Kelly J. Rohan

A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder.

BACKGROUND Melanopsin, a non-visual photopigment, may play a role in aberrant responses to low winter light levels in Seasonal Affective Disorder (SAD). We hypothesize that functional sequence variation in the melanopsin gene could contribute to increasing the light needed for normal functioning during winter in SAD. METHODS Associations between alleles, genotypes, and haplotypes of melanopsin in SAD participants (n=130) were performed relative to controls with no history of psychopathology (n=90). RESULTS SAD participants had a higher frequency of the homozygous minor genotype (T/T) for the missense variant rs2675703 (P10L) than controls, compared to the combined frequencies of C/C and C/T. Individuals with the T/T genotype were 5.6 times more likely to be in the SAD group than the control group, and all 7 (5%) of individuals with the T/T genotype at P10L were in the SAD group. LIMITATIONS The study examined only one molecular component of the non-visual light input pathway, and recruitment methods for the comparison groups differed. CONCLUSION These findings support the hypothesis that melanopsin variants may predispose some individuals to SAD. Characterizing the genetic basis for deficits in the non-visual light input pathway has the potential to define mechanisms underlying the pathological response to light in SAD, which may improve treatment.

Tree pollen peaks are associated with increased nonviolent suicide in women

SIR—Research on seasonality of suicide has identified a highly replicated and robust peak in late spring and a somewhat less consistent peak in late summer and early fall. While a number of psychosocial and environmental factors, such as increased exposure to light in the spring, have been suggested to be associated with the spring peak, none satisfactorily explains the temporal association of the peak in suicide with the proposed environmental trigger. Based on the influence of cytokines on mood, cognition, and behavior in healthy individuals and patients with medical and psychiatric conditions, the reciprocal immune–brain interactions, and the cytokine expression during allergic reactions, we hypothesized that tree pollen (which peaks in spring) and ragweed pollen (which peaks in late summer/ early fall) may act as environmental triggers for suicide in vulnerable individuals. We explored this hypothesis by comparing the suicide rates before, during and after periods of peak atmospheric pollen. Tree and ragweed pollen data were obtained from the American Academy of Allergy, Asthma, & Immunology for the years 1995–1998 for the continental US and Canada. Periods of allergen exposure were derived from histograms expressing pollen counts as particles per cubic meter (p/m) on a log scale from 0 to 1000 (y-axis) by months (x-axis) within each year. Raters identified three periods for each allergen in time units of quartermonths at each location for up to 4 years divided as follows: a prepollen period (pollen countso10p/m3 for trees and omid-way on the log scale between 1 and 10p/m for ragweed), a peak-pollen period (4100p/m for trees and4mid-way on the log scale between 10 and 100p/m for ragweed), and a postpollen period when concentrations returned to the prepollen levels. Intervals with intermediate pollen counts were discarded. Suicide data were obtained from the General Mortality Database compiled by the National Center for Health Statistics. Each suicide was classified by county and state of occurrence, date, sex, age, and type (violent, nonviolent, other, or unknown) based on the ICD-9 codes. Suicides by other or unknown means accounted for 6% of the total. For annual rates, person-years were estimated by summing each county’s population from the 2000 Census across the years of observation by sex and age categories. For the analysis of rates and relative rates (RRs) by allergen season and pollen-level period, person-years were estimated by multiplying the population for each age and sex category in each county by the total number of days in each pollen-level period (1⁄4number of quarter months days per quarter month (1⁄47.6 days)) summed across years of observation and divided by 365.25 days per year. Annual and seasonal suicide rates, RRs, and their standard errors were estimated in Poisson’s regression models. RRs for each allergen season and suicide type were estimated setting the prepollen period as the referent and peak and postpollen periods as indicator variables. Since interaction by sex and age was found to be significant, rates and RRs for the effect of allergen exposure were calculated separately by the four age by sex strata. A post hoc analysis of a possible confounding effect of light (using a proxy measure, ‘sunshine’) was performed for the specific pollen periods that showed significant differences in suicide rates using mixed effects repeated measures ANOVAwith pollenperiod and year as within-location effects. The total population of these counties in 2000 was 37 824174 (Table 1). The total number of quarter months of peak-pollen was 670 in the tree season (mean1⁄414.3) and 476 in the ragweed season (mean1⁄49.5). In 92705 505 person-years, 9528 suicides were recorded (rate1⁄410.3/100 000 personyears, 95% confidence interval (CI)1⁄410.1, 10.5) (Table 2). As in other population-based samples of completed suicide, the rate in males was greater than in females (RR1⁄4 4.1, 95% CI1⁄43.9, 4.3), and greater in older people compared with younger (RR1⁄41.4, 95% CI1⁄41.3, 1.5). The rate in older males was greater than in younger males (RR1⁄41.8, 95% CI1⁄4 1.7, 1.9). No difference by age was seen in females. A total of 2417 suicides were recorded in the tree season and 1811 in the ragweed season (Table 3). During the tree allergy season, there was a two-fold increase in the rate of nonviolent suicides among younger females in the peak-pollen period compared with the prepollen period (95% CI1⁄4 1.3, 3.0) (Table 3). There was no difference between the postpollen period and the prepollen period. In older females, the rate of nonviolent suicide in the postpollen period was 4.6 times that of the prepollen period (95% CI1⁄41.2, 17.8), with no increase in the peak-pollen period relative to the prepollen period (Table 3). It is unlikely that a greater exposure to natural light during the peak-pollen season would have spuriously increased suicide rates in younger women, because a greater suicide rate was found in the peak-pollen period, while a greater ‘sunshine’ was found in the postpollen period. However, in older women, it is possible that a greater light exposure during the postpollen period could have spuriously inflated the rate of suicide during that period. The differences in the tree pollen period effect between younger and older women may also represent a consequence of Molecular Psychiatry (2005) 10, 232–238 & 2005 Nature Publishing Group All rights reserved 1359-4184/05

