The effect of coronal plane angulation on patient reported outcome measures of operatively treated distal femur fractures: A multi-center prospective evaluation.

OBJECTIVES: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures. DESIGN: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months. There was clinical outcome data available for 105 patients at 3 months, 95 patients at 6 months and 81 patients at one year. INTERVENTION: Lateral locked plating or retrograde intramedullary nailing MAIN OUTCOME MEASUREMENTS: Radiographic alignment, functional scoring including SMFA, Bother Index, and EQ-5D. Clinical scoring of walking ability, need for ambulatory support and ability to manage stairs. RESULTS: At 3 months, there was no difference between groups (varus, neutral or valgus) with respect to any of the clinical functional outcome scores measured. At 6 months, compared to those with neutral alignment, patients with varus angulation had a worse Stair Climbing score (4.33 vs. 2.91, p = 0.05). At 12 months, the average patient with neutral or valgus alignment needed less ambulatory support than the average patient in varus. Walking distance ability was no different between the groups at any time point. With respect to the validated patient-based outcome scores, we found no statistical difference in in the SMFA, Bother, or EQ-5D between patients with valgus or varus mal-alignment and those with neutral alignment at any time point (p > 0.05). Regardless of coronal angulation, the SMFA trended towards lower (improved) scores over time, while EQ-5D scores for patients with varus angulation did not improve over time. CONCLUSIONS: Valgus angulation and neutral angulation may be better tolerated in terms of clinical outcomes like stair climbing and need for ambulatory support than varus angulation, though patient reported outcome measures like the SMFA, Bother Index and EQ-5D show no statistical significance. Most patients with distal femur fractures tend to improve during the first year after injury but many remain significantly affected at 12 months post injury.

Indications and anatomic landmarks for the application of lower extremity traction: a review.

PURPOSE: Fractures of the lower extremity, particularly of the femur and acetabulum, may be difficult to immobilize with splinting alone. These injuries may be best stabilized with the application of various types of skeletal traction. Often, traction is applied percutaneously in an emergent setting, making the knowledge of both superficial and deep anatomy crucial to successful placement. METHODS: Review was performed via PubMed search as well as referencing the Orthopaedic literature. Relevant articles to the anatomy of the knee, ankle and calcaneus as they pertain to traction placement were referenced in compiling the optimal recommendations for traction placement. CONCLUSION: By palpating and marking superficial landmarks and observing specific anatomic relationships, safe application of traction pins can be performed while minimizing iatrogenic injury to vital anatomic structures, and avoiding intra-articular placement which could potentially lead to joint infection.

[Cognitive-psychoeducational group programme for bipolar disorder: pilot study with two-year follow-up]. / Kognitiv-psychoedukative Gruppenintervention bei bipolar erkrankten Patienten: Pilotstudie mit Zwei-Jahres-Katamnese.

52 patients with bipolar disorder were treated with psychopharmacotherapy and a cognitive psychoeducational group programme that was established at the Department of Psychiatry and Psychotherapy of the Ludwig Maximilian University, Munich, Germany. The programme covers psychoeducation, identifying and coping with depressive and manic symptoms, relapse prevention and establishing a stable life style. 96 % rated the group to be helpful and felt well informed about their illness. There were significant gains in knowledge (F = 25,714, p < 0.001) and improvements in the severity of the illness (CGI; F = 68,255, p < 0.001) post-treatment. With regard to sociodemographic and clinical variables, only the level of work qualification showed a differential treatment response: patients with higher qualifications had a more favourable course of the illness (F = 4,125, p = 0.048). At one and two year follow-up 25 % and, respectively, 30 % of the sample had to be readmitted. A higher number of previous hospitalisations (p = 0.010) and male sex (p = 0.031) turned out to be significant predictors of relapse (R² = 0.358, p = 0.004) at two year follow-up. This disorder-specific group programme represents a key component of treatment offering emotional support for patients and their relatives. Patients are to be involved in the treatment process and need information about the illness, its psychosocial and pharmacological treatment as well as help in learning practical skills to improve their living with the disease. Being integrated and committed to a supporting network may increase their quality of life.

