Seasonality in Psychiatric Disorders

Adaptation to environmental changes, such as light-dark cycles , are critical to the survival of many species, including humans. Modern humans emerged near the equator, where day and night are equally long (12h/12h pattern) and constant throughout the year.

During early migrations out of Africa, modern humans spread across continents, including high-latitude areas with significant seasonal variations in photoperiods. A geographically explicit model suggests that genetic adaptations of the circadian clock to daylight may be related to susceptibility to mood disorders. Indeed, the prevalence of psychiatric disorders, including seasonal affective disorders (SAD), major depression, schizophrenia, and suicide attempts in bipolar disorder, increases with latitude.

The greater seasonality of depressive symptoms is reported more in high latitude regions than in countries closer to the equator. Malfunctioning biological adaptations to environmental changes, such as large light variations in high-latitude regions, could increase vulnerability to certain psychiatric disorders.

In addition to light, there are many environmental variables that alter across latitudes, such as changes in temperature, ultraviolet radiation, allergens and viral exposures, among others. However, it has been suggested that changes in photoperiod primarily contribute to these genetic adaptations. Humans are very sensitive to light, even at low intensities such as twilight transitions.

Findings from well-controlled human laboratory studies show that the internal clock adapts to changes in day length.

Specifically, after chronic exposure to day/night cycles , artificially induced in the laboratory environment, endogenous circadian rhythms adjust to the experimental conditions.

An early study conducted between 1964 and 1979 reported conserved seasonal circadian rhythm patterns in men that remain isolated from external cues. This suggests that circadian rhythms are trained to seasonal changes in daylight and that there is an imprinting of biological clocks for the light/dark cycles to which biological clocks have previously been exposed.

Patients suffering from psychiatric disorders show dysfunctions in behavior, emotion, and cognition, which significantly impair their social, occupational, or interpersonal functioning. Seasonal patterns of mood and behavior are typically assessed with questionnaires that detect neuropsychological (mood, energy, social activity, sleep) and metabolic (appetite, weight) activities.

Seasonality and a higher global seasonality score associated with more severe phenotypes were observed in psychiatric disorders. While seasonal-related social factors and stressors, e.g., school schedules, vacations, may affect symptoms, evidence indicates that biological processes play a critical role in the observed seasonality.

The seasons influence several biological pathways, including transcription genes neurotransmitters and neuropeptides and immunity, metabolic and neuroendocrine processes.

However, it is not yet known how biological adaptations affect seasonal patterns of mood and behavior, whether a biological response to stronger seasonal changes has beneficial effects on mood stabilization, and why some people experience greater seasonality than others with negative consequences for their daily life and performance.

The authors’ literature research, primarily on possible mechanisms by which seasons influence psychiatric disorders, focused on brain adaptation, as brain tissue is among those that exhibit seasonality in transcriptomes.

To identify seasonal fluctuations in some psychiatric symptoms, it has been proposed to use day length and the rate of change in day length. For example, in the northern hemisphere, days are longest at the summer solstice in June and shortest at the winter solstice in December, while rates peak at the March/spring equinox. while the rates of photoperiod decrease, at the September/autumn equinox.

In affective disorders (major depression, bipolar I and II), manic episodes generally peak in spring/summer, with a smaller peak in autumn.

Depressive episode peaks in winter and mixed episode peaks in early spring/mid/late summer. It is estimated that around 10-22% of patients show seasonal onset or exacerbation of symptoms and are classified as having SAD. However, prevalence is probably underestimated as seasonality is often not assessed.

It is notable that greater seasonality of symptoms was associated with more severe depression and mania, and a greater number of relapses. Patients with major depression or bipolar I disorder who exhibited patterns of greater seasonality reported higher levels of suicide ideation and attempts. Atypical depression and somatic symptoms , such as hypersomnia, hyperphagia, psychomotor slowness, fatigue, and reduced physical activity, are more common in patients with seasonal affective disorders (SAD) than without SAD. The seasonality of schizophrenia is less studied compared to affective disorders.

