The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. METHODS: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. RESULTS: Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. CONCLUSION: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Inhibition-related differences between tic-free and tic-related obsessive-compulsive disorder: evidence from the N2 and P3.

Tic-related OCD (obsessive-compulsive disorder) was introduced as an OCD subtype in the DSM-5 based mainly on family and clinical data that showed differences between OCD in dependence of accompanying tics. Little is known, however, regarding neurocognitive differences between subtypes. We used the stop-signal task to examine whether differences exist in response inhibition between OCD patients without tics (n = 21), patients with tic-related OCD (n = 12), and 21 healthy controls. The groups were carefully matched for gender, age and level of education. The stop-signal reaction time (SSRT) and inhibition-related N2 and P3 were used to examine behavioral and neural correlates of response inhibition and inhibition-related processes. In the SSRT, no difference was found between groups. P3 amplitude was larger in tic-free compared to tic-related OCD and healthy controls. No group differences were found in the N2 amplitude. For tic-related OCD, SSRT data indicate intact response inhibition, and P3 data indicate intact neural aftereffects of inhibition like the evaluation of the outcome. This is similar to what is found in patients with TD and may, thus, be interpreted as a support for shared mechanisms in relation to TD. In OCD, alterations in P3 amplitude indicate hyperactivity in the evaluation of the outcome of the inhibition process. This is in line with hyperactivity generally found in performance monitoring in OCD.

Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

OBJECTIVE: The etiology of obsessive-compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD. METHOD: A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first-degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire. RESULTS: Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive-compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls. CONCLUSION: Our results provide further evidence for a diathesis-stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed.

Conflict monitoring and adaptation as reflected by N2 amplitude in obsessive-compulsive disorder.

BACKGROUND: Feelings of doubt and perseverative behaviours are key symptoms of obsessive-compulsive disorder (OCD) and have been linked to hyperactive error and conflict signals in the brain. While enhanced neural correlates of error monitoring have been robustly shown, far less is known about conflict processing and adaptation in OCD. METHOD: We examined event-related potentials during conflict processing in 70 patients with OCD and 70 matched healthy comparison participants, focusing on the stimulus-locked N2 elicited in a flanker task. Conflict adaptation was evaluated by analysing sequential adjustments in N2 and behaviour, i.e. current conflict effects as a function of preceding conflict. RESULTS: Patients with OCD showed enhanced N2 amplitudes compared with healthy controls. Further, patients showed stronger conflict adaptation effects on reaction times and N2 amplitude. Thus, the effect of previous compatibility was larger in patients than in healthy participants as indicated by greater N2 adjustments in change trials (i.e. iC, cI). As a result of stronger conflict adaptation in patients, N2 amplitudes were comparable between groups in incompatible trials following incompatible trials. CONCLUSIONS: Larger N2 amplitudes and greater conflict adaptation in OCD point to enhanced conflict monitoring leading to increased recruitment of cognitive control in patients. This was most pronounced in change trials and was associated with stronger conflict adjustment in N2 and behaviour. Thus, hyperactive conflict monitoring in OCD may be beneficial in situations that require a high amount of control to resolve conflict, but may also reflect an effortful process that is linked to distress and symptoms of OCD.

Influence of maternal thyroid hormones during gestation on fetal brain development.

Thyroid hormones (THs) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence TH synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programing of brain development, with implications for early identification of risk, primary prevention and intervention.

Altered emotion regulation in obsessive-compulsive disorder as evidenced by the late positive potential.

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with marked anxiety, which triggers repetitive behaviours or mental rituals. The persistence of pathological anxiety and maladaptive strategies to reduce anxiety point to altered emotion regulation. The late positive potential (LPP) is an event-related brain potential (ERP) that reflects sustained attention to emotional stimuli and is sensitive to emotion-regulation instructions. We hypothesized that patients with OCD show altered electrocortical responses during reappraisal of stimuli triggering their symptoms. METHOD: To test our hypothesis, ERPs to disorder-relevant, generally aversive and neutral pictures were recorded while participants were instructed to either maintain or reduce emotional responding using cognitive distraction or cognitive reappraisal. RESULTS: Relative to healthy controls, patients with OCD showed enhanced LPPs in response to disorder-relevant pictures, indicating their prioritized processing. While both distraction and reappraisal successfully reduced the LPP in healthy controls, patients with OCD failed to show corresponding LPP modulation during cognitive reappraisal despite successfully reduced subjective arousal ratings. CONCLUSIONS: The results point to sustained attention towards emotional stimuli during cognitive reappraisal in OCD and suggest that abnormal emotion regulation should be integrated in models of OCD.

