Seasonality

Introduction

Seasonality refers to recurrent changes in mood, behavior, and physiological patterns that are consistently linked to specific times of the year, such as fall or winter.^[1] While these seasonal fluctuations have been recognized for a long time, a distinct syndrome, Seasonal Affective Disorder (SAD), was formally defined as recurrent depression occurring in fall and winter, with symptoms alleviating in spring and summer.^[1] Although SAD is not classified as a separate clinical entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM), these manuals do include a “seasonal pattern” specifier for major depressive episodes that exhibit a consistent temporal relationship with particular seasons.^[1]Seasonality is often assessed using standardized questionnaires, such as the Seasonal Pattern Assessment Questionnaire (SPAQ), which generates a Global Seasonality Score (GSS) based on an individual’s responses to various indices of seasonal changes and their impact on functioning.^[1]

Biological Basis

Research indicates that seasonality has a significant genetic component. Studies have estimated that genetic factors account for approximately 29% of the overall variation in seasonality in both men and women, as assessed by the SPAQ.^[1] This suggests a polygenic architecture, meaning that many genes of small effect likely contribute to the trait, rather than a few common genetic variants with large effects.^[1] A meta-analysis of genome-wide association studies (GWAS) identified rs11825064 , an intergenic single nucleotide polymorphism (SNP) located on chromosome 11, as the most significant association with seasonality, though it did not reach genome-wide significance.^[1]Intriguingly, genetic studies have revealed a significant overlap in genetic risk factors between seasonality and several psychiatric disorders. There is strong evidence for a shared genetic basis between seasonality and schizophrenia (SCZ), with SCZ genetic profile scores explaining up to 3.1% of the variance in global seasonality.^[1] Milder, but still significant, evidence suggests genetic overlap with bipolar disorder (BD).^[1]However, no genetic overlap has been detected between seasonality and major depressive disorder (MDD) in some studies.^[1]The heritability of vitamin D (25OHD) levels, which can also show seasonal variation, has been observed to differ by season, with higher SNP-based heritability in summer compared to winter.^[2]

Clinical Relevance

The clinical implications of seasonality are most evident in conditions like SAD, where seasonal changes profoundly impact mental health. Distinctions exist between major depressive disorder with a seasonal pattern and bipolar disorder with a seasonal pattern, particularly regarding the severity of the course and hospitalization rates, which are higher in the bipolar form.^[1] Notably, even unipolar SAD has been clinically conceptualized as potentially belonging to the bipolar spectrum.^[1]The unexpected finding of substantial genetic overlap between seasonality and SCZ, along with BD, has significant potential clinical implications, especially given the observed overlapping cognitive deficits in seasonal affective disorders and SCZ.^[1] Understanding these genetic correlations could inform future diagnostic approaches and treatment strategies for these complex conditions.

Social Importance

Seasonal changes in mood and behavior are a widely recognized human experience, affecting a broad spectrum of the population. The prevalence of seasonality and SAD can vary considerably across different populations; for instance, the Amish population has been observed to have a particularly low prevalence of SAD, suggesting a relative resilience to seasonality.^[1]Gaining deeper insights into the genetic underpinnings of seasonality and its connections to major psychiatric disorders can lead to improved public health strategies, targeted interventions, and enhanced understanding of human adaptation to environmental changes.

Methodological and Statistical Power Constraints

The genetic investigation of seasonality faces significant challenges due to limitations in study design and statistical power. The meta-analysis, encompassing a total sample size of 4,156 individuals, was likely underpowered to detect individual genetic variants contributing to a complex trait like seasonality.^[1]This is particularly relevant given that seasonality is hypothesized to follow a polygenic model, where numerous common alleles each exert only small effects on the phenotype.^[1]As a result, no single genetic locus reached genome-wide significance, suggesting that common variants with unusually large effects are unlikely to exist for seasonality in the populations examined.^[1] For example, the Australian sample had only 50.8% power to detect a variant explaining 1% of the phenotypic variance, underscoring the necessity for substantially larger cohorts in future genetic discovery efforts.^[1]A further constraint was the lack of replication of initial findings across distinct cohorts. No single nucleotide polymorphisms (SNPs) that showed significance in the Australian sample were replicated in the Amish cohort.^[1]This replication gap highlights potential population-specific genetic architectures, environmental confounders, or the possibility of false-positive associations in the initial discovery phase. The absence of robust, genome-wide significant associations suggests that while genetic correlations with psychiatric disorders like schizophrenia were observed, the precise genetic underpinnings of seasonality remain elusive without the statistical power afforded by larger, more diverse datasets.

