Pain Assessment Discrepancies: A Cross-Sectional Study Highlights the Amount of Underrated Pain.

BACKGROUND: Inadequately treated postoperative pain can lead to longer healing processes, longer hospital stays, and the development of chronic pain. In a 900-bed university hospital in Switzerland, pain scores were assessed systematically. The study's primary aim was to define whether the routine pain assessment on the ward is accurate and reproducible. Subsequently the obtained data were used for a benchmark analysis to determine the hospital's performance in pain assessment quality compared with similar centers. METHODS: During a 3-month period, PAIN OUT questionnaires were used for patients' interviews. Patients were included randomly according to the daily surgical schedule. Pain scores were assessed routinely by nursing staff on the wards and compared to PAIN OUT data. The ascertained data were analyzed by descriptive statistics as well as the Wilcoxon test for nonparametric values using IBM SPSS. RESULTS: 658 patients were included in the study. Comparing routine pain measurements with PAIN OUT results revealed that within the first 24 hours on the ward, pain scores were significantly lower than measured with PAIN OUT questionnaires. This difference increased with increasing pain scores. The quality of pain management of the hospital in which this study was performed ranged around the 50th percentile when compared to similar centers. CONCLUSION: The cross-sectional data comparison of pain assessment by the ward staff and by interviews with the PAIN OUT questionnaire showed a large gap of underrated pain. The benchmark analysis with the method of PAIN OUT suggests a decent pain management among reference groups.

Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter Emergency Medical Service.

BACKGROUND: Pain is frequently encountered in the prehospital setting and needs to be treated quickly and sufficiently. However, incidences of insufficient analgesia after prehospital treatment by emergency medical services are reported to be as high as 43%. The purpose of this analysis was to identify modifiable factors in a specific emergency patient cohort that influence the pain suffered by patients when admitted to the hospital. METHODS: For that purpose, this retrospective observational study included all patients with significant pain treated by a Swiss physician-staffed helicopter emergency service between April and October 2011 with the following characteristics to limit selection bias: Age > 15 years, numerical rating scale (NRS) for pain documented at the scene and at hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and National Advisory Committee for Aeronautics score < VI. Univariate and multivariable logistic regression analyses were performed to evaluate patient and mission characteristics of helicopter emergency service associated with insufficient pain management. RESULTS: A total of 778 patients were included in the analysis. Insufficient pain management (NRS > 3 at hospital admission) was identified in 298 patients (38%). Factors associated with insufficient pain management were higher National Advisory Committee for Aeronautics scores, high NRS at the scene, nontrauma patients, no analgesic administration, and treatment by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics were administered. Factors associated with this untreated persisting pain were short time at the scene (below 10 minutes), secondary missions of helicopter emergency service, moderate pain at the scene, and nontrauma patients. Sufficient management of severe pain is significantly better if ketamine is combined with an opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007). CONCLUSIONS: In the studied specific Swiss cohort, nontrauma patients, patients on secondary missions, patients treated only for a short time at the scene before transport, patients who receive no analgesic, and treatment by a female physician may be risk factors for insufficient pain management. Patients suffering pain at the scene (NRS > 3) should receive an analgesic whenever possible. Patients with severe pain at the scene (NRS ≥ 8) may benefit from the combination of ketamine with an opioid. The finding about sex differences concerning analgesic administration is intriguing and possibly worthy of further study.

The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.

Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia.

A presenilin 1 mutation in the first case of Alzheimer's disease: revisited.

BACKGROUND: Recently, a single point mutation in the presenilin 1 (PSEN1) gene of the first described Alzheimer's disease (AD) patient Auguste D was reported by Müller and co-workers. However, the sequencing results of the DNA from a 100-year-old tissue contained some uncertainties. METHODS: We heat extracted DNA from an original histological slice of Auguste D's brain and used nested polymerase chain reaction for the amplification of different exons of genes known to be affected in familial forms of AD. RESULTS: Our sequencing analysis did not validate the reported mutation. Furthermore, an extended sequencing analysis of Auguste D's DNA revealed no indication of a nonsynonymous hetero- or homozygous mutation in the exons of APP, PSEN1, and PSEN2 genes comprising the already known familial AD mutations. CONCLUSION: Despite the wealth of data from Müller and co-workers, our results emphasize the requirement of more detailed analysis of Auguste D's DNA in future.

