Transitional photoperiod induces a mania-like behavior in male mice.

This study aimed to investigate the behavioral responses and circadian rhythms of mice to both rapid and gradual increases in photoperiod, mimicking the transition from winter to summer, which is associated with a heightened prevalence of hospitalizations for mania and suicidal behavior. Behavioral tests were performed in C57BL/6 male mice exposed to a transitional photoperiod, from short to long durations. To determine if circadian rhythms are affected, we measured spontaneous locomotor activity and body temperature. Mice exhibited heightened exploratory and risk-taking behaviors compared with equatorial and static long (16:8 h of light-dark cycle for several days) groups. These behaviors were prevented by lithium. Spontaneous locomotor activity and body temperature rhythms persisted and were effectively synchronized; however, the relative amplitude of activity and interdaily stability were diminished. Additionally, the animals displayed increased activity during the light phase. Photoperiodic transition modulates behavior and circadian rhythms, mirroring certain features observed in bipolar disorder patients. This study introduces an animal model for investigating mania-like behavior induced by photoperiodic changes, offering potential insights for suicide prevention strategies and the management of mood disorders.

Association of BDNF Val66MET Polymorphism With Parkinson's Disease and Depression and Anxiety Symptoms.

An association between Parkinson's disease (PD) and brain-derived neurotrophic factor (BDNF) was suggested by several studies, with contradictory results. BDNF is necessary for the survival of dopaminergic neurons in substantia nigra. Val66Met is a common polymorphism of the BDNF gene that affects cognitive and motor processes. The authors studied 104 Brazilian patients with PD and 96 control participants. The G/G genotype was significantly associated with depression and anxiety symptoms and development of PD. This is the first study that associates this genotype with PD.

Darwin and the biological rhythms.

While the formalization of chronobiology as a scientific discipline occurred in the mid-20th century, the exploration of rhythmic phenomena has a longer history, notably exemplified by De Mairan's observations of Mimosa pudica in darkness in 1729. In this historical narrative, Charles Darwin is known for his investigations into the "sleep movements" of plants. Nevertheless, the complete scope of Darwin's exploration of biological rhythms remains incompletely understood. Through a detailed examination of Darwin's writings, meticulous observations, experiments, and conceptualizations, we unveil a depth of engagement that surpasses his widely acknowledged work on plants, revealing a more extensive interest in and insight into biological rhythms than traditionally recognized.

Hemodialysis-induced chronodisruption and chronotype distribution in patients with chronic kidney disease.

Changes in circadian rhythms have been observed in patients with chronic kidney disease (CKD), and evidence suggests that these changes can have a negative impact on health. This study aimed to investigate the existence of hemodialysis-induced chronodisruption, the chronotype distribution, and their association with sleep quality and quality of life (QoL). This was a cross-sectional study that enrolled 165 patients (mean age: 51.1 ± 12.5 y, 60.6% male) undergoing hemodialysis from three local units. The following instruments were used: the Morning-Eveningness Questionnaire (MEQ); a modified version of the Munich Chronotype Questionnaire (MCQT) to estimate hemodialysis-induced chronodisruption (HIC); the Kidney Disease QoL Short Form (KDQOL-SF); the Epworth Sleepiness Scale (ESS); the Pittsburgh Sleep Quality Index (PSQI) and the 10-Cognitive Screener (10-CS). HIC was present in 40.6% of CKD patients. Morning chronotype was prevalent in CKD patients (69%) compared to evening-type (17.1%) and significantly different from a paired sample from the general population (p < 0.001). HIC and chronotype were associated with different domains of QoL but not with sleep quality. This study suggests that there is a HIC and that morning chronotype is associated with CKD patients undergoing hemodialysis, with implications for QoL.

Layered double hydroxides (LDHs) as efficient and safe carriers for miRNA inhibitors: In vitro and in vivo assessment of biocompatibility.