Population and Phenotype Heterogeneity

The generalizability of findings is limited by the inherent differences between the study populations. The meta-analysis combined data from genetically and geographically diverse cohorts: Australian twins and members of the Old Order Amish community in Pennsylvania.^[1]Substantial geographical and cultural disparities, including varying environmental exposures and prevalence rates of seasonality, likely influenced the genetic findings and contributed to the lack of replication between groups.^[1]Specifically, the Amish population exhibits a notably low prevalence of seasonal affective disorder (SAD) and schizophrenia, which may reflect a unique genetic resilience or founder effects that limit the transferability of genetic associations to other populations.^[1] Moreover, genetic profile scoring analyses were restricted to the Australian cohort, making it challenging to extend these findings to the Amish or other populations.

Phenotype definition also presents a limitation, as seasonality was assessed using the Seasonal Pattern Assessment Questionnaire (SPAQ) to derive a Global Seasonality Score (GSS), which is a screening tool rather than a definitive clinical diagnosis.^[1] A critical omission was the lack of actual clinical diagnoses for mental conditions, which prevented the exclusion of individuals with psychiatric comorbidities prior to genetic profile scoring.^[1]This inability to account for comorbid psychiatric diagnoses hinders the precise investigation of genetic overlap between seasonality and specific disorders in individuals free from other mental health conditions. While the Australian sample was population-based, and thus severe psychiatric disorders are likely infrequent, their presence could still influence the observed genetic correlations.^[1]

Environmental Confounding and Unexplained Genetic Variance

Environmental factors play a crucial role in seasonality, and their potential confounding effects were not fully addressed. The significant geographical differences between the Australian and Amish populations imply substantial variation in environmental exposures, such as sunlight availability and climate, which directly influence seasonal patterns and related biological processes.^[1]Unaccounted environmental variables or complex gene-environment interactions could obscure true genetic associations or lead to spurious findings. For instance, studies on vitamin D levels, a trait known to fluctuate seasonally, have shown that genetic variance can differ substantially between summer and winter, highlighting the profound impact of seasonal environmental changes on genetic expression.^[2]A comprehensive understanding of seasonality genetics necessitates a more explicit consideration and modeling of these intricate environmental influences and gene-environment interactions.

Despite the evidence for a polygenic architecture underlying seasonality, the study did not identify any genome-wide significant loci, indicating that a substantial portion of the trait’s heritability remains unexplained.^[1]This “missing heritability” could be attributed to the cumulative effect of many common variants with very small individual effects, the contribution of rare genetic variants, or complex epistatic interactions not detectable with current sample sizes and methodologies. While the study provides valuable candidate SNPs and initial insights into genetic correlations with psychiatric disorders, significant knowledge gaps persist regarding the specific genetic mechanisms and pathways involved in seasonality.^[1]Future research will require larger cohorts and advanced analytical methods to fully elucidate the complex genetic architecture of seasonality and its interplay with environmental factors.

Variants

Seasonality, characterized by recurrent changes in mood and behavior linked to specific times of the year, is a complex trait influenced by a polygenic architecture, meaning many genes with small effects contribute to its expression. Genetic studies have begun to uncover specific variants that may play a role in this phenomenon, including those with implications for overlapping psychiatric conditions such as schizophrenia and bipolar disorder.^[1]The most significant single nucleotide polymorphism (SNP) identified in a meta-analysis of seasonality wasrs11825064 , an intergenic variant located on chromosome 11.^[1] While intergenic, such variants can influence the expression of nearby genes like B3GAT1-DT (B3GAT1 divergent transcript) and LINC02706(a long intergenic non-coding RNA), potentially affecting neuronal function or regulatory pathways relevant to seasonal mood changes. This particular variant showed a notable association with seasonality, emphasizing the importance of non-coding regions in complex traits.