[The challenge of treating bipolar outpatients]. / Herausforderungen der ambulanten Behandlung von Patienten mit bipolar-affektiven Störungen.

The course of bipolar illness comprises a wide range, which may vary between one single episode once every five years and a severe ultra rapid cycling course with mood changes within days. Even with optimal pharmacological treatment the functional outcome in bipolar patients is still poor. Underlying pathomechanisms are not fully understood yet. This article addresses three possible illness specific-aspects: cognitive defects, high relapse frequency and poor adherence. Causes as well as therapeutic interventions for these therapeutic pitfalls are summarised.

A miniature confocal Raman probe for endoscopic use.

Raman spectroscopy is a powerful tool for studying biochemical changes in the human body. We describe a miniature, confocal fibre optic probe intended to fit within the instrument channel of a standard medical endoscope. This probe has been optimized for the study of the carcinogenesis process of oesophageal malignancy. The optical design and fabrication of this probe is described including the anisotropic wet etching technique used to make silicon motherboards and jigs. Example spectra of PTFE reference samples are shown. Spectra with acquisition times as low as 2 s from resected oesophageal tissue are presented showing identifiable biochemical changes from various pathologies.

Preliminary results of a fine-grain analysis of mood swings and treatment modalities of bipolar I and II patients using the daily prospective life-chart-methodology.

OBJECTIVE: The study aimed to increase the knowledge about the detailed course differences between different forms of bipolar disorder. METHOD: Using the prospective life-chart-clinician version, we compared the fine-grain analysis of mood swings and treatment modalities of 18 bipolar II with 31 bipolar I patients. RESULTS: During an observational period of a mean of 26 months we observed an increase of euthymic days, and a decrease of (sub)depressive and (hypo)manic days. Days in a (sub)depressed state were more frequent than days of (hypo)mania as well as days of subdepression or hypomania in comparison to days of full-blown depression or mania. Bipolar II patients showed an increase in hypomanic days receiving more frequently antidepressants. Bipolar I patients, with a decrease of manic days, were significantly taking more often mood stabilizers. CONCLUSION: Treatment in a specialized bipolar clinic improves the overall outcome, but bipolar II disorder seems to be still treated sub-optimally with a possible iatrogenic increase of hypomanic days.

Lamotrigine in bipolar disorder: results of a mirror-image evaluation using the NIMH Lifechart-Methodology.

BACKGROUND: Lamotrigine (LTG) is characterized by prophylactic efficacy against bipolar depression (BPD). We evaluated retro- and prospectively the naturalistic treatment outcome with LTG analysing lifecharts of patients from the bipolar outpatient clinic. METHODS: Lifechart-data of 20 patients routinely treated with LTG for the first time were evaluated, comparing number and duration of manic, depressive and mixed episodes prior to LTG and after initiation of treatment (mirror-image evaluation). The mean prospective evaluation period based on the lifechart was 18.1 months. Also we compared the number and severity of "switches" from depression in mania. Additionally, CGI-BP, YMRS, IDS-C and GAF scores at the monthly visits were compared for time after LTG initiation. RESULTS: We found no significant differences in the absolute number of manic, depressive and mixed episodes, respectively, before and after initiation of LTG. The number of "switches" did not differ significantly. A significant difference in duration of time patients suffered from a depressive state before and after initiation of LTG was observed in favour of LTG treatment (p=.006). A similar finding was observed for the time spent in mixed episodes (p<.001). No significant difference was observed for scores of mood scales at the monthly visits (CGI-BP, YMRS, IDS-C, GAF). LIMITATIONS: Generalizability of these results is limited due to the uncontrolled design and the issues in comparing prospective and retrospective data. CONCLUSION: These data underline not only the antidepressant profile of LTG, but also the usefulness of the Lifechart-Methodology (LCM) in the evaluation of treatment outcome under routine conditions.

[Alzheimer's disease and vascular dementia. Determination of atrophy of the corpus callosum and cerebral cortex]. / Alzheimer-Krankheit und vaskuläre Demenz. Bestimmung der Atrophie des Corpus callosum und des zerebralen Kortex.