Medial prefrontal brain activation to anticipated reward and loss in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation.

Learning to detect but not to grasp suppressed visual stimuli.

A central implication of the two-visual-systems hypothesis (TVSH) is that the dorsal visuomotor system (vision-for-action) can make use of invisible information, whereas the ventral system (vision-for-perception) cannot (Milner & Goodale, 1995). Therefore, actions such as grasping movements should be influenced by invisible information while conscious reports remain unaffected. To test this assumption, we used a dichoptic stimulation technique--continuous flash suppression (CFS)--which has the potency to render stimuli invisible for up to seconds (Tsuchiya & Koch, 2005). In two experiments using CFS, participants were asked to grasp for invisible bars of different sizes (Experiment 1) or orientations (Experiment 2), or to report both measures verbally. Target visibility was measured trial-by-trial using the perceptual awareness scale (PAS). We found no evidence for the use of invisible information by the visuomotor system despite extensive training (600 trials) and the availability of haptic feedback. Participants neither learned to scale their maximum grip aperture to the size of the invisible stimulus, nor to align their hand to its orientation. Careful control of stimulus visibility across training sessions, however, revealed a robust tendency towards decreasing perceptual thresholds under CFS. We discuss our results within the framework of the TVSH and with respect to alternative models which emphasize the close functional interaction between the dorsal and ventral visual systems.

Impulsivity, self-control, and hypnotic suggestibility.

Hypnotic responding might be due to attenuated frontal lobe functioning after the hypnotic induction. Little is known about whether personality traits linked with frontal functioning are associated with responsiveness to hypnotic suggestions. We assessed whether hypnotic suggestibility is related to the traits of self-control and impulsivity in 154 participants who completed the Brief Self-Control Scale, the Self-Regulation Scale, the Barratt Impulsiveness Scale (BIS-11), and the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A). BIS-11 non-planning impulsivity correlated positively with HGSHS:A (Bonferroni-corrected). Furthermore, in the best model emerging from a stepwise multiple regression, both non-planning impulsivity and self-control positively predicted hypnotic suggestibility, and there was an interaction of BIS-11 motor impulsivity with gender. For men only, motor impulsivity tended to predict hypnotic suggestibility. Hypnotic suggestibility is associated with personality traits linked with frontal functioning, and hypnotic responding in men and women might differ.

Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.

Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.

Impaired decision making and feedback evaluation in borderline personality disorder.

BACKGROUND: Increased impulsivity is considered to be a core characteristic of borderline personality disorder (BPD) and has been shown to play a significant role in decision making and planning. Neuropsychological studies in BPD revealed impairments of executive functions, and it is assumed that these deficits are related to altered feedback processing. However, research on executive functions in BPD is still limited and the underlying deficits remain an open question. The present study, therefore, explored whether decision-making deficits are related to altered feedback evaluation in BPD. METHOD: A total of 18 BPD patients and 18 matched healthy controls underwent a modified version of the Iowa Gambling Task while an electroencephalogram was recorded. Feedback processing was examined by measuring the feedback-related negativity (FRN) and the P300 as electrophysiological correlates of feedback evaluation. RESULTS: Behavioural results revealed that BPD patients, relative to controls, made more risky choices and did not improve their performance. With regard to the FRN, amplitudes in BPD patients did not discriminate between positive and negative feedback information. Further, BPD patients showed reduced FRN amplitudes, which were associated with enhanced impulsivity and enhanced risk taking. In contrast, the P300 amplitudes following negative feedback were increased in BPD patients, relative to controls. CONCLUSIONS: This study indicates that BPD patients are impaired in decision making, which might be related to a dysfunctional use of feedback information. Specifically, BPD patients did not learn to avoid disadvantageous selections, even though they attended to negative consequences.

The effects of donepezil on postlearning sleep EEG of healthy older adults.