Layered double hydroxides (LDHs) have been employed as nano-sized carriers for therapeutic/bio-active molecules, including small interfering RNAs (siRNAs). However, the potential of LDHs nanoparticles for an efficient and safe antisense oligonucleotide (AMO) delivery still requires studies. In this research, we have tested the suitability of a Mg-Al-LDH-based nanocarrier loaded with a miRNA-196b-5p inhibitor. LDHs (and LDH-Oligo complex) were synthesized by the coprecipitation method followed by physicochemical characterization as hydrodynamic size, surface charge, crystallinity, and chemical groups. Thymic endothelial cell line (tEnd.1) were transfected with LDH-Oligo and were evaluated for i. cell viability by MTT, trypan blue, and propidium iodide assays; ii. transfection efficiency by flow cytometry, and iii. depletion of miRNA-196b-5p by RT-qPCR. In addition, Drosophila melanogaster larvae were fed LDHs and evaluated for: i. larval motility; ii. pupation rate; iii. larval-pupal transition; iv. lethality, and v. emergence rate. We demonstrated that LDHs nanoparticles are stable in aqueous solutions and exhibit a regular hexagonal shape. The LDH-AMO complex showed a transfection efficiency of 93.95 ± 2.15 % and induced a significant depletion of miRNA-196b-5p 48h after transfection. No cytotoxic effects were detected in tEnd.1 cells at concentrations up to 50 µg/ml, as well as in Drosophila exposed up to 500 µg of LDH. In conclusion, our data suggest that LDHs are biocompatible and efficient carriers for miRNA inhibitors and can be used as a viable and effective tool in functional miRNA inhibition assays.

Associations between chronotype, sleep quality, maternal mental health, and child development in mother-infant dyads.

OBJECTIVE/BACKGROUND: Studies on circadian rhythms throughout development and their physiological and behavioral impacts at early stages are still scarce. Previous studies have shown that mother-infant interactions are important for both sleep and child development. In this cross-sectional study we investigated whether infants' chronotype, sleep and development were associated with their respective mothers' chronotype, sleep, mental health and socioeconomic status. PATIENTS/METHODS: the following were used to evaluate mothers: the Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Self-Reporting Questionnaire 20 (SRQ-20). To assess the infants' characteristics, the following were used: the 19th question from the Morningness-Eveningness Questionnaire (MEQ), infant nocturnal midpoint of sleep (iMSF), Brief Infant Sleep Questionnaire (BISQ) and Ages and Stages Questionnaire-3 (ASQ3). Socioeconomic aspects were assessed using the Brazilian Economic Class Criterion of the Brazilian Association of Research Companies (ABEP). RESULTS: A hundred and eight mother-infant dyads participated in the study. Sleep disorders were observed in 38 (35%) infants and atypical development (ASQ3) in 35 (32%). The infants' sleep phases were partially explained by the mother's chronotype. Infants' sleep duration was negatively correlated with sleep latency, which was higher in the group with atypical development. Mothers of infants with sleep disorders or discordant chronotypes (32%) had higher Pittsburgh scores (worse sleep quality) and higher SRQ-20 scores (screen for Common Mental Disorders). CONCLUSIONS: We found evidence for the contribution of sleep quality and chronotypes to mothers' mental health and infant development. However, further studies are needed to confirm the influence of sleep and circadian phenotypes in the early stages.

Lack of association between rs211037 of the GABRG2 gene and juvenile myoclonic epilepsy in Brazilian population.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy syndrome with genetic basis and accounts for 10% of all forms of epilepsy. Despite the existence of rare mutations responsible for some familial forms inherited in a Mendelian pattern, the genetics of JME is complex and probably involves multiple genes. Because of widespread distribution in the central nervous system (CNS) and their ability to produce postsynaptic inhibition, GABA (A) receptor subunits (GABRs) encoding genes represent high ranking candidates for epilepsy susceptibility. AIM: This case/control study was designed to investigate whether the rs211037 of the GABRG2 gene is a risk factor for JME in the Brazilian population. MATERIALS AND METHODS: The polymorphism was genotyped in 98 patients and 130 controls using polymerase chain reaction-restriction fragment length polymorphism method. Descriptive and statistical analyses were performed using SNP stat software. RESULTS: Genotype proportions and allele frequencies for the rs211037 polymorphism of the GABARG2 gene did not differ significantly between the groups, even when the odds ratio was adjusted for clinical variables. CONCLUSION: These results present no evidence for an association of rs211037 with JME. Further studies are required to investigate the involvement of the GABRG2 gene in the genetic susceptibility to this epileptic syndrome.