Several studies from the northern and southern hemispheres consistently show the association of the timing of hospitalization or onset of the first episode of schizophrenia with shorter photoperiods (peak in winter), although one study reported an additional peak in June. However, it is not clear whether positive symptoms (e.g., hallucinations, delusions) or negative symptoms (attenuation of affect, loss of motivation, and social withdrawal) are what motivate hospitalizations. Patients with SAD are considered to be at greater risk of suicidal behavior.

Suicides and suicide attempts peak in the spring/summer months and are predominant in people with mood disorders compared to people without such disorders, and increase with distance from the equator, indicating the influence of changes in the duration of daylight. In the US, deaths from intentional drug overdose have a positive linear relationship with day length.

Furthermore, not only day length but also rapid changes in day length could increase suicide rates, which would explain the repeatedly observed spring spikes. An international study reported that, in bipolar I disorder, pronounced shifts from sunlight in the winter to the light of the summer months appear to be a significant risk factor for attempted suicide.

Interestingly, the authors say, Swedish studies showed a spring peak in suicides in patients with alcohol use disorder while patients with major depression experienced a peak in the fall. For better suicide prevention, it would be important to investigate in the future whether seasonality in suicide attempts differs between psychiatric disorders.

Furthermore, despite the general pattern, with a peak in spring/summer , countries vary in the degree of seasonality, indicative of the contribution of social and cultural influences. Recent studies take advantage of large Internet data sets to investigate seasonality in mental problems in the population. Literature research showed that, over a 5-year period, peaks occur in winter in both the northern and southern hemispheres. Seasonal rhythms in mood are also seen around the world, and are associated with changes in day length.

Positive affect is higher when days are longer and is higher when changes in day length are greater.

On the other hand, no influence of seasonal changes on negative affect was found. In accordance with this, in a representative population sample from Switzerland, of people who did not meet the seasonal criterion, seasonal rhythms were present with more well-being/psychological symptoms (mood, social contact, energy) and fewer vegetative symptoms (sleep, appetite, weight) in spring/summer than in autumn/winter, but to a lesser extent than among those who met the criteria.

In sum, although most studies are retrospective and cross-sectional, sample sizes in population surveys are larger than in clinical studies. Most survey studies rely on the calendar for seasonal classification, but in the future, the use of the astronomical calendar, which considers variations in day length and involves greater measurement of time, could increase sensitivity for study the relationship between day/night cycles and psychiatric symptoms.

Overall, seasonal patterns in psychiatric disorders are consistently observed across countries, pointing to underlying mechanisms beyond those driven by cultural components.

Seasonal variations of multiple neurotransmitter systems have been reported. The most studied are the serotonergic (5-HT) and dopaminergic systems, due to their essential role in mood, cognition and reward.

> Dopamine

Postmortem studies have examined midbrain dopaminergic neurons in people who died in winter vs. summer and found that tyrosine hydroxylase (rate-limiting enzyme of dopaminergic synthesis) and the dopamine transporter, the immunological reactivity of neurons was qualitatively lower in winter than in summer. Likewise, a positron emission tomography (PET) study showed lower availability of the striatal dopaminergic transporter measured with ß-CIT in depressed and symptomatic SAD patients than in healthy controls.

Tyrosine hydroxylase and dopamine transporter dynamically regulate the homeostasis of the dopaminergic system. The decreased synthesis of dopamine due to the lower expression of tyroine hydroxylase could be compensated by the negative regulation of the dopamine transporter, to increase the duration of dopaminergics in the extracellular space and vice versa.

A postmortem study reported higher levels of dopamine or its metabolites in autumn/winter compared to the spring/summer period in the hypothalamic tissue of healthy controls and in the ventral striatal tissue in schizophrenic patients. Consistent with this, cerebrospinal fluid findings in healthy adults, patients with schizophrenia, and patients with Alzheimer’s documented increased concentrations of dopaminergic metabolites in autumn/winter compared to spring/summer.

