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Objective: The primary aim was to relate Toxoplasma gondii seropositivity and serointensity to scores on the self-rated Suicide Assessment Scale (SUAS-S). Another aim was to reevaluate the previously reported positive association between T gondii serointensity and a history of nonfatal suicidal self-directed violence. Method: This cross-sectional, observational study compared T gondii serointensity and seropositivity in plasma from 54 adult suicide attempters (inpatients at Lund University Hospital, Lund, Sweden) and 30 adult control subjects (randomly selected from the municipal population register in Lund, Sweden) recruited between 2006 and 2010.The potential of patients and controls for self-directed violence was evaluated with the SUAS-S. Psychiatric diagnoses were made according to DSM-IV criteria. Plasma samples were tested for immunoglobulin G antibodies to T gondii, cytomegalovirus, and herpes simplex virus type 1. Data were analyzed using multivariable logistic regression to investigate the association between T gondii serointensity or seropositivity and a history of nonfatal suicidal self-directed violence; multivariable linear regression was used to explore the relationship between T gondii serointensify or seropositivity and the SUAS-S. Both regression models included sex, age, and body mass index as covariates. Results: Seropositivity of T gondii (adjusted odds ratio [OR]=7.12; 95% CI, 1.66-30.6; P=.008) and serointensity of T gondii (adjusted OR=2.01; 95% CI, 1.09-3.71; P=.03) were positively associated with a history of nonfatal suicidal self-directed violence. Seropositivity of T gondii was associated with higher SUAS-S scores, a relationship significant for the whole sample (P=.026), but not for suicide attempters only. No significant associations with other pathogens were identified. Conclusions: These results are consistent with previous reports on the association between T gondii infection and nonfatal suicidal self-directed violence. Confirming these results in future large longitudinal studies and including suicide as an outcome may lead to novel individualized approaches in suicide prevention. J Clin Psychiatry 2012;73 (8):1069-1076 (c) Copyright 2012 Physicians Postgraduate Press, Inc.

Background: Bright-light treatment is a safe and effective treatment for the management of winter seasonal affective disorder (SAD). In a recent study, we found that the relative duration of reading was positively associated with likelihood of remission after six weeks of light treatment. Methods: Two technicians measured the illuminance of a light box with a light meter directed towards the center of reading material that was placed on a table in front of the light box. The measurement was also performed after reading material was removed. The two measurements were performed in a randomized order. Friedman analysis of variance with Wilcoxon post-hoc tests were used to compare illuminance with vs. without reading. Results: The presence of the reading material increased illuminance by 470.93 lux (95% CI 300.10–641.75), p Limitations: This is a technical report done under conditions intended to mimic those of typical ambulatory light treatment as much as possible. Conclusions: As reading materials reflect light from the light box, reading during light therapy increases ocular illuminance. If confirmed by future studies using continuous recordings in randomized design, instructing SAD patients to read during light therapy may contribute to a more complete response to light treatment. The downside of specific relevance for students, is that reading, in particular, with bright light in the late evening/early night may induce or worsen circadian phase delay, adversely affecting health and functioning.

Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that infects roughly a third of the world population. In an immunocompetent host, infection is generally chronic and asymptomatic, as the immune system keeps T. gondii confined to cysts and the intracellular space within the muscle and brain. Seropositivity has been linked to schizophrenia, car accidents, changes in personality, and more recently, suicidal attempts. Very recently, seroprevalence for 20 European countries was found to be associated with increased suicide rates. Although suicide rates were age-standardized, given that T. gondii seroprevalence increases with age and that the blood samples were drawn in women, we now retested in women only the association between suicide and T. gondii seropositivity, stratified by age. Simple correlations between ranked T. gondii seropositivity and suicide rate identified statistically significant relationships in women 60 years or older (p

Background Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity – important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers. Methods Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers ( n = 31) and patients with MDD with ( n = 14) and without ( n = 16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels. Results KYN levels differed across groups ( F = 4.03, df = (2,58), and p = 0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters ( t = 2.105, df = 58, and p = 0.040), who did not differ from healthy volunteers ( t = 0.418, df = 58, and p = 0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters. Conclusion These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.

The aims of our study were to evaluate whether there is any relationship between the environmental temperature and the response to the cold pressor test and if this relationship is different in younger and older hypertensive patients. We studied 100 mild-to-moderate hypertensives, aged 21 to 75 years. In the > or = 45 years group (46 patients) a significant positive correlation between the environmental temperature and the heart rate and blood pressure response to the cold pressor test was found. The relative humidity was not correlated with the response to the cold pressor test, but multiplying the mean temperature and the mean relative humidity enhanced the correlations of the environmental temperature. An increase in the mean temperature for the 20 days before the cold pressor test (the best correlated period) by 10 degrees C correlated with increases in the systolic blood pressure response by 10.5 mm Hg (P = .0195), the diastolic blood pressure response by 8 mmHg (P = .0079), the mean blood pressure by 9 mmHg (P = .0058), and the heart rate response by 3.8 beats/min (P = .0134). In < 45 years patients no environmental relationship of the response to cold pressor test was found. A chronic exposure to low temperatures is correlated with higher blood pressure levels--as previously reported--and, in contrast (but only in elderly), with a lower blood pressure response to acute cold stress. Our findings confirm the higher meteorological dependence of hemodynamics in the elderly, and suggest that the research protocols using the cold pressor test should adjust the response for the previous environmental temperature.

Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking.Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson's χ² tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic symptoms during mood episodes.Seropositivity for influenza A (p=0.004), B (p0.0001) and coronaviruses (p0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p=0.001) and history of psychotic symptoms (p=0.005).The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed.The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics.

Objective To investigate the association between sleep disordered breathing (SDB) and parent report of attention and behavioral problems in children, as well as the association between sleep stage duration and measures of child functioning in a clinically referred sample. Methods A chart review was conducted of 95 children with clinical history of SDB who completed an overnight polysomnography study in a pediatric sleep laboratory. Child functioning was assessed at the time of the sleep study by parent report on the Child Behavior Checklist (CBCL). The apnea hypopnea index was used as a measure of SDB severity. Results The apnea hypopnea index was associated with externalizing behavior, but not attention problems on the CBCL. In children 2-3 years old, stage 4 sleep duration was associated with externalizing behavior. In children 4-16 years old, REM sleep duration was associated with externalizing behavior. Conclusions Children with increased SDB severity may be at greater risk for behavioral problems. Differences between the association of sleep stages and externalizing behavior in toddlers compared with older children suggests possible developmental differences in the association between sleep and behavior.

It has been reported that allergies are associated with depression and possibly suicide in women. Aggression is an important behavioral component that predisposes depressed individuals to suicidal acts. In the present study we examined the relationship between allergies and aggression to determine a potential contribution of allergies in factors of risk for suicidal behavior. Because stress plays a critical role in the manifestation of clinical symptoms of allergies and also in suicidal behavior, we also studied the role of acute stress. Female inbred Brown Norway rats known for their susceptibility to respiratory allergies were sensitized and challenged with a mixture of tree pollen and evaluated in the resident-intruder test for detection of aggressive behaviors. They were also subjected to acute stress by sessions of inescapable forced swimming and re-evaluated in the resident intruder test. Animals made allergic to tree pollen and subjected to acute stress displayed increased aggressive-like behavior as compared with control-saline treated animals or to their own aggressive scores previous to the stress session. These results suggest that allergies and stress increases aggressive-like behavior, indicating that these conditions may be important factors promoting altered emotional reactivity with the potential to influence suicidal behavior.

Allergic inflammation is associated with mood disorders, exacerbation of depression, and suicidal behavior. Mediators of inflammation modulate sleep , with Th1 cytokines promoting NREM sleep and increasing sleepiness and Th2 cytokines (produced during allergic inflammation) impairing sleep. As sleep impairment is a rapidly modifiable suicide risk factor strongly associated with mood disorders, we review the literature leading to the hypothesis that allergic rhinitis leads to mood and anxiety disorders and an increased risk of suicide via sleep impairment. Specifically, allergic rhinitis can impair sleep through mechanical (obstructive) and molecular (cytokine production) processes. The high prevalence of mood and anxiety disorders and allergy, the nonabating suicide incidence, the currently available treatment modalities to treat sleep impairment and the need for novel therapeutic targets for mood and anxiety disorders, justify multilevel efforts to explore disturbance of sleep as a pathophysiological link. Language: en

Suicide is a serious public health problem. Prevention of suicide depends to a great degree on identification and mitigation of its risk factors. Allergy has been associated with mood and anxiety disorders, risk factors for suicidality. Antiallergic medication could modulate or mediate these predictive associations. Recently, the FDA issued a warning raising concerns about the suicidality potential of montelukast and other leukotriene (LT) antagonists.The purpose of this review is to integrate the emerging interpretations of the link between suicidality, suicide risk factors, allergy and treatment of allergy in particular, with LT antagonists.We reviewed the available reports on the possible relationships between montelukast, allergy, suicide, suicidality and suicide risk factors. We also present the positions of the FDA, manufacturer, and national organizations of allergists and immunologists on the possible role of montelukast in suicidality.At present, there is insufficient data to prove that there is a link between montelukast and suicidality. Inquiring about mood changes and suicidal ideation should be integrated in general medical practice.

