Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

BACKGROUND: Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. METHODS: Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. RESULTS: In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). CONCLUSION: Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Age Trends in Actigraphy and Self-Report Sleep Across the Life Span: Findings From the Pittsburgh Lifespan Sleep Databank.

OBJECTIVE: Sleep changes over the human life span, and it does so across multiple dimensions. We used individual-level cross-sectional data to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human life span. METHODS: The Pittsburgh Lifespan Sleep Databank consists of harmonized participant-level data from sleep-related studies conducted at the University of Pittsburgh (2003-2019). We included data from 1065 (n = 577 female; 21 studies) Pittsburgh Lifespan Sleep Databank participants aged 10 to 87 years without a major psychiatric, sleep, or medical condition. All participants completed wrist actigraphy and the self-rated Pittsburgh Sleep Quality Index. Main outcomes included actigraphy and self-report sleep duration, efficiency, and onset/offset timing, and actigraphy variability in midsleep timing. RESULTS: We used generalized additive models to examine potentially nonlinear relationships between age and sleep characteristics and to examine sex differences. Actigraphy and self-report sleep onset time shifted later between ages 10 and 18 years (23:03-24:10 [actigraphy]; 21:58-23:53 [self-report]) and then earlier during the 20s (00:08-23:40 [actigraphy]; 23:50-23:34 [self-report]). Actigraphy and self-report wake-up time also shifted earlier during the mid-20s through late 30s (07:48-06:52 [actigraphy]; 07:40-06:41 [self-report]). Self-report, but not actigraphy, sleep duration declined between ages 10 and 20 years (09:09-07:35). Self-report sleep efficiency decreased over the entire life span (96.12-93.28), as did actigraphy variability (01:54-01:31). CONCLUSIONS: Awareness of age trends in multiple sleep dimensions in healthy individuals-and explicating the timing and nature of sex differences in age-related change-can suggest periods of sleep-related risk or resilience and guide intervention efforts.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BACKGROUND: Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers. METHODS: Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment. RESULTS: The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94). CONCLUSIONS: These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

Longitudinal Association Between Depressive Symptoms and Multidimensional Sleep Health: The SWAN Sleep Study.

BACKGROUND: Depressive symptoms and sleep disturbances disproportionately affect midlife women. While there may be a bidirectional association, few studies have examined whether depressive symptoms are longitudinally associated with subsequent sleep. Sleep is typically considered unidimensional, despite emerging evidence that multidimensional sleep health provides novel information on the sleep-health link. PURPOSE: The current study examined whether higher depressive symptoms were longitudinally associated with poorer multidimensional sleep health. METHOD: Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale across six to nine annual assessments in 302 midlife women from the Study of Women's Health Across the Nation. Six months after their last assessment, actigraphy (mean ± standard deviation = 29.3 ± 6.9 days) and self-report were used to assess sleep health components: efficiency, duration, mid-sleep timing, regularity, alertness, and satisfaction, which were dichotomized and summed to create a composite multidimensional sleep health score. Mixed-effects models were used to evaluate the longitudinal associations between depressive symptoms and multidimensional sleep health, as well as individual sleep health components, adjusting for covariates. Exploratory analyses stratified models by race/ethnicity. RESULTS: Higher depressive symptoms were associated with subsequent poorer multidimensional sleep health (p < .0.001) and lower alertness (p < .0001) and satisfaction with sleep (p < .0001). CONCLUSIONS: Our finding that higher average depressive symptoms were associated longitudinally with actigraphy-measured poorer sleep health in midlife women is novel and converges with the larger body of evidence that these two common symptoms are strongly associated. The bidirectional relationship between these two prevalent symptoms needs to be studied in prospective longitudinal studies.

Comparison of Food Cue-Evoked and Resting-State Functional Connectivity in Obesity.

