[Interplay between genetic background and environmental factors in psychiatry: current situation and future prospects]. / Samenspel tussen genetische achtergrond en omgevingsfactoren in de psychiatrie: stand van zaken en toekomstperspectief.

BACKGROUND: The hypothesis that etiopathogeneses of psychiatric disorders are determined by interplay between genetic background and environmental factors, as well their interactions can increasingly be put to direct scientific test, based on a wave of methodological, technological and knowledge developments.
AIM: To provide insight into and to provide perspective on some important scientific developments and facilitate challenges in this area.
METHOD: Narrative overview of the scientific literature and formulation of a concept and future perspective.
RESULTS: The overview points to concrete progress in the fields of genetic epidemiology, environmental analyses, gene-environment interactions and epigenetics in psychiatry. For example, recent studies have provided evidence for the existence of interactions and correlations between genetic and environmental factors, interdependence of risk-influencing effects of environmental factors, and translational neurobiological studies have identified biological processes that influence the impact of (or the response to) environmental influences on individuals mediate. These important steps to translate epidemiological research into testable biological hypotheses are facilitated by new techniques and the availability of large and relevant clinical and biological datasets.
CONCLUSION: Scientific progress on the interplay between genetic background and environmental factors enriches the conceptual framework of the etiopathogenesis of mental disorders and provides a future perspective in which we are likely to receive answers to a number of clinically relevant questions in the coming decade.
.

Polygenic liability for schizophrenia and childhood adversity influences daily-life emotion dysregulation and psychosis proneness.

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness.

'False-positive' self-reported psychotic experiences in the general population: an investigation of outcome, predictive factors and clinical relevance.

AIMS.: Self-reported psychotic experiences (SRPE) by individuals from the general population are often unconfirmed by clinical interview and referred to as 'false-positive' (FP) SRPE. FP SRPE have been suggested to represent the mildest form of risk along the extended psychosis continuum. However, little is known about their (clinical) outcome and evolution over time. Aims of this study were to prospectively examine, in individuals with FP SRPE, (1) the prevalence of remission, persistence and transition to validated PE at 3-year follow-up; (2) potential baseline psychopathological and psychosocial predictors of persistence of FP SRPE and transition to validated PE; and (3) whether those with persistent FP SRPE and validated PE already differed on psychopathology and psychosocial factors at baseline. We tested the hypotheses that (i) individuals with FP SRPE would be more likely to have SRPE and validated PE at follow-up; and (ii) that FP SRPE would be predictive of lower functioning and more psychopathology and help-seeking behaviour at follow-up. METHODS.: Baseline (n = 6646) and 3-year follow-up (n = 5303) data of the second the Netherlands Mental Health Survey and Incidence Study (NEMESIS-2), a general population research project on prevalence, incidence, course and consequences of psychiatric disorders was used. Self-report of PE was followed by clinical interview to determine clinical validity. The presence of mood, anxiety and substance use disorders, childhood adversity, help-seeking and functioning as well as PE characteristics (number, frequency, distress and impact) were used in the analyses which included only individuals with complete data for both assessments waves (n = 4683). RESULTS.: At baseline, 454 participants had any FP SRPE; of these 372 participants had complete follow-up data available. Those with baseline FP SRPE were significantly more likely to report SRPE (OR = 3.58; 95% CI 2.38-5.40, p < 0.001) and validated PE (OR = 6.26; 95% CI 3.91-10.02, p < 0.001) at follow-up. Baseline FP SRPE also predicted the presence of mood and anxiety disorders, reduced functioning and help-seeking at follow-up. Several baseline psychopathological, psychosocial and PE characteristics were predictive for the persistence of SRPE. These factors also differentiated groups with FP SRPE or validated PE from those with remitted FP SRPE at follow-up. CONCLUSIONS.: 'FP SRPE' are not truly 'false' as they index risk for the development of clinically relevant psychotic symptoms, development of mood and anxiety disorders and reduced functioning. Self-reported PE, even unconfirmed, warrant 'watchful waiting' and follow-up over time, especially when they are reported by individuals with reduced psychosocial functioning and general psychiatric problems.

