Manana Lapidus

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.

Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder.

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.

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

Abstract 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. Pearsons 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.

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

Manalai P, Hamilton RG, Langenberg P, Kosisky SE, Lapidus M, Sleemi A, Scrandis D, Cabassa JA, Rogers CA, Regenold WT, Dickerson F, Vittone BJ, Guzman A, Balis T, Tonelli LH, Postolache TT. Pollen‐specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season. Bipolar Disord 2012: 14: 90–98.

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

Abstract 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.

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.

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.

A Prospective Longitudinal Study of Seasonality in African Students Living in the Greater Washington, D.C. Metropolitan Area

We conducted a prospective, longitudinal study of seasonality in a vulnerable population, i.e., African students who migrated to a temperate climate. Consistent with previous cross-sectional studies, we hypothesized lower mood and energy, and higher appetite and weight, in fall/winter than in spring/summer. Four cohorts of African students attending a year-long nursing school program without vacation in Washington, D.C., were assessed monthly for 1 year. Forty-three subjects (mean age = 33.46 ± 6.25), consisting of predominantly females (76.7%), completed the study. The cohorts began their academic program in different seasons (one each in winter, spring, summer, and fall), inherently minimizing confounding influences on seasonality, such as academic and immigration stress, as well as allowing adjustment for an order effect. At each assessment, students completed three 100-mm visual analog scales for mood, energy, and appetite, and were weighed on a digital scale. For each standardized dependent variable, a repeated measure ANOVA was used and, if a significant effect of month was identified, averages for spring/summer and fall/winter were compared using paired ttests. In addition, a mixed model for repeated measures was applied to raw (nonstandardized) data. Body weight was significantly higher in fall/winter than in spring/summer (p < 0.01). No seasonal differences in mood, energy, or appetite were found. Benefiting from certain unique features of our cohorts allowing adjustment for order effects, this is the first study to identify a seasonal variation in body weight with a peak in winter using longitudinal monthly measurements.

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.

Psychiatric manifestations of latent toxoplasmosis. Potential mediation by indoleamine 2,3-dioxygenase

Abstract Toxoplasma gondii, a prevalent neurotropic parasite, induces immunological reactions that have the potential to affect brain and behavior. One possible connection between molecular mediators of inflammation (cytokines) and brain function and behavior is the activation of the enzyme indole-amine 2,3-dioxygenase, a mechanism implicated in containing T. gondii in the immunocompetent host, resulting in relative tryptophan depletion and kynurenine production. This could potentially lead to mood and behavioral dysregulation in latent toxoplasmosis.