Showing papers in "Neuropsychobiology in 2013"
TL;DR: This review is a call-to-action that urges researchers to consider the importance of understanding the neuroscience of physical exercise and its contributions to sports science.
Abstract: The neuroscience of exercise is a growing research area that is dedicated to furthering our understanding of the effects that exercise has on mental health and athletic performance. The present study examined three specific topics: (1) the relationship between exercise and mental disorders (e.g. major depressive disorder, dementia and Parkinson's disease), (2) the effects of exercise on the mood and mental health of athletes, and (3) the possible neurobiological mechanisms that mediate the effects of exercise. Positive responses to regular physical exercise, such as enhanced functional capacity, increased autonomy and improved self-esteem, are frequently described in the recent literature, and these responses are all good reasons for recommending regular exercise. In addition, physical exercise may improve both mood and adherence to an exercise program in healthy individuals and might modulate both the performance and mental health of athletes. Exercise is associated with the increased synthesis and release of both neurotransmitters and neurotrophic factors, and these increases may be associated with neurogenesis, angiogenesis and neuroplasticity. This review is a call-to-action that urges researchers to consider the importance of understanding the neuroscience of physical exercise and its contributions to sports science.
663 citations
TL;DR: Developing pharmacological strategies facilitating the release of BDNF from synapses or prolongation of the half-life of secreted BDNF may improve the therapeutic responses of humans expressing the BDNF polymorphism.
Abstract: Background/Aims: Anxious responses are evolutionarily adaptive, but excessive fear can become disabling and lead to anxiety disorders. Translational models of anxiety might be useful sources for understanding the neurobiology of fear and anxiety and can contribute to future proposals of therapeutic intervention for the disorders studied. Brain-derived neurotrophic factor (BDNF), which is known for its importance on neuroplasticity and contextual memory, has emerged as a relevant element for emotional memory. Recent studies show that the Val 66 Met BDNF polymorphism
504 citations
TL;DR: It is concluded that physical exercise improves the response to treatment, especially aerobic training, however, the efficacy of exercise in the treatment of depression was influenced by age and severity of symptoms.
Abstract: Objective: The aim of this meta-analysis is to evaluate the effect of aerobic training and strength training as a treatment for depression in patients diagnosed w
219 citations
TL;DR: A randomized controlled trial of MBSR for older adults and its effects on executive function, left frontal asymmetry of the EEG alpha band, and antibody response, which produced small but significant changes inExecutive function, mindfulness, and sustained left frontal alpha asymmetry.
Abstract: Background/Aims: Mindfulness-based stress reduction (MBSR) has enhanced cognition, positive emotion, and immunity in younger and middle-aged samples; its benefits are less well known for older persons. Here we report on a randomized controlled trial of MBSR for older adults and its effects on executive function, left frontal asymmetry of the EEG alpha band, and antibody response. Methods: Older adults (n = 201) were randomized to MBSR or waiting list control. The outcome measures were: the Trail Making Test part B/A (Trails B/A) ratio, a measure of executive function; changes in left frontal alpha asymmetry, an indicator of positive emotions or approach motivation; depression, mindfulness, and perceived stress scores, and the immunoglobulin G response to a protein antigen, a measure of adaptive immunity. Results: MBSR participants had a lower Trails B/A ratio immediately after intervention (p lower antibody responses 24 weeks after antigen challenge (p Conclusions: MBSR produced small but significant changes in executive function, mindfulness, and sustained left frontal alpha asymmetry. The antibody findings at follow-up were unexpected. Further study of the effects of MBSR on immune function should assess changes in antibody responses in comparison to T-cell-mediated effector functions, which decline as a function of age.
173 citations
TL;DR: It is suggested that elevated hair cortisol levels do not necessarily constitute a health risk and can serve as a noninvasive and painless biomarker of chronic stress and mental disorders; however, additional research is needed.
Abstract: Objective: Depressive symptoms are a common mental health problem among young adults, but the physiological mechanisms that mediate between stress and depressive
53 citations
TL;DR: Findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients, which is likely to persist beyond acute phases of the illness.