Is sensitivity to daily stress predictive of onset or persistence of psychopathology?

PURPOSE: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology. METHODS: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model. RESULTS: Linear analyses showed that emotional stress reactivity was not associated with onset (ß=.02; P=.56) or persistence (ß=-.01; P=.78) of symptoms. There was a significant effect of baseline symptom score (ß=.53; P<.001) and average negative affect (NA: ß=.19; P<.001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (ß=.25; P<.001), but not moderate (ß=-.03; P=.65) or severe (ß=-.06; P=.42), stressors was associated with symptom persistence one year later. DISCUSSION: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

The role of stress-regulation genes in moderating the association of stress and daily-life psychotic experiences.

OBJECTIVE: The interaction of single nucleotide polymorphisms with both distal and proximal environmental factors across the extended psychosis phenotype is understudied. This study examined (i) the interaction of relevant SNPs with both early-life adversity and proximal (momentary) stress on psychotic experiences (PEs) in an extended psychosis sample; and (ii) differences between early-psychosis and non-clinical groups for these interactions. METHODS: Two hundred and forty-two non-clinical and 96 early-psychosis participants were prompted randomly eight times daily for 1 week to complete assessments of current experiences, including PEs and stress. Participants also reported on childhood trauma and were genotyped for 10 SNPs on COMT, RGS4, BDNF, FKBP5, and OXTR genes. RESULTS: Unlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early-psychosis than in the non-clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early-psychosis group. No interactions emerged with COMT or BDNF variants. CONCLUSION: Individual differences in relevant stress-regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily-life manifestation of PEs across the psychosis continuum.

The functional and clinical relevance of childhood trauma-related admixture of affective, anxious and psychosis symptoms.

OBJECTIVE: Previous work has shown that across different patient samples, patients with childhood trauma are more likely to have co-occurrence of affective, anxious and psychosis symptoms than non-traumatized patients. However, the clinical relevance of trauma-related admixture remains to be established. METHOD: We examined patients with mood disorder (NEMESIS-2; n = 1260), anxiety disorder (NEMESIS-2; n = 896) or psychotic disorder (GROUP; n = 532) in terms of symptom profiles, quality of life (QOL) and social functioning. RESULTS: Results showed that mood disorder patients with both trauma and co-occurrence of affective, anxious and psychosis symptoms had a lower QOL (B-12.6, 95% CI -17.7 to -7.5, P < 0.001), more help-seeking behaviour [odds ratio (OR) 2.5, 95% CI 1.1-5.7, P = 0.031] and higher prevalence of substance use disorders (OR 7.8, 95% CI 1.1-58.0, P = 0.044), compared with patients without trauma history and symptom admixture (Trauma-/CL-). Similar results were found in patients with an anxiety disorder. Traumatized patients with a psychotic disorder and admixture showed lower QOL (B-0.6, 95% CI -0.9 to -0.4, P < 0.001), higher prevalence of drug disorders (OR 2.2, 95% CI 1.2-3.9, P = 0.008) and lower global assessment of functioning (B-12.8, 95% CI -17.1 to -8.5, P < 0.001) than Trauma-/CL- patients. CONCLUSION: Stratification according to childhood trauma exposure thus identifies a phenotype characterized by admixture of affective, anxiety and psychotic symptoms that, when combined, has clinical relevance. Identification of functionally meaningful aetiological subgroups may aid clinical practice.

Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology.