Sensitivities of rat primary sensory afferent nerves to magnesium: implications for differential nerve blocks.

CONTEXT: Contrasting findings have been published regarding the role of magnesium sulphate used as an additive to local anaesthetics in peripheral nerve blocks. OBJECTIVE: To clarify the effect of magnesium sulphate on nerve excitability. SETTING: C and Aß compound action potentials were recorded extracellularly in vitro in saphenous nerves from adult rats. ANIMALS: Saphenous nerves (n = 30) from male Wistar rats (n = 19), 12 to 16 weeks old. INTERVENTION: Primary sensory afferents were tested with a computerised threshold tracking program (QTRAC) with a supramaximal 1 ms current pulse either alone or after 300 ms of conditioning polarising ramp currents in the presence and absence of 10 mmol l magnesium sulphate, 80 µmol l lidocaine and a combination of both. MAIN OUTCOME MEASURES: Changes in current thresholds to elicit compound action potential amplitudes of 40% of the maximal response. RESULTS: Magnesium sulphate increased excitability thresholds to a greater extent in Aß fibres than in C fibres. It enhanced the effects of lidocaine in both Aß fibres [mixture 0.470 mA (SD 0.105) versus lidocaine 0.358 mA (SD 0.080), P < 0.001] and C fibres [mixture 2.531 mA (SD 0.752) versus lidocaine 2.385 mA (SD 0.656), P = 0.008]. Preconditioning experiments also showed that magnesium sulphate had an enhancing effect with lidocaine in Aß fibres [mixture 0.620 mA (SD 0.281) versus lidocaine 0.543 mA (SD 0.315), P = 0.005], but not in C fibres [mixture 2.412 mA (SD 0.641), lidocaine 2.461 mA (SD 0.693), P = 0.17]. CONCLUSION: These results suggest that the binding of magnesium ions depends on both the type and conformational state of voltage-gated sodium channels. They also may help to explain the conflicting reports regarding the clinical effects of magnesium sulphate as an additive to lidocaine in peripheral nerve blocks.

Preconditioning depolarizing ramp currents enhance the effect of sodium channel blockers in primary sensory afferents.

OBJECTIVES: The conformational state of voltage-gated sodium channels is an important determinant for the efficacy of both local anesthesia and electrical neuromodulation techniques. This study investigated the role of subthreshold preconditioning ramp currents on axonal nerve excitability parameters in the presence of sodium channel blockers in myelinated A and unmyelinated C fibers. MATERIALS AND METHODS: A- and C-fiber compound action potentials were recorded extracellularly in vitro in saphenous nerve from adult rats. Nerve fibers were stimulated with a supramaximal current pulse either alone or after a 300-msec conditioning polarizing ramp current (between -10% and +100% of the original threshold current) in the presence and absence of lidocaine and tetrodotoxin (TTX). A computerized threshold tracking program (QTRAC), Institute of Neurology, University College London, London, UK) was used to determine the membrane thresholds. RESULTS: Preconditioning ramp currents of weak strengths increased membrane excitability. Stronger preconditioning ramp currents enhanced the potency of lidocaine and TTX to increase excitability thresholds. In A and C fibers stimulated with ramp currents of 110% (A fibers) and 40% (C fibers), lidocaine (80 µM) induced a 168 ± 15% (p < 0.001) and 302 ± 23% (p < 0.001) increase in threshold, respectively (no ramp current: 135 ± 9% and 124 ± 4%, respectively). TTX (16 nM) induced an increase in threshold of 455 ± 45% (p < 0.001) and 214 ± 22% (p = 0.005), respectively (no ramp current: 205 ± 12% and 128 ± 6%, respectively). CONCLUSIONS: Slow preconditioning ramp stimuli inactivate sodium currents. In the presence of sodium channel blockers, stronger ramp stimuli cause an increase in threshold, which is larger than that caused by the sodium channel blocker alone. Therefore, we conclude that small depolarizing ramp currents could be used to increase excitability threshold in the presence of low concentrations of local anesthetics. These additive effects might represent a target to address with peripheral nerve stimulation in order to suppress afferent pain signaling.

