Seasonal Affective Disorder Research Articles

Lifestyle modification as intervention for seasonal affective disorder: A systematic review

Bright light therapy (BLT) and pharmacological therapies currently represent the first line treatments for patients with seasonal affective disorder (SAD). Lifestyle modifications offer a diverse field of additional intervention options. Since it is unclear, if lifestyle modifications are effective in SAD patients, this systematic review aims to synthesize the current evidence on their effectiveness and safety.We systematically searched for randomized controlled trials (RCTs) assessing lifestyle modifications (nutrition, exercise, staying outdoors, sleep, social aspects, mindfulness methods) in SAD patients. We defined the primary outcome as the post-therapeutic extent of depressive symptoms, measured by validated psychiatric symptom scales. Due to the insufficient number of studies and the high heterogeneity of the interventions we were not able to calculate a meta-analysis.We identified 6 studies from the following areas of lifestyle modification: diet, exercise, staying outdoors, sleep and music therapy. All studies showed improvements of depression scores in the intervention as well as in the control groups. The risk of bias was rated as high for all studies and the certainty of evidence was rated as very low.The results point towards the possible effectiveness of the interventions examined, but due to the small number of studies found, too small sample sizes and methodological limitations, we cannot draw a valid conclusion about the effectiveness of lifestyle-modifying measures in SAD patients. Larger, high-quality RCTs are needed to make evidence-based recommendations and thus to expand the range of therapeutic options for SAD.

The peak of the ‘Blue Monday’ depression and winter blues.

IntroductionFor many people, January is the most depressing month of the year. “Blue Monday” encompasses the generally accepted belief that Monday is the hardest day of the week compared to Friday and Saturday, which are the most anticipated days of the week. The connection between the color blue and Monday is in the emotional stage, which is presented as emotional anger. The third Monday in January is currently known as the most depressing day of the year. Speaker Cliff Arnall was the first to declare that day in 2014. The theory says that this is the time of the year when respiratory diseases are common, the day is shorter, the weather conditions are worse, and the time when people are burdened with guilt about whether they will achieve their New Year’s resolutions.ObjectivesThe aim of this work was to investigate that on third Monday in January there were more suicide attempts and that there were more depressive disorders in emergency psychiatric admissions.Methods In the research, we included participants who were examined at the Emergency Psychiatric Admission of the Clinical Hospital Center in Split, in the period from 2019. until 2023. Inclusion criteria were respondents of both sexes, examined in the outpatient clinic on Mondays in January for five years.ResultsThere were 198 of them in total. The primary outcome of the research is to determine the occurrence (incidence) of psychological deterioration in patients diagnosed with the anxiety-depressive spectrum. The secondary research outcomes are of a descriptive nature, patient follow-up, examination outcome, and psychiatric heredity.ConclusionsFor now, there are no strong scientific foundations that justify the formula of “the most depressing day” of the year, some scientists believe that it is a marketing trick to achieve higher tourist revenues. However, the post-holiday period can have an impact on individuals.Disclosure of InterestNone Declared

Seasonal Affective Disorder: A Narrative Review

This narrative review of research includes summaries of 46 papers on seasonal affective disorder that were published during the period 2019-2023. The publications are primarily cross-sectional studies of risk factors, randomized controlled trials for light therapy and cognitive behavioral therapy and systematic reviews. A few of the papers are focused on the prevalence of seasonal affective disorder which has varied by latitudes and climates from 3% in Saudi Arabia to 21% in Norway, suggesting length of day and sunlight effects. Only a few studies focused on the negative effects of seasonal affective disorder including sleep problems, depression and poor performance on memory tasks. Most of the research has addressed risk factors for developing seasonal affective disorder including younger age, female gender, dependent personality, seasonal beliefs, chronotype (eveningness), inactivity, insomnia and depression. Very few potential underlying mechanism studies appeared in this literature with the exception of MRI studies suggesting reduced brainstem volume. In contrast, many intervention studies were published recently including light therapy and cognitive behavioral therapy. Methodological problems relate to the variability in the assessments of seasonal affective disorder, the reliance on self-report measures and the cross-sectional data that are not definitive about directionality of predictors and effects of seasonal affective disorder.