Beyond intergenic regions, several genes directly involved in cellular signaling and neurodevelopment are implicated. For instance, rs10766194 is associated with PDE3B, which encodes Phosphodiesterase 3B. This enzyme is crucial for regulating levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), second messengers that play vital roles in neuronal excitability, neurotransmitter release, and the intricate machinery of the circadian clock. Variations in PDE3B can thus alter these fundamental processes, potentially contributing to the seasonal regulation of mood and behavior. Similarly, the variant rs139459337 is linked to ZBTB20, a gene encoding a zinc finger transcription factor. ZBTB20 is known to be involved in neurodevelopment, metabolic regulation, and the establishment of circadian rhythms, making its genetic variations relevant to how individuals adapt to seasonal environmental shifts.^[1] Other variants point to roles in cellular transport, structural integrity, and gene regulation. The rs112170428 variant is found near RRAS2 and COPB1. RRAS2 is a small GTPase involved in cell signaling pathways critical for cell growth and migration, processes that underpin neuronal plasticity and brain development. COPB1, on the other hand, is a subunit of the COPI coat complex, essential for vesicle transport within cells, a mechanism vital for efficient communication between neurons. Alterations in these genes, influenced by rs112170428 , could affect the intricate signaling networks that govern mood and behavior. Another variant, rs8022510 , is associated with SEC23A, a component of the COPII complex responsible for protein transport from the endoplasmic reticulum. Proper protein trafficking is fundamental for neuronal health and function, and variations in SEC23A could impact the stability and activity of proteins crucial for mood regulation. Furthermore, rs28607847 is linked to MEGF11, a gene involved in cell adhesion and receptor signaling, which are important for maintaining neuronal connections and communication within the brain.^[1]Several long intergenic non-coding RNAs (lincRNAs) and pseudogenes also feature among the associated variants, highlighting the broad regulatory landscape of seasonality. Variants likers12411769 (near RPS26P39 and LINC02641), rs77826363 (near LINC01622 and FOXQ1), rs1325765 (near LINC01523 and LINC03079), and rs9364726 (near RN7SL366P and C6orf118) suggest that gene regulation through these non-coding elements is a critical aspect of seasonal adaptation. LincRNAs are known to modulate gene expression, affecting a wide range of biological processes, including brain development and function. Similarly, pseudogenes can act as regulatory elements, influencing the expression of their functional counterparts. The collective impact of these diverse genetic factors, from signaling molecules to regulatory RNAs, underscores the complex interplay that contributes to an individual’s susceptibility to seasonal fluctuations in mood and behavior, and their genetic overlap with psychiatric conditions.^[1]

Key Variants

RS ID	Gene	Related Traits
rs10766194	PDE3B	BMI-adjusted hip circumference BMI-adjusted waist-hip ratio vitamin D amount seasonality
rs112170428	RRAS2 - COPB1	level of T-cell leukemia/lymphoma protein 1A in blood protein seasonality
rs8022510	SEC23A	seasonality
rs28607847	MEGF11	seasonality
rs12411769	RPS26P39 - LINC02641	seasonality
rs77826363	LINC01622 - FOXQ1	seasonality
rs1325765	LINC01523 - LINC03079	seasonality
rs9364726	RN7SL366P - C6orf118	seasonality
rs139459337	ZBTB20	seasonality
rs11825064	B3GAT1-DT - LINC02706	seasonality

Defining Seasonality and Related Conditions

Seasonality refers to recurrent patterns of changes in mood, behavior, or biological processes that align with specific times of the year.^[1] This phenomenon exists on a spectrum within the general population, ranging from subtle alterations to significant distress and impairment.^[1] The extreme end of this spectrum is recognized as Seasonal Affective Disorder (SAD), a syndrome initially defined by Rosenthal et al. as recurrent depression primarily occurring in the fall and winter, with symptom alleviation in spring and summer.^[1]SAD is characterized by specific depressive symptoms such as altered sleep patterns, weight fluctuations, reduced energy, and decreased social engagement during particular seasons, followed by at least partial remission when the season changes.^[1] The most commonly observed form is winter-pattern SAD.^[1]