BACKGROUND: Evidence suggests that in affective, non-psychotic disorders: (i) environmental exposures increase risk of subthreshold psychotic experiences (PEs) and strengthen connectivity between domains of affective and subthreshold psychotic psychopathology; and (ii) PEs are a marker of illness severity. METHOD: In 3021 adolescents from the Early Developmental Stages of Psychopathology cohort, we tested whether the association between PEs and presence of DSM-IV mood disorder (MD)/obsessive-compulsive disorder (OCD) would be moderated by risk factors for psychosis (cannabis use, childhood trauma and urbanicity), using the interaction contrast ratio (ICR) method. Furthermore, we analysed whether the interaction between environment and PEs was mediated by non-psychotic psychopathology. RESULTS: The association between PEs and MD/OCD was moderated by urbanicity (ICR = 2.46, p = 0.005), cannabis use (ICR = 3.76, p = 0.010) and, suggestively, trauma (ICR = 1.91, p = 0.063). Exposure to more than one environmental risk factor increased the likelihood of co-expression of PEs in a dose-response fashion. Moderating effects of environmental exposures were largely mediated by the severity of general non-psychotic psychopathology (percentage explained 56-68%, all p < 0.001). Within individuals with MD/OCD, the association between PEs and help-seeking behaviour, as an index of severity, was moderated by trauma (ICR = 1.87, p = 0.009) and urbanicity (ICR = 1.48, p = 0.005), but not by cannabis use. CONCLUSIONS: In non-psychotic disorder, environmental factors increase the likelihood of psychosis admixture and help-seeking behaviour through an increase in general psychopathology. The findings are compatible with a relational model of psychopathology in which more severe clinical states are the result of environment-induced disturbances spreading through a psychopathology network.

Childhood abuse and neglect in relation to the presence and persistence of psychotic and depressive symptomatology.

BACKGROUND: The association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma. METHOD: In a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period. RESULTS: A dose-response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period. CONCLUSIONS: In congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.

Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries.

BACKGROUND: Meta-analyses link childhood trauma to depression, mania, anxiety disorders, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life. METHOD: We used data from a representative general population sample (NEMESIS-2, n = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP, n = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. RESULTS: In NEMESIS-2, largely comparable associations were found between childhood trauma and depression, mania, anxiety and psychosis. However, childhood trauma was considerably more strongly associated with their lifetime admixture. These results were confirmed in the patient samples, in which it was consistently found that patients with a history of childhood trauma were more likely to have a combination of multiple symptom domains compared to their non-traumatized counterparts. This pattern was also found in exposed individuals who did not meet criteria for a psychotic, affective or anxiety disorder and who did not seek help for subclinical psychopathology. CONCLUSIONS: Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries, and this admixture may already be present in the earliest stages of psychopathology. These findings may have significant aetiological, pathophysiological, diagnostic and clinical repercussions.

[Water-filtered infrared-A (wIRA) promotes wound healing]. / Wassergefiltertes Infrarot A (wIRA) hilft Wunden heilen.

Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and low thermal load to the skin surface which promotes the healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic effects. Water-filtered infrared-A increases tissue temperature (+ 2.7 °C at a tissue depth of 2 cm), tissue oxygen partial pressure (+ 32 % at a tissue depth of 2 cm) and tissue perfusion. These three factors are decisive for a sufficient supply of tissue with energy and oxygen and consequently also for wound healing and infection defense. Water-filtered infrared-A promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain. These effects have been proven in a total of seven prospective studies (of these six randomized controlled studies) with most of the effects having an evidence level of Ia or Ib. The additional cases of complicated courses of wound healing presented in this article illustrate the proven effects of wIRA. Not only in the 6 presented cases wIRA turned the complicated courses of wound healing for the better and facilitated the healing of the wounds after varying total times of irradiation (in the 6 cases 51-550 h) and after variable times of wound care and mostly after transplantation of split skin grafts. In complicated courses of wound healing wIRA does not replace consultation and, when indicated, treatment by an experienced plastic surgeon and by a surgeon specialized in septic surgery. With these limitations wIRA can be recommended as a valuable complement for the treatment of acute as well as of chronic wounds.