PET studies have documented higher striatal presynaptic dopaminergic levels measured with F18-DOPA and lower striatal D2/D3 receptor availability, measured with I123-IBZM in winter, which could reflect increased dopaminergic levels competing for binding with I123-IBZM, or reduced levels of D2/D3 receptors.

In winter, when the day is shorter, melatonin release is prolonged, which could help explain these seemingly contradictory findings.

Specifically, preclinical studies have reported that while melatonin inhibits striatal postsynaptic dopaminergic signaling it also promotes presynaptic neuronal dopaminergic integrity. In contrast to PET findings, studies using spontaneous ocular blink rate, as an indirect measure of dopaminergic signaling, showed higher blink rates in spring/summer than in autumn/winter, both in healthy participants and patients. with schizophrenia. However, initial evidence for eyeblink rates as a biomarker of dopaminergic brain activity is inconsistent.

>  Serotonin

In the postmortem human brain , 5-HT levels in the hypothalamus were lower in winter. Likewise, a study that measured blood samples from 101 healthy men found the lowest level of 5-HT turnover in winter, which increased with prolonged exposure to bright light. PET showed that greater availability of the 5-HT1A receptor was associated with longer photoperiods and total light intensity. Measurements were made with C11-WAY-100635 in the 5-HT projection regions, in the frontal, temporal, insular, cingulate, amygdala and hippocampus cortices, where 5-HT1A receptors are mostly postsynaptic.

On the contrary, the greater availability of the serotonin transporter (TrS), responsible for the reuptake of 5-HT in presynaptic neurons, measured with C11-DASB in the prefrontal cortex, striatum, thalamus and midbrain, was associated with longer photoperiods. short and, in healthy participants, peaked in autumn/winter. However, this observation was not confirmed in the SPECT study with within-subject design, using I123-ADAM. Variants in 5-HT1A and TrS signaling could evidence seasonal mood changes, just as antidepressants exert their therapeutic effects, in part, by blocking TrS and increasing postsynaptic 5-HT1A signaling.

In patients with seasonal affective disorders (SAD), TrS availability in the brain (including the anterior cingulate and prefrontal cortices) was upregulated in winter. This increase was greater in patients with SAD than in healthy controls, and it was proposed that the development of winter depression symptoms in patients with SAD could reflect the lack of downregulation of TrS.

Individuals with seasonal affective disorders (SAD), resistant to downregulation in winter , were thought to have the benefit of maintaining stable synaptic 5-HT level. Cortical regions in SAD-resilient individuals that showed seasonal adjustments of TrS levels included the right posterior medial and left inferior portions of the temporal and occipital cortices and the angular gyrus.

A recent PET study examined monoamine oxidase A (MAO-A), an enzyme that degrades amine neurotransmitters, including dopaminergic, 5-HT in healthy controls and SAD patients, with repeated measurements in fall/winter and spring/summer. Although SAD patients do not differ from healthy controls in brain MAO-A, they show seasonal dynamics, with reduced MAO-A. In healthy controls, MAO-A decreased from autumn/winter to spring/summer, which was not observed in patients with SAD. Of note, bright light therapy for 3 weeks significantly reduced MAO-A levels in the brains of SAD patients, suggesting an important role of light in the regulation of MAO-A.

In summary, there is strong support for seasonal variations of 5-HT and subcortical dopaminergic signaling in the brains of healthy controls and individuals with seasonal affective disorders (SAD). However, the findings are difficult to interpret considering that several studies have evaluated different measures (direct vs. indirect), objectives (metabolites, synthesis, receptor, transporter) and regions (cerebrospinal fluid, cortical, subcortical).

On the other hand, 5-HT and dopaminergic are not independent systems and have strong interactions with each other.

For example, animal studies show that activation of the 5HT1A receptor stimulates dopaminergic release in the prefrontal cortex while inhibiting dopaminergic release in the striatum. According to human studies, cortical TrS and striatal dopaminergic transporter apparently show opposite seasonal patterns, which in turn SAD are associated with symptoms of depression. Thus, it is likely that the ratio and balance between dopaminergic and 5-HT is relevant to the presentation and severity of psychiatric symptoms.

