Prediction of outcome of bright light treatment in patients with seasonal affective disorder: Discarding the early response, confirming a higher atypical balance, and uncovering a higher body mass index at baseline as predictors of endpoint outcome.

BACKGROUND: We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. METHODS: Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. RESULTS: No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. LIMITATIONS: Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. CONCLUSION: Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

Light treatment for seasonal Winter depression in African-American vs Caucasian outpatients.

AIM: To compare adherence, response, and remission with light treatment in African-American and Caucasian patients with Seasonal Affective Disorder. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Pollen-specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season.

OBJECTIVE: An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examined a hypothesized relationship between allergen-specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores. METHODS: In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen-specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts, measured according to the National Allergy Bureau guidelines). We compared Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) depression score changes in 41 patients with mood disorders [25 with major depression and 16 with bipolar I disorder, diagnosed by Structured Clinical Interview for DSM (SCID)] seropositive for tree or ragweed pollen-specific IgE antibody versus 53 patients with mood disorders (30 with major depression and 23 with bipolar I disorder) seronegative for aeroallergen-specific IgE. RESULTS: Worsening in total depressive scores from low to high pollen exposure was greater in allergen-specific IgE-positive patients as compared to allergen-specific IgE antibody-negative patients (p = 0.01). When stratified by polarity, the association was significant only in patients with bipolar I disorder (p = 0.004). This relationship was resilient to adjustment for changes in allergy symptom scores. CONCLUSION: To our knowledge, this is the first report of coupling a molecular marker of vulnerability (allergen-specific IgE) with a specific environmental trigger (airborne allergens) leading to exacerbation of depression in patients with bipolar I disorder.

Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder.

The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States-Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by -1.3 (p = 0.02) on the BDI-II and -1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals.

Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts.

BACKGROUND: 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. METHODS: 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. RESULTS: Seropositivity for influenza A (p=0.004), B (p<0.0001) and coronaviruses (p<0.0001) 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). LIMITATIONS: The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. CONCLUSIONS: 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.

Sleep architecture and behavioral abnormalities in children and adolescents.

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.

Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders.

Toxoplasma gondii (T.gondii) is an obligate intracellular protozoan parasite infecting one-third of the world population, residing relatively silently in the brain of the immunocompetent host. We hypothesized that T.gondii seropositivity and serointensity are associated with having a history of attempting suicide and, in those attempting suicide, a greater number of attempts. T.gondii seropositivity and antibody titers were compared between (a) patients with recurrent mood disorders with history of suicide attempt (99 individuals) versus (b) patients with recurrent mood disorders without history of suicide attempt (119 individuals), and (c) healthy controls (39 individuals). Diagnosis was made using the Structured Clinical Interview for DSM-IV. Statistical methods included chi square, analysis of variance, and linear and logistic regression analyses. Suicide attempters had higher T.gondii antibody titers than nonsuicide attempters (p = 0.004). The logistic regression analysis revealed a predictive association between titers of anti- T.gondii antibodies and history of suicide attempt with OR = 1.55 (1.14-2.12), p = 0.006. No significant relationship was found between T.gondii seropositivity and suicide attempt status, number of prior suicide attempts, and recurrent mood disorder diagnosis. Although preliminary and bearing replication, this is the first report, to our knowledge, of an association between attempting suicide and T. gondii.

Changes in allergy symptoms and depression scores are positively correlated in patients with recurrent mood disorders exposed to seasonal peaks in aeroallergens.

Although growing evidence supports an association between allergy, allergens and depression, it remains unknown if this relationship is between "states" (possible triggers) or "traits" (possible vulnerabilities). We hypothesized that patients with recurrent mood disorders who are sensitized to tree pollen (as determined by allergen specific IgE antibodies), in comparison to those who are not sensitized, would report larger negative changes in mood during exposure to tree pollen in spring. We also hypothesized that differences between high and low tree pollen periods in self reported allergy symptoms would correlate positively with differences in self reported depression scores. We present 1-year preliminary data on the first 51 patients with unipolar or bipolar disorder (age: 19-63 years, 65% female, twelve patients were tree-pollen IgE positive). Ratings of mood and allergic disease status were performed 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. Linear regression models were developed to examine associations of changes in depression scores (dependent variable) with tree pollen sensitization, changes in the allergy symptom severity score, adjusted for gender and order of testing. We did not confirm the hypothesized relationship between a specific tree pollen sensitization and changes in mood during tree pollen exposure. We did confirm the hypothesized positive relationship between the changes in allergy symptoms and changes in subjects' depression scores (adjusted p<0.05). This result is consistent with previous epidemiological evidence connecting allergy with depression, as well as our recent reports of increased expression of cytokines in the prefrontal cortex in victims of suicide and in experimental animals sensitized and exposed to tree pollen. A relationship between changes in allergy symptom scores and changes in depression scores supports a state-level rather than only trait-level relationship, and thus lends optimism to future causality-testing interventional studies, which might then lead to novel preventative environmental interventions in mood disorders.