Abstract: Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated with the highest suicide rate among psychiatric disorders. Even though neurobiological bases of BD have still to be further elucidated, recent neuroimaging studies provided compelling evidence about functional correlates of cognitive deficits in BD patients, with working memory (WM) impairment being one of the most commonly reported findings. Such dysfunctions are likely to persist beyond acute phases of the illness, so they qualify as endophenotypic markers for the disorder. This review sought to synthesize, through a MEDLINE search up to December 2012, published functional magnetic resonance imaging (fMRI) studies on WM networks, conducted through N-back task in euthymic BD I patients and including a control comparison group. Eight studies meeting the search criteria were identified. Despite heterogeneity across findings, particularly in relation to task performance (i.e. accuracy and reaction time), most studies reported a loss of connectivity in BD patients' prefrontal networks, traditionally involved in WM, as well as patterns of abnormal activation in the dorso/ventrolateral prefrontal cortex, other prefrontal areas and the parietal and temporal cortex. These findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients. Further investigation in the field is warranted.
45 citations
TL;DR: Glu/Cr ratios in the ACC in untreated adolescents with GAD may relate to the severity of anxiety symptoms and raise the possibility that dysregulation of Glu within the ACC may be linked to the pathophysiology of pediatric GAD.
Abstract: Background/Aims: This study used proton magnetic resonance spectroscopy (1H MRS) to evaluate the neurochemistry of the anterior cingulate cortex (ACC)
44 citations
TL;DR: Qualitative and quantitative psychomotor deficits seem to be independent phenomena in stabilized patients with schizophrenia, which is related to a loss of drive and not to problems in the quality of movement execution.
Abstract: Aims: The aim of the present study was to investigate the predictive value of qualitative psychomotor performance levels and subaspects of the negative syndrome for quantitative motor activity levels in patients with schizophrenia. Methods: Twenty-seven stabilized patients with schizophrenia and 22 age- and sex-matched healthy controls were included in the study. An extensive battery of psychomotor performance tests (Finger Tapping Test, Purdue Pegboard Test, Line Copying Test, Neurological Evaluation Scale, Salpetriere Retardation Rating Scale), clinical rating scales (Positive and Negative Syndrome Scale) and 24-hour actigraphy were administered to all participants. Results: Correlational analyses showed that motor activity levels were associated with avolition as well as clinically assessed psychomotor slowing. However, in a regression model, only avolition was found to be a significant predictor for motor activity levels in patients with schizophrenia; none of the psychomotor performance tests nor the severity of emotional expressivity deficits contributed to the model. Conclusion: Qualitative and quantitative psychomotor deficits seem to be independent phenomena in stabilized patients with schizophrenia. The diminishing in motor activity in patients with schizophrenia is related to a loss of drive and not to problems in the quality of movement execution.
42 citations
TL;DR: Independent component NFB in OCD proved useful in percentage improvement of compulsions and it is hypothesized that it targeted a network related to treatment resistance.
Abstract: Aims: The goal of this study was to assess the effect of independent component neurofeedback (NFB) on EEG and clinical symptoms in patients with obsessive-compuls
42 citations
TL;DR: The findings of this study, the first to report longitudinal serum BDNF levels in MVA survivors, suggest that elevated serumBDNF levels could be a biomarker of PTSD after a traumatic event.
Abstract: Background: This prospective cohort study investigated the serum levels of brain-derived neurotrophic factor (BDNF), which mediates synaptic plasticity crucial fo
38 citations
TL;DR: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia and indicate the involvement of the brainstem in the pathogenesis of schizophrenia.
Abstract: Background: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their i
TL;DR: Findings suggest the effects of catechol-O-methyltransferase Val158Met polymorphism on resilience could be modulated by BDNF Val66 Met polymorphism in males.