Effects of age and sex on photoperiod modulation of nucleus accumbens monoamine content and release in adolescence and adulthood

Day length, or photoperiod, is a reliable environmental cue encoded by the brain's circadian clock that indicates changing seasons and induces seasonal biological processes. In humans, photoperiod, age, and sex have been linked to seasonality in neuropsychiatric disorders, as seen in Seasonal Affective Disorder, Major Depressive Disorder, and Bipolar Disorder. The nucleus accumbens is a key locus for the regulation of motivated behaviors and neuropsychiatric disorders. Using periadolescent and young adult male and female mice, here we assessed photoperiod's effect on serotonin and dopamine tissue content in the nucleus accumbens core, as well as on accumbal synaptic dopamine release and uptake. We found greater serotonin and dopamine tissue content in the nucleus accumbens from young adult mice raised in a Short winter-like photoperiod. In addition, dopamine release and clearance were greater in the nucleus accumbens from young adult mice raised in a Long summer-like photoperiod. Importantly, we found that photoperiod's effects on accumbal dopamine tissue content and release were sex-specific to young adult females. These findings support that in mice there are interactions across age, sex, and photoperiod that impact critical monoamine neuromodulators in the nucleus accumbens which may provide mechanistic insight into the age and sex dependencies in seasonality of neuropsychiatric disorders in humans.

Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database

ObjectiveBupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. MethodsAll data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. ResultsThe results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. ConclusionThese findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.

Bright daylight produces negative effects on affective and cognitive outcomes in nocturnal rats

The daily light/dark cycle affects animals' learning, memory, and cognition. Exposure to insufficient daylight illumination negatively impacts emotion and cognition, leading to seasonal affective disorder characterized by depression, anxiety, low motivation, and cognitive impairment in diurnal animals. However, how this affects memory, learning, and cognition in nocturnal rodents is largely unknown. Here, we studied the effect of daytime light illuminance on memory, learning, cognition, and expression of mRNA levels in the hippocampus, thalamus, and cortex, the higher-order learning centers. Two experiments were performed. In experiment one, rats were exposed to 12 L:12D (12 h light and 12 h dark) with a 10, 100, or 1000 lx daytime light illuminance. After 30 days, various behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, and passive avoidance test) were performed. In experiment 2, rats since birth were raised either under constant bright light (250 lx; LL) or a daily light-dark cycle (12 L:12D). After four months, behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, passive avoidance test, Morris water maze, and Y-maze tests) were performed. At the end of experiments, rats were sampled, and mRNA expression of Brain-Derived Neurotrophic Factor (Bdnf), Tyrosine kinase (Trk), microRNA132 (miR132), Neurogranin (Ng), Growth Associated Protein 43 (Gap-43), cAMP Response Element-Binding Protein (Crebp), Glycogen synthase kinase-3β (Gsk3β), and Tumour necrosis factor-α (Tnf-α) were measured in the hippocampus, cortex, and thalamus of individual rats. Our results show that exposure to bright daylight (100 and 1000 lx; experiment 1) or constant light (experiment 2) compromises memory, learning, and cognition. Suppressed expression levels of these mRNA were also observed in the hypothalamus, cortex, and thalamus. These results suggest that light affects differently to different groups of animals.

MOOD SWINGS AND THE FIRM SIZE PREMIUM

Evidence accumulated in the literature indicates that the size effect is related to corporate and macroeconomic variables and is paid to compensate for bearing risk. We show that the size premium is also driven by daily variations in investors’ moods. We focus on two conditions often cited as possible mechanisms that drive variations in mood: Monday and seasonal affective disorder. The findings are consistent with the evidence that mood deteriorates on Mondays and in the fall and are consistent with the claim that the size effect manifests during economic expansion but weakens in the contraction phase of the economic cycle.

Replicating the Bright-Light Therapy of Seasonal Affective Disorder Using Dual-Gate Dielectric Synaptic Transistors: An Exploration of Neuromorphic Computing Approaches

Replicating the Bright-Light Therapy of Seasonal Affective Disorder Using Dual-Gate Dielectric Synaptic Transistors: An Exploration of Neuromorphic Computing Approaches

Effect of Short Photoperiod on Behavior and Brain Plasticity in Mice Differing in Predisposition to Catalepsy: The Role of BDNF and Serotonin System.