Prevalence of medication overuse headache in an interdisciplinary pain clinic.

BACKGROUND: Medication overuse headache (MOH) has been recognized as an important problem in headache patients although the pathophysiological mechanisms remain unclear. The diagnosis of MOH is based on clinical characteristics defined by the International Headache Society. The aim was the evaluation of the diagnostic criteria of MOH in a mixed population of chronic pain patients to gain information about the prevalence and possible associations with MOH. METHODS: Data of all patients referred to the interdisciplinary pain clinic at the University Hospital of Zurich between September 2005 and December 2007 were retrospectively analyzed. Demographic data (age, sex, history of migration), as well as data about duration of pain disease, category of pain disease (neurological, psychiatric, rheumatologic, other), use of medication, history of trauma, and comorbidity of depression and anxiety have been collected. RESULTS: Totally 178 of 187 consecutive chronic pain patients were included in the study. A total of 138 patients (78%) used analgesics on 15 or more days per month. Chronic headache was more prevalent among patients with analgesic overuse (39.8%) than without analgesic overuse (18%). The prevalence of MOH was 29%. The odds ratio (OR) for a patient with medication overuse to have chronic headache was 13.1 if he had a history of primary headache, compared to a patient without a primary headache syndrome. Furthermore, history of headache (OR 2.5, CI [1.13;5.44]), history of migration (OR 2.9, CI [1.31;6.32]) and comorbid depression (OR 3.5, CI [1.46;8.52]) were associated with overuse of acute medication, in general. CONCLUSIONS: Primary headaches have a high risk for chronification in patients overusing analgesics for other pain disorders. Whereas history of headache, history of migration and comorbidity of depression are independentely associated with analgesic overuse in this group of patients.

Impact of restrictive intravenous fluid replacement and combined epidural analgesia on perioperative volume balance and renal function within a Fast Track program.

BACKGROUND AND OBJECTIVE: Key factors of Fast Track (FT) programs are fluid restriction and epidural analgesia (EDA). We aimed to challenge the preconception that the combination of fluid restriction and EDA might induce hypotension and renal dysfunction. METHODS: A recent randomized trial (NCT00556790) showed reduced complications after colectomy in FT patients compared with standard care (SC). Patients with an effective EDA were compared with regard to hemodynamics and renal function. RESULTS: 61/76 FT patients and 59/75 patients in the SC group had an effective EDA. Both groups were comparable regarding demographics and surgery-related characteristics. FT patients received significantly less i.v. fluids intraoperatively (1900 mL [range 1100-4100] versus 2900 mL [1600-5900], P < 0.0001) and postoperatively (700 mL [400-1500] versus 2300 mL [1800-3800], P < 0.0001). Intraoperatively, 30 FT compared with 19 SC patients needed colloids or vasopressors, but this was statistically not significant (P = 0.066). Postoperative requirements were low in both groups (3 versus 5 patients; P = 0.487). Pre- and postoperative values for creatinine, hematocrit, sodium, and potassium were similar, and no patient developed renal dysfunction in either group. Only one of 82 patients having an EDA without a bladder catheter had urinary retention. Overall, FT patients had fewer postoperative complications (6 versus 20 patients; P = 0.002) and a shorter median hospital stay (5 [2-30] versus 9 d [6-30]; P< 0.0001) compared with the SC group. CONCLUSIONS: Fluid restriction and EDA in FT programs are not associated with clinically relevant hemodynamic instability or renal dysfunction.

Protons regulate the excitability properties of rat myelinated sensory axons in vitro through block of persistent sodium currents.