Abstract: Purpose: Resilience refers to the individual positive capacity to cope with stress and to restore homeostasis, which may be mediated by adaptive neurobiological changes in the brain. We investigated the genetic influence of the catechol-O-methyltransferase (COMT) Val158Met and the brain-derived neurotrophic factor (BDNF) Val66Met for individual differences in resilience in healthy Korean college students. Methods: A sample of 321 healthy college volunteers (167 males, 154 females) was assessed by genotyping and with the 25-item Connor-Davidson Resilience Scale. Two-way analysis of covariance was used to test the association between participants' COMT and BDNF functional polymorphisms and their resilience. Results: A significant main effect of the COMT polymorphism on resilience and a gene-gene interaction effect between the COMT and BDNF on resilience were observed for males. Male subjects with the COMT Met-present genotype had a significantly higher resilience than those with the Val/Val genotype. Among males with the COMT Val/Val genotype, subjects with the homozygous Val allele of the BDNF tended to have lower resilience than the BDNF Met carriers, while among males with the COMT Met-present genotype, those with the homozygous Val allele of the BDNF tended to have higher resilience than BDNF Met carriers. No main or interaction effects of the COMT and BDNF on resilience were observed for females. Conclusion: These findings suggest the effects of COMT Val158Met polymorphism on resilience could be modulated by BDNF Val66Met polymorphism in males.
TL;DR: A significant prevalence of hyperhomocysteinemia is found in bipolar depressed patients during an acute episode and the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid is corroborated.
Abstract: Background: Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitam
TL;DR: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD, suggesting the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.
Abstract: Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univoc
TL;DR: Elevation of serum hs-CRP levels, an indicator of inflammation, may be associated with reduced volume of the orbitofrontal cortex, a sign of persistent inflammation in the euthymic phase of bipolar disorder.
Abstract: Objective: C-reactive protein (CRP), a marker of underlying low-grade inflammation, has been associated with the pathophysiology of bipolar disorder. Additionally, bipolar disorder may be accompanied by functional or structural cerebral alterations. We attempted to discover whether serum high-sensitivity CRP (hs-CRP) levels are linked to the structural volume change of a specific brain region along with cognitive performance. Methods: We recruited 17 physically healthy patients with bipolar I disorder (DSM-IV), aged 18-45 years and euthymic, to undergo the Wisconsin Card Sorting Test (WCST) and volumetric magnetic resonance imaging at 1.5 T. The analytic method was based on the hidden Markov random field model with an expectation-maximization algorithm, and the volume of each brain region was presented as a percentage of the total intracranial volume. Results: Among the various regions, only the orbitofrontal cortex had a significantly negative correlation with serum hs-CRP levels after adjustment for age and gender (left and right orbitofrontal cortex: r = -0.62, p Conclusion: Elevation of serum hs-CRP levels, an indicator of inflammation, may be associated with reduced volume of the orbitofrontal cortex. Persistent inflammation in the euthymic phase of bipolar disorder may involve the pathogenesis or pathophysiology of alteration of the frontal pathway.
TL;DR: The findings of this study support the notion that behavioral differences might also derive from self-related processes and not necessarily from frontal lobe pathology, and that attenuated deactivation is related to the behavioral findings.
Abstract: Background: The failure to inhibit pleasurable but inappropriate urges is associated with frontal lobe pathology and has been suggested as a possible cause of pedophilic behavior. However, imaging and neuropsychological findings about frontal pathology in pedophilia are heterogeneous. In our study we therefore address inhibition behaviorally and by means of functional imaging, aiming to assess how inhibition in pedophilia is related to a differential recruitment of frontal brain areas. Method: Eleven pedophilic subjects and 7 nonpedophilic controls underwent fMRI while performing a go/no-go task composed of neutral letters. Results: Pedophilic subjects showed a slower reaction time and less accurate visual target discrimination. fMRI voxel-level ANOVA revealed as a main effect of the go/no-go task an activation of prefrontal and parietal brain regions in the no-go condition, while the left anterior cingulate, precuneus and gyrus angularis became more activated in the go condition. In addition, a group × task interaction was found in the left precuneus and gyrus angularis. This interaction was based on an attenuated deactivation of these brain regions in the pedophilic group during performance of the no-go condition. The positive correlation between blood oxygen level-dependent imaging signal and reaction time in these brain areas indicates that attenuated deactivation is related to the behavioral findings. Conclusion: Slower reaction time and less accurate visual target discrimination in pedophilia was accompanied by attenuated deactivation of brain areas belonging to the default mode network. Our findings thus support the notion that behavioral differences might also derive from self-related processes and not necessarily from frontal lobe pathology.
