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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.

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Ropivacaine is a local anesthetic widely used for regional anesthesia. One of its advantages is low toxicity at plasma concentrations reached systemically during continuous peripheral or central nervous block. The objective of this study was to test the effect of systemic ropivacaine on pain, hyperalgesia, dynamic allodynia, and flare response. This randomized, double-blinded, placebo-controlled, crossover study was carried out in at the Clinical Trials Centre, University of Zurich, Switzerland. Twenty healthy male volunteers were included in the study. Exclusion criteria were contraindications or hypersensitivity to local anesthetics, vulnerable subjects (intellectually or mental impaired), drug, alcohol or nicotine abuse, known peripheral neuropathies, diabetes mellitus and/or congestive heart disease. Ropivacaine and saline were infused intravenously during a subcutaneous electrical stimulation. The stimulation software adjusted the stimulus strength according to the rating on a numeric rating scale (NRS; 0–10) maintaining a NRS of 5. Areas of punctate hyperalgesia, dynamic allodynia, and flare response were measured before and after the infusion. The area of hyperalgesia increased significantly with saline (303 ± 380%, P< 0.05) and ropivacaine (186 ± 137%, P< 0.05). The area of allodynia (253 ± 299%, P< 0.05) and flare response (112 ± 24%, P< 0.05) increased only during the placebo infusion. The results of this study imply that systemic ropivacaine may diminish pain sensitization processes.

Pharmacotherapy in patients with neuropathic pain syndromes (NPS) can be associated with long periods of trial and error before reaching satisfactory analgesia. The aim of this study was to investigate whether a short intravenous (i.v.) infusion of lidocaine may have a predictive value for the efficacy of oxcarbazepine.In total, 16 consecutive patients with NPS were studied in a prospective, uncontrolled, open-label study design. Each patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term oral oxcarbazepine treatment (900–1,500 mg/day). During an observation period of 28 days, treatment response was documented by a questionnaire including the average daily pain score documented on a numeric rating scale (NRS).A total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine treatment due to side effects. In an interim analysis predictive value of the lidocaine infusion was low with a Kendall’s tau correlation coefficient of 0.29 and coefficient of determination R2of 0.119 (95% confidence interval –0.29 to 0.72). As a consequence of this low correlation, the study was discontinued for ethical reasons.In conclusion, lidocaine infusion has a low predictive value for effectiveness of oxcarbazepine—if at all.

The dopaminergic system has been previously associated to behavioral facilitation and aggression, hence making the pathway a good candidate for suicidal behavior. We studied gene variants in the tyrosine hydroxylase (rs3842727, rs6356) and DOPA decarboxylase (rs1451371, rs1470750, rs998850) genes in a sample of 571 individuals consisting of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide and 312 German control subjects. TH variants were not associated with suicide (uncorrected P = 0.023) and related traits. Some marginal associations could be observed for DDC with suicide, violence, anger, and aggression. In conclusion, our study does not support the involvement of TH gene variants as major contributors to suicide, whereas DDC variants could mediate some features related to suicide and be involved in violent suicidal behavior. © 2007 Wiley‐Liss, Inc.

Nitric oxide (NO) is a neurotransmitter which modulates depressive and aggressive behaviors. We studied gene variants of NOS‐I (rs2682826;rs1353939;rs2293049;rs693534) and NOS‐III (rs2070744;rs1799983;rs891512) in a total of 571 cases (167 German suicide attempters, 92 Caucasian suicide completers and 312 German healthy subjects). A NOS‐I risk haplotype C‐G‐G (rs2682826‐rs1353939‐rs693534) was associated with suicidal behavior (P = 0.01), and more specifically with suicide attempts (P = 0.01). Sliding windows analysis showed similar results for the haplotype G‐G (rs1353939‐rs693534) being a risk factor for suicidal behavior (P = 0.01) again especially in suicide attempters (P = 0.004). Additionally, the G‐allele of rs693534 was associated with suicidal behavior (P = 0.005) and more specifically with suicide attempts (P = 0.003). Interestingly, the same haplotype (G‐G) as well as the rs693534 G‐allele were also associated with increased aggression. Regarding NOS‐III, a protective haplotype C‐T‐A (rs2070744‐rs1799983‐rs891512) was observed (P = 0.01) with a pronounced effect against suicide completion (P = 0.005). Sliding window analysis showed the same effect of haplotype T‐A (rs1799983–rs891512) (P = 0.01) which was again protective against suicide completion (P = 0.006). Single marker analysis showed the same protective effect of the rs891512 A‐allele (P = 0.009) again especially against suicide completion (P = 0.007). Additionally, a second haplotype (T‐T‐G) was associated with increased aggression (P = 0.0002; sliding haplotype T‐G, P = 0.002). In conclusion, our study suggests a possible involvement of NOS‐I and NOS‐III gene variants in suicidal behavior and related intermediate phenotypes. © 2007 Wiley‐Liss, Inc.