Little information is available on the pH sensitivity of the excitability properties of mammalian axons. Computer-assisted threshold tracking in humans has helped to define clinically relevant changes of nerve excitability in response to hyperventilation and ischaemia, but in vivo studies cannot directly differentiate between the impact of pH and other secondary factors. In this investigation, we applied an excitability testing protocol to a rat saphenous skin nerve in vitro preparation. Changes in extracellular pH were induced by altering pCO(2) in the perfusate, and excitability properties of large myelinated fibres were measured in the pH range from 6.9 to 8.1. The main effect of protons on nerve excitability was a near linear increase in threshold which was accompanied by a decrease in strength-duration time constant reflecting mainly a decrease in persistent sodium current. In the recovery cycle, late subexcitability following 7 conditioning stimuli was substantially reduced at acid pH, indicating a block of slow but not of fast potassium channels. Changes in threshold electrotonus were complex, reflecting the combined effects of pH on multiple channel types. These results provide the first systematic data on pH sensitivity of mammalian nerve excitability properties, and may help in the interpretation of abnormal clinical excitability measurements.

Imaginative resonance training (IRT) achieves elimination of amputees' phantom pain (PLP) coupled with a spontaneous in-depth proprioception of a restored limb as a marker for permanence and supported by pre-post functional magnetic resonance imaging (fMRI).

Non-pharmacological approaches such as mirror therapy and graded motor imagery often provide amelioration of amputees' phantom limb pain (PLP), but elimination has proved difficult to achieve. Proprioception of the amputated limb has been noted in studies to be defective and/or distorted in the presence of PLP, but has not, apparently, been researched for various stages of amelioration up to the absence of PLP. Previous studies using functional magnetic resonance imaging (fMRI) suggested that pathological cortical reorganisation after amputation may be the underlying neurobiological correlate of PLP. We report two cases of permanent elimination of PLP after application of imaginative resonance training. The patients, 69 years and 84 years old, reported freedom from PLP together with in-depth achievement of proprioception of a restored limb at the end of the treatment, which may thus be taken as an indication of permanence. Pre/post fMRI for the first case showed, against a group of healthy controls, analogous changes of activation in the sensorimotor cortex.

Reduced laterality as a trait marker of schizophrenia--evidence from structural and functional neuroimaging.

Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia.

Spinal opioid receptor-sensitive muscle afferents contribute to the fatigue-induced increase in intracortical inhibition in healthy humans.

We investigated the influence of spinal opioid receptor-sensitive muscle afferents on cortical changes following fatiguing unilateral knee-extensor exercise. On separate days, seven subjects performed an identical five sets of intermittent isometric right-quadriceps contractions, each consisting of eight submaximal contractions [63 ± 7% maximal voluntary contraction (MVC)] and one MVC. The exercise was performed following either lumbar interspinous saline injection or lumbar intrathecal fentanyl injection blocking the central projection of spinal opioid receptor-sensitive lower limb muscle afferents. To quantify exercise-induced peripheral fatigue, quadriceps twitch force (Q(tw,pot)) was assessed via supramaximal magnetic femoral nerve stimulation before and after exercise. Motor evoked potentials and cortical silent periods (CSPs) were evaluated via transcranial magnetic stimulation of the motor cortex during a 3% MVC pre-activation period immediately following exercise. End-exercise quadriceps fatigue was significant and similar in both conditions (Q(tw,pot) -35 and -39% for placebo and fentanyl, respectively; P = 0.38). Immediately following exercise on both days, motor evoked potentials were similar to those obtained prior to exercise. Compared with pre-exercise baseline, CSP in the placebo trial was 21 ± 5% longer postexercise (P < 0.01). In contrast, CSP following the fentanyl trial was not significantly prolonged compared with the pre-exercise baseline (6 ± 4%). Our findings suggest that the central effects of spinal opioid receptor-sensitive muscle afferents might facilitate the fatigue-induced increase in CSP. Furthermore, since the CSP is thought to reflect inhibitory intracortical interneuron activity, which may contribute to central fatigue, our findings imply that spinal opioid receptor-sensitive muscle afferents might influence central fatigue by facilitating intracortical inhibition.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

BACKGROUND: Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients. OBJECTIVE: To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions. DESIGN: A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259) SETTING: University College London Hospitals Pain Management Centre. PATIENTS: Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment. INTERVENTION: IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days. MEASUREMENTS: The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment. RESULTS: 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported. LIMITATION: The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation. CONCLUSION: IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed. PRIMARY FUNDING SOURCE: Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

Continuous elastomeric pump-based ropivacaine wound instillation after open abdominal aortic surgery: how reliable is the technique?