TL;DR: FMRI findings during performance of the n-back working memory task in a bipolar patient who showed a marked improvement in subsyndromal affective symptoms after receiving eye movement desensitization and reprocessing (EMDR) therapy supports the potential therapeutic overall benefit of EMDR in traumatized bipolar patients and suggests a possible neurobiological mechanism of action: normalization of default mode network dysfunction.
Abstract: Background: Some functional imaging abnormalities found in bipolar disorder are state related, whereas others persist into euthymia. It is uncertain to what exten
TL;DR: The hypothesis that improvements in treatment-resistant depression patients after ECT are due to changes in BDNF levels is not supported and the results do not support the hypothesis.
Abstract: Electroconvulsive therapy (ECT) is the most effective treatment in treatment-resistant depression; it may modulate intracellular processes in such patients. This study aimed to investigate the association between changes in plasma brain-derived neurotrophic factor (BDNF) levels and the clinical improvements after ECT for patients with treatment-resistant depression. Fifty-five inpatients with treatment-resistant depression were recruited. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the Clinical Global Impression-Severity (CGI-S) before ECT, after every 3 sessions of ECT, and at the end of ECT. Plasma BDNF levels were measured in all subjects before and after ECT. The severity of depression was significantly reduced on the HAMD-17 (p < 0.001) and the CGI-S (p < 0.001) after the end of ECT. There were no significant differences in plasma BDNF levels after ECT (p = 0.615). No significant correlation was found between changes in plasma BDNF levels and changes in HAMD-17 scores (r = 0.188, p = 0.169). Our results do not support the hypothesis that improvements in treatment-resistant depression patients after ECT are due to changes in BDNF levels.
TL;DR: Data suggest that NTF4 might serve as a biomarker for anorexia nervosa patients and BDNF and GDNF serum levels appear to be associated with personality traits and executive function.
Abstract: Objectives: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behaviors as w
TL;DR: This attentional bias appears to be linked to hypoactivity of the rACC which impedes effective emotional interference reduction, leading instead to a ruminative processing of the stimulus content.
Abstract: Background: Health anxiety (HA) is defined as the objectively unfounded fear or conviction of suffering from a severe illness. Predominant attention allocation to
TL;DR: The findings support an association between rs1344706 and alterations in DLPFC activity during WM for faces and suggest thatWM for faces may be a useful intermediate phenotype in the investigation of genetic susceptibility to psychosis.
Abstract: Background: Genetic susceptibility to schizophrenia (SZ) has been suggested to influence the cortical systems supporting working memory (WM) and face processing. Genetic imaging studies link the SZ risk variant rs1344706 on the ZNF804A gene to psychosis via alterations in functional brain connectivity during WM, but no work has looked at the effects of ZNF804A on WM with face-processing components. Methods: We therefore investigated healthy controls that were genotyped for rs1344706 with a face WM task during functional magnetic resonance imaging. We suggested that variation at the rs1344706 locus would be associated with similar alterations as patients previously tested using the same WM task for faces. Results: The rs1344706 risk allele was indeed associated with altered activation in the right dorsolateral prefrontal (rDLPFC) cortex. We established that the rDLPFC was activated in a task-dependent manner, suggesting that the differences in activation between rs1344706 genotype groups reflected alterations in task processing. Furthermore, we demonstrated that the rDLPFC region showed significant volumetric overlap with the rDLPFC which had previously been reported to be altered during task processing for patients with SZ. Conclusions: The findings support an association between rs1344706 and alterations in DLPFC activity during WM for faces. We further suggest that WM for faces may be a useful intermediate phenotype in the investigation of genetic susceptibility to psychosis.