Considering clinical and animal evidence suggesting a relationship between allergy and anxiety, we hypothesized that, from low to high aeroallergen exposure, changes in anxiety symptom scores in patients with primary mood disorders will correlate with changes in allergy symptom scores. We also anticipated that sensitization to tree pollen, as determined by allergen specific IgE antibodies, will predict a greater worsening of anxiety during exposure to tree pollen. 51 patients with unipolar or bipolar disorder (age: 19-63 years, 65% female) were recruited. Tree- pollen IgE positive subjects (12) were included as the experimental group and patients negative to a multi-allergen serological test (39) were included in the control group. Self reports of anxiety and allergy symptoms were obtained once during the peak airborne pollen counts and once during the period of low airborne pollen counts, as reported by two local pollen counting stations. Using linear regression models, we confirmed a significant positive association between allergy scores and anxiety scores (p

Rapid Cycling Bipolar Disorder (RCBD) outpatients completed twice-daily mood self-ratings for 3 consecutive months. These ratings were matched with local measurements of atmospheric pressure, cloud cover, and temperature. Several alternative second order differential equation models were fit to the data in which mood oscillations in RCBD were allowed to be linearly coupled with daily weather patterns. The modeling results were consistent with an account of mood regulation that included intrinsic homeostatic regulation as well as coupling between weather and mood. Models were tested first in a nomothetic method where models were fit over all individuals and fit statistics of each model compared to one another. Since substantial individual differences in intrinsic dynamics were observed, the models were next fit using an ideographic method where each individual’s data were fit separately and best-fitting models identified. The best-fitting within-individual model for the largest number of individuals was also the best-fitting nomothetic model: temperature and the first derivative of temperature coupled to mood and no effect of barometric pressure or cloud cover. But this model was not the best-fitting model for all individuals, suggesting that there may be substantial individual differences in the dynamic association between weather and mood in RCBD patients. Heterogeneity in the parameters of the differential equation model of homeostatic equilibrium as well as the coupling of mood to an inherently unpredictable (i.e., nonstationary) process such as weather provide an alternative account for reported broadband frequency spectra of daily mood in RCBD.

The high rate of comorbidity of asthma and mood disorders would imply the possibility of potential shared pathophysiologic factors. Proposed links between asthma and mood disorders include a vulnerability (trait) and state connection. Vulnerability for both asthma and mood disorders may involve genetic and early developmental factors. State-related connections may include obstructive factors, inflammatory factors, sleep impairment, psychological reactions to chronic medical illness, as well as exacerbation of asthma in individuals with chronic stress. Treatment for asthma may also exacerbate mood disorders. New research suggests involvement of the central nervous system in asthma and allergy. Further characterization of clinical, psychological, cellular and molecular interconnections between asthma and mood disorders is needed to better evaluate and treat these patients. A close collaboration between mental health professionals and allergists could result in improved symptom control, quality of life, overall functioning and ultimately, decreased mortality.

Epidemiological and clinical studies report higher incidences of anxiety and increased emotional reactivity in individuals suffering from respiratory allergies. To evaluate if respiratory allergies are capable of promoting anxiety-like behavior in rodents, we used models of allergic rhinitis and behavioral evaluations followed by assessment of mRNA for cytokines in relevant brain regions. Mice and rats were sensitized to ovoalbumin or pollen respectively following standard sensitization and challenge protocols. After challenge, the animals were evaluated in the open field, elevated plus maze and resident intruder tests. Cytokines and corticotropin releasing factor expression were assessed in several brain regions by real-time RT-PCR and plasma corticostereone concentrations by radioimmunoassay. Mice and rats sensitized and exposed to allergen showed increased anxiety-like behavior and reduced social interaction without any overt behavioral signs of sickness. T-helper type 2 (TH2) cytokines were induced in both rats and mice in the olfactory bulbs and prefrontal cortex and remained unchanged in the temporal cortex and hypothalamus. The same results were found for CRF mRNA expression. No differences were observed in corticosterone concentrations one hour after the last behavioral test. These results show that sensitization and challenge with allergens induce anxiety across rodent species and that these effects were paralleled by an increased expression of TH2 cytokines and CRF in the prefrontal cortex. These studies provide experimental evidence that sensitized rodents experience neuroimmune-mediated anxiety and reduced social interaction associated with allergic rhinitis.

Light therapy is an effective treatment of seasonal affective disorder (SAD), when administered daily for at least several weeks. We have previously reported a small improvement in mood in SAD patients following exposure to the first hour of treatment. We now reevaluate retrospectively mood changes during shorter exposures comparing depression ratings at baseline, 20, 40, and 60 minutes of light. Participants were 15 depressed patients with SAD, untreated, who were tested during the winter season. The treatment consisted of 10,000 lux of white cool fluorescent light. Depression was measured using the 24-item NIMH scale (24-NIMH). The data were analyzed using ANOVA on ranks and Wilcoxon signed rank tests. Light resulted in significant improvement in mood at every interval when compared with baseline (p< .001). The 40 minute exposure resulted in a greater improvement than the 20 minute exposure (p < .001) but was not different from the 60 minute exposure (p < = .068). We conclude that immediate improvement in mood can be detected after the first session of light with exposures as short as 20 minutes, and that 40 minutes of exposure is not less effective than 60 minutes.