Classification Systems and Diagnostic Criteria

While SAD was historically described as a distinct syndrome, the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5) do not classify SAD as an independent clinical entity.^[3]Instead, these manuals incorporate a “longitudinal seasonal pattern specifier” that can be applied to major depressive episodes within recurrent Major Depressive Disorder (MDD) or Bipolar I or II Disorder (BD).^[1]This specifier requires a consistent temporal relationship between the onset of depressive episodes and specific seasons, such as fall or winter, over at least two years, with full remission or a switch to hypomanic/manic symptoms occurring at other times of the year.^[1] Despite this, some researchers have advocated for SAD to be recognized as an independent clinical disorder.^[4] Distinct differences exist between MDD with a seasonal pattern and BD with a seasonal pattern, particularly in terms of recurrence and severity, with the bipolar form often associated with higher rates of hospitalization.^[1]

Approaches and Operational Definitions

The assessment of seasonality often relies on structured questionnaires and specific operational definitions for research and clinical purposes. A widely utilized tool for evaluating seasonality and screening for SAD is the Seasonal Pattern Assessment Questionnaire (SPAQ).^[1]The SPAQ generates a Global Seasonality Score (GSS) based on Likert scale responses to six indices of seasonal change, alongside a “problem scale” that quantifies the degree of functional impairment caused by these changes.^[1] For research studies, operational definitions of seasonal depression can be broad, such as identifying individuals who report their depressions tend to begin in a particular season, with winter or fall onsets commonly assigned as seasonal cases.^[5] Clinically, individuals diagnosed with SAD can present with severe symptoms and cognitive deficits comparable to those observed in nonseasonal depression, and these symptoms are notably responsive to bright light therapy.^[1]

Genetic Architecture and Environmental Interaction

Seasonality is influenced by genetic factors, which are estimated to account for approximately 29% of the overall variance in seasonal changes in mood and behavior, as measured by the SPAQ.^[1]Research indicates that seasonality exhibits a polygenic architecture, suggesting involvement of multiple genetic variants.^[1] While candidate gene studies for SAD have been conducted, consistently replicable findings have been challenging to establish.^[1]Genome-wide association studies (GWAS) are instrumental in identifying genetic variants associated with seasonality, revealing overlapping genetic risk factors with psychiatric disorders.^[1]Notably, studies have found evidence of genetic overlap between seasonality and bipolar disorder, and an unexpected, larger overlap with schizophrenia.^[1] Furthermore, seasonal fluctuations provide a natural experimental context to investigate gene-environment (GxE) interactions, such as those influencing the synthesis and excretion of 25-hydroxyvitamin D (25OHD).^[2] For instance, genetic factors contribute a larger proportion of variance to 25OHD concentrations in summer compared to winter, reflecting an increase in genetic variance during summer.^[2]

Neurobiological Foundations of Seasonal Rhythms

The body’s ability to adapt to seasonal changes in photoperiod is intricately linked to core neurobiological systems, particularly the circadian clock. Key circadian clock genes, including Per2, Arntl, and Npas2, are fundamental in regulating both daily and seasonal biological rhythms.^[5] These genes oversee the molecular and cellular processes that synchronize an organism’s internal timing with external environmental cues, primarily light-dark cycles, ensuring proper physiological and behavioral responses to the changing seasons.^[5] Disruptions within these complex regulatory networks can lead to imbalances in homeostasis, which in turn can manifest as seasonal variations in mood and behavior.^[5] Central to this process is the perception of light, mediated by specialized photoreceptors such as melanopsin, encoded by the OPN4 gene.^[5] A specific missense variant (P10L) in the OPN4 gene has been identified in individuals with Seasonal Affective Disorder (SAD), suggesting its role in how the brain processes and responds to changes in day length.^[5] Furthermore, the serotonin neurotransmitter system is a crucial component in mood regulation and its interaction with light-driven biological rhythms; polymorphisms in the serotonin transporter promoter (5-HTTLPR) and the serotonin-2A receptor gene, such as rs731779 and the -1438G/A promoter polymorphism, have been associated with seasonality and SAD.^[1]

