb\u003e(see Supplementary Table S5)\u003c/b\u003e. Any defects reported on multiple (2 or more) teeth of single individuals and assigned to the same developmental stage were considered as broadly contemporaneous and taken to represent a stressful period, whether a single event or a series of closely timed events. Developmental stages, rather than biological ages, were used in this study to mitigate any potential effects of differences in dental growth patterns between Neanderthals and modern humans. Even if it is argued that Neanderthals had accelerated growth rates compared to modern humans [\u003cspan additionalcitationids=\"CR54\" citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e], they seem to follow a sequence of crown formation comparable to those of modern humans [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData analysis focused on assessing differences in the rate and timing of defect manifestations in the hominin groups using generalized linear mixed models (GLMMs). Models were implemented in R (version 4.2.1) with the brms package, which fits Bayesian models using Stan [\u003cspan additionalcitationids=\"CR71\" citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]. Two GLMMs were generated based on a Bernoulli distribution with logit-link to compare, between Neanderthals and UPMH, the likelihood of: 1) a tooth manifesting at least one hypoplastic defect of any form for each tooth type and for an average of all tooth types combined, and 2) an individual experiencing a stressful period at each of the predefined 11 developmental stages. Both models included \u003cem\u003etaxon\u003c/em\u003e (NEA, UPMH) as the main factor predictor and \u003cem\u003eindividual\u003c/em\u003e and \u003cem\u003esite ID\u003c/em\u003e as random components to account for the repeated measurements of single individuals and/or sites [\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eModel 1 further included the factor predictor \u003cem\u003etooth type\u003c/em\u003e and the interaction between \u003cem\u003etooth type\u003c/em\u003e and the main factor predictor \u003cem\u003etaxon\u003c/em\u003e. Permanent teeth were divided by tooth type (I1, I2, C, P3, P4, M1, M2, M3) albeit without regard to side or jaw, while deciduous teeth were combined into a single category due to low sample sizes when split by type. This approach allowed for the inclusion of all teeth within our sample (N\u0026thinsp;=\u0026thinsp;867 teeth of which 423 belong to 75 Neanderthals and 444 to 102 UPMH), including those that were found in isolation.\u003c/p\u003e \u003cp\u003eModel 2 included, as a covariate, a smooth interaction term based on the standardized continuous predictor \u003cem\u003edevelopmental stage\u003c/em\u003e (Stages 1\u0026ndash;11) grouped by the factor predictor \u003cem\u003etaxon\u003c/em\u003e. Additionally, it should be noted that since this second model assessed the likelihood of individuals manifesting a systemic stress period, it was run based on a more restricted sample of the 35 NEA and 37 UPMH individuals manifesting linear defects whose timing of occurrence was assigned to the same developmental stage, i.e., whose vertical locations within crown thirds were broadly matched on at least two concurrently forming tooth crowns in single individuals.\u003c/p\u003e \u003cp\u003eBoth models were fit using weakly informative prior distributions (normal with \u003cem\u003emean\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0 and \u003cem\u003es.d.\u003c/em\u003e=1 for intercept and coefficients, exponential (1) for standard deviations) and their performance evaluated with posterior predictive model checking, which compares model predictions with observed data. We ran 4 Markov-Chain-Monte-Carlo (MCMC) chains for each model and obtained coefficient estimates from a total of 16000 postwarmup samples.\u003c/p\u003e \u003cp\u003eAll model parameters reached reliable conversion indicators [\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e]: A Monte Carlo standard error smaller than 5% of the posterior s.d., an effective posterior sample size greater than 10% of the total sample size, and an \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\widehat{R}\\)\u003c/span\u003e\u003c/span\u003e statistic value smaller than 1.01 [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]. Using customized code based on Santon et. al. [\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e], we graphically display the results as the medians of response values across or within the predictors\u0026rsquo; and their 95% credible intervals (CIs) of the posterior distributions of fitted values for the population average obtained from the joint posterior distributions of the model parameters [84]. We further used the package \u003cem\u003eemmeans\u003c/em\u003e [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e] to compute from Model 1 the pairwise contrast odds ratios and their CIs between Neanderthals and UPMH for each tooth type. Effect size strength increases with increasing deviation of ratios from 1, and the robustness of the result increases with decreasing degree of overlap of the 95% compatibility intervals (CIs) with one.