Maja Lačković

Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

BACKGROUND Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. METHODS The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. CONCLUSIONS The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide.

Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia.

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion.

Skin and Sural Nerve Biopsies: Ultrastructural Findings in the First Genetically Confirmed Cases of CADASIL in Serbia

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2–6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with severe factor XII deficiency

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited adult-onset microangiopathy caused by missense mutations in the Notch3gene on chromosome 19. However, common vascular risk factors may additionally modify clinical expression and progression of the disease. The role of various prothrombotic factors has also been implied. We report a case of a middle-aged man with typical clinical, neuroimaging and histological features of CADASIL, but with notably prolonged activated partial thromboplastin time. Hematological investigations revealed severe clotting Factor XII deficiency. This case illustrates that the occurrence of vascular risk factors should not be overlooked in patients with CADASIL.

Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults.

BACKGROUND Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults. METHODS Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay. RESULTS After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores. LIMITATIONS The temperaments were estimated on the basis of self-report questionnaire. CONCLUSIONS Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.

sVCAM-1, sICAM-1, TNF-α and IL-6 levels in bipolar disorder type I: Acute, longitudinal and therapeutic implications

Abstract Objectives: To explore the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients with bipolar disorder (BD), with regard to acute episode characteristics, course of the disorder and treatment. Methods: The study group consisted of 83 patients diagnosed with BD type I. The control group consisted of 73 healthy individuals, matched with the study group according to age, gender and body mass index. The serum levels of sVCAM-1, sICAM-1, TNF-α and IL-6 were measured by ELISA. Results: Compared with healthy controls, significantly elevated levels of IL-6 and sICAM-1 and significantly lower levels of TNF-α and sVCAM-1 were identified in acute and remission phases of BD. The acute serum levels of sVCAM-1 were associated with the type and severity of acute mood symptoms as well as with course of illness characteristics. TNF-α was associated with duration of untreated disorder and type of treatment. Conclusions: BD is related to both acute and long-term alterations of immune mediators, including adhesion molecules. The potential immunomodulatory role of pharmacotherapeutic treatment is also to be considered in BD.

Acute and Long-term Overall Severity of Bipolar Disorder Related to Sicam-1 and Svcam-1 Serum Levels in Bipolar Depression

Introduction Interplay between nervous and immune systems plays an important part in clinical presentation and course of affective disorders. Aims The aim of the study has been to assess the relation between soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1), in acute and remission phase of bipolar depression, in regard to acute and long-term measures of overall severity of the bipolar disorder. Methods The study has explored serum levels of sVCAM-1 and sICAM-1 in 43 patients with bipolar depression. The adhesion molecules’ levels of patient group have been analyzed in acute and remission phases, in regard to bipolarity index (BPIX) and in regard to global functioning (measured by Global Assesment of Functioning Scale- GAF) Results The acute serum levels of sICAM-1 have been associated to BPIX. Moreover, sVCAM-1 serum selevels have been associated to BPIX in both phases of the disorder. In addition, acute sVCAM-1 levels have been associted to GAF score in accute phase. Conclusions Our results suggest that cellular adhesion is an important factor in clinical presentation and overall severity of bipolar disorder.