Assessment of Cognitive Function, Social Disability and Basic Life Skills in Euthymic Patients with Bipolar Disorder.

BACKGROUND: Data from the literature suggests the presence of cognitive impairments which persist in the euthymic phase of bipolar disorder (BD) and have significant consequences in regards to psychosocial functioning. THE AIMS OF OUR STUDY WERE: 1) to ascertain the cognitive function (CF), social disability (SD) and basic life skills (BLS) of euthymic patients diagnosed with BD, 2) their relationship and 3) to compare CF, SD and BLS in euthymic patients diagnosed with BD to euthymic patients with recurrent major depressive disorder (rMDD). SUBJECTS AND METHODS: Ninety eight euthymic patients diagnosed either with BD (N=48, mean age 48.79 years, SD = 8.587) or rMDD (N=50, mean age 50.02 years, SD = 9.826) underwent testing using the Brief Assessment of Cognition in Affective Disorders (BAC-A) test, the Sheehan Disability Scale (SDS) and the UCSD performance-based skills assessment (UPSA-brief). RESULTS: Euthymic patients with BD demonstrated significantly lower scores as compared to normal population values in verbal, learning and working memory, verbal fluency, attention and processing speed, affective memory for negative and positive words (p<0.01 each) and motor speed (p<0.05), but not for reasoning/problem solving (p=0.05). Furthermore, their mean total SDS score of 17.60 (SD = 6.450, Sk = -0.833) and its subscale scores were higher, while their UPSA-B total scores were lower (M = 76.01, SD = 17.148, Sk = -0.412). There was a correlation between CF, SD and BLS scores (p<0.01), as well as between BLS and SD scores (p<0.05). The analysis of variance did not however show significant differences between subgroups of patients. CONCLUSION: Patients with euthymic BD had lower cognitive function, greater social disability and lower basic life skills. There were similar decreases in cognitive and psychosocial function between patients in the euthymic phase of either BD or MDD.

Internet use during coronavirus disease of 2019 pandemic: Psychiatric history and sociodemographics as predictors.

Coronavirus disease of 2019 (COVID-19) pandemic and related containment measures have grossly affected the daily living and created a need for alternative ways of social communication and entertainment. The aim of this study was to explore the use of various Internet contents depending on sociodemographics and on psychiatric history of participants. This cross-sectional, population-based study is a part of a wider international multicenter study. A total of 1275 participants across Serbia (71.1% of females; average age = 41.81 ± 12.52 years) were recruited using two-level chain-referral sampling method. The participants filled in an anonymous online questionnaire that included questions on sociodemographic data, psychiatric history, and various aspects of increased Internet use since the pandemic. The data were analyzed using a series of multiple logistic regressions. About two-thirds of the sample reported using Internet more during the pandemic. All of the tested regression models, apart from models predicting browsing religion and travel/tourism, were significant, explaining from about 2% (for the contents specific for COVID-19) up to 34.4% (for the sexual content) of variance of use. Reporting a previously diagnosed psychiatric disorder was a significant predictor of greater Instagram use and browsing sexual and sport-related content since the pandemic. To the best of our knowledge, the study is the first to report on the relationship between Internet using and mental health, during COVID-19 pandemic, in the Balkan region. The findings showed various patterns of the increased use of Internet contents since the pandemic referring to both potentially positive and negative Internet influences.

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

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.

Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.

Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.

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.

Tryptophan Hydroxylase 1 Variant rs1800532 is Associated with Suicide Attempt in Serbian Psychiatric Patients but does not Moderate the Effect of Recent Stressful Life Events.

Tryptophan hydroxylase 1 (TPH1) gene, coding for serotonin synthesizing enzyme, and recent stressful life events (SLEs) have been commonly associated with suicidal behavior. TPH1 has been also hypothesized to be involved in stress-response mechanisms. The aim of this study was to assess TPH1 variant rs1800532 and its possible interaction with recent SLEs as risk factors for suicide attempt (SA) in Serbian psychiatric patients, including 165 suicide attempters and 188 suicide nonattempters. rs1800532 and recent SLEs were independently associated with SA, while rs1800532 did not moderate the effect of recent SLEs on SA vulnerability among Serbian psychiatric patients.

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.

MiR-155 expression level changes might be associated with initial phases of breast cancer pathogenesis and lymph-node metastasis.

BACKGROUND: Breast carcinoma is heterogeneous disease. Understanding the process of invasion and metastasis and the selection of the therapy for patients with breast carcinomas still remains difficult. MicroRNAs are powerful gene expression regulators. Because of inconsistent findings, we have analyzed potential difference in miR-155 levels in three breast cancer groups. OBJECTIVES: Our goals were to examine miR-155 expression levels in normal tissue, non-invasive and invasive breast carcinomas, and their association with standard clinical and pathological parameters and oncomiR-21, and to investigate the ability of miR-155 to separate invasive breast carcinomas with non-invasive component from pure invasive. METHODS: In the group of 40 breast tissue samples, relative expression levels of miR-155 were examined with stem-loop quantitative real-time PCR using TaqMan technology. RESULTS: The significant difference among four examined groups of the breast tissue was detected (p = 0.001). In the group of pure invasive tumors, patients with positive nodal status had significantly higher miR-155 levels (p = 0.046). CONCLUSION: Our results suggest that miR-155 might be involved in breast cancer pathogenesis and in tumor spreading to the lymph nodes, and that it might be used as biomarker for additional stratification of patients with invasive breast carcinomas with non-invasive component.