Genetic Architecture and Regulatory Mechanisms

Seasonality exhibits a polygenic architecture, indicating that its expression is influenced by the combined effects of multiple common genetic variants.^[1] While initial candidate gene studies for SAD did not yield consistently replicable findings, broader genome-wide association studies (GWAS) are beginning to uncover the complex genetic landscape underlying seasonal patterns.^[1] For example, a meta-analysis identified rs11825064 , an intergenic SNP on chromosome 11, as a significant marker, suggesting that non-coding regions may play important regulatory roles in seasonal biological responses.^[1] The gene ZBTB20 has also been identified as a candidate susceptibility gene for SAD.^[5]The genetic underpinnings of seasonality demonstrate a significant overlap in risk factors with psychiatric conditions such as schizophrenia (SCZ) and bipolar disorder (BD), though not with major depressive disorder (MDD).^[1] This shared genetic predisposition suggests common regulatory networks and biological pathways that contribute to both seasonal mood variations and severe mental illnesses.^[1]Epigenetic modifications and dynamic gene expression patterns, which are themselves influenced by environmental factors like season, likely contribute to the heritability of seasonality, estimated at 29%, underscoring a complex interplay between an individual’s genetic makeup and their environment.^[1]

Hormonal and Metabolic Influences

Vitamin D, a critical biomolecule, plays a substantial role in the etiology of several conditions, including schizophrenia, and is also implicated in the regulation of seasonal mood.^[1]Its primary synthesis is dependent on exposure to ultraviolet B (UVB) radiation, which fluctuates significantly with the seasons, geographical latitude, and individual factors such as skin exposure, use of sunscreen, and body weight.^[1]For instance, a higher body mass index (BMI) is associated with reduced concentrations of 25-hydroxyvitamin D (25OHD), thereby affecting systemic vitamin D levels.^[2] The concentration of 25OHD in the body exhibits distinct seasonal fluctuations, with both higher mean levels and a greater proportion of variance attributable to genetic factors observed during summer months compared to winter.^[2]This observation suggests that genetic influences on vitamin D metabolism become more pronounced during periods of increased sun exposure, highlighting a crucial gene-environment interaction.^[2]Clinical studies have shown that vitamin D supplementation can improve mood in healthy individuals during winter and alleviate depressive symptoms in patients with SAD, emphasizing its potential as a therapeutic agent and its role in mediating the body’s seasonal biological adaptations.^[1]

Pathophysiological Processes and Clinical Overlap

Seasonal Affective Disorder (SAD) is clinically defined by recurrent episodes of depression that typically occur during the fall and winter, with a subsequent remission of symptoms in the spring and summer.^[1]From a clinical perspective, SAD has often been conceptualized as a variant within the bipolar spectrum, given observed differences in the recurrence and severity of seasonal major depressive disorder compared to seasonal bipolar disorder, with the latter showing higher rates of hospitalization.^[1] These distinctions suggest underlying pathophysiological processes and disruptions in homeostatic mechanisms that differentiate seasonal mood patterns from non-seasonal forms of depression.^[1]The unexpected genetic overlap between seasonality and schizophrenia, coupled with observations of shared cognitive deficits, warrants further investigation into common disease mechanisms.^[1] While therapies such as light therapy are established and effective treatments for SAD, working by modulating photoperiodic signals and influencing neurochemical pathways, the intricate connections between seasonal biology and broader psychiatric conditions imply complex systemic consequences that extend beyond simple mood regulation.^[1] A deeper understanding of these interconnections at the tissue and organ levels, particularly within the brain and endocrine systems, is crucial for identifying novel therapeutic targets.^[1]

Clinical Relevance

Understanding seasonality, defined as seasonal changes in mood and behavior, holds significant clinical relevance for the diagnosis, risk stratification, and management of various psychiatric conditions. Research, including meta-analyses of genome-wide association studies (GWAS), has revealed a polygenic architecture for seasonality and specific genetic correlations with major psychiatric disorders, underscoring its role beyond a simple environmental influence. This genetic overlap provides a foundation for integrating seasonality into comprehensive patient care strategies, moving towards more personalized and effective interventions.