Seasonal affective disorder is characterized by depression during fall/winter as a result of shorter daylight. Catalepsy is a syndrome of some grave mental diseases. Both the neurotransmitter serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are involved in the pathophysiological mechanisms underlying catalepsy and depressive disorders. The aim was to compare the response of behavior and brain plasticity to photoperiod alterations in catalepsy-resistant C57BL/6J and catalepsy-prone CBA/Lac male mice. Mice of both strains were exposed for six weeks to standard-day (14 h light/10 h darkness) or short-day (4 h light/20 h darkness) conditions. Short photoperiod increased depressive-like behavior in both strains. Only treated CBA/Lac mice demonstrated increased cataleptic immobility, decreased brain 5-HT level, and the expression of Tph2 gene encoding the key enzyme for 5-HT biosynthesis. Mice of both strains maintained under short-day conditions, compared to those under standard-day conditions, showed a region-specific decrease in the brain transcription of the Htr1a, Htr4, and Htr7 genes. After a short photoperiod exposure, the mRNA levels of the BDNF-related genes were reduced in CBA/Lac mice and were increased in the C57BL/6J mice. Thus, the predisposition to catalepsy considerably influences the photoperiodic changes in neuroplasticity, wherein both C57BL/6J and CBA/Lac mice can serve as a powerful tool for investigating the link between seasons and mood.

A COMPARATIVE STUDY TO ASSESS THE LEVEL OF DEPRESSION AMONG THE ELDERLY LIVING IN OLD AGE HOMES AND COMMUNITY, PUDUCHERRY

Depression is a state of mental illness. It is characterized by deep, long lasting feelings of sadness or despair. Depression can change an individual’s thinking/feelings and also affects his/her social behaviour and sense of physical well-being. It can affect people of any age group, including young children and teens. It can run in families and usually starts between the ages of 15 and 30 years. Women and elderly people are more commonly affected than men. There are several types of depression such as major depression it is a change in mood that lasts for weeks or months. It is one of the most severe types of depression. Dysthymia is a less severe form of depression but usually lasts for several years. Psychotic depression a severe form of depression associated with hallucinations and delusions .Seasonal depression, occurring only at certain time of the year usually winter, also known as winter blues’. Some of the common factors that may cause depression are genetics , trauma and high levels of stress, mental illnesses such as schizophrenia and substance abuse, postpartum depression (women may develop depression after the birth of the baby), serious medical conditions such as heart disease, cancer and HIV, use of certain medications, alcohol and drug abuse, individuals with low self-esteem, trauma and high levels of stress due to financial problems, breakup of a relationship or loss of a loved one. The signs and symptoms of depression include feeling of sadness and loneliness, loss of interest in activities once found enjoyable, feeling of hopelessness, worthlessness or excessive guilt, fatigue or loss of energy, sleeping too little or too much, loss of appetite, restlessness and being easily annoyed. Diagnose the depression based on the detailed history and sign and symptoms of the individual. Laboratory tests such as blood tests to screen for alcohol/drugs in blood. Psychological evaluation of the individual’s thoughts, feelings and behaviour patterns. The most common treatments of depression are Counselling & Psychotherapy, Medication, Electro convulsive therapy. Medications such as anti-depressants are given to help balance chemicals in the brain known as ‘neuro transmitters’. Electroconvulsive therapy (ECT) is carried out in case the treatment with other therapies such as medications has failed. Preventive measures include regular exercise, healthy diet and stable relationships. Statement Of The Problem: A comparative study to assess the level of depression among the elderly living in old age homes and community, Puducherry’’. Objectives: To assess the level of depression among the elderly. • To compare the level of depression among elderly residing in old age home and those living in community. • To associate the level of depression among elderly with their selected demographic variables. Materials and Methods: The investigator obtained formal permission from Hospital authority and Institutional Ethical Committee of Sri Manakula Vinayagar Medical College and Hospital. The study was conducted at help age India old age home and thirubhuvanai community area, Puducherry. The period of data collection was four weeks .The study was conducted quantitative research approach ,descriptive research design and convenient sampling technique was used to select the sample .The sample size was 60 elderly depression patient, 30 were inmates of old age home and 30 were living in community. The investigator explained the procedure to the clients and assessed level of depression among elderly people’s. After obtaining oral consent primarily the demographic data was obtained from the samples. Standardized Hamilton depression rating scale prepared by the investigator was used to assess the level of depression among the elderly living in old age homes and community. This scale consists of 17 items. The data variables were collected from the elderly residing at help age India and thirubhuvanai community area .This was continued for 15-20 minutes in a day. Sample is reassessed to analyze the intervention on depression. Data analysis was done using descriptive and statistical analysis. Result: The findings shows that, the mean score of the level of depression among the elderly living in the old age homes was 16.47 ± 4.637 and the community was 12.73 ± 6.341.The calculated independent ‘t’ test value of t = -2.603 shows statistically significant difference between Comparison between the level of depression among the elderly living in old age homes and community respectively. Conclusion: Out of 60 samples in Frequency and percentage wise distribution of level of depression among the elderly living in old age homes and community .In old age homes, Majority of the elderly10 (33.3%) had moderate level of depression, 9 (30%) had severe level of depression, 8 (26.7%) had mild level of depression, 2 (6.7%) had extremely severe level of depression and 1 (3.3%) had normal level.