OBJECTIVE: Obesity is associated with differences in task-evoked and resting-state functional brain connectivity (FC). However, no studies have compared obesity-related differences in FC evoked by high-calorie food cues from that observed at rest. Such a comparison could improve our understanding of the neural mechanisms of reward valuation and decision making in the context of obesity. METHODS: The sample included 122 adults (78% female; mean age = 44.43 [8.67] years) with body mass index (BMI) in the overweight or obese range (mean = 31.28 [3.92] kg/m). Participants completed a functional magnetic resonance imaging scan that included a resting period followed by a visual food cue task. Whole-brain FC analyses examined seed-to-voxel signal covariation during the presentation of high-calorie food and at rest using seeds located in the left and right orbitofrontal cortex, left hippocampus, and left dorsomedial prefrontal cortex. RESULTS: For all seeds examined, BMI was associated with stronger FC during the presentation of high-calorie food, but weaker FC at rest. Regions exhibiting BMI-related modulation of signal coherence in the presence of palatable food cues were largely located within the default mode network (z range = 2.34-4.91), whereas regions exhibiting BMI-related modulation of signal coherence at rest were located within the frontostriatal and default mode networks (z range = 3.05-4.11). All FC results exceeded a voxelwise threshold of p < .01 and cluster-defining familywise error threshold of p < .05. CONCLUSIONS: These dissociable patterns of FC may suggest separate neural mechanisms contributing to variation in distinct cognitive, psychological, or behavioral domains that may be related to individual differences in risk for obesity.

Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma.

OBJECTIVE: To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses. RESULTS: Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES-D ≥ 22). Females had higher CES-D score than males (Mann-Whitney U = 7135, P = .014, Padj  = .028). Being unemployed/disabled (Kruskal-Wallis = 14.732, P = .001, Padj  = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL-2 (Kruskal-Wallis = 17.261, P = .001, Padj  = .005) were found to be negatively associated with education level. Gender (ß = .177, P = .035), income (ß = -.252, P = .004), whether the patient's income met their basic needs (ß = .180, P = .035), and IL-1ß (ß = -.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms. CONCLUSIONS: Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender-targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.

Photoperiod is associated with hippocampal volume in a large community sample.

Although animal research has demonstrated seasonal changes in hippocampal volume, reflecting seasonal neuroplasticity, seasonal differences in human hippocampal volume have yet to be documented. Hippocampal volume has also been linked to depressed mood, a seasonally varying phenotype. Therefore, we hypothesized that seasonal differences in day-length (i.e., photoperiod) would predict differences in hippocampal volume, and that this association would be linked to low mood. Healthy participants aged 30-54 (M=43; SD=7.32) from the University of Pittsburgh Adult Health and Behavior II project (n=404; 53% female) were scanned in a 3T MRI scanner. Hippocampal volumes were determined using an automated segmentation algorithm using FreeSurfer. A mediation model tested whether hippocampal volume mediated the relationship between photoperiod and mood. Secondary analyses included seasonally fluctuating variables (i.e., sleep and physical activity) which have been shown to influence hippocampal volume. Shorter photoperiods were significantly associated with higher BDI scores (R(2)=0.01, ß=-0.12, P=0.02) and smaller hippocampal volumes (R(2)=0.40, ß=0.08, P=0.04). However, due to the lack of an association between hippocampal volume and Beck Depression Inventory scores in the current sample, the mediation hypothesis was not supported. This study is the first to demonstrate an association between season and hippocampal volume. These data offer preliminary evidence that human hippocampal plasticity could be associated with photoperiod and indicates a need for longitudinal studies.

Circadian photoentrainment varies by season and depressed state: associations between light sensitivity and sleep and circadian timing.

STUDY OBJECTIVES: Altered light sensitivity may be an underlying vulnerability for disrupted circadian photoentrainment. The photic information necessary for circadian photoentrainment is sent to the circadian clock from melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The current study tested whether the responsivity of ipRGCs measured using the post-illumination pupil response (PIPR) was associated with circadian phase, sleep timing, and circadian alignment, and if these relationships varied by season or depression severity. METHODS: Adult participants (N = 323, agem = 40.5, agesd = 13.5) with varying depression severity were recruited during the summer (n = 154) and winter (n = 169) months. Light sensitivity was measured using the PIPR. Circadian phase was assessed using Dim Light Melatonin Onset (DLMO) on Friday evenings. Midsleep was measured using actigraphy. Circadian alignment was calculated as the DLMO-midsleep phase angle. Multilevel regression models covaried for age, gender, and time since wake of PIPR assessment. RESULTS: Greater light sensitivity was associated with later circadian phase in summer but not in winter (ß = 0.23; p = 0.03). Greater light sensitivity was associated with shorter DLMO-midsleep phase angles (ß = 0.20; p = 0.03) in minimal depression but not in moderate depression (SIGHSAD < 6.6; Johnson-Neyman region of significance). CONCLUSIONS: Light sensitivity measured by the PIPR was associated with circadian phase during the summer but not in winter, suggesting ipRGC functioning in humans may affect circadian entrainment when external zeitgebers are robust. Light sensitivity was associated with circadian alignment only in participants with minimal depression, suggesting circadian photoentrainment, a possible driver of mood, may be decreased in depression year-round, similar to decreased photoentrainment in winter.