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.

Cannabis and psychosis revisited.

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.

Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders.

OBJECTIVES: Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability. METHODS: Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory-Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors. RESULTS: ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse. CONCLUSIONS: SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.

Serum levels of interleukin-6 and tumor necrosis factor-alpha in exacerbation and remission phase of schizophrenia.

BACKGROUND: The variations in proinflamatory cytokine levels have been associated with schizophrenia (SCH), duration of illness, psychopathology and treatment. The aim of the study was to investigate serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in schizophrenic patients during exacerbation and remission, and its association with course of illness and therapy. SUBJECTS AND METHODS: We measured serum levels of IL-6 and TNF-α in 43 schizophrenic patients in exacerbation and remission and compared them to 29 healthy controls, matched by sex, age, body mass index (BMI) and smoking habits. The severity of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: There was no difference in levels of IL-6 and TNF-α in exacerbation compared to remission in schizophrenic patients. IL-6 was higher and TNF-α was lower in schizophrenic patients in both exacerbation and remission in comparison with healthy controls. TNF-α in exacerbation was in negative correlation with IL-6 in remission. No statistical significance was found between levels of cytokines and sex, age, BMI, smoking habits, antipsychotic medication, duration of treatment and duration of illness. IL-6 levels were in positive correlation with the age of onset and the duration of untreated psychosis. In schizophrenic patients on adjunctive treatment with mood stabilizers, TNF-α levels increased in remission. CONCLUSION: Our results suggest that the connection between schizophrenia, cytokines and medication is multifaceted, and not necessarily linear. Adjunct mood stabilizers not only ameliorate psychopathology, but might convey immunomodulatory effects as well. Further longitudinal studies could elucidate potential beneficial effect of combined therapy in treatment of SCH.

Melancholic and atypical major depression--connection between cytokines, psychopathology and treatment.

BACKGROUND AND PURPOSE: Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment. METHOD: We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS). RESULTS: IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression. CONCLUSION: Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.

Knowledge: a possible tool in shaping medical professionals' attitudes towards homosexuality.

BACKGROUND: The attitudes of medical professionals towards homosexuals can influence their willingness to provide these individuals with medical help. The study evaluated the medical professionals' knowledge about homosexuality and their attitudes towards it. SUBJECTS AND METHODS: The sample consisted of 177 participants (physicians n=79 and students n=98). The study respondents anonymously completed three questionnaires (socio-demographic questionnaire, the questionnaire on knowledge, and the questionnaire on attitudes towards homosexuals). RESULTS: Male and religious participants showed a lower level of knowledge and a greater tendency to stigmatize. Furthermore, the subjects who knew more about homosexuality tended to hold less stigmatizing attitude. Age group, specialty (psychiatry, gynecology, internal medicine and surgery), and student's/physician's status had no effect on stigmatization. The study showed that the final year students/ residents had more knowledge than the second year students/specialists did. Knowledge had significant negative predictive effect on attitudes in the analyzed predictive model. CONCLUSIONS: To our knowledge, this has been the first study in Serbia and Eastern Europe, which provides information on knowledge and attitudes of health professionals towards homosexuality. We would like to point out the degree of knowledge on homosexuality as a possible, but not exclusive tool in shaping the attitudes towards homosexuals and reducing stigmatization. However, regardless of the personal attitude, knowledge and variable acceptance of the homosexuals' rights, medical professionals' main task is to resist discriminative behavior and provide professional medical help to both homosexual and heterosexual patients.

The framework of family therapy in clinical practice and research in Serbia.

In the last two decades, Serbia has had to deal with multiple social and economic problems reflecting on society's demographics and seemed to weaken its core cell - the family. The paper describes the framework of family therapy in clinical practice and research, within the recent transition of the Serbian family. Family therapy treatment in Serbia uses the systemic family therapy (SFT) approach, applied according to the standards of the European Association for Psychotherapy. A large number of professionals who practise in Serbia hold European qualifications, setting high standards in education, clinical practice, and research. Although SFT is also available in the private sector, the majority of patients are still treated in state institutions. Family therapy is often used for adults and adolescents with psychosis and addictions in psychiatric hospital settings. However, in counselling centres it is used for marital and relationship problems. Interestingly, family therapy has recently started to emerge as a more frequent tool in consultation-liaison, particularly psycho-oncology but also in correctional institutions. The clinical practice and research interests are interlinked with changes in social settings.