Death and Dying: Grapevine Survival, Cold Hardiness, and BLUPs and Winter BLUEs in North Dakota Vineyards.

A total of fourteen diverse, interspecific hybrid grapevines (Vitis spp.) were evaluated for their adaptability to North Dakota winter conditions using differential thermal analysis (DTA) of low-temperature exotherms (LTE) and bud cross-sectional assessment of survival techniques. This research was conducted in two vineyard locations in eastern North Dakota. This work demonstrates the use of DTA for monitoring and selecting cultivars capable of withstanding sub-zero temperatures. These results were assessed for quantitative genetic traits. High heritability was observed for bud LTE traits and may thus be a useful target for cold hardiness breeding programs; however, it is necessary to ensure that variance is reduced when pooling multiple sample events. After DTA sampling, grapevines were assessed for survival of primary and secondary dormant buds using cross-sectional visual evaluation of death. 'Valiant' had the greatest primary bud survival (68%), followed by 'Frontenac gris', 'Crimson Pearl', and 'King of the North'. These varieties are among those with potential for production in eastern North Dakota's environment. The newly evaluated relationships between traits and the heritability of DTA results provide valuable tools to grapevine breeders for the development of cold-tolerant genotypes for future climatic challenges.

“I Would Rather Lose Everything Else I Possess”: Love of Nature and L.M. Montgomery’s Intuitive Wellness Strategies, 1901-11

L.M. Montgomery’s use of “rambles” to de-escalate depressive episodes and restore her mental wellness is well documented in the entries she made in her PEI journals while living in Cavendish and Halifax from 1901 to 1911. Modern-day research on forest bathing and seasonal affective disorder provides scientific explanations for why the time Montgomery spent in nature may have boosted her mental health during a pivotal period in her career, particularly during the winter of 1905 to 1906, when she was composing Anne of Green Gables.

The Effect of Seasonal Depression on Stock Market Returns

The study analyses the statistical relationship between the degree of seasonal depression and stock index returns. For this analysis, we examine the daily returns of two US and five European stock indices using OLS regression. The analysis found a statistically significant relationship between seasonal depression and the change in returns. However, due to the limited use of the reduced form, this only confirms the link between seasonal depression and returns, and further observations would be required to confirm a causal relationship.

Awareness of Seasonal Affective Disorder

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Prospectively assessed summer mood status in major depression, recurrent with seasonal pattern: Evidence for SAD's construct validity

ObjectiveSeasonal patterns are often undetectable in population-based depression studies, calling into question the existence of winter seasonal affective disorder (SAD). If SAD has construct validity, individuals with SAD should show spontaneous depression remission in the summer. Data are sparse on prospectively assessed summer mood status in confirmed SAD patients. MethodWe conducted prospective summer followup of community adults who, the winter before, were diagnosed with Major Depression, Recurrent with Seasonal Pattern on the Structured Clinical Interview for DSM-IV Axis I Disorders, developed a current SAD episode on the Structured Interview Guide for the Hamilton Rating Scale for Depression—Seasonal Affective Disorder Version (SIGH-SAD), and enrolled in a clinical trial comparing group cognitive-behavioral therapy for SAD and light therapy. In July/August after treatment, 143/153 (93.5 %) participants provided data on the SIGH-SAD, the Beck Depression Inventory-Second Edition, and the Longitudinal Interval Followup Evaluation (LIFE). ResultsSummer mean depression scores were in the normal range, with the substantial majority in remission across different measures. On the LIFE, 113/143 (79.0 %) experienced complete summer remission, 19/143 (13.3 %) experienced partial summer remission, and 11/143 (7.7 %) had major depression in the summer. Depression scores were significantly lower at summer than post-treatment in both treatments, indicating incomplete treatment response. LimitationsThis was a single-site study with a relatively homogeneous sample. ConclusionsSupporting construct validity for SAD, the substantial majority experienced complete summer remission, with a minority in partial remission and a very small minority in episode. Both treatments left residual symptoms at treatment endpoint compared to summer.