The role of retinal irradiance estimates in melanopsin-driven retinal responsivity: A reanalysis of the post-illumination pupil response (PIPR) in seasonal affective disorder.

To isolate melanopsin contributions to retinal sensitivity measured by the post-illumination pupil response (PIPR), controlling for individual differences in non-melanopsin contributions including retinal irradiance is required. When methodologies to negate such differences present barriers, statistical controls have included age, baseline diameter, iris pigmentation, and circadian time of testing. Alternatively, the pupil light reflex (PLR) and calculations estimating retinal irradiance both reflect retinal irradiance, while the PLR also reflects downstream pathways. We reanalyzed data from an observational, correlational study comparing the PIPR across seasons in seasonal affective disorder (SAD) and controls. The PIPR was measured in 47 adults in Pittsburgh, Pennsylvania (25 SAD) over 50 s after 1 s red and blue stimuli of 15.3 log photons/cm2/s. The PLR was within 1 s while PIPR was averaged over 10-40 seconds post-stimulus. Two raters ranked iris pigmentation using a published scale. We evaluated model fit using Akaike's Information Criterion (AIC) across different covariate sets. The best fitting models included either estimated retinal irradiance or PLR, and circadian time of testing. The PLR is collected contemporaneously in PIPR studies and is an individually specific measure of nonspecific effects, while being minimally burdensome. This work extends the prior publication by introducing theoretically grounded covariates that improved analytic model fits based on AIC specific to the present methods and sample. Such quantitative methods could be helpful in studies which must balance participant and researcher burden against tighter methodological controls of individual differences in retinal irradiance.

Do sleep and circadian characteristics predict alcohol use in adult drinkers?

BACKGROUND: While sleep and circadian rhythms are recognized contributors to the risk for alcohol use and related problems, few studies have examined whether objective sleep and circadian measures can predict future alcohol use in humans, and no such studies have been conducted in adults. This study examined whether any baseline sleep and/or circadian characteristics of otherwise healthy adults predicted their alcohol use over the subsequent 12 months. METHODS: Participants (21-42 years) included 28 light and 50 heavy drinkers. At baseline, a comprehensive range of self-reported and objective sleep/circadian measures was assessed via questionnaires, wrist actigraphy, and measurement of dim light melatonin onset and circadian photoreceptor responsivity. Following this, the number of alcoholic drinks per week and binge drinking episodes per month were assessed quarterly over the subsequent 12 months. Anticipated effects of alcohol (stimulation, sedation, and rewarding aspects) were also assessed quarterly over the 12 months. Analyses included generalized linear mixed-effects models and causal mediation analysis. RESULTS: Across the range of measures, only self-reported insomnia symptoms and a longer total sleep time at baseline predicted more drinks per week and binges per month (ps <0.02). There was a trend for the anticipated alcohol effect of wanting more alcohol at the 6-month timepoint to mediate the relationship between insomnia symptoms at baseline and drinks per week at 12 months (p = 0.069). CONCLUSIONS: These results suggest that in otherwise healthy adults, insomnia symptoms, even if subclinical, are a significant predictor of future drinking, and appear to outweigh the influence of circadian factors on future drinking, at least in otherwise healthy adults. Insomnia symptoms may be a modifiable target for reducing the risk of alcohol misuse.

Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura.

AIMS: The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR ; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR ; EC 2.1.1.13) and methionine synthase reductase ( MTRR ; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR , MTR , and MTRR . METHODS: Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( N = 367), migraine without aura ( N = 85), migraine with aura ( N = 167), and no headache ( N = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. RESULTS: Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. CONCLUSIONS: These results suggest that MTRR variants may protect against migraine with aura in an older population.

Lack of association between the MTHFR C677T variant and migraine with aura in an older population: could selective survival play a role?