Does social defeat mediate the association between childhood trauma and psychosis? Evidence from the NEMESIS-2 Study.

OBJECTIVE: Based on theoretical considerations and animal studies, mediation of 'social defeat' (SD) in the association between childhood trauma (CT) and psychosis was investigated. METHOD: Trained interviewers administered a structured interview assessing CT, psychotic experiences and other psychopathology in 6646 participants in the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). RESULTS: Childhood trauma was associated with psychotic experiences making up the extended psychosis phenotype (EPP), as well as with a diagnosis of psychotic disorder (PD). Similarly, CT was associated with a priori selected items indexing SD (discouraged, hopeless, worthless, loss of self-confidence, low self-esteem, better off dead, suicidal thoughts) and with a measure of affective dysregulation (AD), which in turn were also associated with psychosis. While SD and AD individually acted as mediators in the association between CT and EPP, only SD acted as a mediator in the association between CT and PD. Cannabis use did not mediate the association between CT and EPP or PD. CONCLUSION: The present results suggest a developmental model implicating SD as an important mediator in the link between childhood adverse experiences and later development of psychotic experiences. The combined mediation by SD and AD is compatible with an 'affective pathway' to early psychosis.

Distally based perforator flaps for reconstruction of post-traumatic defects of the lower leg and foot. A review of the anatomy and clinical outcomes.

STUDY AIMS: To report the surgical anatomy of the perforator arteries at the lower leg, analyse clinical outcomes in previous studies, and forward methodological recommendations for future studies of post-traumatic perforator flap reconstructions. METHODS: A study sample of 640 human patients drawn from 24 clinical reports was included for review. The sample comprised of four subsets: sural flap reconstructions (n=257), saphenous flaps (n=122), supramalleolar flaps (n=92), and propeller flaps (n=169). RESULTS: Statistical analysis of samples from anatomical studies documents significant differences in the perforator distribution from the tibial and peroneal artery; peroneal perforator arteries are randomly organised whereas tibial artery perforators are clustered at three definite levels. The failure rates in clinical studies ranged from 0% to 6%, being lowest for supramalleolar flap reconstructions and highest for saphenous flaps; however, differences between the four subsets were not statistically significant at the 95% confidence level. Due to methodological flaws, outcome comparisons in the actual study sample should be interpreted cautiously; in most clinical studies both risk variables and outcome indicators are poorly defined. The outcome of Dynamic Infrared Thermography imaging of post-transposition changes of flap perfusion is reported. SUMMARY: Fasciocutaneous perforator flaps seem to have high survival rates and represent a feasible approach to post-traumatic reconstructions, especially in low-resource settings. A template for data gathering is recommended for higher accuracy in future comparative studies, and for scientific analysis of success and risk factors. New imaging techniques indicate a promising potential of micro-circular angiogenesis during the first two weeks after flap transpose.

Dysmetabolic features of the overweight patients receiving antipsychotic drugs: a comparison with normal weight and obese subjects.

BACKGROUND: Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI=25-29.9) without metabolic syndrome or diabetes has not been thoroughly investigated. OBJECTIVE: To assess the metabolic health of overweight patients receiving antipsychotic drugs. METHODS: We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes. RESULTS: Compared with the normal weight subjects (n=286), overweight patients (n=212) had higher fasting insulin resistance as assessed with the homeostatic model (P=0.023), insulin secretion during the oral glucose tolerance test (P=0.0037), triglycerides (P=0.0004) and low-density lipoprotein cholesterol (P=0.0089), and lower levels of high-density lipoprotein cholesterol (P=0.0014). The obese (n=50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P=0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups. CONCLUSIONS: Overweight (BMI=25-29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.

Systematic review and collaborative recalculation of 133,693 incident cases of schizophrenia.

