Aberrant white matter microstructure in treatment-resistant schizophrenia✰.

Treatment response in schizophrenia divides into three subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS), and ultra-treatment-resistant schizophrenia (UTRS). White matter abnormalities could drive antipsychotic resistance but little work has investigated differences between TRS and UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were obtained using tract-based spatial statistics. Analysis of variance and post-hoc t-tests were conducted for each measure. Those with TRS had lower FA than healthy controls in superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). No post-hoc tests survived corrections for multiple comparisons and no differences in MD, AD or RD were observed. These data suggest that microstructural deficits in white matter could contribute to TRS but suggest that other mechanisms may be more relevant for UTRS.

The Effect of Combined Patching and Citalopram on Visual Acuity in Adults with Amblyopia: A Randomized, Crossover, Placebo-Controlled Trial.

Nonhuman animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a crossover, randomized, double-blind, placebo-controlled design, participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our prespecified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean ± SD change = 0.08 ± 0.16 logMAR) and the placebo (mean change = -0.01 ± 0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo blocks. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration, and recruitment challenges. This study was preregistered as a clinical trial (ACTRN12611000669998).

Increased sensorimotor network connectivity associated with clozapine eligibility in people with schizophrenia.

Schizophrenia is a heterogeneous disorder that exhibits variable responsiveness to treatment between individuals. Here we conducted a resting-state functional magnetic resonance imaging (rs-fMRI) study to determine whether resistance to first-line antipsychotics is reflected in resting-state connectivity. rs-fMRI data were collected from 15 people who had failed to respond to first-line antipsychotics (clozapine-eligible) and 10 first-line treatment responders (FLR). Image pre-processing and analysis were performed using FMRIB's software library (FSL). Data was decomposed into spatial and temporal components using independent components analysis. Connectivity within each independent component was compared between groups using t-tests and the Bonferroni correction for multiple comparisons. Gender was added as a covariate. Clozapine-eligible individuals exhibited enhanced functional connectivity within the sensorimotor network compared with FLR. Those eligible for clozapine showed additional connectivity with the precuneus compared with FLR. No other comparisons reached statistical significance and no effect of gender was observed. These data reveal differences in functional connectivity between FLR and those eligible for clozapine and suggest that greater connectivity between the SMN and precuneus may be indicative of treatment resistance in people with schizophrenia.

Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia.

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n=18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n=16). Data were pre-processed using the Advanced Normalization Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p<0.05). Post-hoc t-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future work must determine whether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis.

Disgust but not Health Anxiety Graphic Warning Labels Reduce Motivated Attention in Smokers: A Study of P300 and Late Positive Potential Responses.

Background: Graphic health warning labels (GHWLs) on tobacco products attempt to leverage avoidance-promoting emotions, such as anxiety and disgust, to encourage cessation. Prior studies have relied on self-report or attentional metrics that may not accurately illuminate GHWLs' ability to motivate change. This report evaluates the impact of disgust- and anxiety-based GHWLs on electroencephalograph (EEG) measures of motivated attention among two groups of smokers-those that report higher versus lower cigarette dependence. We hypothesized that both anxiety and disgust GHWLs would reduce appetitive attention, as indexed by lowered P300 (P3) and late positive potential (LPP) activations. Methods: Sixty-one smokers provided demographic and smoking history before completing an oddball paradigm consisting of three counterbalanced stimuli blocks. Each block (100 trials) contained a neutral, GHWL-anxiety, or GHWL-disgust frequent image and a smoking cue as the oddball image (20%). Oddball trials for each block were averaged, P3 and LPP were identified at midline electrode positions (Fz, Cz, and Pz), and mean amplitude was analyzed. Results: Separate mixed-model ANOVAs of P3 and LPP reactivity revealed disgust-focused GHWLs reduced motivated attentional processing. Conversely, the anxiety-focused GHWL appeared to increase the salience of the smoking cue (Fz only). Less-dependent smokers showed lower P3 reactivity than those with higher dependence at Fz, but greater P3 reactivity at Cz and Pz. Conclusion: These results extend prior work in demonstrating that disgust, but not anxiety-based GHWLs, may reduce EEG-assessed motivated attention to smoking cues. Disgust may thus represent a more fruitful target for public health cessation efforts. Implications: Most GHWL evaluations have focused on fear (or anxiety) elicitation rather than disgust, an emotion that may have a unique link to smoking, having evolved specifically to facilitate the avoidance of contaminants via oral incorporation. Analyses of P300 and LPP responses to GHWLs suggest that disgust-focused images interfere with the EEG-indexed attentional processing of smoking cues and do so better than health anxiety-focused messages. However, interaction effects at different electrode sites indicated that GHWLs have complex effects in more versus less-dependent smokers and that an understanding of how smoking cues and anti-smoking imagery become associated over time is needed to identify relevant targets for public health efforts.