Wound infection by multiresistant Staphylococcus sciuri identified by molecular methods.

We describe a case of wound infection by multidrug-resistant Staphylococcus sciuri in a patient admitted to hospital for injuries in Agreste Alagoas, Brazil, identified through broad-spectrum PCR and sequencing of 16S rDNA gene. Due to its high resistance profile, the infection was characterized as methicillin-resistant Staphylococcus presenting sensitive only to vancomycin and chloramphenicol. The injury resulting from trauma associated with infection resulted in amputation of the infected limb.

Nutritional adjuvants with antioxidant properties in the treatment of canine leishmaniasis.

Clinical improvement of dogs treated for canine leishmaniasis (CanL) requires reducing Leishmania infantum loads, which depend on intracellular oxidant compounds to destroy the parasite. However, oxidative species' excess and antioxidants consumption can culminate in oxidative stress, resulting in increased, widespread inflammation. We aimed to evaluate if early or late addition of nutritional adjuvants (NAs) - omega-3 polyunsaturated fatty acids and B vitamins - to anti-Leishmania drugs (ALDs) in the treatment of CanL would be clinically beneficial. For that, serum biomarkers including oxidative stress parameters were analyzed during 12 months in dogs allocated to two treatment groups: (G1) NAs administered from 30 days prior to the beginning of ALDs; and (G2) NAs administered from 61 days after the beginning of ALDs. Both G1 and G2 continued to receive NAs until the 12th month. The ALDs administered were metronidazole associated with ketoconazole (40 days), followed by allopurinol from day 41 until the 12th month. G1 exhibited superior inflammation control, with reduced globulins (p = 0.025), specific anti-Leishmania immunoglobulins (p = 0.016), total protein (p = 0.031), and an increased serum albumin/globulin ratio (p = 0.033), compared to G2. The early use of NAs associated with ALDs is clinically beneficial in treating dogs with CanL.

Expression of new red cell-related genes in erythroid differentiation.

Using a suppression subtractive hybridization method, we have previously identified genes differentially expressed in erythroid cells heterozygous for large deletions in beta-like globin cluster. Herein, we investigated the expression of four newly detected red cell-related genes in erythroid differentiation. ARID1B and TSPYL1, genes with chromatin remodeling properties, presented similar patterns of expression with an upregulation after erythropoietin (EPO) addition, similar to previous data found in reticulocytes. ZHX2, a transcriptional repressor, was downregulated, and a redoxin-related gene, SH3BGRL2, had higher levels of expression on differentiation. These are the first investigations of these newly described genes in erythroid differentiation and demonstrate that the expression of these genes is affected by EPO stimulation. These genes may participate in globin regulation and may be important in the normal physiology of erythrocytes.

Depression and anxiety symptoms correlate with diurnal preference, sleep habits, and Per3 VNTR polymorphism (rs57875989) in a non-clinical sample.