TL;DR: The effect of the interaction between 5-HTTLPR and separation life events on panic disorder and its potential endophenotype could suggest the importance of the Anxiety Sensitivity Index-revised (ASI-R) and harm avoidance in the Temperament and Character Inventory (HA).
Abstract: Background: The polymorphisms of serotonergic genes (5-HTTLPR and HTR1A rs6295) and separation life events have been studied to find an association with panic dis
TL;DR: Results support the hypothesis that in FOS emotional faces are more salient and evoke higher arousal, and larger impairment in AR performance combined with higher salience and arousal may contribute to the occurrence of violent acts in schizophrenia patients.
Abstract: We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) are more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become apparent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and fear stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly larger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces are more salient and evoke higher arousal. Larger impairment in AR performance combined with higher salience and arousal may contribute to the occurrence of violent acts in schizophrenia patients.
TL;DR: Investigation of abstinent male alcohol-dependent patients shows that relapse is clearly more related to aggression than to impulsivity, depression and anxiety and may be facilitated if persons are sensitive to frustrating conditions of non-reward caused by social partners.
Abstract: Background: Personality traits like depression on the one hand and aggression and impulsivity on the other are assumed to be predisposing factors for different types of alcohol dependence. Both types are associated with sensitivity to frustration, but this may be different for the two types of personality according to whether they are confronted with frustrations caused by withdrawal from positive or infliction of negative events. It has not been shown so far if both types of personality factors and the two different sources of frustration are differently relevant for the propensity of relapse. This was investigated here in a study on 60 abstinent male alcohol-dependent patients. Methods: Correlations between the number of previous detoxifications reflecting liability to relapse and questionnaire scores on personality factors and on reactions to frustration were computed. Results: Bonferroni-corrected correlations yielded significant relationships between the number of detoxifications and the personality factor of aggression as well as pronounced depressive reactions to frustrating conditions of non-reward caused by humans. Controlling for impulsivity, aggression and depression revealed that depressive reactions to frustration are genuine predictors for probability of relapse independent of underlying personality factors. Persons particularly sensitive to frustrations from human denial of positive reinforcers are liable to relapse which fits the theory of sensitivity to reward in drug-addicted individuals. Conclusion: Results demonstrate that relapse is clearly more related to aggression than to impulsivity, depression and anxiety and may be facilitated if persons are sensitive to frustrating conditions of non-reward caused by social partners.
TL;DR: It is found that repeated MS modestly disrupted reversal learning performance in the Morris water maze and decreased BDNF protein expression in the mPFC.
Abstract: Aims: Early postnatal maternal and/or sibling separation (MS) can play an important role in the development of psychopathologies during ontogeny. The purpose of the present study is to investigate the effects of repeated MS on the cognitive and brain-derived neurotrophic factor (BDNF) function of rats. Methods: We investigated the effects of repeated MS that lasted 3 h/day during postnatal days 1-21 on spatial learning and reversal learning in Morris water maze tests in male rats. The rats were tested in 4 trials. Moreover, we examined the effects of MS on BDNF protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens, and the hippocampus via immunohistochemistry measurements. Results: We found that repeated MS modestly disrupted reversal learning performance in the Morris water maze and decreased BDNF protein expression in the mPFC. Conclusion: The present study enhances our understanding of the neurobiological and behavioral consequences of repeated episodes of MS in rats to some degree. (C) 2013 S. Karger AG, Basel
TL;DR: In this paper, the National Research Foundation (NRF), North-West University, Potchefstroom, South Africa, and the Metabolic Syndrome Institute, France, provided the funding for the study.
Abstract: Funding for this study was provided by the National Research
Foundation (UID 65607), North-West University, Potchefstroom,
South Africa, and the Metabolic Syndrome Institute,
France.