Prepartum and postpartum depression have negative, and sometimes devastating, effects on women and their families. As inflammatory processes are related to depression in general, we hypothesized that inflammatory perturbations, prepartum and postpartum, contribute to triggering and worsening of symptoms of peripartum depression. We conducted a longitudinal preliminary study on 27 women at high risk for developing postpartum depression measuring SIGH-SAD scores at three time points: 35-38 weeks gestation, 1-5 days postpartum, and 5-6 weeks postpartum. Serum C-reactive protein and interleukin-6, both markers of inflammation, as well as tryptophan, kynurenine, and the kynurenine/tryptophan ratio, as consequences of inflammation and pathophysiological steps towards depression, were measured at each time point. C-reactive protein levels were found to be positively related to atypical and total depression scores in the prepartum period and with atypical depression scores in the early postpartum period. Tryptophan was found to be negatively associated with total depression scores in the prepartum, as well. These findings warrant further investigation that could lead to novel interventions to decrease poor outcomes from peripartum depression.

The rates of depression, anxiety, and sleep disturbance (suicide risk factors) are greater in patients with allergic rhinitis than in the general population. The rate of allergy is also greater in patients with depression. Preliminary data suggest that patients with a history of allergy may have an increased rate of suicide. Clinicians should actively inquire to diagnose allergy in patients with depression and depression in patients with allergy. Spring peaks of suicide are highly replicated, but their origin is poorly understood. Preliminary epidemiologic data suggest that seasonal spring peaks in aeroallergens are associated with seasonal spring peaks in suicide. Our research in Brown Norway rats demonstrates that sensitization and exposure to aeroallergens induces anxiety-like and aggressive behaviors as well as allergy-related helper T-cell type 2 (Th2) cytokine gene expression in the prefrontal cortex. Thus, it is possible that sensitization and exposure to aeroallergens, which peak in spring, may be conducive to seasonal exacerbation of suicide risk factors such as anxiety, depression, hostility/aggression, and sleep disturbance. Connecting allergy with suicide and suicide risk factors adds to previous neurologic literature connecting allergy with migraines and seizure disorders. Our recent report of Th2 (allergy-mediating) cytokine expression in the orbitofrontal cortex of suicide victims should lead to future studies to test the hypothesis that mediators of allergic inflammation in the nasal cavities may result in Th2 cytokine expression in the brain, influencing affect and behavioral modulation. Certain medications used to treat allergy can exacerbate suicide risk factors, potentially worsening suicide risk and even triggering suicide. Systemic (but not topical) corticosteroids have been associated with manic and depressive episodes and mixed mood states. Recently, the US Food and Drug Administration started investigating the possibility that montelukast may trigger suicide. Although this association requires further exploration and confirmation, clinicians should err on the side of caution, inquiring about past suicide attempts; hopelessness; reasons for living; and suicidal ideation, intent, or plan; and referring the patient to a mental health professional for evaluation if appropriate.

The purpose of this paper is to review the evidence estimating an impact of occupational factors on mood disorders and suicide, and the efficacy of interventions. This review is based on literature searches using Medline and Psych INFO from 1966 to 2007 (keywords: work stress, job insecurity, job strain, shift work, violence, occupational health, mood disorders, depression, and suicide). To establish the relationship between occupational variables and mood disorders, we focused on clinically significant disorders rather than depressive symptoms. During the last decade, prospective epidemiological studies have suggested a predictive association between the work environment and mood disorders. Recently, increasing numbers of clinical trials have shown favorable effect size of intervention and suggested preferable return-on-investment results. However, low awareness and social stigma still decrease workers access to treatment. Mental health professionals in conjunction with employers have to devise a creative system to make the quality care being offered more accessible to employees. In addition, further outcome data is needed to evaluate the benefit of managing mood disorders in the workplace, and to foster awareness of positive implications for employees, employers, their families, and the society at large. In addition, the work environment, with its chemical (e.g. chemosensory factors, pollutants), physical (e.g. lighting, noise, temperature, outdoor views and activities), biological (e.g., chronobiological factors, allergens, infectious agents), psychological (e.g. demand-control, effort-reward balance), social (e.g. cohesiveness, support), and organizational (e.g. leadership styles) component should meet minimal standards, and may improve with striving towards the optimum.