Genetic Predisposition and Psychiatric Comorbidity

Seasonality exhibits a polygenic architecture and strong genetic correlations with severe mental illnesses, particularly schizophrenia (SCZ) and bipolar disorder (BD).^[1]Genetic profile scores derived from SCZ GWAS explain a notable proportion of the variance in seasonality, indicating a substantial shared genetic risk.^[1]While BD also shows a significant, albeit weaker, genetic overlap, major depressive disorder (MDD) does not appear to share common genetic risk factors with seasonality at the molecular level.^[1] This genetic insight aligns with historical clinical observations dating back to the early 19th century, which recognized seasonal patterns in psychiatric symptoms, including affective, psychotic, and cognitive features.^[1]The clinical implications of these genetic associations are profound, suggesting that seasonality is not merely an environmental modifier but an intrinsic aspect of these disorders. For instance, the co-occurrence of seasonal affective disorder (SAD) symptomatology and schizophrenia, especially in high-latitude regions, points to overlapping phenotypes and potential shared underlying mechanisms, including cognitive deficits.^[1]Furthermore, studies have documented seasonal variations in hospital admissions for SCZ, BD, and depression, as well as seasonality in the onset of symptoms in first-episode schizophrenia, highlighting the prognostic value of recognizing seasonal patterns in disease progression and severity.^{[6], [7], [8]}The presence of seasonality can differentiate clinical courses, with bipolar forms of seasonal depression often linked to higher hospitalization rates and greater severity compared to MDD with seasonal patterns.^[1] Family studies further support these connections, showing an increased prevalence of nonseasonal depression in the families of individuals with SAD.^{[9], [10], [11]}

Risk Stratification and Personalized Care

The identification of genetic links between seasonality and psychiatric disorders offers a crucial avenue for improved risk stratification and the development of personalized medicine approaches. By assessing an individual’s seasonality, for example, using tools like the Seasonal Pattern Assessment Questionnaire (SPAQ), clinicians can gain insights into their genetic predisposition for conditions like SCZ and BD, even in the absence of a full diagnosis.^{[1], [11]} This knowledge can facilitate the identification of high-risk individuals who may benefit from early interventions or more intensive monitoring, moving beyond a reactive treatment model.

Considering the genetic overlap, especially with SCZ, understanding seasonality allows for a more nuanced risk assessment. For example, individuals presenting with significant seasonality might warrant closer scrutiny for symptoms indicative of SCZ or BD, guiding early diagnostic efforts. This approach supports the concept of personalized medicine by tailoring preventative strategies and clinical vigilance based on an individual’s seasonal phenotypic expression and underlying genetic predispositions. Such strategies could encompass environmental modifications, lifestyle adjustments, and targeted prophylactic interventions aimed at mitigating seasonal exacerbations or preventing the progression of associated disorders. The observed seasonality of births in SCZ and BD, as well as SAD, further supports the importance of early life factors in risk assessment.^{[12], [13]}

Therapeutic and Monitoring Strategies

Integrating seasonality into clinical practice has direct implications for diagnostic utility, treatment selection, and ongoing monitoring strategies. While seasonal affective disorder is recognized as a “seasonal pattern specifier” in diagnostic manuals rather than a distinct disorder, the underlying genetic factors linking it to SCZ and BD suggest that seasonality serves as a critical clinical indicator.^[1]This implies that a thorough assessment of seasonality, including the degree of functional impairment, should be a standard component of psychiatric evaluation, particularly for mood and psychotic disorders.^[1]For treatment selection, the shared genetic factors between seasonality and psychiatric conditions may uncover novel therapeutic targets.^[1]One notable area is the role of vitamin D, which has been hypothesized as a risk-modifying factor for SCZ and is known to influence mood and depression scores in SAD.^{[1], [14]}Genetic studies have shown that the genetic variance of 25-hydroxyvitamin D concentrations is higher in summer compared to winter, and high BMI is associated with reduced vitamin D levels, highlighting a complex interplay of genetic and environmental factors.^[2]Therefore, interventions such as vitamin D supplementation, light therapy, and behavioral adjustments related to seasonal changes could be more strategically employed as part of a comprehensive, personalized treatment plan. Ongoing monitoring of seasonal patterns in mood, behavior, and cognitive function is essential to anticipate and manage potential exacerbations, ensuring continuous patient well-being and preventing severe outcomes in at-risk individuals.

Population Studies

The study of seasonality, encompassing seasonal changes in mood and behavior, involves diverse population-level investigations to understand its prevalence, underlying genetic architecture, and environmental influences. These studies often employ large cohorts, cross-population comparisons, and sophisticated genetic methodologies to unravel the complex interplay of factors contributing to seasonal patterns.