TL;DR: This study suggests that BDNF plays a role in the transient psychotic symptoms associated with cocaine consumption, and in the non-CIP group, the increase in serum BDNF appears to be driven by the effects of chronic cocaine consumption and withdrawal.
Abstract: Background: Cocaine-induced psychosis (CIP) is among the most serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels ha
TL;DR: The results support the interaction effect between the BDNFVal66Met polymorphism and childhood maltreatment in determining anxiety and further emphasize the possible moderating role of gender in this gene-environment interaction.
Abstract: Background: Although the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is thought to play an important role in the pathophysio
TL;DR: Gender appeared to be more strongly associated with cognitive impairment and seizure activity than treatment approaches in these psychiatric conditions and continuing the administration of sodium valproate neither adversely affects, nor enhances cognitive impairments or seizure duration, but reduces seizure threshold during ECT in patients suffering from manic episodes.
Abstract: Objectives: The aim of the present study was two-fold: (1) to compare, in a controlled double-blind quasi-randomized clinical trial, treatment improvements, treatment outcome, and cognitive impairments in patients suffering from current manic episodes, while treated with electroconvulsive therapy (ECT) with and without concurrent sodium valproate therapy, and (2) to compare ECT seizure characteristics in patients with and without concurrent sodium valproate therapy. Methods: A total of 40 inpatients (mean age = 31.80 years, SD = 8.06; 75% males) suffering from bipolar disorders and currently in a manic state took part in the study. They were quasi-randomly assigned either to the target (continuation of sodium valproate administration) or to the control group (discontinuation of sodium valproate administration). All patients underwent bifrontal ECT for at least 6 sessions. Improvements and cognitive impairments were assessed, and seizure characteristics (duration, threshold) were also recorded. Results: Manic episodes improved significantly over time, and irrespective of the group (target vs. control group). Cognitive impairments did not alter over time or between groups. Seizure duration did not change over time or between groups. Seizure threshold did not change over time, but was lower in the target than in the control group. Conclusions: Continuing the administration of sodium valproate neither adversely affects, nor enhances cognitive impairments or seizure duration, but reduces seizure threshold during ECT in patients suffering from manic episodes. Moreover, gender appeared to be more strongly associated with cognitive impairment and seizure activity than treatment approaches in these psychiatric conditions.
TL;DR: Findings suggest a positive association between VNTR polymorphism in IL1RN and BD, and further stratification of the BD patients into IL1 RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1 RNA carriage and prolongation of the disease.
Abstract: Background/Aims: Several lines of evidence point to the role of neurobiological mechanisms and genetic background in bipolar disorder (BD). The interleukin-1 receptor antagonist (IL-1Ra) is the principal regulator of IL-1α and IL-1β bioactivities. This study aimed to investigate the potential role of the variable number of tandem repeats (VNTR) polymorphisms of the IL-1Ra gene (IL1RN) in conferring susceptibility to BD. Methods: In total, 217 patients meeting DSM-IV-TR criteria for BD and 212 controls were recruited for the study. Genotyping of IL1RN was determined by polymerase chain reaction amplification of VNTR of 86 base pairs in intron 2 of IL1RN. Results: The genotype distribution of IL1RN polymorphism was significantly different between BD patients and controls. The IL1RN*1/2 genotype was more prevalent in BD patients than in controls (44.2 vs. 30.2%, p = 0.003). Multiple logistic regression analysis demonstrated that IL1RN*1/2 heterozygotes had a significantly higher risk for BD (OR 1.83 and 95% CI 1.22–2.74, p = 0.003). Further stratification of the BD patients into IL1RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1RN*2 carriage and prolongation of the disease (p = 0.02). Conclusions: These findings suggest a positive association between VNTR polymorphism in IL1RN and BD. Additional studies, particularly with a prospective approach, are necessary to clarify the precise role of the VNTR polymorphism on the disease in different ethnic populations.