OBJECTIVE: Based on the reported association between cytokines with depression and suicide, and evidence of increased markers of inflammation in the brain of suicide victims, the present study examined the expression of cytokines in the orbitofrontal cortex of suicide victims. METHOD: In a postmortem sample obtained from the Brodman area 11 of suicides (n = 34) and controls (n = 17), real-time RT-PCR was used to compare the expression of mRNA species for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, 4, 5, 6, and 13. RESULTS: Increased expression of IL-4 was found in women suicide victims and IL-13 in men suicide victims. Elevated but not significant cytokine expression was also observed for TNF-alpha in women suicide victims. CONCLUSION: To our knowledge, these results provide the first evidence of the presence of mRNA transcripts of type 2 T-helper cytokines in the human orbitofrontal cortex and their increased expression in the brain of suicides. Language: en

Duration of nocturnal melatonin secretion, a marker of “biological night” that relates to sleep duration, is longer in winter than in summer in patients with seasonal affective disorder (SAD), but not in healthy controls. In this study of African and African American college students, we hypothesized that students who met criteria for winter SAD or subsyndromal SAD (S-SAD) would report sleeping longer in winter than in summer. In addition, based on our previous observation that Africans report more “problems” with change in seasons than African Americans, we expected that the seasonal changes in sleep duration would be greater in African students than in African American students. Based on Seasonal Pattern Assessment Questionnaire (SPAQ) responses, African American and African college students in Washington, D.C. (N = 575) were grouped into a winter SAD/S-SAD group or a no winter diagnosis group, and winter and summer sleep length were determined. We conducted a 2 (season) × 2 (sex) × 2 (ethnicity) × 2 (winter diagnosis group) ANCOVA on reported sleep duration, controlling for age. Contrary to our hypothesis, we found that African and African American students with winter SAD/S-SAD report sleeping longer in the summer than in the winter. No differences in seasonality of sleep were found between African and African American students. Students with winter SAD or S-SAD may need to sacrifice sleep duration in the winter, when their academic functioning/efficiency may be impaired by syndromal or subsyndromal depression, in order to meet seasonally increased academic demands.

To our knowledge, this paper is the first to estimate seasonality of mood in a predominantly Caucasian sample, living in areas with hot summers and a relative unavailability of air conditioning. As a summer pattern of seasonal depression was previously associated with a vulnerability to heat exposure, we hypothesized that those with access to air conditioners would have a lower rate of summer seasonal affective disorder (SAD) compared to those without air conditioning. A convenience sample of 476 Romanian postgraduate students completed the Seasonal Pattern Assessment Questionnaire (SPAQ), which was used to calculate a global seasonality score (GSS) and to estimate the rates of winter- and summer-type SAD. The ratio of summer- vs. winter-type SAD was compared using multinomial probability distribution tests. We also compared the ratio of summer SAD in individuals with vs. without air conditioners. Winter SAD and winter subsyndromal SAD (S-SAD) were significantly more prevalent than summer SAD and summer S-SAD. Those with access to air conditioners had a higher, rather than a lower, rate of summer SAD. Our results are consistent with prior studies that reported a lower prevalence of summer than winter SAD in Caucasian populations. Finding an increased rate of summer SAD in the minority of those with access to air conditioners was surprising and deserves replication.

Selective serotonin reuptake inhibitors (SSRIs) reduce platelet serotonin and are associated with increased gastrointestinal bleeding, an effect that is enhanced when taken with NSAIDs or aspirin. The best method to evaluate hemorrhagic events in patients taking SSRIs has not been determined. Platelet aggregation, which is not widely available, shows SSRI inhibition of platelet function; we tested whether a platelet function analyzer could detect SSRI inhibition of platelet function. Two groups of outpatients with mood disorders were recruited; each patient was taking a stable dose of either an SSRI or bupropion for at least 6 weeks. They were tested using the platelet function analyzer-100 (PFA-100; Dade International Inc, Miami, Fla) concomitantly with platelet aggregation. Fifty-eight patients were analyzed. We detected significant differences between the groups using aggregation methods with arachidonic acid (aggregation, P = 0.00001; release, P = 0.009) and collagen (aggregation, P = 0.016; release, P = 0.006). The PFA-100 did not detect differences between the groups or results outside the reference range. The PFA-100 does not detect the inhibitory effects of SSRIs on platelet function, but it can be used to direct evaluation of bleeding in a patient taking an SSRI. Abnormal PFA-100 results suggest additional evaluation for von Willebrand disease, other platelet inhibitory medications, or underlying intrinsic platelet dysfunction.