Substance P is involved in the modulation of depression, anxiety, and suicidal‐related behaviors. We studied gene variants of Tachykinin Receptor 1 (TACR1—rs3771810, rs3771825, rs726506, rs1477157) in 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. The rarest rs3771825 T allele however showed a marginal association with higher Reactive Aggression scores on the Questionnaire for Measuring Factors of Aggression (FAF) (F = 9.86, df = 1; P = 0.0017). Haplotype analyses confirmed the finding. Violence or impulsivity of suicide attempt and State‐Trait Anger Expression Inventory (STAXI) scores were not associated with gene variants. In conclusion, our study suggests that TACR1 gene variants have no major influence on suicidal behavior but may modulate aggression features. © 2007 Wiley‐Liss, Inc.

The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide‐related behaviors. We studied gene variants of both receptors in suicide attempters and completers. The sample was composed of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312 German healthy subjects, 152 Italian suicide attempters (major depression n = 68 and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP: rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP: rs1423691, rs878567, and rs6295) variants were analyzed in the German sample. HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype analysis in relation to suicidal behaviors did not reveal any significant association. Single markers and haplotypes were not or only marginally associated with other related features, such as violence of suicide attempt, family history for suicide attempt or State‐Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the notion that HTR2C and HTR1A gene variants are major contributors to suicide‐, anger‐, or aggression‐related behaviors in our sample. © 2006 Wiley‐Liss, Inc.

Diagnosis and therapy of dementia have made considerable progress in recent years. Drugs have been developed which improve cognitive performance, delay the loss of abilities of daily living and prevent early nursing home placement in a considerable number of patients. With the various pharmacological and non-pharmacological approaches, effective treatment options of AD are available at present and the therapeutic potential will even increase in future. Thus, the treatment of dementia should more focused and explicit in its goals for the doctor, the patient and the relatives. Therapeutic targets must be defined on the basis of the individual needs and deficits and with regard to different levels of the disease process. Ideally, treatment should always aim at an etiological and / or a pathophysiological level. At present, however, aiming at the neurotransmitter level, the core syndrome of cognitive deficits can be approached by treatment options. Further therapeutic targets can be defined on the level of activities of daily living, following a resource focused approach, as well as on the level of behavioral disturbances. Additional therapeutic targets should be seen under a humanitarian or palliative perspective. And finally, family members are also targets for therapy in dementia, even if such therapy is not directed towards the demented patient. All these treatment targets have to be evaluated and adapted under the perspective of time because prominent symptoms in AD change considerably with disease progression. Selection and adaptation of medication becomes easier if such targets are considered and if therapeutic effects are monitored targetspecifically.