BACKGROUND: This systematic review and collaborative recalculation was set up to recalculate schizophrenia incidence rates from previously published studies by age and sex. METHOD: PubMed, EMBASE and PsycINFO databases were searched (January 1950 to December 2009) for schizophrenia incidence studies. Numerator and population data were extracted by age, sex and, if possible, study period. Original data were requested from the authors to calculate age- and sex-specific incidence rates. Incidence rate ratios (IRRs) with their 95% confidence intervals (CIs) were computed by age and sex from negative binomial regression models. RESULTS: Forty-three independent samples met inclusion criteria, yielding 133 693 incident cases of schizophrenia for analysis. Men had a 1.15-fold (95% CI 1.00-1.31) greater risk of schizophrenia than women. In men, incidence peaked at age 20-29 years (median rate 4.15/10,000 person-years, IRR 2.61, 95% CI 1.74-3.92). In women, incidence peaked at age 20-29 (median rate 1.71/10,000 person-years, IRR 2.34, 95% CI 1.66-3.28) and 30-39 years (median rate 1.24/10,000 person-years, IRR 2.25, 95% CI 1.55-3.28). This peak was followed by an age-incidence decline up to age 60 years that was stronger in men than in women (χ² = 57.90, p < 0.001). The relative risk of schizophrenia was greater in men up to age 39 years and this reversed to a greater relative risk in women over the age groups 50-70 years. No evidence for a second incidence peak in middle-aged women was found. CONCLUSIONS: Robust sex differences exist in the distribution of schizophrenia risk across the age span, suggesting differential susceptibility to schizophrenia for men and women at different stages of life.

[Cannabis use and the risk of psychotic disorders. An update]. / Cannabis als risicofactor voor psychose: een update.

BACKGROUND: The use of cannabis has been linked to an increased risk for psychosis, irrespective of confounding factors such as age, gender, use of other drugs and reverse causality. Over the last few years a great deal of research has been done to broaden our understanding of the underlying mechanisms of this link. AIM: To update studies that have examined the link between cannabis use and psychosis and that have investigated the possible mechanisms underlying this link. METHOD: This article discusses recent epidemiological and experimental research that sheds light on the nature of the link and the influence of interactions between genes and environment. RESULTS: The long-term effects of cannabis on the risk factors for psychosis and psychotic disorders are influenced to a large extent by genetic and environmental factors. Furthermore, patients with a psychotic disorder seem to be extremely vulnerable to the acute effects of cannabis. CONCLUSION: Studies show that cannabis use is an important risk factor for psychosis and psychotic disorders. So far, however, less research has been done into the effects of cannabis use on patients already suffering from a psychotic disorder.

[Saphenous perforator flap]. / Der Saphenusperforatorlappen.