To compare adherence, response, and remission with light treatment in African-American and Caucasian patients with Seasonal Affective Disorder.Seventy-eight study participants, age range 18-64 (51 African-Americans and 27 Caucasians) recruited from the Greater Baltimore Metropolitan area, with diagnoses of recurrent mood disorder with seasonal pattern, and confirmed by a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV, were enrolled in an open label study of daily bright light treatment. The trial lasted 6 wk with flexible dosing of light starting with 10000 lux bright light for 60 min daily in the morning. At the end of six weeks there were 65 completers. Three patients had Bipolar II disorder and the remainder had Major depressive disorder. Outcome measures were remission (score ≤ 8) and response (50% reduction) in symptoms on the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-SAD) as well as symptomatic improvement on SIGH-SAD and Beck Depression Inventory-II. Adherence was measured using participant daily log. Participant groups were compared using t-tests, chi square, linear and logistic regressions.The study did not find any significant group difference between African-Americans and their Caucasian counterparts in adherence with light treatment as well as in symptomatic improvement. While symptomatic improvement and rate of treatment response were not different between the two groups, African-Americans, after adjustment for age, gender and adherence, achieved a significantly lower remission rate (African-Americans 46.3%; Caucasians 75%; P = 0.02).This is the first study of light treatment in African-Americans, continuing our previous work reporting a similar frequency but a lower awareness of SAD and its treatment in African-Americans. Similar rates of adherence, symptomatic improvement and treatment response suggest that light treatment is a feasible, acceptable, and beneficial treatment for SAD in African-American patients. These results should lead to intensifying education initiatives to increase awareness of SAD and its treatment in African-American communities to increased SAD treatment engagement. In African-American vs Caucasian SAD patients a remission gap was identified, as reported before with antidepressant medications for non-seasonal depression, demanding sustained efforts to investigate and then address its causes.

Objective: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. Method: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman’s analysis of variance and the Wilcoxon signed ranks test. Results: The patients’ scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. Conclusions: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer’s light or other factors are the main contributors to this difference. (Am J Psychiatry 1998; 155:1614‐1616)

Because aeroallergens produce inflammation in the respiratory airways, and inflammation triggers depression in vulnerable individuals, we hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen, will be associated with a greater seasonality of mood. Since pollen is absent during winter, we specifically predicted that mood sensitivity to tree pollen will predict non-winter SAD but not winter SAD.A convenience sample of African and African American college students who lived in the Washington DC metropolitan area for at least the past 3 years completed the Seasonal Pattern Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS) was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was derived, a seasonal pattern (winter vs non-winter) identified, and self-reported mood changes during high pollen counts obtained. A Mann-Whitney test was used to compare GSS between participants with vs without mood worsening during high pollen counts. The capability of mood worsening with high pollen counts, gender, ethnicity, and age to predict non-winter SAD was analyzed with logistic regressions.GSS was greater (z=5.232, p0.001) in those who reported mood worsening with high pollen counts. Mood sensitivity to pollen predicted non-winter SAD (p=0.017), but not winter SAD.The SPAQ is not a definitive tool to assess seasonality, and self-reported mood worsening with high pollen counts relies on recollection. No direct measures of depression scores or pollen counts were collected. The non-winter SAD concept has not been previously established.Our study, which should be considered preliminary in light of its limitations, suggests that self-reported mood-worsening with high pollen count is associated with a greater seasonality of mood, and predicts SAD of non-winter type.

Bright light treatment is the most potent melatonin suppressor and circadian phase shifter and is a safe nonpharmacologic antidepressant for seasonal depression. In addition, bright light treatment may restore performance in conditions of sleep debt and misalignment between peak performance and the athletic event. This article discusses the therapeutic use of bright light treatment, its side effects, and mechanisms of action.

The function of pro-inflammatory cytokines and chemokines in brain injury and autoimmune diseases has been long recognized. There is however, a significant lack of information regarding the role of constitutively expressed immune genes in the normal brain. The current evidence points to the involvement of certain cytokines and major histocompatibility complex (MHC) molecules in synaptic function and plasticity. Furthermore, constitutively expressed chemokines in neurons provide an additional indication of a role for these molecules in neural function. In addition, clinical data suggests a dysregulation of immune genes in the cerebrospinal fluid of psychiatric patients who have neither brain injury nor autoimmune diseases. This review will discuss recent data indicating a role for immune genes in synaptic stability and will also discuss the implications for specific brain functions involving mood and cognition.

Habitual sleep duration varies greatly among individuals. The physiological basis of this variation is unknown. We sought to determine whether individual differences in sleep duration are associated with systematic differences in the duration of the biological night that is programmed by the circadian pacemaker and reflected in the nocturnal interval of circadian rhythms in neuroendocrine function, body temperature, and arousal. Ten young, healthy long sleepers (sleep duration >9 h) and 14 short sleepers (

Levels of 25-Hydroxy Vitamin D [25(OH)D] were reported to be decreased in cardiovascular disease (CVD) and in other chronic immunopathologies. In multiple studies, 25(OH)D has been shown to be significantly linked to mortality. Supplementation with Vitamin D2 or D3 has been suggested to improve clinical outcomes. Nevertheless, supplementation may require high doses to achieve efficient blood levels of 25(OH)D. In contrast to this causal assumption, we hypothesize that decreased 25(OH)D levels are secondary phenomena to inflammation, and not as pathophysiologically relevant as suggested by the current hype. Under these conditions, low 25(OH)D levels might be caused by the oxidative stress that results from chronic inflammation encountered in patients with CVD. The oxidative environment most likely interferes with key enzymes, disturbing the biosynthesis as well as biodegradation of 1.25 (OH)D. There is no clear evidence of a beneficial effect of Vitamin D supplementation, except for treating Vitamin D deficiency (i.e. levels of