Visual cue-specific craving is diminished in stressed smokers.

BACKGROUND: Craving among smokers is increased by stress and exposure to smoking-related visual cues. However, few experimental studies have tested both elicitors concurrently and considered how exposures may interact to influence craving. OBJECTIVE: The current study examined craving in response to stress and visual cue exposure, separately and in succession, in order to better understand the relationship between craving elicitation and the elicitor. METHOD: Thirty-nine smokers (21 males) who forwent smoking for 30 minutes were randomized to complete a stress task and a visual cue task in counterbalanced orders (creating the experimental groups); for the cue task, counterbalanced blocks of neutral, motivational control, and smoking images were presented. Self-reported craving was assessed after each block of visual stimuli and stress task, and after a recovery period following each task. RESULTS: As expected, the stress and smoking images generated greater craving than neutral or motivational control images (p < .001). Interactions indicated craving in those who completed the stress task first differed from those who completed the visual cues task first (p < .05), such that stress task craving was greater than all image type craving (all p's < .05) only if the visual cue task was completed first. Conversely, craving was stable across image types when the stress task was completed first. CONCLUSIONS: Findings indicate when smokers are stressed, visual cues have little additive effect on craving, and different types of visual cues elicit comparable craving. These findings may imply that once stressed, smokers will crave cigarettes comparably notwithstanding whether they are exposed to smoking image cues.

Fluoxetine Does Not Enhance Visual Perceptual Learning and Triazolam Specifically Impairs Learning Transfer.

The selective serotonin reuptake inhibitor fluoxetine significantly enhances adult visual cortex plasticity within the rat. This effect is related to decreased gamma-aminobutyric acid (GABA) mediated inhibition and identifies fluoxetine as a potential agent for enhancing plasticity in the adult human brain. We tested the hypothesis that fluoxetine would enhance visual perceptual learning of a motion direction discrimination (MDD) task in humans. We also investigated (1) the effect of fluoxetine on visual and motor cortex excitability and (2) the impact of increased GABA mediated inhibition following a single dose of triazolam on post-training MDD task performance. Within a double blind, placebo controlled design, 20 healthy adult participants completed a 19-day course of fluoxetine (n = 10, 20 mg per day) or placebo (n = 10). Participants were trained on the MDD task over the final 5 days of fluoxetine administration. Accuracy for the trained MDD stimulus and an untrained MDD stimulus configuration was assessed before and after training, after triazolam and 1 week after triazolam. Motor and visual cortex excitability were measured using transcranial magnetic stimulation. Fluoxetine did not enhance the magnitude or rate of perceptual learning and full transfer of learning to the untrained stimulus was observed for both groups. After training was complete, trazolam had no effect on trained task performance but significantly impaired untrained task performance. No consistent effects of fluoxetine on cortical excitability were observed. The results do not support the hypothesis that fluoxetine can enhance learning in humans. However, the specific effect of triazolam on MDD task performance for the untrained stimulus suggests that learning and learning transfer rely on dissociable neural mechanisms.

Using fMRI to compare the effects of benzylpiperazine with dexamphetamine - Their differences during the Stroop paradigm.

RATIONALE: Benzylpiperazine (BZP) has been found to increase neural activation in the dorsal striatum when compared to placebo in response to a Stroop paradigm, in addition, subjective effects have been compared to dexamphetamine (DEX). Despite their similarities, the two have not been directly compared in respect to their effects on selective attention and inhibition. OBJECTIVES: To use a double-blind placebo-controlled crossover study to compare the acute effects of BZP and DEX on executive function using functional magnetic resonance imaging (fMRI) and an event-related Stroop task. METHODS: Eleven healthy participants aged 18-40 years undertook the Stroop task 90[Formula: see text]min after taking an oral dose of either BZP (200[Formula: see text]mg), DEX (20[Formula: see text]mg) or placebo. RESULTS: BZP induced a greater increase in activation than DEX in the inferior frontal gyrus (IFG) during the Stroop task. DEX increased BOLD signal in the thalamus and decreased it in the IFG in comparison to placebo. CONCLUSION: Despite BZP and DEX reportedly inducing similar subjective effects, there are different patterns of neural activation. We believe this differential activity is due to pharmacological differences in their receptor binding profiles and that subsequent inhibitory effects might be due to their direct effect on dopaminergic activity.

A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population.