OBJECTIVE: Replacement of full thickness soft tissue defects in the lower leg and ankle, appropriate to the defect and following the course of blood vessels feeding the skin of a distally hinged fasciocutaneous flap most reliably based on the individual anatomy of distal perforators of the posterior tibial artery. INDICATIONS: Full thickness soft tissue defects, up to 12 cm in length and up to 8 cm in width. Sufficient vascularization of the foot required, in osteomyelitis, and when joints, fractures, implants and tendons are exposed and when a split skin graft, a local flap, a suralis perforator flap or a free flap is not indicated. CONTRAINDICATIONS: For patients, in whom a 1-2 h operation is not possible; necessity of angioplasty; decollement or scars around the distal perforators of the posterior tibial artery; local infection or necrosis of soft tissues and/or bone, which cannot be totally excised. SURGICAL TECHNIQUE: Radical debridement; flap dissection without tourniquet; microdissection; design of the flap on the skin: pivot point ~ 10 cm (6-14 cm) proximal of the tip of the medial malleolus; base ~ 5 cm in width, between the course of the saphenous nerve and of the great saphenous vein and the Achilles tendon; adipofascial pedicle up to 15 cm in length sited over the septum between soleus and flexor digitorum muscles, following the course of the saphenous nerve, with a central skin stripe, which expands into a proximal skin island; skin island is outlined similar to the defect, but larger by 1 to 2 cm, surrounded by an adipofascial border: adjustment of the planning as well as of the elevation of these flaps according to the individual position and the caliber of perforators requires in each case the search for a perforator at the estimated pivot point. Delay of transposition, if the division of more than one perforator proximal to the pivot point obviously diminishes circulation. No "tunnelling "of the pedicle; defects of skin due to the elevation of the flap are replaced by split and meshed skin grafts or temporary by "artificial skin". A gap in the bandage over the skin island allows for observation. POSTOPERATIVE MANAGEMENT: Protocol of controls of vascularization: color and time for revascularization; antibiotic treatment according to bacteriological testing. In case of edema or discoloration of the flap: immediate removal of sutures, administration of leeches, operative revision. Split skin graft 1 week after flap transposition, if the skin had been temporary substituted. RESULTS: Retrospective uncontrolled study with over 70 saphenous perforator flaps from 1995-2011. Full soft tissue defects 62 times with osteomyelitis, 3 times with endoprothesis, 3 times with fractures, 2 times with exposed tendons. From 1995-2006, 44/50 (88 %) flaps healed completely or at least to 3/4 without the necessity of further flaps; from 2007-2011, 13/20 (65 %) flaps healed completely and 6/20 (30 %) flaps healed at least to 3/4 without the necessity of further flaps, loss of one flap (5 %).

[Biomechanical investigation of the tensile strength of tendon sutures - locking sutures increase stability]. / Biomechanische Untersuchung der Zugfestigkeit von Sehnennähten - blockierende Zwischenknoten erhöhen die Stabilität.

PURPOSE: In this study we examined the tensile strength of core sutures of tendons. In particular, we examined the effect of having 2 or 4 stitch strands in the core suture as well as the effect of additional locking sutures on the tensile strength. MATERIAL AND METHOD: 60 flexor tendons from the forepaws of freshly slaughtered swines were harvested for biomechanical testing. They were divided into 4 groups (A, B, C and D) of 15 sutures each. Group A: core suture after Zechner with 2 strands; group B: modified core suture with 4 strands; group C: modified core suture with 2 strands and 4 locking sutures; group D: modified core suture with 4 strands and 4 locking sutures. The primary tensile strength of the sutures was measured in Newton using the testing machine with a traction speed of 0.1 mm/s. Simultaneously, the increasing space forming at the suture was filmed against graph paper. Our command variables were force measured in Newton when forming a space of 2 mm as well as the force at which the suture failed. Statistical analysis was carried out with the software SPSS to produce a multivariate analysis with a statistical significance of p<0.05. RESULTS: Results are presented as averages including the 1st and 3rd quartile (1Q/3Q). Under traction to form a 2 mm space, the force measured with group A was 14.2 N (12.9/15.1 N). In group B the force 22.5 N (20.0/24.7 N) was significantly higher (p<0.05). Group C required a traction force of 28.7 N (23.5/35.8 N) which was significantly higher than for groups A and B. Group D required the significantly highest traction force of 42.0 N (39.5/46.0 N) to produce a 2 mm space. The force required for the suture to fail in group A was 19.9 N (17.9/22.8 N), in group B: 26.2 N (24.5/29.7 N), in group C 32.0 N (27.1/40.1 N) and in Group D 46.5 N (41.5/50.0 N); the differences between the gloups were all statistically significant. CONCLUSION: The primary tensile strength of core sutures after Zechner on flexor tendons from the forepaws of swines was significantly increased by doubling the number of sutures and also by use of 4 additional locking sutures.

Childhood adversity and psychosis: examining whether the association is due to genetic confounding using a monozygotic twin differences approach.