INTRODUCTION: We aimed at quantifying the impact of continuous wound infusion with ropivacaine 0.33% on morphine administration and subjective pain relief in patients after open abdominal aortic repair in a double-blind, placebo-controlled study. METHODS: Before closing the abdominal wound, 2 multihole ON-Q® Soaker Catheters™ (I-Flow Corporation, Lake Forest, California, USA) were placed pre-peritoneally in opposite directions. Either ropivacaine 0.33% or saline 0.9% was delivered by an elastomeric pump at a rate of 2 mL/h for 72 hours in each of the catheters. Postoperative pain and morphine administration were assessed using the numerical rating scale (NRS) in 4-hour intervals. Total plasma concentrations of ropivacaine, unbound ropivacaine, and α1-acid glycoprotein (AAG) were measured daily. Mean arterial pressure, pulse rate, oxygen saturation, total amount of morphine administration, ventilation time, and length of stay in the intensive care unit (ICU) were recorded. At the end of the study period, the wound site and the condition of the catheters were assessed. RESULTS: The study was terminated prematurely due to a malfunction of the elastomeric balloon pump resulting in toxic serum levels of total ropivacaine in 2 patients (11.4 µmol/L and 10.0 µmol/L, respectively) on the second postoperative day. Six patients had been allocated to the ropivacaine group, and 9 patients had been allocated to the control group. Demographic and surgical data were similar in both groups. During the first 3 postoperative days, no difference between the ropivacaine and the control group was found in NRS (P = .15, P = .46, and P = .88, respectively) and morphine administration (P = .48). Concentrations of unbound serum ropivacaine (0.11 ± 0.08 µmol/L) were below toxic level in all patients. CONCLUSION: Continuous wound infusion of ropivacaine 0.33% 2 mL/h using an elastomeric system was not reliable and did not improve postoperative pain control in patients after open abdominal aortic surgery.

Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS.

The CNS-restricted versican splice-variant V2 is a large chondroitin sulfate proteoglycan incorporated in the extracellular matrix surrounding myelinated fibers and particularly accumulating at nodes of Ranvier. In vitro, it is a potent inhibitor of axonal growth and therefore considered to participate in the reduction of structural plasticity connected to myelination. To study the role of versican V2 during postnatal development, we designed a novel isoform-specific gene inactivation approach circumventing early embryonic lethality of the complete knock-out and preventing compensation by the remaining versican splice variants. These mice are viable and fertile; however, they display major molecular alterations at the nodes of Ranvier. While the clustering of nodal sodium channels and paranodal structures appear in versican V2-deficient mice unaffected, the formation of the extracellular matrix surrounding the nodes is largely impaired. The conjoint loss of tenascin-R and phosphacan from the perinodal matrix provide strong evidence that versican V2, possibly controlled by a nodal receptor, organizes the extracellular matrix assembly in vivo.

Specialization in the default mode: Task-induced brain deactivations dissociate between visual working memory and attention.

The idea of an organized mode of brain function that is present as default state and suspended during goal-directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task-induced deactivations across a wide range of cognitive tasks. In this event-related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task-induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention-selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM-selective deactivations were found predominantly in the right hemisphere including the medial-parietal, the lateral temporo-parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task-specific functional connectivity. These findings demonstrate that task-induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand ("the core DMN") and a part whose deactivation depends on the specific task.

Influence of neuronal cell adhesion molecule (NCAM1) variants on suicidal behaviour and correlated traits.

Suicide is a public health problem all around the world. Family studies showed a strong heritability but, to date, few genetic data are available. Thus, in the present study we investigated whether a panel of single nucleotide polymorphisms (SNPs) in neuronal cell adhesion molecule 1 (NCAM) 1 was associated with suicidal behaviour as well as specific traits related to suicide. A total of two hundred and fifty-nine individuals with a positive history of suicidal behaviour and 312 healthy subjects were enrolled in the study. Rs2301228, rs1884, rs1245113, rs1369816, rs2196456 and rs584427 in NCAM1 were genotyped. No marker was significantly associated with suicidal behaviour vs. controls or with sub-types of attempted vs. completed, violent vs. non-violent, impulsive vs. non-impulsive suicide. Nonetheless rs1884 and rs2196456 SNPs were both marginally associated with the trait "inhibition of aggressiveness" in suicide attempters. Even though the investigated SNPs in NCAM1 do not seem to be directly associated with suicidal behaviour, our results could suggest that SNP variants in NCAM1 may impact on related traits, particularly by mediating inhibition of aggressiveness. However, independent studies are needed to validate these results.