The influence of the circadian pacemaker and of the duration of time awake on the electroencephalogram (EEG) was investigated in 19 humans during approximately 40 h of sustained wakefulness. Two circadian rhythms in spectral power density were educed. The first rhythm was centered in the theta band (4.25-8.0 Hz) and exhibited a minimum approximately 1 h after the onset of melatonin secretion. The second rhythm was centered in the high-frequency alpha band (10.25-13.0 Hz) and exhibited a minimum close to the body temperature minimum. The latter rhythm showed a close temporal association with the rhythms in subjective alertness, plasma melatonin, and body temperature. In addition, increasing time awake was associated with an increase of power density in the 0.25- to 9.0-Hz and 13.25- to 20. 0-Hz ranges. It is concluded that the waking EEG undergoes changes that can be attributed to circadian and homeostatic (i.e., sleep-wake dependent) processes. The distinct circadian variations of EEG activity in the theta band and in the high-frequency alpha band may represent electrophysiological correlates of different aspects of the circadian rhythm in arousal.

The electroencephalogram (EEG) of nine healthy individuals was recorded at half-hourly intervals during approximately 40 h of sustained wakefulness in a constant routine protocol. EEG power density in the 0.75-9.0 Hz range exhibited a global increasing trend, and a local trough in the evening, centered approximately 6 h prior to the temperature minimum. The former could be attributed to a wake-dependent influence, and the latter to a circadian influence. Power density in the 9.25-12.0 Hz band showed a circadian modulation, the trough coinciding with the minimum of the endogenous rhythm of body temperature, whereas a wake-dependent influence was not evident. Power density in the 12.25-25.0 Hz range exhibited a wake-dependent increase, whereas a circadian modulation was absent. It is concluded that the circadian pacemaker and the wake-dependent (i.e. homeostatic) process affect the waking EEG in a frequency-specific manner.

Background Seasonal affective disorder (SAD) is a subtype of recurrent depression involving major depressive episodes during the fall and/or winter months that remit in the spring. The central public health challenge in the management of SAD is prevention of winter depression recurrence. Light therapy (LT) is the established and best available acute SAD treatment. However, long-term compliance with daily LT from first symptom through spontaneous springtime remission every fall/winter season is poor. Time-limited alternative treatments with effects that endure beyond the cessation of acute treatment are needed to prevent the annual recurrence of SAD. Methods/design This is an NIMH-funded R01-level randomized clinical trial to test the efficacy of a novel, SAD-tailored cognitive-behavioral group therapy (CBT) against LT in a head-to-head comparison on next winter outcomes. This project is designed to test for a clinically meaningful difference between CBT and LT on depression recurrence in the next winter (the primary outcome). This is a concurrent two-arm study that will randomize 160 currently symptomatic community adults with major depression, recurrent with seasonal pattern, to CBT or LT. After 6 weeks of treatment in the initial winter, participants are followed in the subsequent summer, the next winter, and two winters later. Key methodological issues surround timing study procedures for a predictably recurrent and time-limited disorder with a focus on long-term outcomes. Discussion The chosen design answers the primary question of whether prior exposure to CBT is associated with a substantially lower likelihood of depression recurrence the next winter than LT. This design does not test the relative contributions of the cognitive-behavioral treatment components vs. nonspecific factors to CBT’s outcomes and is not adequately powered to test for differences or equivalence between cells at treatment endpoint. Alternative designs addressing these limitations would have required more patients, increased costs, and reduced power to detect a difference in the primary outcome. Trial registration Clinicaltrials.gov identifier NCT01714050

Objective This study analyzed a relationship between prenatal mood states and serologic evidence of immune response to Toxoplasma gondii . A secondary aim was to determine whether thyroid peroxidase autoantibody status was related to T gondii status. Study Design Pregnant women (n = 414) were measured at 16-25 weeks' gestation with demographic and mood questionnaires and a blood draw. All plasma samples were analyzed for thyroid peroxidase and T gondii immunoglobulin G, tryptophan, kynurenine, and neopterin. T gondii serotypes were also measured in the women who were T gondii positive. Cytokines were available on a subset (n = 142). Results Women with serologic evidence of exposure to T gondii (n = 44) showed positive correlations between immunoglobulin G levels and the Profile of Mood States depression and anxiety subscales. Plasma tumor necrosis factor–α was higher in women who were positive for T gondii . Serotypes were type I (27%), type II (31%), and unclassified (42%, which shows intermediate levels of reactivity). The depression and anxiety scores were highest in type I, but this was not significant. The Profile of Mood States vigor score was lowest in type II, compared with the type I or unclassified groups. Conclusion Higher T gondii immunoglobulin G titers in infected women were related to anxiety and depression during pregnancy. Subclinical reactivation of T gondii or immune responses to T gondii may worsen mood in pregnant women.