On the other hand, there is evidence of attenuated seasonal effects. Regulation of neurotransmitter system, e.g., TrS and MAO-A in patients with SAD. Dysregulation of the 5-HT and dopaminergic systems has been assumed to underlie several psychiatric disorders. However, seasonal 5-HT and dopaminergic variations still need to be examined in psychiatric disorders other than mood disorders. Beyond 5-HT and dopaminergic, accumulating evidence has supported seasonal fluctuation in other neurotransmitter systems.

A recent study reported a U-shaped relationship between day length and mu opioid receptor availability in humans. Animal studies have revealed other positive and negative correlations of day length with norepinephrine and acetylcholine, respectively, that have not been examined in humans.

In contrast to the extensive biochemical studies on seasonality, very few have investigated seasonal effects on brain activity, which are tightly modulated by neurotransmitters. A cross-sectional study from Belgium demonstrated seasonal variations of cognitive brain responses in 28 healthy young participants, after living without seasonal cues for 4.5 days, suggesting there may be a "photic memory" for the photoperiod to which the participants were previously exposed. of the study.

The authors reported different seasonal patterns for various cognitive components while basic attentional processes were associated with day length, higher level of executive brain responses covaried with day length variations, each day. In U.S. young adults, the amplitude of the P300 event-related brain potential, which reflects processes involved in higher-level cognition, such as evaluation and decision making, was greater when testing was done during spring/summer compared to those made in autumn/winter.

Although patients with psychiatric disorders show lower performance in several cognitive domains compared to healthy controls, it remains unclear whether cognitive deficits vary across seasons. Furthermore, neuroimaging studies of brain activations associated with seasonal fluctuations in affective control and reward function are still lacking.

Another promising area of ​​research is seasonal variations using resting fMRI , which is less affected by study-specific factors and allows comparisons between studies. In particular, functional connectivity at rest is highly correlated with brain activation patterns during task performance.

In a recent German study, with 14 healthy male volunteers, resting fMRI signal variance drops endogenously (i.e., not evoked by external cues) sometimes coinciding with dawn and dusk in sensory regions including the bilateral visual cortices, the somatosensory and auditory cortex.

The sensorimotor network has tight recurrent connections consistent with localized processing of external stimuli. Therefore, the sensorimotor network could be the core of a cortical network that receives information from the intracranial clock and transmits information about the length of the day to the rest of the brain. There have already been some observations on the associations of the dynamic brain network with different affective states.

In bipolar disorder, it has been suggested that the change of manic and depressive phases is related to the balance between the default mode network and the sensorimotor network.

Intrinsic brain activity shifted toward the default mode network during the depressive phase, characterized by internal thoughts and rumination, and toward the sensorimotor network during the manic phase, characterized by excessive focus on external environmental stimuli and psychomotor overarousal. .

Longitudinal evidence further supports interoceptive-sensorimotor involvement during the hypomania phase and the default mode network during the depression phase of bipolar disorder. However, seasonal effects were not considered in these studies, and seasonal patterns were not evaluated in patients with bipolar disorders. It remains to be confirmed whether patients with seasonal disease patterns showed comparable network dynamics to patients with non-seasonal patterns.

Brain structure studies that studied seasonal effects focused on subcortical regions relevant to emotional regulation, using large data sets. Cross-sectional studies in healthy UK and US adults documented positive associations of day length with volumes in subcortical regions, including the hippocampus, amygdala, and brainstem, which are regions that show seasonal variations in 5-HT signaling.

Based on evidence from preclinical studies, cortical regions may also show seasonal volumetric changes, requiring further investigation in prospective, repeated-measures clinical studies. So far, researchers have not found any studies that examine seasonal effects on structural or functional connectivity in the human brain.