INTRODUCTION: Aging is associated with cholinergic hypofunction and memory decline. Cholinergic activity also plays a crucial role in sleep-dependent memory consolidation. The acetylcholinesterase inhibitor (AChE-I) donepezil has been found to increase sleep-related procedural memory consolidation in healthy older adults in a previous study. METHODS: Data of the former study were reanalyzed with regard to the effects of donepezil on the sleep EEG of healthy older adults. This analysis was conducted with a special focus on spectral parameters of sleep, which have previously been linked to plasticity-related processes during sleep, i.e., sigma and delta activity. Forty-two participants (aged: 60-77 years) received 5 mg of the AChE-I donepezil orally 30 min before bedtime in a placebo-controlled, double-blind design. Power values for EEG delta, theta, alpha1, alpha 2, sigma, beta and gamma frequency bands were calculated for stage 2 NREM sleep, SWS and REM sleep. RESULTS: In line with our hypotheses, the AChE-I donepezil led to an increase in sigma activity during stage 2 NREM sleep and delta activity during slow wave sleep. CONCLUSION: These results suggest that an AChE-I facilitates processes of sleep-dependent memory consolidation in older adults.

[Impairments of action control in the context of neuropsychological findings in schizophrenia]. / Störungen der Handlungskontrolle im Kontext neuropsychologischer Befunde bei Schizophrenie.

Based on a review of neurobiological and neuropsychological findings in schizophrenia, we illustrate how experimental neuropsychological research contributes to the understanding of schizophrenia. It is shown that cognitive performance deficits are a central feature of schizophrenia. They are closely connected with changes of brain physiology and appear to reflect disturbances of basic cognitive functions. It is difficult to identify these functions, because task performance usually taps various cognitive processes. However, isolation of functions is possible by experimental variation of tasks that require a small number of well defined processes. To illustrate this, we review several recent studies that experimentally analyzed deficits in the control of fast eye movements (saccades). In the antisaccade task schizophrenia patients show distinct, temporally stable and often replicated performance deficits. The reviewed studies suggest that these deficits predominantly reflect a weakness in the volitional initiation of action.

Effects of scopolamine on matching to sample paradigm and related tests in human subjects.

This was a double-blind placebo-controlled study with a cross-over design to examine the effects of scopolamine on cognitive functions in young healthy subjects. Scopolamine hydrobromide was administered subcutaneously to 12 subjects (mean +/- SD age 23.8 +/- 2.2 years) at doses of 0.3 and 0.6 mg in comparison with two placebo conditions. Scopolamine at both doses produced marked sedation as rated by subjects and an observer. In the continuous performance test, vigilance was impaired by both doses of scopolamine. The span of apprehension test showed differing results (only the high dose of scopolamine showed a performance decrement only in the three-character version of the span of apprehension test). Significant impairment by both doses of scopolamine was seen in immediate and delayed free recall, continuous visual recognition, running word recognition and running picture recognition. While scopolamine caused a significant slowing in average reaction times for simultaneous matching as well as for delayed matching, subjects made more errors under scopolamine compared to placebo only in delayed matching, not in simultaneous matching. Also, the main outcome of matching to sample showed significant effects only in delayed matching, not in simultaneous matching. Notable in this study is the incongruity between the simultaneous matching test and the span of apprehension test on the one hand and the other cognitive tests used on the other. These results demonstrated that scopolamine has a greater effect on memory than on attention. Thus, the scopolamine-induced effects in the present study seem to be more relevant to Alzheimer's disease in an advanced phase than to normal aging.

[The "AMDP-rating scale for obsessive-compulsive symptoms": The 2nd version]. / Das AMDP-Modul zur Erfassung von Zwangssymptomen: 2. Version.

The "Association of Methodology and Documentation in Psychiatry" (AMDP) has developed the 2nd version of a new observer-rated scale for a quick and precise assessment of obsessive-compulsive symptoms. The first version of the scale comprised 20 items on the dimensions "description", "distress and impairment" and "emotion and cognition". The item pool of the 2. version was enlarged to 44 items to accomplish a differentiated assessment of obsessions and compulsions and to assess the associated passive avoidance behaviour. The results of an empirical study (n = 141) demonstrated excellent internal consistency (Cronbach's alpha = 0,93), a split-half reliability of 0,83 (Spearman-Brown), a test-retest reliability of r = 0,84, a high interrater-reliability, a high differential validity and good convergent validity with the Hamburger Zwangsinventar (HZI) and the SCL-90-R. The results are presented and their implications on the final steps of the development of the scale will be discussed.

Psychopathology in dual-diagnosis and nonaddicted schizophrenics: are there differences?