BACKGROUND: Evidences suggest that alterations in circadian rhythms trigger the development of mental disorders. Eveningness, sleep behavior, and circadian genes polymorphisms have been associated with depression and anxiety symptomatology. However, the mechanism underlying these interactions is not well understood. We investigated the contribution of diurnal preference, sleep habits, and PER3 VNTR polymorphism (rs57875989) to depression and anxiety symptoms in a Northeast sample from the Brazilian population. METHODS: Eight hundred and four young adults completed the Morningness-Eveningness (MEQ), Munich Chronotype (MCTQ), Center for Epidemiologic Studies - Depression (CES-D), and Beck Anxiety Inventory (BAI) questionnaires. All participants were genotyped and linear regression was performed to test the interactions between the genetic /behavioral variants and depression/ anxiety symptoms. RESULTS: Eveningness and sleep behaviors (bedtime, wake-up time, sleep duration, and midpoint of sleep) were correlated with depression symptomatology, specifically in somatic factors of the CES-D questionnaire. No correlation was found between diurnal preference/sleep habits with anxiety symptoms for both BAI total score and its factors. However, women with PER34/4 genotype showed less interpesonal affect in depression symptomatology and more anxiety symptoms in four factors of the BAI questionnaire. LIMITATIONS: Mainly because this study was based on self-report questionnaires and was limited to undergraduate students aging 18 to 30 years old. CONCLUSION: These results reinforce a role for sleep and diurnal preference in depression, and PER3 VNTR polymorphism in anxiety symptomatology, particularly in women.

Environmental temperature as a mediator on the association between photoperiod at birth and chronotype.

The association between chronotypes and season of birth (SOB) remains an inconclusive issue due, in some extension, to the lack of investigations of mediation mechanisms. We evaluated the association of photoperiod at birth (PAB) with chronotypes and sleep duration in Brazil (n = 810), and the mediating effect of meteorological factors, sex, age and rs4753426 polymorphism in the melatonin receptor MTNR1B. Longer PAB was associated with a delayed mid-sleep phase with a suppressive effect of maximum environmental temperature. No significant interactions were identified for the other variables. These findings suggest that photoperiod and environmental temperature modulate chronotype development at early stages.

Chronobiology of limbic seizures: Potential mechanisms and prospects of chronotherapy for mesial temporal lobe epilepsy.

Mesial Temporal Lobe Epilepsy (mTLE) characterized by progressive development of complex partial seizures originating from the hippocampus is the most prevalent and refractory type of epilepsy. One of the remarkable features of mTLE is the rhythmic pattern of occurrence of spontaneous seizures, implying a dependence on the endogenous clock system for seizure threshold. Conversely, circadian rhythms are affected by epilepsy too. Comprehending how the circadian system and seizures interact with each other is essential for understanding the pathophysiology of epilepsy as well as for developing innovative therapies that are efficacious for better seizure control. In this review, we confer how the temporal dysregulation of the circadian clock in the hippocampus combined with multiple uncoupled oscillators could lead to periodic seizure occurrences and comorbidities. Unraveling these associations with additional research would help in developing chronotherapy for mTLE, based on the chronobiology of spontaneous seizures. Notably, differential dosing of antiepileptic drugs over the circadian period and/or strategies that resynchronize biological rhythms may substantially improve the management of seizures in mTLE patients.

Melatonin receptor 1B -1193T>C polymorphism is associated with diurnal preference and sleep habits.

BACKGROUND: Melatonin modulates the master circadian clock through the activation of G-protein-coupled receptors MT1 and MT2. It is presumed, therefore, that genetic variations in melatonin receptors can affect both sleep and circadian phase. We investigated whether the -1193T > C (rs4753426) polymorphism in the promoter of MT2 receptor gene (MTNR1B) is associated with diurnal preference and sleep habits. This polymorphism was previously associated with sunshine duration, suggesting a role in circadian entrainment. METHODS: A total of 814 subjects who completed the Morningness-Eveningness and the Munich Chronotype questionnaires were genotyped for the selected polymorphism. Linear and multinomial regression were performed to test the interaction between gene variants and diurnal preference/sleep habits. RESULTS: The -1193C variant was associated with the extreme morningness phenotype in a codominant model (C/C vs. T/T), recessive model (C/C + C/T vs. T/T) and alleles (C vs. T). A negative correlation was found between -1193C alleles and social jetlag scores. The frequency of -1193T allele was higher in the group that stay in bed more than 8 h/night compared to the group that stay in bed less than 8 h/night on weekends. CONCLUSION: To the best of our knowledge, these data provide the first insights into the role of MTNR1B gene in the regulation of sleep, biological rhythms, and entrainment in humans.

Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy.

The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm output, including circadian oscillation of body temperature, locomotor activity, EEG pattern as well as the transcriptome. However, the molecular mechanisms underlying this cross-talk remain unclear. In this study, we systematically evaluated the temporal expression of seven core circadian transcripts (Bmal1, Clock, Cry1, Cry2, Per1, Per2, and Per3) and the spontaneous locomotor activity (SLA) in post-status epilepticus (SE) model of mTLE. Twenty-four hour oscillating SLA remained intact in post-SE groups although the circadian phase and the amount and intensity of activity were changed in early post-SE and epileptic phases. The acrophase of the SLA rhythm was delayed during epileptogenesis, a fragmented 24 h rhythmicity and extended active phase length appeared in the epileptic phase. The temporal expression of circadian transcripts Bmal1, Cry1, Cry2, Per1, Per2, and Per3 was also substantially altered. The oscillatory expression of Bmal1 was maintained in rats imperiled to SE, but with lower amplitude (A = 0.2) and an advanced acrophase in the epileptic phase. The diurnal rhythm of Cry1 and Cry2 was absent in the early post-SE but was recovered in the epileptic phase. Per1 and Per2 rhythmic expression were disrupted in post-SE groups while Per3 presented an arrhythmic profile in the epileptic phase, only. The expression of Clock did not display rhythmic pattern in any condition. These oscillating patterns of core clock genes may contribute to hippocampal 24 h cycling and, consequently to seizure periodicity. Furthermore, by using a pool of samples collected at 6 different Zeitgeber Times (ZT), we found that all clock transcripts were significantly dysregulated after SE induction, except Per3 and Per2. Collectively, altered SLA rhythm in early post-SE and epileptic phases implies a possible role for seizure as a nonphotic cue, which is likely linked to activation of hippocampal-accumbens pathway. On the other hand, altered temporal expression of the clock genes after SE suggests their involvement in the MTLE.

Usual normalization strategies for gene expression studies impair the detection and analysis of circadian patterns.

Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered. In this study, we controlled experimental conditions from the amount of initial brain tissue samples through extraction steps, cDNA synthesis, and quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total RNA concentration. We also identified that the normalization of the RNA's yield affected the rhythmic profiles of different genes, including Per1-2 and Bmal1. Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented rhythmic variations not detected by geNorm algorithm. In addition, the analysis of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction suggests that the yield was affected by total RNA concentration, which may impact circadian studies of small RNAs. The results indicate that the approach of tissue normalization without total RNA equalization prior to cDNA synthesis can avoid bias from endogenous broad variations in transcript levels. Also, the circadian analysis of 2-Cycle threshold (Ct) data, without HKGs, may be an alternative for chronobiological studies under controlled experimental conditions.

Green Tobacco Sickness among Brazilian farm workers and genetic polymorphisms.

OBJECTIVE: Green Tobacco Sickness (GTS) is an occupational illness caused by dermal absorption of nicotine from tobacco leaves. It affects thousands of farm workers worldwide. Brazil is the second tobacco producer in the world; despite this, there are few studies on GTS among Brazilian harvesters. This study aimed to determine the prevalence of GTS among a population of tobacco workers from a producing area in northeastern Brazil and investigate whether the occurrence of the disease was influenced by factors such age, gender and smoking status. In addition, it was investigated if there was association between the onset of GTS and genetic polymorphisms in genes that encode some detoxification enzymes. A semi-structured questionnaire was used to collect demographic, behavioral and occupational data from the referred workers. Polymorphisms were tested through the Polymerase Chain Reaction technique. RESULTS: The total prevalence of GTS found was 56.9%, with a significant difference between genders (71.7% for women and 35.3% for men, p < 0.0001). No association was identified between the investigated polymorphisms and GTS. This study confirms the occurrence of GTS among tobacco harvesters in Brazil with high prevalence. The investigation suggests the need to take preventive measures to protect tobacco workers against this disease.

Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample.

Genetic susceptibility contributes to the etiology of sporadic Parkinson's Disease (PD) and worldwide studies have found positive associations of polymorphisms in the alpha-synuclein gene (SNCA) with the risk for PD. However, little is known about the influence of variants of SNCA in individual traits or phenotypical aspects of PD. Further, there is a lack of studies with Latin-American samples. We evaluated the association between SNCA single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs - rs2583988, rs356219, rs2736990, and rs11931074) and PD risk in a Brazilians sample. In addition, we investigated their potential interactions with environmental factors and specific clinical outcomes (motor and cognitive impairments, depression, and anxiety). A total of 105 PD patients and 101 controls participated in the study. Single locus analysis showed that the risk allele of all SNPs were more frequent in PD patients (p < 0.05), and the associations of SNPs rs2583988, rs356219, and rs2736990 with increased PD risk were confirmed. Further, the G-rs356219 and C-rs2736990 alleles were associated with early onset PD. T-rs2583988, G-rs356219 and C-2736990 alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. In addition, in a logistic regression model, we found an association of cognitive impairment with PD, and the practice of cognitive activity and smoking habits had a protective effect. This study shows for the first time an association of SNCA polymorphism and PD in a South-American sample. In addition, we found an interaction between SNP rs356219 and a specific clinical outcome, i.e., the increased risk for cognitive impairment in PD patients.

Association of TNFA (-308G/A), IFNG (+874 A/T) and IL-10 (-819 C/T) polymorphisms with protection and susceptibility to dengue in Brazilian population.

OBJECTIVE: To evaluate gene polymorphisms and their association with susceptibility to dengue. METHODS: A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system. RESULTS: We observed a protective association of IL-10 (-819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34-0.91) against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01-4.38) and T/T (P = 0.008, OR = 3.82, CI = 1.38-10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA -308 GA + AA (P = 0.043, OR = 0.45, CI = 0.20-1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P = 0.02, OR = 0.46, CI = 0.24-0.89) and DHF (P = 0.034, OR = 0.43, CI = 0.19-0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18-7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P = 0.035, OR = 0.28, CI = 0.08-0.90) with protection against the development of DHF. CONCLUSIONS: This research identifies the association of the IFNG (+874 A/T), TNFA (-308G/A), IL-10 (-819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.

Do suicide attempts occur more frequently in the spring too? A systematic review and rhythmic analysis.

BACKGROUND: Seasonal variations in suicides have been reported worldwide, however, there may be a different seasonal pattern in suicide attempts. The aim of this study was to perform a systematic review on seasonality of suicide attempts considering potential interfering variables, and a statistical analysis for seasonality with the collected data. METHOD: Observational epidemiological studies about seasonality in suicide attempts were searched in PubMed, Web of Science, LILACS and Cochrane Library databases with terms attempted suicide, attempt and season. Monthly or seasonal data available were evaluated by rhythmic analysis softwares. RESULTS: Twenty-nine articles from 16 different countries were included in the final review. It was observed different patterns of seasonality, however, suicide attempts in spring and summer were the most frequent seasons reported. Eight studies indicated differences in sex and three in the method used for suicide attempts. Three articles did not find a seasonal pattern in suicide attempts. Cosinor analysis identified an overall pattern of seasonal variation with a suggested peak in spring, considering articles individually or grouped and independent of sex and method used. A restricted analysis with self-poisoning in hospital samples demonstrated the same profile. LIMITATIONS: Grouping diverse populations and potential analytical bias due to lack of information are the main limitations. CONCLUSIONS: The identification of a seasonal profile suggests the influence of an important environmental modulator that can reverberate to suicide prevention strategies. Further studies controlling interfering variables and investigating the biological substrate for this phenomenon would be helpful to confirm our conclusion.