Taken together, there are multiple gaps in research, including neuroimaging studies on seasonal variations in brain function and structure in patients with psychiatric disorders. To do this, longitudinal designs are needed with samples of sufficient size and high temporal resolution to examine photoperiod and rates of photoperiod change, with comparison of patients with healthy controls.

Genes in the brain and gonads showed the strongest seasonal expression profiles among 46 tissues, based on transcriptomic analysis of postmortem tissues from 932 donors, and immune-related genes were enriched among genes showing expression profiles. seasonal, consistent with previous findings.

During winter in Europe and Oceania, the immune system has a profound pro-inflammatory transcriptomic profile, with increased levels of soluble IL-6 receptors and C-reactive protein. It is highlighted that emerging evidence suggests that, in psychiatric disorders, there is a link between immune dysfunction and changes in the structure and function of patients’ brains.

Associations of the frontal and temporal regions that participate in cognitive and affective control have been reported. From a behavioral point of view, correlations have been observed between inflammatory biomarkers and poor cognitive performance. Neuroinflammation could be a potential mechanism contributing to the seasonality of psychiatric disorders. However, so far, no studies have examined seasonal changes in immune function in patients, and how they differ from healthy participants.

Given the immunity-brain relationship observed in psychiatric disorders, future studies should evaluate its implication in the seasonality of the effects reported for frontotemporal regions and its association with cognitive and emotional symptoms. Furthermore, investigation of the specific immunological processes that could be involved in the seasonal expression of psychiatric diseases could lead to possible therapeutic interventions.

Humans have intrinsic circadian rhythms that are slightly longer than 24 hours (approximately 24.2 hours) and exquisitely sensitive to light.

Near-24-h oscillations can be found in almost all biological and physiological processes in the brain and human body. Light is the most prominent environmental signal that entrains the endogenous circadian rhythm to the 24-h day. The suprachiasmatic nucleus , the master circadian pacemaker in the brain, receives light input and transmits synchronized information regulating neuronal activity, body temperature, and hormonal signals.

Postmortem studies of the human brain suggest that the suprachiasmatic nucleus not only plays a role in the temporal organization of nearly 24-h circadian processes but also in seasonal control. in almost all biological and physiological processes in the brain and human body. In young subjects, the volume and number of vasopressin neurons in the suprachiasmatic nucleus, which transmit photic information to the brain, vary throughout the day with 2 peaks around twilight.

The same group from the Netherlands also reported seasonal changes in subjects aged 6 to 91 years. The volume and number of vasopressin neurons are highest during October, when day length becomes shorter and day length decline rates are greatest, while they are lowest around June, when photoperiod It is longer and the variations in the photoperiod are minimal. In addition to the peak in October there is another smaller peak around March, when the acceleration of day length increases.

The annual 2-peak pattern around the spring and autumn equinox was even more prominent when only young subjects were included. Taken together, increases in neuronal volume and number in the suprachiasmatic nucleus (SCN) could optimally help respond to the sudden photic transition during twilight and equinox, which is critical for the regulation of daily and annual activities. . Melatonin and core body temperature have been used to measure endogenous circadian rhythms in humans.

It is surprising, say the authors, that seasonal variations of the core temperature period are reflected in the pattern of NSA morphology. The period was shorter around the spring and autumn equinox (shorter in spring) than that of summer and winter. In terms of rhythm timing, oral temperature peak time was earlier in December than in March or June. Direct comparison of two core body temperature studies is difficult since the latter has lower temporal resolution, while oral temperature is not always accurate for assessing core body temperature.

It is notable that few studies have examined the fluctuation of melatonin across the seasons. In young men, a French study with 4 measurements in January, March, June and October reported higher levels of plasma melatonin in June than in January. In contrast, in an experimental setup, the duration of melatonin secretion was shorter after exposure to the ’summer’ photoperiod along with shorter sleep duration. In extreme environments such as at an arctic latitude, changes over time were observed rather than the release of melatonin.