Analysis of 447 schizophrenic inpatients found a lifetime prevalence for substance use of 42.9% (3-month prevalence 29%). While the overall differences were small between schizophrenics using (dual diagnosis) and those not using substances, dual-diagnosis patients in general reported more positive symptoms, especially more intense hallucinations. These differences were observed in patients with current (3-month) substance use on admission but not on discharge, possibly as a result of substance use. The most marked differences were in previous suicide attempts and delinquency, which were more prevalent in dual-diagnosis schizophrenics. These findings indicate that patients with dual diagnosis are more disturbed than other schizophrenics. We discuss the implications for the self-medication hypothesis for substance use in schizophrenia and future research in this area are discussed.

Stability of exploratory eye movements as a marker of schizophrenia--a WHO multi-center study. World Health Organization.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers.

Vigabatrin increases gamma aminobutyric acid (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T). Preclinical studies suggest anxiolytic effects in vigabatrin treated rats. Anxiolytic effects in patients with panic disorder (PD) could therefore be expected. To evaluate putative anxiolytic properties of vigabatrin in humans, CCK-4-induced panic symptoms were studied in healthy volunteers before and after vigabatrin treatment. After placebo-controlled administration of 50 microg CCK-4, ten healthy volunteers received vigabatrin for seven days with a daily dosage of 2 g. The treatment period was followed by a second CCK-4 challenge. Panic and anxiety were assessed using the Acute Panic Inventory (API) score and a DSM-IV derived panic-symptom-scale (PSS). ACTH and cortisol plasma levels were determined during the CCK-4 challenge. All subjects reported a marked reduction of CCK-4-induced panic symptoms and anxiety after seven days of vigabatrin treatment both in the API- and PSS-scores. Moreover, there was a significant attenuation of CCK-induced elevation of ACTH and cortisol levels following vigabatrin treatment. In conclusion, our data show that GABA-transaminase inhibitors exert anxiolytic effects in CCK-4-induced panic in healthy volunteers and suggest that GABA transaminase inhibitors might be useful in ameliorating panic symptoms also in patients with PD.

In-vivo analysis of the human planum temporale (PT): does the definition of PT borders influence the results with regard to cerebral asymmetry and correlation with handedness?

The aim of our study was to examine whether the degree of planum temporale (PT) asymmetry and the possible correlation of morphological PT asymmetries with handedness are influenced by the definition of PT borders. For this reason, we applied three different anatomical PT definitions formerly used in the literature. The PT total (with the end of the Sylvian fissure (SF) as its posterior border) was separated into anterior and posterior regions. The border between anterior and posterior PT was set according to the following definitions: at the end of Heschl's gyrus (1st definition); at the start of the ascending SF ramus according to the 'knife-cut' method (2nd definition); and at the bifurcation of the SF (3rd definition). Thirty right-handed healthy men were recruited. MRI data sets analyzed with the software program BRAINS were used for in vivo PT volumetry. The Edinburgh Handedness Inventory (EHI) and the Hand Dominance Test were used to determine the degree of handedness. In summary, we detected that the type and the degree of asymmetry between left and right PT were strongly dependent on the definition used for PT borders: a left>right asymmetry was found in all PT regions, except a right>left asymmetry of the anterior PT according to our 1st PT definition (lateral to Heschl's gyrus) and a symmetry of the posterior PT according to our 3rd PT definition (posterior to SF bifurcation). In addition, a significant correlation was found between the degree of handedness measured by the EHI and the right posterior PT (3rd definition). We conclude that the influence of the definition of PT borders on the investigated variables may explain some of the variances between former investigations on PT asymmetry and handedness. The possible implications of the correlation between handedness and the extension of the right parietal PT are discussed and have to be elucidated by further studies.

Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia.

OBJECTIVE: This study investigated the effect on brain morphology of an interleukin-1beta genetic polymorphism (C-->T transition at position -511) in patients with schizophrenia. METHOD: In vivo magnetic resonance imaging and genotype analysis were used in the examination of 44 male schizophrenic patients and 48 healthy male comparison subjects. RESULTS: No association between the interleukin-1beta polymorphism and schizophrenia was detected. Within the patient group, bifrontal-temporal gray matter volume deficits and generalized white matter tissue deficits in allele 2 carriers (genotype T/T or C/T) were found. In contrast, the interleukin-1beta polymorphism had no influence on brain morphology within the healthy subjects. CONCLUSIONS: The data suggest that allele 2 within the promoter region of the interleukin-1beta gene at position -511 contributes to structural brain alterations in patients with schizophrenia.