Association between resting state functional connectivity and major depressive disorder

Introduction: Major Depressive Disorder (MDD) is a cluster of symptoms, primarily diagnosed with depressed mood and loss of interest in daily activities, Globally, MDD is 4th leading cause of disability. Resting State Functional Connectivity (RSFC) uses blood oxygen level dependent signals to assess the connectivity between target brain regions, when subject is not doing any active task. Previous studies have found the important association of lateral Habenula with MDD. This study was aimed to evaluate the RSFC of Habenula with a few target areas and to assess the correlation between individual diagnostic symptoms of MDD. Methods: The data of the sample population is pulled from the parent study from Baylor School of Medicine, Houston, Texas. Case-control Study design was used. Controls were selected from the psychiatric population in the same setting. Depression scales (PHQ-9, SCID) were used to assess the severity of MDD symptoms and seed based RSFC analysis used for imaging data. CONN extension of MATLAB was used for imaging analysis and correlational coefficients. STATA and Microsoft Excel analysis software used for t-test and regression analysis. Using the evidence from literature, target areas selected to compare with lateral habenula were striatum, putamen, caudate nucleus, nucleus accumbens, raphe nucleus, paracentral lobule and locus coeruleus. SCID questionnaire was used to assess the individuality of the diagnostic symptoms and their mutual correlations. Results: Cases (n=139, 44.84%, age 30.65 ± 11.84 years) were compared to controls (n=171, 55.16 %, age=30.83 ± 12.65 years). Left and right sided habenula were found significantly connected (p\u3c 0.05) to Putamen, striatum, caudate nucleus and nucleus accumbens, even after analyzing for left and right sides of these target areas in addition to analyzing them as a whole structure. Significant correlation was found between clinical symptoms (p\u3c 0.05). Conclusion: The functional connectivity of lateral habenula with target areas was validated though the findings of this study. Positive correlation between multiple diagnostic symptoms could further help to categorize MDD for categorized management plans in future. Valid sample size, use of clinical and imaging data together, and psychiatry controls makes this study noteworthy

Plasma soluble L-selectin in medicated patients with schizophrenia and healthy controls

<div><p>Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls. In patients, psychotic symptom severity and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and the NIH Toolbox Cognitive Test Battery respectively. C-reactive protein (CRP) and Body Mass Index (BMI) were measured in patients and controls. Comparison of selectin levels between patients and controls was done with t-tests and linear regression. Pearson correlation coefficients between plasma selectins and PANSS and cognitive measures were calculated. Geometric mean plasma soluble L-selectin level was lower in patients compared to controls from unadjusted (606.7 ± 1.2 ng/ml vs. 937.7 ± 1.15 ng/ml, p < 0.001) and adjusted analyses (β = 0.59; CI 0.41 to 0.88, p = 0.011). There was a trend towards higher plasma soluble P-selectin in patients compared to controls (90.4 ± 1.2ng/ml vs. 71.8 ± 1.2ng/ml, p = 0.059) in the unadjusted analysis. There was no association between the selectins and psychotic symptoms or cognitive function in the patients. In addition, the selectins were not significantly associated with CRP or BMI. The limitations of this study include small sample size and unavailability of information on medications and blood cell counts. The potential utility of soluble L-selectin as a biomarker of antipsychotic exposure in patients with schizophrenia and the concomitant change in immune response with the use of antipsychotics should be further evaluated.</p></div

Comparison of demographic characteristics of patients and control group.

<p>Comparison of demographic characteristics of patients and control group.</p

Comparison of selectin levels in patients and control group.

<p>Comparison of selectin levels in patients and control group.</p

Plasma soluble L-selectin in medicated patients with schizophrenia and healthy controls - Fig 1

<p><b>Plasma soluble L-selectin (A), P-selectin (B) and E-selectin (C) levels in patients with schizophrenia and healthy controls.</b> Error bars are representing 95% confidence intervals, and the little circle stands for the mean of the log-transformed value of each selectin. Plasma soluble P-, E- and L-selectin concentration were log transformed to normalize the data. Geometric means reported in the text were calculated by exponentiating mean log-transformed P-, E- and L-selectin for adjusted and unadjusted comparisons of patients and controls.</p