Mental imagery vividness as a trait marker across the schizophrenia spectrum.

We investigated the vividness of mental imagery and its possible relationship with the predisposition towards hallucinations in 52 schizophrenia (SZ) patients, 44 of their first-degree relatives (R) and two healthy control groups (high-schizotypy [CHS; n=24]; low-schizotypy [CLS; n=24]). We investigated phenomenological and cognitive trait markers of schizophrenia, including cognitive correlates of hallucinations and vividness of mental imagery, and the influence of individual psychopathology. Overall, scores on the mental imagery questionnaire (QMI [Sheehan, P.W., 1967. Reliability of a short test of imagery. Perceptual and Motor Skills 25, 744.]) suggested higher mental imagery vividness in first-degree relatives, high-schizotypy controls and patients, than in low-schizotypy controls. However, vividness of mental imagery was independent of predisposition towards hallucinations and cognitive test performance scores. These results suggest that vividness of mental imagery may be a trait marker across the schizophrenia spectrum. In addition we propose that imagery proneness is relatively independent of the individual psychopathology.

Conversion to dementia in mild cognitive impairment is associated with decline of N-actylaspartate and creatine as revealed by magnetic resonance spectroscopy.

The purpose of the present study was to longitudinally track changes of metabolite markers detectable by magnetic resonance spectroscopy (MRS) in subjects with mild cognitive impairment (MCI) and to analyze these changes with respect to the rate of cognitive decline and clinical disease progression. Fifteen subjects with MCI and 12 healthy elderly controls were investigated longitudinally (average follow-up period: 3.4 years) using absolute quantification of metabolites within the mid-parietal grey matter and the parietal white matter [N-acetylaspartate (NAA), myo-inositol, choline, creatine, glutamine)] Our main findings include that a longitudinal decline in cognitive function (particularly in memory function) within the MCI group was predicted by a decline in absolute concentrations of the metabolic markers NAA and creatine. This effect was mainly explained by a significant decrease of NAA and creatine in those MCI subjects who converted to Alzheimer's dementia (AD) during the follow-up period. No differences were found at baseline between MCI converters and stable subjects, indicating that at least in the present study MRS did provide a predictive discrimination between converters and stable subjects. Our findings support the use of MRS as a tool for objectively monitoring disease progression even during the earliest stages of AD.

Anatomical brain connectivity and positive symptoms of schizophrenia: a diffusion tensor imaging study.

Structural brain changes in schizophrenia are well documented in the neuroimaging literature. The classical morphometric analyses of magnetic resonance imaging (MRI) data have recently been supplemented by diffusion tensor imaging (DTI), which mainly assesses changes in white matter (WM). DTI increasingly provides evidence for abnormal anatomical connectivity in schizophrenia, most often using fractional anisotropy (FA) as an indicator of the integrity of WM tracts. To better understand the clinical significance of such anatomical changes, we studied FA values in a whole-brain analysis comparing paranoid schizophrenic patients with a history of auditory hallucinations and matched healthy controls. The relationship of WM changes to psychopathology was assessed by correlating FA values with PANSS scores (positive symptoms and severity of auditory hallucinations) and with illness duration. Schizophrenic patients showed FA reductions indicating WM integrity disturbance in the prefrontal regions, external capsule, pyramidal tract, occipitofrontal fasciculus, superior and inferior longitudinal fasciculi, and corpus callosum. The arcuate fasciculus was the only tract which showed increased FA values in patients. Increased FA values in this region correlated with increased severity of auditory hallucinations and length of illness. Our results suggest that local changes in anatomical integrity of WM tracts in schizophrenia may be related to patients' clinical presentation.