Winter depression recurrence one year after cognitive-behavioral therapy, light therapy, or combination treatment.

30.00

Anxiety sensitivity, the menstrual cycle, and panic disorder: A putative neuroendocrine and psychological interaction

The central public health challenge in the management of seasonal affective disorder (SAD) is prevention of depression recurrence each fall/winter season. The need for time-limited treatments with enduring effects is underscored by questionable long-term compliance with clinical practice guidelines recommending daily light therapy during the symptomatic months each year. We previously developed a SAD-tailored group cognitive-behavioral therapy (CBT) and tested its acute efficacy in 2 pilot studies. Here, we report an intent-to-treat (ITT) analysis of outcomes during the subsequent winter season (i.e., approximately 1 year after acute treatment) using participants randomized to CBT, light therapy, and combination treatment across our pilot studies (N=69). We used multiple imputation to estimate next winter outcomes for the 17 individuals who dropped out during treatment, were withdrawn from protocol, or were lost to follow-up. The CBT (7.0%) and combination treatment (5.5%) groups had significantly smaller proportions of winter depression recurrences than the light therapy group (36.7%). CBT alone, but not combination treatment, was also associated with significantly lower interviewer- and patient-rated depression severity at 1 year as compared to light therapy alone. Among completers who provided 1-year data, all statistically significant differences between the CBT and light therapy groups persisted after adjustment for ongoing treatment with light therapy, antidepressants, and psychotherapy. If these findings are replicated, CBT could represent a more effective, practical, and palatable approach to long-term SAD management than light therapy.

Biological and Psychological Mechanisms of Seasonal Affective Disorder: A Review and Integration

The 2:1 female-to-male sex difference in the prevalence of panic disorder (PD) suggests that there is a sex-specific vulnerability involved in the etiology and/or maintenance of this disorder. The purpose of this paper is to present a new conceptual model, which emphasizes the interaction between a cognitive vulnerability for PD, anxiety sensitivity, and the effects of progesterone and its metabolite, allopregnanolone, on behavioral and physiological responses to stress during the premenstrual phase. This interaction is proposed to be a potential sex-specific pathway that may initiate and/or maintain panic and anxiety symptoms in women. This review paper presents preliminary evidence from both the human and animal literatures to support this new model. Specific topics reviewed include: psychopathology related to the menstrual cycle, anxiety sensitivity and its relationship to the menstrual cycle, PMS, and PMDD, anxiety-modulating effects of progesterone and its neuroactive metabolite, allopregnanolone, and how results from the neuroendocrine literature relate to psychopathology or symptoms associated with the menstrual cycle.

Outcomes One and Two Winters Following Cognitive-Behavioral Therapy or Light Therapy for Seasonal Affective Disorder.

This article: (1) describes and reviews evidence for hypothesized biological and psychological mechanisms of winter seasonal affective disorder (SAD), (2) advocates for an integrative approach to studying SAD etiology that incorporates both biological and psychological mechanisms, and (3) delineates areas for future research from an integrative perspective. Exciting progress has been made within sub-paradigms testing candidate biological mechanisms (i.e., biological rhythm abnormalities, retinal subsensitivity to light, neurotransmitter alterations, and genetic variations) and psychological mechanisms (i.e., maladaptive cognitions and behaviors) of SAD. However, research from an integrative biological/ psychological perspective is currently lacking. In contrast to a continued exclusive focus on micro-models, we argue that an integrative approach would maximize the capacity to predict and understand the onset, maintenance, and course of SAD. An integrative approach also provides a comprehensive theoretical framework for developing strategies to effectively treat acute SAD, maintain acute treatment gains throughout the winter, and prevent future episodes of this highly recurrent form of depression.