Posttraumatic stress disorder in a World War II concentration camp survivor caused by the attack of two German shepherd dogs: case report and review of the literature.

A 79-year-old woman suffered from acute posttraumatic stress disorder (PTSD) and a loco typico, non-displaced fracture of her right distal radius due to an incident involving the assault of two unleashed owned dogs, which suddenly ran into her and aggressively jumped on her chest and knocked her down to the ground. Recovery for her damage claim concerning pain and disability due to her right forearm fracture caused by the incident, was not the issue in the litigation concerned. However, the issue of delayed impact of her previous Holocaust experience placed a significant challenge on M.N., as a plaintiff, in establishing a causal link between the posttraumatic stress disorder concerned and the alleged harmful action of the defendants, the owners of the two dogs. The case reported here proved interesting and instructive not only in the sense of addressing main issues relevant to litigation for psychological damage related to reactivated PTSD and delayed PTSD, but also in the sense of pointing at the clinical relevance of dog assaults on humans which, even without dog bite injuries, may result in a severe traumatization and eventual civil lawsuit.

Schizophrenia and apolipoprotein E gene polymorphism in Serbian population.

Apolipoprotein E (APOE) gene variants are associated with alterations in brain function and increased risk of Alzheimer's disease (AD) and conflicting results have been reported in schizophrenia. Our results showed no significant differences in APOE allele or genotype frequencies between the Serbian schizophrenic patients and control individuals. However, we observed a possible association between particular subtypes of schizophrenia and APOE epsilon3/epsilon3 genotype (p = .01221) and epsilon4 allele showed a tendency toward positive association with responding to typical neuroleptics. APOE genotypes have no major influence on risk of schizophrenia, treatment and response to conventional antipsychotics, and age of onset in schizophrenia.

Comparative analysis of soft neurological signs in positive and negative subtype of schizophrenia.

BACKGROUND: The objective of the study was to investigate neurological deficit in schizophrenia and to compare soft neurological signs in positive and negative subtypes of schizophrenia. SUBJECTS AND METHODS: 66 patients with schizophrenia were evaluated with the Positive and Negative Syndrome Scale to classify the subtype of schizophrenia: positive subtype (36 patients) and negative subtype (30 patients), all of which were entering into remission. To examine the neurological soft signs we compared scores on the Neurological Evaluation Scale (NES) for positive and negative subtype. RESULTS: The negative subtype of schizophrenia showed significantly higher neurological soft signs in comparison to the positive subtype, with reduced functioning in the sensory integration and motor coordination subscale as well as the other subscale. CONCLUSION: The main finding in this study indicates that patients with schizophrenia have neurological impairment, and that the negative subtype has significantly higher neurological impairment than the positive subtype. The results further support the significance of the soft neurological signs as a possible marker of different subtypes of schizophrenia.

Lamotrigine versus lithium augmentation of antidepressant therapy in treatment-resistant depression: efficacy and tolerability.

BACKGROUND: Mood stabilizer augmentation of standard antidepressant drugs has been shown to be effective in treatment-resistant depression. Despite the reported high overall efficacy, lithium has been relatively underused in recent years. Lamotrigine, a novel anticonvulsant recently recognized as a mood stabilizer, seems to have putative antidepressive properties. The aim of the study was to investigate lamotrigine efficacy and tolerability as antidepressant augmentation for unipolar treatment-resistant depression compared to lithium. SUBJECTS AND METHODS: 88 patients suffering from treatment-resistant Major depressive disorder, having acute recurrent depressive episodes according to DSM-IV criteria, were enrolled in the study. This was an open-label trial with a flexible dosing regimen. All patients, received antidepressants in full therapeutic doses. They were divided into two augmentation groups: 46 patients received 50-200 mg/day lamotrigine, and 42 patients received 600-1200 mg/day lithium. The Hamilton Rating Scale for Depression (HAM-D) and The Clinical Global Impression scale (CGI) were used to monitor therapeutic efficacy. Patients were evaluated weekly for an 8 week treatment period. RESULTS: The HAM-D total score was significantly reduced in both treatment groups at the study endpoint, without any difference between the groups. However, significant clinical improvement was reached within the second treatment week in the lamotrigine group compared to the lithium group (p=0.01 vs. lithium). Lamotrigine showed significant efficacy on the HAM-D item 1(depressed mood; p=0.01), item 7 (work and interest; p=0.01) and CGI-Improvement scale (p=0.02). The drop-out rate due to treatment failure was lower in the lamotrigine group (n=1) compared to the lithium (n=4) group. Also, the incidence of side effects did not differ between the groups. CONCLUSIONS: Our results suggest that lamotrigine could be useful as augmentation of antidepressants for treatment-resistant unipolar depression. Also, lamotrigine may accelerate the onset of antidepressant action, and therefore might be useful in treatment of major depression in general.