Background: Behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. Because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjects. Methods: Fourteen patients who had winter seasonal affective disorder and 16 healthy volunteers were studied once in winter and once in the subsequent summer. We administered a phenyl ethyl alcohol detection threshold test to each side of the nose in a counterbalanced order, with the nostril contralateral to the tested site occluded. Patient and control data were compared using a 4-way repeated measure analysis of covariance (with group and gender as between-subjects factors, season and side-of-the-nose as within-subjects factors, and age as a covariate). Results: The patients exhibited lower thresholds than did the controls (F1,25=9.2; P=.006). There was no main effect of season. Conclusion: In humans, marked seasonal behavioral rhythms with recurrent winter depression may be associated with a more acute sense of smell. Arch Gen Psychiatry. 2002;59:1119-1122

Background: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. Methods: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. Results: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0±1.3 vs 8.4±1.3 hours; P=.001) but in healthy volunteers there was no change (9.0±1.6 vs 8.9±1.2 hours; P=.5). Conclusions: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder. Arch Gen Psychiatry. 2001;58:1108-1114

Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms, the potential role, if any, of catecholaminergic pathways has not been fully explored.Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10000-lux light therapy were enrolled in a double-blind, placebo-controlled, randomized crossover study. We compared the effects of tryptophan depletion with catecholamine depletion and sham depletion. Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines. Diphenhydramine hydrochloride was used as an active placebo during sham depletion. The effects of these interventions were evaluated with measures of depression, plasma tryptophan levels, and plasma catecholamine metabolites.Tryptophan depletion significantly decreased plasma total and free tryptophan levels. Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Both tryptophan depletion and catecholamine depletion, compared with sham depletion, induced a robust increase (P.001, repeated-measures analysis of variance) in depressive symptoms as measured with the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version.The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion. These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved.

Background/Objective: We examined seasonality and winter seasonal affective disorder (SAD) in the Old Order Amish of Lancaster County, Pennsylvania, a unique population that prohibits use of network electric light in their homes. Methods: We estimated SAD using the seasonal pattern assessment questionnaire (SPAQ) in 1306 Amish adults and compared the frequencies of SAD and total SAD (i.e., presence of either SAD or subsyndromal-SAD) between men and women, young and old, and awareness of (ever vs. never heard about) SAD. Heritability of global seasonality score (GSS) was estimated using the maximum likelihood method, including a household effect to capture shared environmental effects. Results: The mean (7 SD) GSS was 4.36 (73.38). Prevalence was 0.84% (95% CI: 0.36–1.58) for SAD and 2.59% (95% CI: 1.69–3.73) for total SAD. Heritability of GSS was 0.147 0.06 (SE) (p¼ 0.002) after adjusting for age, gender, and household effects. Limitations: Limitations include likely overestimation of the rates of SAD by SPAQ, possible selection bias and recall bias, and limited generalizability of the study. Conclusions: In the Amish, GSS and SAD prevalence were lower than observed in earlier SPAQ-based studies in other predominantly Caucasian populations. Low heritability of SAD suggests dominant environmental effects. The effects of awareness, age and gender on SAD risk were similar as in previous studies. Identifying factors of resilience to SAD in the face of seasonal changes in the Amish could suggest novel preventative and therapeutic approaches to reduce the impact of SAD in the general population.

Levels of 25-hydroxy vitamin D [25(OH)D] are reported to be decreased in cardiovascular disease (CVD) and in other chronic immunopathologies. Vitamin D (vitD) has been shown to be significantly linked to mortality, and is thought to be a predictor of survival. Therefore, supplementation with vitD has been suggested as an option to improve clinical outcomes. In contrast to the causal assumption, we hypothesize that the decreased vitD levels, seen in patients with CVD and chronic immunopathologies is secondary to inflammation and not as pathophysiologically relevant as currently suggested. Under these conditions, low vitD might be mainly caused by oxidative stress that results from chronic, immune-mediated vascular and systemic inflammation seen in patients with CVD. The oxidative environment most likely causes biodegradation of vitD and interferes with key enzymes, disturbing the biosynthesis of 25(OH)D and 1,25(OH)D. Thus far, no clear evidence of a beneficial effect of vitD supplements exists, beyond treating vitD deficiency to improve skeletal health. Moreover, a prolonged and/or high dose vitD supplementation, unless needed to correct actual vitD deficiency [levels of 25(OH)D