The visualization of brain structure through computed tomography (CT) and magnetic resonance imaging (MRI) has greatly advanced our knowledge of psychiatric and neuropsychiatric diseases. Further and more refined information about structural and developmental abnormalities in psychiatric disorders can be expected from recent advances in structural MRI such as diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI), which have already been applied to the investigation of white matter defects in, for example, Alzheimer's disease (AD) and schizophrenia . The metabolic changes that underlie or accompany neuropsychiatric diseases, on the other hand, can be probed with the traditional radiotracer methods and with magnetic resonance spectroscopy (MRS), a technique that allows the non-invasive study of in vivo neurochemistry and has already gained a place in the differential diagnosis and the monitoring of the metabolic effects of drug treatment in a number of diseases []. However, if we want to find out how these changes bring about the respective neuropsychiatric diseases, we need to integrate the clinical pictures and structural and metabolic brain imaging with information about deficits in brain function that can, at present, only be obtained through the methods of nuclear medicine and non-invasive neurophysiology and neuroimaging . The large bodies of studies of abnormal brain function with radiotracer methods (for review see, e.g., ) or non-invasive electrophysiology (for review see, e.g., ) in psychiatric patients fall outside the scope of this paper. They do, however, provide the background for the more recent attempts to visualize normal brain function and functional abnormalities using functional MRI (fMRI) based on the blood oxygenation-dependent (BOLD) effect , and most neuropsychiatric fMRI presuppose the findings of earlier radiotracer or electroencephalographic studies. While BOLD fMRI is a particularly promising tool for the study of mental illness, because it can be applied and repeated easily, is widely available, and lends itself to the study of individual functional anatomy , many groups working in the field of psychiatric neuroimaging apply more than one technique, and multimodal neuroimaging, combining fMRI with other functional, metabolic, and structural techniques, will be required for a understanding of the way morphological and neurochemical abnormalities shape the clinical picture of neuropsychiatric disorders . In this paper, we will present the state of fMRI research into the two most widespread neuropsychiatric disorders, schizophrenia and Alzheimer's disease. These disorders have, owing to their multi-faceted neurobiology, so far eluded any attempts at defining unequivocal aetiologies and pathomechanisms. At the same time, they present major public health and socioeconomic issues. It is therefore not surprising that they have attracted the attention of the neuroimaging community in a particular manner.

Background: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns.

The case of a patient with largely preserved intelligence, but severe and persistent memory impairments is reported. FA, a 46-year-old patient with the diagnosis of prolonged depression was investigated repeatedly over a two year period with neuroradiological, neuropsychological, neuromonitoring and other methods. While no brain damage was detectable in FA, he manifested continued and severe anterograde and retrograde memory disorders together with an inhibition in his thinking processes. Otherwise, his intellectual capabilities were in the normal range, that is he was not pseudo-demented. Various approaches with drug treatment and psychotherapy failed to improve his condition. The condition is interpreted as ‘mnestic block syndrome’ and is considered to be related to an altered brain metabolism which may include changes in various transmitter and hormonal systems (GABA-agonists, glucocorticoids, acetylcholine). Whether depression contributes to this syndrome is uncertain from FA's cognitive performance, but may be a possibility.

Topographic brain mapping of EEG and evoked potentials permits the display of spontaneous and event-related activity of the brain. This new method is superior to conventional polygraphy because of the topographic approach which delineates structural and functional brain lesions. Data from 16 to 20 scalp electrodes were evaluated. Not only spontaneous EEG but also EEG during various testing conditions which activated particular brain regions was measured. For EEG fast Fourier transformation (FFT) was used for mapping. For late evoked potentials (VEP, AEP, SEP and P300) a single value representing the amplitude of EP at each 2-ms poststimulus latency point was used. Statistical techniques (Students'-test, correlation coefficient) were used to render the regions where a clinical population differs from normal subjects. The results show abnormalities of EGG and EP in patients with psychiatric and neurological diseases.

Summary Endogenous components of event related potentials are of particular interest in psychiatric diseases because of their relations to cognitive and behavioral processes. We studied the topography of these potentials in order to find out whether there are different scalp distributions in schizophrenic and depressive patients in relation to the psychopathological state and compared to normal controls. Furthermore variations of the topographical scalp distribution of P300 in normal volunteers after administration of physostigmine and biperiden was investigated. We demonstrated a clear relationship of the P300 amplitude with the negative symptom axis and found different topographical scalp distributions in different groups and experimental conditions. Topography of event related potentials is therefore a promising field of investigation for a better understanding of psychiatric disorders.