It has been reported that in winter there was a delay in the circadian phase accompanied by later and poor quality sleep. However, these studies are limited by their very small sample sizes (5–7 subjects in each study) and need to be replicated. Taken together, several circadian processes, such as core body temperature and melatonin release, could show different seasonal profiles.

Questions remain as to whether different patterns of circadian processes contribute to the onset of psychiatric symptoms at different times of the year, whether there is a misalignment between various seasonal biological processes, and the seasonality of mood symptoms and other behaviors. Specifically, whether the SCN responds to the equinox in the spring and autumn by affecting psychiatric symptoms that appear in summer and winter. More rigorous studies are required to answer these questions. Both momentary and periodic rhythms could be important for understanding how circadian processes participate in seasonal adaptations and expansion of 2-time point measurement, e.g., winter vs. winter. summer from the highest temporal measurements, to capture the complex seasonal dynamics.

Seasonal adjustment of circadian rhythms can influence brain function by modulating neurotransmission. Preclinical studies documented reciprocal connections between the NAQ, the dorsal raphe nucleus (main center for 5-HT), and the ventral tegmental area and nucleus accumbens (main centers for dopaminergics). In animals, circadian patterns are seen in dopaminergic and 5-HT activities while dopaminergic activity is greater during the active phase, mRNA levels of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT biosynthesis , has a peak around the light transition.

The sudden and persistent impact of photoperiod on serotonergic neurons depends on melatonin signaling. Thus, the SCN can adjust 5-HT and dopamine signaling for photoperiod, thus adjusting modulatory functions to environmental changes. 5-HT and dopaminergic afferents also transmit information to the SCN and modulate its activity. While 5-HT increases or decreases the light-induced circadian phase shift, depending on the activated receptor subtype and location (e.g., presynaptic vs. postsynaptic), dopamine agonists reduce the effect of the induced phase shift. for the light. Therefore, disrupted and unbalanced neurotransmitter systems in patients with psychiatric disorders could affect their circadian adaptations to seasonal changes.

Of note, the authors say, immune factors modulate the phase adjustment of circadian clocks and could therefore contribute to seasonal changes in circadian adaptations. It is possible that people with immune dysfunctions, such as those reported in some psychiatric illnesses, may have difficulty adjusting circadian rhythms to light/dark cycles as they vary throughout the seasons.

Finally, mismatched circadian rhythms could disrupt activity and rest rhythms and reduce light exposures, which would further destabilize circadian rhythms.

Although there are many unknowns, the current findings support the belief that greater seasonal adjustment of neurotransmitters is likely to be beneficial in maintaining a stable mood throughout the year. This is consistent with the greater seasonal dynamics of TrS and brain MAO-A observed in healthy controls compared to SAD patients. On the other hand, there is indirect evidence from studies with exposure to artificial light that has been shown to suppress the seasonality of biological rhythms and sleep-wake cycles, and could increase the risks of SAD.

In non-industrial societies , individuals were exposed only to natural sunlight, with maximum exposure in the morning while sleep onset varied across the seasons, averaging 3.3 h after sunset. of the sun. In contrast, for urban dwellers who are exposed to bright light, at an average of 3.5 h/day, DLMO and sleep timing are not associated with sunrise or sunset, or differ between winter and summer. In this regard, it is interesting that the Old Order Amish in Pennsylvania, who live a rural life without electric lights, have a much lower prevalence of SAD than the nearby population of Maryland, suggesting that biological adjustment to natural day cycles /night could bring benefits to well-being.

It is likely that over millions of years of evolution, biological processes have evolved to adjust to seasonal changes.

Artificial light , which was first introduced in the early 1700s, interferes with the seasonal adjustment of biological processes, which could lead to dysfunctions in mood and behavior. More research is still needed to understand whether failed seasonal adjustment is the cause of the greater seasonality of symptoms in patients with psychiatric disorders.

While studying seasonal effects at the population level is the first step, closer examination and a greater understanding of interindividual differences is crucial to developing personalized interventions in psychiatric disorders. On the other hand, there are shared risk factors in increased seasonality, exhibited by mood and psychiatric behavior.