Epidemiological Patterns and Population-Specific Effects

Seasonality manifests across a spectrum within the general population, ranging from subtle changes to severe forms like Seasonal Affective Disorder (SAD), which is characterized by recurrent depression during specific seasons, typically fall and winter, with symptom alleviation in spring and summer.^[1]Epidemiological research has explored the prevalence and incidence of seasonality, noting that even subclinical seasonal changes can cause significant distress and impairment.^[1] Studies have indicated variations in the prevalence of SAD across different latitudes.^[5]suggesting a geographic component to its expression. Furthermore, investigations into psychiatric hospital admissions have consistently revealed seasonal patterns for conditions such as bipolar disorder, depression, and schizophrenia.^[8]with additional findings on the seasonality of births in individuals with schizophrenia and bipolar disorder.^[12] These observations underscore the widespread influence of seasonal factors on mental health outcomes and highlight the need for population-specific analyses to capture nuanced demographic and environmental correlates.

Genetic Architecture and Shared Psychiatric Risk

Large-scale cohort studies have been instrumental in elucidating the genetic underpinnings of seasonality, revealing its polygenic architecture rather than reliance on common SNPs of very large effect.^[1] A meta-analysis of genome-wide association studies (GWAS) involving Australian twin populations and an Old Order Amish cohort, totaling 4,156 individuals, identified rs11825064 as the most significant associated SNP, although it did not reach genome-wide significance.^[1]This research, along with a separate GWAS for SAD using European ancestry controls from various biobanks, indicates that genetic factors account for a significant portion of the variance in seasonality, estimated at 29% in men and women.^[1]Intriguingly, these studies have also uncovered shared genetic risk factors between seasonality and psychiatric disorders, with particularly strong evidence for overlap with schizophrenia, explaining 3% of the variance in global seasonality scores, and milder associations with bipolar disorder, but no significant overlap with major depressive disorder.^[1] Such findings suggest common biological pathways underlying these conditions, offering valuable insights into their etiology.

Methodological Approaches and Environmental Interactions

Population studies on seasonality employ diverse methodologies to capture its complex nature, including large-scale GWAS, twin studies, and meta-analyses.^[1]Phenotyping is often achieved through standardized questionnaires like the Seasonal Pattern Assessment Questionnaire (SPAQ), which evaluates global seasonality based on a Likert scale for various indices, or the Diagnostic Interview for Genetic Studies (DIGS), used to ascertain seasonal depressive episodes.^[1]While these designs facilitate the identification of genetic associations, considerations regarding sample size, representativeness, and generalizability are paramount; for instance, the lack of replication of Australian findings in the Amish cohort highlights the importance of cross-population validation.^[1] Furthermore, studies on gene-environment interactions provide crucial insights, as demonstrated by research in the UK Biobank showing that the heritability of 25-hydroxyvitamin D concentration varies seasonally, with a larger proportion of variance attributed to genetic factors in summer compared to winter.^[2]This seasonal fluctuation offers a natural experiment to dissect genetic components influencing vitamin D metabolism, underscoring the dynamic interplay between genetic predispositions and environmental exposures in shaping seasonal traits.

Frequently Asked Questions About Seasonality

These questions address the most important and specific aspects of seasonality based on current genetic research.

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1. Why do I feel so down every winter, but my friend doesn’t?

Your individual genetic makeup likely plays a significant role in how you experience seasonal mood changes. Studies show that about 29% of the variation in seasonality is due to genetics, meaning some people are more predisposed to these shifts than others. It’s not about one single gene, but many genes working together, which can lead to different sensitivities to environmental cues like light and temperature.

2. Is my winter sadness just ‘all in my head’ or something real?

Your winter sadness is definitely real and has a biological basis, not just “in your head.” Research confirms a significant genetic component to seasonality, contributing to how your body and mood respond to the changing seasons. It’s recognized clinically as a “seasonal pattern” specifier for major depressive episodes, showing it’s a consistent, biological phenomenon for many individuals.

3. My family gets the ‘winter blues’ too; am I stuck with it?

While seasonality does have a genetic component, accounting for about 29% of its variation, you’re not entirely “stuck” with it. This genetic predisposition means it can run in families, but it’s a complex trait influenced by many genes and your environment. Understanding your genetic tendency can empower you to proactively manage seasonal changes through lifestyle adjustments and other interventions.

4. Can I pass on my ‘winter blues’ tendency to my kids?

Yes, there’s a genetic component to seasonality, meaning you can pass on a predisposition to your children. Studies estimate that genetic factors account for approximately 29% of the overall variation in seasonality. However, it’s a polygenic trait, meaning many genes with small effects contribute, so it’s not a simple, single-gene inheritance pattern, and environmental factors also play a significant role.