BACKGROUND: Several studies, but not all, of primarily middle-aged or younger adults have suggested that the common MTHFR C677T variant is a genetic risk factor for migraine with aura (MA). Here, we consider whether this variant is associated with MA risk in an older non-clinical population (AGES-Reykjavik cohort). METHODS: Participants are a sub-sample ( N = 1976) of subjects from the Reykjavik Study (RS; mean age 50) and its continuation, AGES-RS (mean age 76). We estimated the relative odds of MA in TT versus CC carriers using multinomial logistic regression. As both MA and the TT genotype may be linked with modestly reduced longevity, we performed a simple simulation to illustrate the effect that selective survival may have had on our observed gene-disease association. RESULTS: TT versus CC carriers were at marginally reduced odds of MA (ORTT 0.55 (0.3-1.0), P = 0.07), significantly for women (ORTT 0.45 (0.2-0.9), P = 0.03). Assuming the 'true' (e.g. mid-life) effect of the TT genotype is ORTT 1.26, from a recent meta-analysis, our simulation suggested that if 25-year mortality had been (hypothetically) 13% higher in MA subjects with the TT versus CC genotype, the measured effect of the TT genotype on MA would have been attenuated to non-significance (e.g. ORTT 1.00). Our observed protective effect was consistent with the most extreme selective mortality scenario, in which essentially all of the previously reported increased mortality in MA subjects was (hypothetically) found in CT or TT carriers. CONCLUSION: The MTHFR 677TT genotype was associated with marginally reduced risk of MA in our older population. Our simulation illustrated how even modest selective survival might obscure the apparent effect of a genetic or other risk factor in older populations. We speculate that some of the heterogeneity previously observed for this particular genetic variant may be due to age range differences in the studied populations.

The role of beliefs about sleep in nightly perceptions of sleep quality across a depression continuum.

BACKGROUND: Poor sleep quality is common in depression, but complaints of poor sleep quality are not necessarily tied to objective sleep, and the construct of sleep quality remains poorly understood. Previous work suggests that beliefs about sleep may influence sleep quality appraisals, as might sleep variability from night to night. OBJECTIVE: We tested whether beliefs about sleep predict daily sleep quality ratings above and beyond nightly variability of actigraphy and diary-assessed sleep over the course of multiple nights. METHODS: Eighty-eight participants aged 18-65 years across a depressive continuum completed sleep diaries and reported their sleep quality and mood each morning; actigraphy was also completed for 67 of those participants. Multilevel models were used to test previous night's total sleep time and sleep efficiency as predictors of self-reported sleep quality (VAS-SQ) and mood (VAS-M), and whether unhelpful beliefs about sleep predicted VAS-SQ and VAS-M above and beyond the sleep variables. RESULTS: Individuals across a depression continuum with greater unhelpful beliefs about sleep reported worse sleep quality and worse mood upon awakening, even when accounting for nightly variation in actigraphy or diary assessed total sleep time and sleep efficiency. CONCLUSIONS: These results suggest that people are influenced by unhelpful sleep beliefs when making judgements about sleep quality and mood, regardless of how well they slept the previous night. Working with these unhelpful sleep beliefs in cognitive behavioral therapy can thus promote better sleep and mood in people across the depressive continuum.

Publication guidelines and recommendations for pupillary measurement in psychophysiological studies.

A variety of psychological and physical phenomena elicit variations in the diameter of pupil of the eye. Changes in pupil size are mediated by the relative activation of the sphincter pupillae muscle (decrease pupil diameter) and the dilator pupillae muscle (increase pupil diameter), innervated by the parasympathetic and sympathetic branches, respectively, of the autonomic nervous system. The current guidelines are intended to inform and guide psychophysiological research involving pupil measurement by (1) summarizing important aspects concerning the physiology of the pupil, (2) providing methodological and data-analytic guidelines and recommendations, and (3) briefly reviewing psychological phenomena that modulate pupillary reactivity. Because of the increased ease and tractability of pupil measurement, the goal of these guidelines is to promote accurate recording, analysis, and reporting of pupillary data in psychophysiological research.

Sleep and circadian rhythm profiles in seasonal depression.