\u003c/p\u003e \u003cp\u003eFinally, using the method of finite differences, we estimated the first derivatives of the non-linear trends of Model 2 to identify periods of marked increase or decrease in systemic stress manifestation for each taxon [\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e]. Such periods are identified as developmental stages where the credible intervals of the first derivatives do not include zero and are highlighted by arrows in the graphical display \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGerman Research Foundation\u0026nbsp;Project number 353106138\u0026nbsp;(SEZ, KH)\u003c/p\u003e\n\u003cp\u003eBaden-W\u0026uuml;rttemberg Ministry for Science, Research and Art (Baden-W\u0026uuml;rttemberg State Research Award 2014, KH)\u003c/p\u003e\n\u003cp\u003eKH is further supported by the German Research Foundation (DFG FOR 2237) and the European Research Council (ERC-AdG-101019659).\u003c/p\u003e\n\u003cp\u003eOpen Access Publishing Fund of University\u0026nbsp;of T\u0026uuml;bingen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that all data generated or analyzed during this study are included in this published article. For requesting the R code from this study, the first author of the study, Laura Limmer, should be contacted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Conceptualization: SEZ, LSL, KM\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Methodology: LSL, MS, SEZ, KM\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Investigation: LSL\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Visualization: LSL, MS\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Writing\u0026mdash;original draft: LSL, SEZ, MS\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Writing\u0026mdash;review \u0026amp; editing: LSL, SEZ, MS, KH, KM\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStaubwasser, M. \u003cem\u003eet al.\u003c/em\u003e Impact of climate change on the transition of Neanderthals to modern humans in Europe. 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R package version 1.8.4\u0026ndash;1.\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimpson, G. L. Modelling Palaeoecological Time Series Using Generalised Additive Models. Frontiers in Ecology and Evolution 6, 149 (2018).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3757968/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3757968/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNeanderthals’ lives historically portrayed as highly stressful, shaped by constant pressures to survive in harsh ecological conditions, thus potentially contributing to their extinction. Recent work has challenged this interpretation, leaving the issue of stress among Paleolithic populations highly contested and warranting in-depth examination.\u003c/p\u003e\n\u003cp\u003eHere, we analyze the frequency of dental enamel hypoplasia, a physiological stress induced pathology, in the largest sample of Neanderthal and Upper Paleolithic dentitions investigated to date. To track potential species-specific patterns in the ontogenetic distribution of childhood stress, we present the first comprehensive Bayesian modelling of the likelihood of occurrence of individual and matched enamel growth disruptions throughout ontogeny.\u003c/p\u003e\n\u003cp\u003eOur findings support similar overall stress levels in both groups but reveal species-specific patterns in its ontogenetic distribution. While Neanderthal children faced increasing stress starting with the weaning process and culminating in intensity post-weaning, physiological stress in Upper Paleolithic children was found to be limited to the period of weaning and substantially dropping right after its completion. These results might, at least in part, reflect differences in childcare or other behavioral strategies between the two taxa, including those that were advantageous for modern humans’ long-term survival.\u003c/p\u003e","manuscriptTitle":"Differences in childhood stress between Neanderthals and early modern humans as reflected by dental enamel growth disruptions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-08 05:21:14","doi":"10.21203/rs.3.rs-3757968/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-25T15:27:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-05T23:02:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"dfe73e25-56d9-4139-897b-72848dee02b4","date":"2024-01-04T14:29:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-04T11:32:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-04T11:25:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-01-04T11:22:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-04T11:18:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2023-12-15T09:47:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f85f734a-654e-4789-8ed3-747bb38b736f","owner":[],"postedDate":"January 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":27985920,"name":"Biological sciences/Evolution/Anthropology/Biological anthropology"},{"id":27985921,"name":"Biological sciences/Evolution/Archaeology"}],"tags":[],"updatedAt":"2024-05-03T15:08:38+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-08 05:21:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3757968","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3757968","identity":"rs-3757968","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}