5. Could my seasonal mood swings be connected to other health issues?

Surprisingly, yes, there can be genetic connections between seasonality and other psychiatric conditions. Research shows strong genetic overlap with schizophrenia and significant overlap with bipolar disorder. This doesn’t mean you’ll develop these conditions, but it highlights shared genetic pathways that influence brain function and mood regulation, which is important for understanding your overall health.

6. Why do some people seem immune to seasonal changes?

Some individuals do appear more resilient to seasonal changes, and genetics likely play a role in this immunity. While seasonality has a genetic component, specific populations, like the Amish, show a remarkably low prevalence of seasonal affective disorder, suggesting genetic or environmental factors can offer protection. It’s part of the natural variation in how people’s bodies and minds adapt to their environment.

7. Does my background affect how much seasons bother me?

Yes, your background can absolutely influence how much seasons bother you. Studies have found that the prevalence of seasonality can differ significantly across various populations and geographical locations. These differences might be due to a combination of unique genetic architectures, varying environmental exposures, and cultural factors that shape how people experience seasonal changes.

8. I heard seasonal depression is like bipolar disorder; are they actually linked?

There’s indeed a recognized link between seasonal depression and bipolar disorder. Clinically, even unipolar seasonal affective disorder has been conceptualized as potentially belonging to the bipolar spectrum due to its recurrent nature. Furthermore, genetic studies have found significant genetic overlap between seasonality and bipolar disorder, suggesting shared biological pathways in how these conditions manifest.

9. Does taking vitamin D help with my seasonal feelings?

While research has observed that the heritability of vitamin D levels can vary by season, with a higher genetic influence in summer, the article doesn’t directly state whether supplementing vitamin D helps with seasonal feelings. However, adequate vitamin D levels are crucial for overall health and brain function. It’s a common recommendation to discuss with your doctor, especially if you experience seasonal mood changes.

10. Why don’t scientists find one specific “winter blues” gene?

Scientists haven’t found one single “winter blues” gene because seasonality is believed to have a polygenic architecture. This means many different genes, each having only a small effect, combine to influence your seasonal sensitivity, rather than one or two major genes. Current studies are also often underpowered to detect all these small genetic contributions, making it harder to pinpoint specific culprits with strong statistical significance.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Byrne EM et al. Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder.J Clin Psychiatry. 2015;76(2):e191-e198.

[2] Revez JA et al. Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration. Nat Commun. 2020;11(1):1733.

[3] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th Ed.). 1994.

[4] Rosenthal NE. Issues for DSM-V: seasonal affective disorder and seasonality.The American journal of psychiatry. 2009 Aug; 166(8):852–853.

[5] Ho KWD et al. Genome-wide association study of seasonal affective disorder. Transl Psychiatry. 2018;8(1):198.

[6] Clarke, M., et al. “Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.”Schizophrenia research 34.3 (1998): 143-149.

[7] Strous, R. D., et al. “Seasonal admission patterns in first episode psychosis, chronic schizophrenia, and nonschizophrenic psychoses.”The Journal of nervous and mental disease 189.9 (2001): 642-644.

[8] Daniels, B. A., et al. “Seasonal variation in hospital admission for bipolar disorder, depression and schizophrenia in Tasmania.”Acta psychiatrica Scandinavica 102.1 (2000): 38-43.

[9] Allen, J. M., et al. “Depressive symptoms and family history in seasonal and nonseasonal mood disorders.”The American journal of psychiatry 150.3 (1993): 443-448.

[10] Sher L. Genetic studies of seasonal affective disorder and seasonality.Comprehensive psychiatry. 2001 Mar-Apr;42(2):105–110.

[11] Madden PA et al. Seasonal changes in mood and behavior. The role of genetic factors. Archives of general psychiatry. 1996 Jan; 53(1):47–55.

[12] Torrey, E. F., et al. “Seasonality of births in schizophrenia and bipolar disorder: a review of the literature.”Schizophrenia research 28.1 (1997): 1-38.

[13] Pjrek, E., et al. “Seasonality of birth in seasonal affective disorder.”The Journal of clinical psychiatry 65.10 (2004): 1389-1393.

[14] McGrath, John. “Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?.”Schizophrenia research 40.3 (1999): 173-177.