Sleep and circadian rhythm disruptions are symptoms of, and hypothesized underlying mechanisms in, seasonal depression. Discrepant observational findings and mixed responses to sleep/circadian-based treatments suggest heterogenous sleep and circadian disruptions in seasonal depression, despite these disruptions historically conceptualized as delayed circadian phase and hypersomnia. This study used a data-driven cluster analysis to characterize sleep/circadian profiles in seasonal depression to identify treatment targets for future interventions. Biobehavioral measures of sleep and circadian rhythms were assessed during the winter in individuals with Seasonal Affective Disorder (SAD), subsyndromal-SAD (S-SAD), or nonseasonal, never depressed controls (total sample N = 103). The following variables were used in the cluster analysis: circadian phase (from dim light melatonin onset), midsleep timing, total sleep time, sleep efficiency, regularity of midsleep timing, and nap duration (all from wrist actigraphy). Sleep and circadian variables were compared across clusters and controls. Despite limited sleep/circadian differences between diagnostic groups, there were two reliable (Jaccard Coefficients >0.75) sleep/circadian profiles in SAD/S-SAD individuals: a 'Disrupted sleep' cluster, characterized by irregular and fragmented sleep and an 'Advanced' cluster, characterized by early sleep and circadian timing and longer total sleep times (>7.5 h). Clusters did not differ by depression severity. Midsleep correlated with DLMO (r = 0.56), irregularity (r = 0.3), and total sleep time (r = -0.27). Sleep and circadian disruptions in seasonal depression are not uniformly characterized by hypersomnia and circadian phase delay. Presence of distinct sleep and circadian subgroups in seasonal depression may predict successful treatment response. Prospective assessment and tailoring of individual sleep and circadian disruptions may reduce treatment failures.

The relationship between fat mass and obesity associated gene polymorphism rs9939609 and resting cerebral blood flow in a midlife sample with overweight and obesity.

Background: The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated fat mass and obesity associated gene (FTO) gene has been linked with increased BMI in adults. Higher BMI has been associated with poor brain health and may exert deleterious effects on neurocognitive health through cerebral hypoperfusion. However, it is unclear if there is a relationship between the FTO genotype and cerebral perfusion, or whether FTO genotype moderates the effects of weight loss on cerebral perfusion. Using data from a randomized controlled behavioral weight loss trial in adults with overweight and obesity, we tested (1) whether carriers of the A allele for FTO rs9939609 demonstrate different patterns of resting cerebral blood flow (rCBF) compared to T carriers, and (2) whether the FTO genotype moderates the effects of weight loss on rCBF. We hypothesized that carriers of the A allele would exhibit lower resting CBF in frontal brain areas compared to T/T homozygotes at baseline, and that intervention-induced weight loss may partially remediate these differences. Methods and results: One hundred and five adults (75.2% female, mean age 44.9 years) with overweight or obesity were included in the analyses. These participants represent a subsample of participants in a larger randomized controlled trial (NCT01500356). A resting pseudo-continuous arterial spin labeling (pCASL) scan was acquired to examine rCBF. Age, sex, and BMI were included as covariates. At baseline, A carriers had greater rCBF in a diffuse cluster extending into the brainstem, motor cortex, and occipital lobe, but lower perfusion in the temporal lobe. We found no evidence that FTO moderated the effect of the intervention group assignment on rCBF changes. Conclusion: Overall, these results indicate that (a) individual variation in rCBF within a sample with overweight and obesity may be attributed to a common FTO variant, but (b) a weight loss intervention is effective at increasing rCBF, regardless of FTO genotype.

Reduced brain activity during a working memory task in middle-aged apolipoprotein E ε4 carriers with overweight/obesity.

Objective: The apolipoprotein E ε4 (APOE ε4) allele and midlife obesity are independent risk factors for Alzheimer's disease (AD). Both of these risk factors are also associated with differences in brain activation, as measured by blood oxygenation level-dependent (BOLD) responses, in the absence of detectable cognitive deficits. Although the presence of these risk factors may influence brain activity during working memory tasks, no study to date has examined whether the presence of the ε4 allele explains variation in working memory brain activity while matching for levels of overweight/obesity. The primary aim of this study was to determine whether the presence of the ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation in adults with overweight/obesity. We predicted that ε4 carriers would have greater brain activation in regions that support working memory. Methods: This ancillary study included 48 (n = 24 APOE ε4 carriers; n = 24 APOE ε4 non-carriers), sedentary middle-aged adults (Mean age = 44.63 ± 8.36 years) with overweight/obesity (Mean BMI = 32.43 ± 4.12 kg/m2) who were matched on demographic characteristics. Participants were a subsample enrolled in 12-month randomized clinical trial examining the impact of energy-restricted diet and exercise on cardiovascular health outcomes. Participants completed a n-back working memory task with fMRI, which were completed within one month of the start of the intervention. Participants also underwent pseudo-continuous arterial spin labeling scans, a MRI measure of cerebral blood flow (CBF). Results: Compared to non-ε4 carriers with overweight/obesity, ε4 carriers with overweight/obesity had lower fMRI brain activity in the middle frontal gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, lateral occipital cortex, and angular gyrus (z range = 2.52-3.56) during the n-back working memory task. Differences persisted even when controlling for CBF in these brain regions. Conclusion: These results indicate that presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is related to altered brain activity during a working memory paradigm, which may confer risk for accelerated neurocognitive decline in late adulthood. Future research is needed to clarify the clinical implications of these findings in the context of risk for AD.