BACKGROUND: Measurement of regional atrophy of the corpus callosum and cortical grey matter may differentiate between primary loss of intracortical projecting neurons and primary fibre degeneration in Alzheimer's disease (AD) and vascular dementia (VD). METHODS: The regional corpus callosum area and cortical grey matter volumes were measured in 30 patients with the clinical diagnosis of probable AD, 20 patients with the clinical diagnosis of probable VD and 24 healthy elderly control subjects using MRI in two centers in Munich and Amsterdam. RESULTS: Patients with AD showed significantly reduced volumes of cortical grey matter in all cerebral lobes and atrophy of anterior and posterior corpus callosum areas. In VD patients only occipital lobe grey matter volume and anterior corpus callosum area were significantly reduced. In AD patients reduction of cortical grey matter volumes was significantly correlated with regional reductions of corpus callosum areas, but not in VD patients or controls. CONCLUSION: These findings support the notion that measurement of the corpus callosum and cortical grey matter atrophy may identify the underlying causes of cortical disconnection in AD and VD and may be helpful to differentiate between both conditions.

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression.

The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the L(A)-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.

Methicillin-resistant Staphylococcus aureus in orthopaedic surgery.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a ubiquitous bacterium in both the hospital and community setting. There are two major subclassifications of MRSA, community-acquired and healthcare-acquired, each with differing pathogenicity and management. MRSA is increasingly responsible for infections in otherwise healthy, active adults. Local outbreaks affect both professional and amateur athletes and there is increasing public awareness of the issue. Health-acquired MRSA has major cost and outcome implications for patients and hospitals. The increasing prevalence and severity of MRSA means that the orthopaedic community should have a basic knowledge of the bacterium, its presentation and options for treatment. This paper examines the evolution of MRSA, analyses the spectrum of diseases produced by this bacterium and presents current prevention and treatment strategies for orthopaedic infections from MRSA.

[Sadistic fetishism--deadly passion. Forensic psychiatric assessment of sex offenders]. / Tödliche Lust--sadistischer Fetischismus. Forensisch-psychiatrische Begutachtung von Sexualstraftätern.

This article reviews current developments in psychiatric assessment of sex offenders for criminal courts. These developments are characterized by constantly changing laws and increasing neurobiological findings about paraphilias. Psychiatrists must prepare their reports taking into account the tension between psychopathological, neurobiological, and normative aspects of their judgement. The complexity of such assessments can best be demonstrated by narratives. This narrative concerns a 47-year-old patient who killed eight women after strangling them and masturbating or having intercourse with the unconscious victims. He explained in detail six of these crimes and gave ample information about his history, sexual development, fantasies, and a number of other sexual crimes he had committed. From this information a plausible explanation of his development to sexual fetishism and from there to sadism could be derived. Brain MRI displayed gliotic scars in the frontal lobe and right hippocampus. Consequences of the various findings on psychiatric assessment of legal culpability are discussed in this paper, concluding that a differentiated approach to the assessment is possible only from a psychopathological point of view in which behaviour, clinical features, and motivations are analysed.

Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study.

Structural alterations in schizophrenia have mainly been regarded as the result of neurodevelopmental processes. However, it remains unresolved whether the pattern of morphological brain changes differs between different stages of disease. We examined structural brain changes in 93 first-episode (FES) and 72 recurrently ill (REZ) patients with schizophrenia (SZ) and 175 matched healthy control subjects (HC) using cross-sectional and conjunctional voxel-based morphometry (VBM) of whole-brain MRI data in a three-step approach. We found significant grey matter density (GMD) reductions in FES compared to HC bilaterally in the temporal and prefrontal areas, including the anterior cingulate gyrus, as well as in both thalami. Hippocampus and amygdala were affected on the left side (P<0.05, corrected). In REZ patients this pattern was spatially extended. The basal ganglia were exclusively reduced in the recurrently ill group compared to controls. Common to both disease groups were reductions in the bilateral perisylvian regions, the opercular region, the insula, prefrontal cortex, left inferior temporal gyrus, limbic system including hippocampus and amygdala, and the thalami. In FES patients there were no regions affected that were not also affected in REZ patients. In contrast, REZ patients showed extended alterations within the frontal and temporal regions, the hippocampus, amygdala and exclusively in the basal ganglia relative to the FES patients. Our findings suggest a system-specific involvement of neuronal networks in schizophrenia. Furthermore, our data suggest that in the advanced stages of schizophrenia additional cortical and subcortical brain areas become involved in the disease process. Longitudinal data will be required to further test this hypothesis.

Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study.

Forty Untreated high-risk (HR) individuals for psychosis and 75 healthy control subjects (HC) matched for age, gender, handedness and educational level were investigated by structural MRI. HR subjects were recruited at the Early Detection and Intervention Centre for Mental Crises (FETZ) of the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Germany. Measurements of gray matter volumes were performed by voxel-based morphometry using SPM5. The sample of HR subjects showed GM volume reductions in frontal, lateral temporal and medial temporal regions compared to the healthy control group. These regions are compatible with structural findings in the clinically apparent disease of schizophrenia.

5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder.

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine(1A) receptor (5-HTR(1A)) gene C -1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program 'BRAINS'. Patients who have the 5-HTR(1A) gene G allele had significantly smaller amygdala volumes than C/C genotype carriers (P = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR(1A) genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression (P = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR(1A) gene C -1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.

Functional BOLD MRI: comparison of different field strengths in a motor task.

The purpose was to evaluate the benefit of an increased field strength for functional magnetic resonance imaging in a motor task. Six right-handed volunteers were scanned at 1.5 T and 3.0 T using a motor task. Each experiment consisted of two runs with four activation blocks, each with right- and left-hand tapping. Analysis was done using BrainVoyagerQX. Differences between both field strengths concerning signal to noise (SNR), blood oxygen level-dependent (BOLD) signal change, functional sensitivity and BOLD contrast to noise (CNR) were tested using a paired t test. Delineation of activations and artifacts were graded by two independent readers. Results were further validated by means of a phantom study. The sensorimotor and premotor cortex, the supplementary motor area, subcortical and cerebellar structures were activated at each field strength. Additional activations of the right premotor cortex and right superior temporal gyrus were found at 3.0 T. Signal-to-noise, percentage of BOLD signal change, BOLD CNR and functional sensitivity improved at 3.0 T by a factor of up to 2.4. Functional imaging at 3.0 T results in detection of additional activated areas, increased SNR, BOLD signal change, functional sensitivity and BOLD CNR.

Age-dependent differences in human brain activity using a face- and location-matching task: an FMRI study.

PURPOSE: To evaluate the differences of cortical activation patterns in young and elderly healthy subjects for object and spatial visual processing using a face- and location-matching task. MATERIALS AND METHODS: We performed a face- and a location-matching task in 15 young (mean age: 28 +/- 9 years) and 19 elderly (mean age: 71 +/- 6 years) subjects. Each experiment consisted of 7 blocks alternating between activation and control condition. For face matching, the subjects had to indicate whether two displayed faces were identical or different. For location matching, the subjects had to press a button whenever two objects had an identical position. For control condition, we used a perception task with abstract images. Functional imaging was performed on a 1.5-tesla scanner using an EPI sequence. RESULTS: In the face-matching task, the young subjects showed bilateral (right > left) activation in the occipito-temporal pathway (occipital gyrus, inferior and middle temporal gyrus). Predominantly right hemispheric activations were found in the fusiform gyrus, the right dorsolateral prefrontal cortex (inferior and middle frontal gyrus) and the superior parietal gyrus. In the elderly subjects, the activated areas in the right fronto-lateral cortex increased. An additional activated area could be found in the medial frontal gyrus (right > left). In the location-matching task, young subjects presented increased bilateral (right > left) activation in the superior parietal lobe and precuneus compared with face matching. The activations in the occipito-temporal pathway, in the right fronto-lateral cortex and the fusiform gyrus were similar to the activations found in the face-matching task. In the elderly subjects, we detected similar activation patterns compared to the young subjects with additional activations in the medial frontal gyrus. CONCLUSION: Activation patterns for object-based and spatial visual processing were established in the young and elderly healthy subjects. Differences between the elderly and young subjects could be evaluated, especially by using a face-matching task.

Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.

In 1965, an adult-onset, autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy was described in a large, multi-generation kindred and named 'scapuloperoneal syndrome type Kaeser' (OMIM #181400). By genetic analysis of the original kindred, we discovered a heterozygous missense mutation of the desmin gene (R350P) cosegregating with the disorder. Moreover, we detected DES R350P in four unrelated German families allowing for genotype-phenotype correlations in a total of 15 patients carrying the same mutation. Large clinical variability was recognized, even within the same family, ranging from scapuloperoneal (n = 2, 12%), limb girdle (n = 10, 60%) and distal phenotypes (n = 3, 18%) with variable cardiac (n = 7, 41%) or respiratory involvement (n = 7, 41%). Facial weakness, dysphagia and gynaecomastia were frequent additional symptoms. Overall and within each family, affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Moreover, histological and immunohistochemical examination of muscle biopsy specimens revealed a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. This study reveals that the clinical and pathological variability generally observed in desminopathies may not be attributed to the nature of the DES mutation alone, but may be influenced by additional genetic and epigenetic factors such as gender. In addition, mutations of the desmin gene should be considered early in the diagnostic work-up of any adult-onset, dominant myopathy, even if specific myofibrillar pathology is absent.

Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results.

OBJECTIVES: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. METHODS: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. RESULTS: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. CONCLUSIONS: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.

Five-year predictive factors of type 2 diabetes in men with impaired fasting glucose.

AIM: The outcome of 743 French men (age 20-60) with impaired fasting glucose (IFG) [blood glucose 6.1-6.9 mmol/l] at T1 was evaluated 5 years later, at T2. METHODS: Personal and family medical history, smoking, nutritional habits, physical activity, blood pressure, body mass index (BMI) and waist girth, fasting biological data were collected at T1 and T2. Predictive factors for developing diabetes were compared between those who returned to normal fasting glucose and those who had diabetes, before and after adjustment for age, BMI, glucose and triglyceride (TG) levels. RESULTS: At T2, 44%, 39%, 17% were classified as normal fasting plasma glucose (FPG), IFG or diabetic, respectively. Odd ratios for diabetes were 4.2 for men with a family history of diabetes (FHD), 3.4 if BMI > or = 25 kg/m(2), 2.9 if waist girth > or = 90 cm, 2.8 if TG > or = 2 mmol/l and 1.9 if no daily dairy products were eaten. Still significant after adjustment for age, BMI, glucose and TG levels were: FHD (P=0.001), no daily dairy products (P=0.001), high alcohol intake (P=0.02) and low physical activity (P = 0.02). CONCLUSION: No daily dairy products, high alcohol intake and low physical activity were independent predictive factors of a 5-year onset of diabetes after adjusting for BMI, FHD, triglyceride and glucose levels at baseline. For a better prevention of diabetes, these findings give clues for behaviour modifications as soon as IFG is detected.

Plexin B3 is genetically associated with verbal performance and white matter volume in human brain.

The presence of genetic influences on cognitive performance and brain volume is well established. However, specific genetic determinants of the variance of these quantitative traits are not yet known. Plexins act as receptors for semaphorins and are implicated in axon guidance, which is a key process in brain development. We have previously shown that plexin B3 is a highly potent stimulator of neurite outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits related to human brain development and cerebral connectivity. We identified several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D and V1596E) conserved at the corresponding positions of the orthologs in mouse and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male patients with schizophrenia. Cognitive performance was measured with the vocabulary test (Wortschatztest (WST)), a method to estimate roughly general intelligence (g). Brain morphology was characterized by magnetic resonance imaging. Compared to subjects not carrying the modern, human-specific haplotype A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis (P=0.0004). This effect could be observed in three independent groups (healthy males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037). Additionally, the haplotype A was associated with increased volume of brain white matter that in turn correlated with performance in the vocabulary test. These findings suggest that plexin B3 may influence cognitive performance, and the development of white matter in vivo in a way similar to its known stimulating effect on neurite outgrowth in vitro. These novel observations warrant further replication in independent samples.