>  Exposure to light

People’s annual sunlight exposure patterns are affected by local environments. In terms of geographic location, photoperiod changes between winter and summer are much larger near the poles than at the equator. Meanwhile, large changes in light/dark cycles induce greater challenges to internal circadian rhythms and influence mental and physical health. In countries at higher latitudes there is greater seasonality of mood and behavior as well as a greater prevalence of SAD.

The earlier onset of bipolar disorder is associated with a maximum monthly increase in solar insolation. However, this association could be attenuated if participants were born in places with a lot of daylight.

It has been suggested that early light exposure could be beneficial in developing an internal clock with flexibility to adapt to the challenges of the external circadian rhythm, which could partially help explain some reports of the impact of the season of birth on psychiatric disorders. . Thus, light not only serves as the main seasonal challenge but also impacts the ability to adapt to changes in light. Furthermore, with globalization, more and more people begin to live far from where they were born. As the internal clock is trained by light exposure early in life, moving to a new environment, especially with greater seasonal changes, requires greater adaptations of biological systems that could increase the probability of seasonal adjustment errors.

>  Chronotype

Greater eveningness is associated with a higher self-reported seasonality perception score, which is independent of electric light use or latitude. For individuals with later chronotypes, phase delay stimuli/evening light are expected to play a larger role than morning light. Thus, in these individuals, longer day length could delay circadian rhythms while shorter days could advance the rhythmic phase. In fact, a delay in the circadian rhythm was observed in spring, compared to winter, in adolescents who are going through a stage of development characterized by a significant phase delay.

This study also showed that adolescents were exposed to more light during the evening hours in spring than in winter, while exposure to daylight, especially morning light, which is critical for the advancing dphase, was comparable. between stations. There is evidence that increased evening hours are associated with poor mental health and increased risk of depression.

A well-accepted hypothesis is that certain detrimental consequences in later chronotypes underlie a greater mismatch between the endogenous circadian phase and that imposed by school/work schedules.

If the main cause is mismatch, there will be worse results, such as a higher level of depression in spring/summer than in autumn/winter, as the phase with the longest photoperiod is delayed in the later chronotype, which still needs to be tried. Furthermore, a better understanding of chronotype in susceptibility to mood disorders across the lifespan would help guide healthier policies regarding school entry during adolescence and help design personalized strategies for evening chronotypes. advanced phase, for those at risk of mood disorders.

Self-reported seasonality is greater in young adults than in older adults and in women than in men. Women have 1.5 times the risk of season-related mood changes and show greater seasonal variations in basic cognitive processes compared to men. During the South Pole winter, women showed more self-reported emotional problems than men.

Seasonal affective disorders (SAD) are more common in young people and women.

The age of onset of bipolar disorder peaks between 15 and 24 years, with bipolar II disorder being more prevalent in women than in men. Among patients with bipolar disorder, women appear to exhibit greater vulnerability to seasonal variations compared to men.

Other findings suggest that women and men with bipolar disorder may have different seasonal patterns. Seasonal patterns for manic episodes were found in both women and men and peaked in spring/summer. A seasonal pattern of depressive and mixed episodes was only observed in women.

On the other hand, there seems to be an interaction of sex with age, such that youth (15-35 years) increases the probability of a seasonal pattern in manic patients and mixed episodes in women, but not in men. Similarly, in patients with psychotic depression, the finding of a significant seasonal pattern was only present in older female patients and less pronounced in younger female patients.

The observation of a season of birth effect was associated with winter/spring births , predominantly in women at higher risk of schizophrenia. Seasonal variations in binge drinking, with a peak in the spring/summer months, and intentional opioid overdoses, with a peak in spring, were also observed in women more than in men.

Overall, women with younger age show the greatest seasonal fluctuations and vulnerability to seasonally related psychiatric symptoms. The greater vulnerability to seasonality in women could be due to their greater sensitivity to circadian modulation than men. Differences in seasonal effects between both sexes have also been reported through neuroimaging studies.