Cognitive vulnerability in moderate, mild, and low seasonality.

This study examined the association between cognitive vulnerability factors and seasonality. Students (N = 88), classified based on the Seasonal Pattern Assessment Questionnaire as experiencing moderate (n = 26) or mild (n = 32) seasonality, and nondepressed, low-seasonality controls (n = 30) completed explicit (i.e., dysfunctional attitudes, automatic negative thoughts, seasonal attitudes, and rumination) and implicit (i.e., implicit associations test) measures of cognitive vulnerability at one winter and one nonwinter assessment. Relative to low- and mild-seasonality participants, moderate-seasonality participants endorsed more automatic thoughts and rumination in winter and more dysfunctional attitudes across both seasons. Moderate- and mild-seasonality participants endorsed more maladaptive seasonal attitudes than did low-seasonality participants. All groups demonstrated increased dysfunctional attitudes, automatic thoughts, and rumination and stronger implicit associations about light and dark during the winter. The findings support a possible cognitive mechanism of winter depression onset and/or maintenance unique to individuals with moderate, as opposed to mild, seasonality.

Predictive validity of the Seasonal Beliefs Questionnaire for discriminating between seasonal and nonseasonal major depressive disorder.

The Seasonal Beliefs Questionnaire (SBQ) is a 26-item self-report measure of a winter seasonal affective disorder (SAD)-specific cognitive vulnerability consisting of maladaptive thoughts about the seasons, light availability, and weather conditions. In a known groups comparison, currently depressed adults with SAD had significantly higher SBQ scores than currently depressed adults with nonseasonal major depressive disorder (MDD) and healthy controls, and the MDD group had significantly higher SBQ scores than controls. Using that database, this study explored the predictive validity of using an SBQ cutoff score to differentiate SAD from MDD. Receiver operator characteristic curve analyses used SBQ total score to predict SAD versus MDD, SAD versus control, and MDD versus control status. The SBQ subscale combined score, derived from multivariable logistic regression with SBQ subscales, was examined as an alternative predictor. SBQ total score with a cutpoint of 132 had good predictive ability for distinguishing SAD from MDD (C-statistic = .792, sensitivity = .798, specificity = .794). The SBQ subscale combination score slightly improved predictive ability for the SAD/MDD distinction (C-statistic = .813), with better sensitivity (.930) but worse specificity (.571). In contrast, the score on a generic measure of depressogenic cognitive vulnerability, the Dysfunctional Attitudes Scale, was poor for differentiating SAD from MDD. SBQ total score was excellent in discriminating SAD cases from controls with a cutpoint of 121 (C-statistic = .962, sensitivity = .939, specificity .873), but had poor sensitivity for discriminating MDD cases from controls. Results support using the SBQ to screen for probable SAD in practice settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Childhood maltreatment reports in adult seasonal affective disorder: Associations with sleep disturbances, maladaptive cognitions, and brooding.

BACKGROUND: Although childhood maltreatment has been studied in multiple psychopathologies, its role in Seasonal Affective Disorder (SAD) is unknown. The current study examined possible mediators of the relationship between retrospectively-reported childhood maltreatment and adult SAD symptom severity during a major depressive episode in winter. METHODS: Participants (N = 113), ages 18 to 65, completed measures of childhood maltreatment, SAD severity, sleep disturbances, ruminative brooding, and maladaptive cognitions. Mediation analyses testing the relationship between childhood maltreatment and SAD symptom severity via sleep and cognitive factors were conducted using PROCESS (Hayes, 2012). RESULTS: Mediation analyses suggested that insomnia, hypersomnia, brooding, and seasonal maladaptive beliefs may account for the association between childhood maltreatment and SAD symptom severity. LIMITATIONS: Analyses were cross-sectional and should be interpreted with caution. Participants completed self-report childhood trauma measure retrospectively as adults. CONCLUSION: The present study is the first to examine childhood maltreatment in SAD, a disorder commonly viewed with circadian etiology. Covariance between childhood maltreatment and SAD symptom severity is indirectly explained by sleep difficulties, cognitive factors, and brooding, which may suggest therapeutic targets if replicated in longitudinal or experimental manipulations of sleep and cognition.