Delivery of bright light therapy within the Veterans Health Administration

BackgroundBright light therapy (BLT) is efficacious for seasonal and non-seasonal depression. However, the current state of BLT use in practice is unknown, impeding efforts to identify and address utilization gaps. This study's objective was to investigate BLT delivery in a nationwide U.S. healthcare system. MethodsThis was a retrospective observational study of electronic medical records from all veterans who received outpatient mood disorder-related care in the Veterans Health Administration (VHA) from October 2008 through September 2020. BLT delivery was measured through the placement of light box consults. ResultsOf the 3,442,826 veterans who received outpatient mood disorder care, only 57,908 (1.68 %) received a light box consult. Consults increased by 548.44 % (99.9 % credible interval: 467.36 %, 638.74 %) over the timeframe and displayed a robust yearly cycle that peaked on either December 21st or December 22nd. Past mental health treatment for a mood disorder was associated with a higher probability of a consult (relative risk = 4.79, 99.9 % CI: 4.21, 5.60). There was low representation related to veteran age, gender, race, and ethnicity. LimitationsNo information on patients who declined light boxes or actual light box use following consult placement. ConclusionsOutpatient BLT delivery for mood disorders in the VHA remains low, despite significant growth over the past decade. It also displays a strong seasonal rhythm that peaks on the winter solstice, suggesting a limited focus on seasonal depression and a suboptimal reactive approach to changing sunlight. Overall, there exists ample opportunity for novel implementation efforts aimed at increasing utilization of BLT.

The Prevalence of Mood Disorders Among Health and Non-health Undergraduate Students in King Saud University, Riyadh, Saudi Arabia: A Cross-Sectional Study.

Mood disorders (MDs) are among the most common of all mental health diagnoses, with increasing prevalence and a devastating impact on individuals, families, and the community. This study aimed to estimate the frequency of MDs among health and non-health profession students. A cross-sectional survey was conducted on 391 students to estimate the self-reported prevalence of different MDs and to screen for bipolar disorder (BD) using the mood disorder questionnaire (MDQ) and for depressive, anxiety, and stress symptoms using the Depression, Anxiety, and Stress Scale - 21 items (DASS-21). MDs were reported by 24.9% (n=50) of health profession students and 22.8% (n=31) of non-health profession students. For BD, it affected 35.3% of students in the health profession and 47.4% (n=46) of students without the health profession, although the difference was not statistically significant. The most reported MDs among health and non-health profession students were major depression (4.9% vs. 4.2%), seasonal affective disorder (SAD) (3.3% vs. 2.1%), dysthymia (2.4% vs. 2.8), and BD (2% vs. 2.8%), respectively. None of the observed differences between the two groups were statistically significant. According to DASS-21 scores for health and non-health profession students, severe depressive and severe anxiety symptoms were more common among non-health students (45.1% and 59.3%, respectively) than among health profession students (41.4% and 51.1%, respectively). However, stress was higher among health-related than non-health-related students (19.4% and 18.1%, respectively). MDs constitute a high burden among university students regardless of their field of study, creating an increased urgency to incorporate ways to promote the mental well-being of students and to manage those with an MD. Further research is needed to identify effective preventive strategies for depression in the future.

Emotional Bias among Individuals at Risk for Seasonal Affective Disorder-An EEG Study during Remission in Summer.

Emotional bias in attention and memory is well researched in depression. Patients with depression prioritize processing of negative information over positive input. While there is evidence that emotional bias exists in seasonal affective disorder (SAD) during winter, it is unclear whether such altered cognition exists also during summer. Moreover, it is unclear whether such bias affects attention, memory, or both. In this study, we investigated 110 individuals in summer, 34 of whom reported suffering from low mood during winter, according to the seasonal pattern assessment questionnaire. While the electroencephalogram was recorded, participants learned 60 emotional pictures and subsequently were asked to recognize them in an old/new task. There were no clear group differences in behavioral measures, and no brain response differences in frontal alpha power during learning. During recognition, at 100-300 ms post stimulus individuals with higher seasonality scores exhibited larger alpha power in response to negative as compared to neutral stimuli, while individuals with low seasonality scores exhibited larger alpha power in response to positive as compared to neutral stimuli. While we cannot draw conclusions whether this is an effect of attention or memory, the finding suggests that early cognitive processes are altered already during summer in individuals with increased likelihood to experience SAD during winter. Our data provide evidence for an all-year-round cognitive vulnerability in this population.