The association between seasonal and premenstrual symptoms is continuous and is not fully accounted for by depressive symptoms.

OBJECTIVE The central public health challenge for winter seasonal affective disorder (SAD) is recurrence prevention. Preliminary studies suggest better long-term outcomes following cognitive-behavioral therapy tailored for SAD (CBT-SAD) than light therapy. The present study is a large, randomized head-to-head comparison of these treatments on outcomes one and two winters after acute treatment. METHOD Community adults with major depression, recurrent with seasonal pattern (N=177) were followed one and two winters after a randomized trial of 6 weeks of CBT-SAD (N=88) or light therapy (N=89). Prospective follow-up visits occurred in January or February of each year, and major depression status was assessed by telephone in October and December of the first year. The primary outcome was winter depression recurrence status on the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD). Other outcomes were depression severity on the SIGH-SAD and the Beck Depression Inventory-Second Edition (BDI-II), remission status based on severity cutoff scores, and major depression status from tracking calls. RESULTS The treatments did not differ on any outcome during the first year of follow-up. At the second winter, CBT-SAD was associated with a smaller proportion of SIGH-SAD recurrences (27.3% compared with 45.6%), less severe symptoms on both measures, and a larger proportion of remissions defined as a BDI-II score ≤8 (68.3% compared with 44.5%) compared with light therapy. Nonrecurrence at the next winter was more highly associated with nonrecurrence at the second winter among CBT-SAD participants (relative risk=5.12) compared with light therapy participants (relative risk=1.92). CONCLUSIONS CBT-SAD was superior to light therapy two winters following acute treatment, suggesting greater durability for CBT-SAD.

Seasonal trends in depressive problems among United States children and adolescents: A representative population survey

Seasonal affective disorder (SAD) frequently co-occurs with premenstrual dysphoric disorder. Explanations of this comorbidity highlighting the cyclical nature of female sex hormones imply that seasonal and premenstrual symptoms should correlate positively even in nonclinical samples. In a sample of 91 female college students, we found a sizable positive correlation (r = .45; p < 0.001) between seasonal and premenstrual symptoms. This relation held up even in a subsample selected on the basis of not qualifying for SAD or subsyndromal SAD on a screening measure. Although the correlation was reduced when depressive symptom severity was statistically controlled, it remained positive and significant. Future research testing possible explanations of the co-occurrence of seasonal and premenstrual symptoms should incorporate the full range of severity on symptom variables, treating them as continua rather than solely as binary categories.

Premenstrual distress predicts panic-relevant responding to a CO2 challenge among young adult females

This study examined season-of-assessment differences in parent and child reports of depressive problems on well-validated instruments in 2009 U.S. children and adolescents, aged 6 to 18 years, from a nationally representative population survey. A parent completed the Child Behavior Checklist (CBCL) for each participant and 1226 of the 11-18-year-olds completed the Youth Self-Report (YSR). Outcome measures were CBCL and YSR withdrawn/depressed syndrome scale scores and rates of clinically elevated scores. Overall fall/winter versus spring/summer differences were not found on the CBCL or YSR for depressive problem severity or rates of depressive problems. Age, sex, and latitude were examined as potential moderators of the association between season-of-assessment and the outcomes. Of these, the effect of season-of-assessment on CBCL depressive problem severity depended upon age. Parents of 16-18-year-old adolescents rated depressive problems as significantly more severe in fall and winter than in spring and summer. Parents also rated depressive problems as significantly more severe in 16-18-year-olds than in 6-15-year-olds, but only when assessed in the fall and winter. There were no season-of-assessment differences among 6-15-year-old children and adolescents. The overall lack of season-of-assessment differences and the finding of age as a moderator on only one of four outcomes suggest minimal seasonality effects.

Cognitive-behavioral therapy vs. light therapy for preventing winter depression recurrence: study protocol for a randomized controlled trial

The current study examined the incremental validity of self-reported premenstrual distress in predicting panic responsivity (self-reported panic symptoms and skin conductance response frequency; SCR) following inhalation of 10% CO(2)-enriched air. A community sample of young adult women (n=46) completed questionnaires assessing substance use patterns, premenstrual symptoms and distress, and anxiety sensitivity and underwent a laboratory biological challenge procedure (4-min 10% CO(2)-enriched air inhalation). As hypothesized, higher premenstrual distress scores significantly predicted greater self-reported panic symptoms following the CO(2) challenge above and beyond other theoretically relevant variables (anxiety sensitivity, cigarette use, and alcohol consumption). In predicting SCR, premenstrual distress exhibited only a trend towards statistical significance. These findings provide preliminary evidence that premenstrual symptoms may serve as a potential risk factor to experience more intense panic symptoms in response to perturbations in bodily sensations.