Compared with men, healthy women showed greater seasonal fluctuations in TrS and in hippocampal volumes, a relevant 5-HT projection region. However, whether patients with psychiatric disorders show similar sex differences has not been investigated. The effect of age could be interrelated with chronotype, since young adults have a delayed circadian phase compared to older adults.

Compared to healthy controls, hypersensitivity of circadian rhythms to light is observed in patients with seasonal affective disorders (SAD) and bipolar disorder, as well as in people at risk of developing bipolar disorder. On the contrary, hypersensitivity was not found in patients with major depression or in a euthymic bipolar state. In cases of SAD, light sensitivity is also reported to be seasonally dependent, such that hypersensitivity was observed in winter and hyposensitivity in summer.

Elevated circadian sensitivity to light could be related to the delayed phase, reported in both bipolar disorder and seasonal affective disorders (SAD). On the other hand, chronotherapeutic treatments, such as the use of blue light-blocking glasses at night, exposure to light therapy, and melatonin treatment, are promising interventions to treat manic and SAD patients.

In healthy adults, there are large interindividual differences in the sensitivity of the circadian rhythm to light, such that there is a >50-fold difference between those with the lowest and highest sensitivity. In non-clinical populations, light hypersensitivity was associated with mood traits related to bipolar disorder (subthreshold symptoms), particularly hypomania and not depression. It is also likely that light sensitivity is partially decreased by the effect of age on seasonality.

Compared to adults, adolescents, at a critical age for the development of various psychiatric illnesses, have greater sensitivity to light with short wavelengths, which could contribute to their delayed phase rhythm.

There are overlapping genetic risk factors for self-reported seasonality, bipolar disorder, and schizophrenia but not for major depression. 5-HT and circadian genes are the most widely studied to explain the inherited components of seasonality. The short allele of TrS linked to the 5-HTTLPR polymorphism was associated with greater seasonality of mood, behavior, and increased risk of SAD.

5-HT levels could affect circadian sensitivity to light. Acute administration of a dose of the selective serotonin reuptake inhibitor citalopram induced a 47% increase in light-induced melatonin suppression. Apart from 5-HT genes, core clock genes, including CLOCK, ARNTL, NPAS2 gene polymorphisms, and PER2 gene polymorphisms, are also implicated in seasonal variations in mood, behavior, and risk of heart disease. develop SAD.

Polymorphisms in the circadian clock gene PER3, which were associated with daytime preferences, were recently linked to seasonal mood traits in transgenic mice. Associations between dopaminergic genes and seasonality have been less investigated. In mice, longer photoperiods increase retinal photosensitivity, which is regulated by dopaminergic ocular signaling. Therefore, genetic differences in dopaminergics are likely to cause interindividual differences in seasonality, in part by modulating light sensitivity.

Furthermore, melanopsin gene variation was associated with SAD and changes over time in rest-activity rhythms in healthy people. Melanopsin is a photopigment expressed in the retina that mediates non-image-forming responses to environmental light and therefore affects circadian entrainment.

Patients with SAD had a higher frequency of minor homozygous (T/T) genotypes for the missense variant 2675703 (P10L) than healthy controls. In individuals without mood disorder, sleep onset of those with the P10L TT genotype was later on longer days and earlier on shorter days, and greater morningness was associated with a shorter photoperiod. Although the findings should be interpreted with caution given the small number of individuals with the TT genotype, participants with the TT genotype show a sleep-wake pattern similar to that expected in late chronotypes.

Summer holidays, Christmas time, for example, generally lead to changes in social interactions. These season-related changes in social interactions may not only influence light exposure patterns but also increase the likelihood of exposure to both disruptive (e.g., drugs, stress) and protective (e.g., support) factors. social), thus modulating mood and behavior.

Since season-related social interactions may vary between countries and cultures, they should be taken into account when conducting multisite studies on seasonal effects.