Risk for Seasonal Affective Disorder (SAD) Linked to Circadian Clock Gene Variants.

Molecular pathways affecting mood are associated with circadian clock gene variants and are influenced, in part, by the circadian clock, but the molecular mechanisms underlying this link are poorly understood. We use machine learning and statistical analyses to determine the circadian gene variants and clinical features most highly associated with symptoms of seasonality and seasonal affective disorder (SAD) in a deeply phenotyped population sample. We report sex-specific clock gene effects on seasonality and SAD symptoms; genotypic combinations of CLOCK3111/ZBTB20 and PER2/PER3B were significant genetic risk factors for males, and CRY2/PER3C and CRY2/PER3-VNTR were significant risk factors for females. Anxiety, eveningness, and increasing age were significant clinical risk factors for seasonality and SAD for females. Protective factors for SAD symptoms (in females only) included single gene variants: CRY1-GG and PER3-VNTR-4,5. Clock gene effects were partially or fully mediated by diurnal preference or chronotype, suggesting multiple indirect effects of clock genes on seasonality symptoms. Interestingly, protective effects of CRY1-GG, PER3-VNTR-4,5, and ZBTB20 genotypes on seasonality and depression were not mediated by chronotype, suggesting some clock variants have direct effects on depressive symptoms related to SAD. Our results support previous links between CRY2, PER2, and ZBTB20 genes and identify novel links for CLOCK and PER3 with symptoms of seasonality and SAD. Our findings reinforce the sex-specific nature of circadian clock influences on seasonality and SAD and underscore the multiple pathways by which clock variants affect downstream mood pathways via direct and indirect mechanisms.

Machine learning analyses reveal circadian clock features predictive of anxiety among UK biobank participants

Mood disorders, including depression and anxiety, affect almost one-fifth of the world’s adult population and are becoming increasingly prevalent. Mutations in circadian clock genes have previously been associated with mood disorders both directly and indirectly through alterations in circadian phase, suggesting that the circadian clock influences multiple molecular pathways involved in mood. By targeting previously identified single nucleotide polymorphisms (SNPs) that have been implicated in anxiety and depressive disorders, we use a combination of statistical and machine learning techniques to investigate associations with the generalized anxiety disorder assessment (GAD-7) scores in a UK Biobank sample of 90,882 individuals. As in previous studies, we observed that females exhibited higher GAD-7 scores than males regardless of genotype. Interestingly, we found no significant effects on anxiety from individual circadian gene variants; only circadian genotypes with multiple SNP variants showed significant associations with anxiety. For both sexes, severe anxiety is associated with a 120-fold increase in odds for individuals with CRY2_AG(rs1083852)/ZBTB20_TT(rs1394593) genotypes and is associated with a near 40-fold reduction in odds for individuals with PER3-A_CG(rs228697)/ZBTB20_TT(rs1394593) genotypes. We also report several sex-specific associations with anxiety. In females, the CRY2/ZBTB20 genotype combination showed a > 200-fold increase in odds of anxiety and PER3/ZBTB20 and CRY1 /PER3-A genotype combinations also appeared as female risk factors. In males, CRY1/PER3-A and PER3-B/ZBTB20 genotype combinations were associated with anxiety risk. Mediation analysis revealed direct associations of CRY2/ZBTB20 variant genotypes with moderate anxiety in females and CRY1/PER3-A variant genotypes with severe anxiety in males. The association of CRY1/PER3-A variant genotypes with severe anxiety in females was partially mediated by extreme evening chronotype. Our results reinforce existing findings that females exhibit stronger anxiety outcomes than males, and provide evidence for circadian gene associations with anxiety, particularly in females. Our analyses only identified significant associations using two-gene combinations, underscoring the importance of combined gene effects on anxiety risk. We describe novel, robust associations between gene combinations involving the ZBTB20 SNP (rs1394593) and risk of anxiety symptoms in a large population sample. Our findings also support previous findings that the ZBTB20 SNP is an important factor in mood disorders, including seasonal affective disorder. Our results suggest that reduced expression of this gene significantly modulates the risk of anxiety symptoms through direct influences on mood-related pathways. Together, these observations provide novel links between the circadian clockwork and anxiety symptoms and identify potential molecular pathways through which clock genes may influence anxiety risk.