PURPOSE: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. METHOD: Childhood adversity and psychotic experiences were assessed in an ongoing sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. RESULTS: In the whole sample, childhood adversity was significantly associated with positive (ß=45; SE=0.16; P=0.008) and negative psychotic experiences (ß=0.77; SE=0.18; P<0.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (ß=71; SE=0.29; P=0.016) and negative psychotic experiences (ß=98; SE=0.38; P=0.014) in a subsample of 85 MZ twin pairs. CONCLUSIONS: Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that this association is not due to genetic confounding.

Testing the hypothesis that psychotic illness begins when subthreshold hallucinations combine with delusional ideation.

OBJECTIVE: While hallucinations and delusions are often considered as a single class of 'positive symptoms', little is known about their dynamic cooccurrence in relation to clinical outcome in non-help-seeking people. METHOD: The Netherlands Mental Health and Incidence Study (NEMESIS-1) is a longitudinal study of mental disorders (n = 7075) with three measurements over a 3-year period. Risk factors, persistence of psychotic experiences, and clinical outcome were analyzed for groups with: i) no psychotic experiences, ii) only delusions, iii) only hallucinations, and iv) both delusions and hallucinations. RESULTS: Hallucinations and delusions occurred together more often (T0, 3.5%; T1, 1.0%; T2, 0.9%) than that predicted by chance (T0, 1.0%; T1, 0.1%; T2, 0.04%). The group with both symptoms showed more 'first-rank'-like delusions compared with the group with only delusions. Having both hallucinations and delusions, compared to isolated symptoms, was associated more strongly with risk factors, comorbid affective symptoms, negative symptoms, and persistence of psychotic experiences. This was not an artifact of having more symptoms in general. CONCLUSION: Experiencing both delusions and hallucinations is an indicator of greater etiological load resulting in more clinical outcome. A specific 'hallucinatory-delusional state' may represent an early phase of exacerbation of aberrant attribution of salience, increasing risk for clinical outcome.

[Results of flexor tendon sutures of the fingers with 2-strand (40 tendons) and 4-strand (64 tendons) core sutures]. / Ergebnisse von Nähten der Beugesehnen der Finger mit Kernnähten aus 2-Strängen (40 Sehnen) und Kernnähten aus 4-Strängen (64 Sehnen).

PURPOSE: This retrospective examination compares the results of finger flexor tendon sutures with 2 strands and 4 strands. It was checked, whether and how 2 more strands influenced the rupture rate, the movement of the finger and the contentment of the patients. METHODS AND MATERIAL: From 1996 to 2000 for the core suture of the flexor tendon of fingers we used 2 strands. 35 patients with 40 tendon sutures of 73 patients were examined. From 2001 to 2005 we used for the core suture 2 loop threads. 53 patients with 64 tendon sutures from a total of 111 patients were examined. At least 12 months had passed between operation and the examination. The rupture rate and the range of movement of each finger joint and the total mobility of the affected fingers were evaluated. Each case was compared to the uninjured opposite hand. The functional result was judged according to the score of Buck-Gramcko. The patient's contentment was recorded by the DASH (disability of arm, shoulder and hand) score. Effects of gender, age, accompanying injuries, zone of the injury and their influence on the results were analysed. RESULTS: The Buck-Gramcko score showed in the 2-strand group a distribution from summarised 70% "excellent" and "good" and 30% "fair" and "poor". In the 4-strand-group the relation was 93.7% "excellent" and "good", 6.3% "fair", one "poor". In the 2-strand group 2/40 (5%) of the tendon sutures ruptured, in the 4-strand group 1/64 (1.6%) ruptured. The average DASH value in the 2-strands-group was 16.6/100, in the 4-strands-group 18.1/100 when 0 is the best possible result and 100 the worst. The patient judgement in the 2-strand group was summarised to 70% for "excellent" and "good" and 30% "fair" and "poor". In the 4-strand group the patient's judgment was summarised in 75% "excellent" and "good" and in 25% "fair". CONCLUSION: The results of flexor tendon sutures with 4-strand core sutures have been superior to the results with 2-strand core suture according to range of motion of the fingers (P <0.005).