BACKGROUND: With a healthcare system burdened by symptomatic and mental-health related conditions, the placebo effect may represent a useful clinical tool. First, however, there is a need to broaden research attention and investigate placebo effects outside laboratories and beyond experimental pain. This study investigated the effectiveness of a take-home placebo treatment in the short-term alleviation of stress, anxiety and symptoms of depression in a non-patient population. METHOD: A sample of 77 participants was randomized to either the 'oxytocin' treatment group (n = 22), the 'serotonin' treatment group (n = 22) or the wait-list control group (n = 33). The two treatment groups were given an 'anti-stress treatment spray' (placebo) to self-administer for 3 days, and completed online measures of perceived stress (Perceived Stress Scale-10), anxiety (Cognitive Somatic Anxiety Questionnaire) and symptoms of depression (Centre for Epidemiological Studies - Depression) before and after the 3-day protocol. RESULTS: Both the 'serotonin' and 'oxytocin' treatment sprays were effective in reducing symptoms of depression; however, only those in the 'oxytocin' group reported less stress and anxiety as compared with controls. Overall, the 'oxytocin' was perceived as more effective. CONCLUSION: Placebo effects can be translated to a real-life setting in the short-term reduction of stress, anxiety and symptoms of depression in a non-patient population. In treating psychological distress, placebos may be useful addition to the treatment repertoire. The information given with treatment may also be an important consideration for practitioners.

Factors Associated With Disability and Sick Leave in Early Complex Regional Pain Syndrome Type-1.

OBJECTIVE: Factors influencing disability and work absence in complex regional pain syndrome type-1 (CRPS)-1 have not been thoroughly described in the literature. We sought to determine whether demographic variables, work-related factors, CRPS clinical severity ratings, pain scores, or psychological variables were associated with disability and sick leave in early CRPS-1. METHODS: A total of 66 CRPS-1 patients were recruited within 12 weeks of CRPS onset. Patients completed measures of pain, depression, anxiety, stress, pain catastrophizing, and pain-related fear. A physical examination was conducted to assess signs and symptoms of CRPS and to calculate a CRPS severity score. Demographic details, clinical details, treatments, work type, and work status were recorded. RESULTS: In multivariate analyses, the following factors were associated with greater disability: higher pain scores, more restricted ankle or wrist extension, and higher levels of depression. Among the 49 who were either working or studying before developing CRPS, 28 had stopped work or study at the time of assessment. Multivariate analyses showed that sick leave was more likely among those whose CRPS was triggered by more severe injuries, whose work was more physically demanding, among those with higher disability scores, and there was also a significant effect of depression on sick leave, which was mediated by disability. DISCUSSION: Although the study was cross-sectional and so cannot differentiate cause from effect, results suggest that even in the early stages of CRPS, a cycle of pain, disability, depression, and work absence can emerge. Treatments aimed to prevent this cycle may help prevent adverse long-term outcomes.

Quantitative EEG and Low-Resolution Electromagnetic Tomography (LORETA) Imaging of Patients Undergoing Methadone Treatment for Opiate Addiction.

Methadone maintenance treatment (MMT) has been used as a treatment for opiate dependence since the mid-1960s. Evidence suggests that methadone binds to mu opiate receptors as do other opiates and induces changes in neurophysiological function. However, little is known, about how neural activity within the higher frequency gamma band (>30 Hz) while at rest changes in those stabilized on MMT despite its association with the excitation-inhibition balance within pyramidal-interneuron networks. Our study investigated differences in resting gamma power (37-41 Hz) between patients undergoing MMT for opiate dependence, illicit opiate users, and healthy controls subjects. Electroencephalographic data were recorded from 26 sites according to the international 10-20 system. Compared with the healthy controls subjects, people either undergoing MMT (mean difference [MD] = 0.32, 95% CI = 0.09-0.55, P < .01) or currently using illicit opiates (MD = 0.31, 95% CI = 0.06-0.56, P = .01) exhibited significant increased gamma power. The sLORETA (standardized low-resolution electromagnetic tomography) between-group comparison revealed dysfunctional neuronal activity in the occipital, parietal, and frontal lobes in the patients undergoing MMT. A more severe profile of dysfunction was observed in those using illicit opiates. Our findings suggest that long-term exposure to opioids is associated with disrupted resting state network, which may be reduced after MMT.

Does cognitive impairment in treatment-resistant and ultra-treatment-resistant schizophrenia differ from that in treatment responders?

This study aimed to investigate whether cognitive impairment is more pronounced in people with treatment-resistant schizophrenia compared with those who respond well to first-line antipsychotic medication. Fifty-one patients with schizophrenia were assigned to one of three groups dependent on their clinical history: (i) 16 people who had responded well to first-line antipsychotic medication, (ii) 20 people who were treatment-resistant but responding to clozapine monotherapy, (iii) 15 people who were ultra-treatment-resistant/clozapine-resistant but responding to antipsychotic polypharmacy. Twenty-two controls were also recruited. Groups were matched for age, sex, disease duration and psychopathology. All participants undertook a computerised battery of neuropsychological tests that assessed multiple cognitive domains. Raw data were converted to z-scores, and test performance was compared between groups. People with schizophrenia performed significantly worse than controls in the majority of neuropsychological tests, with verbal memory, sustained attention, and sensorimotor the most commonly impaired domains. No significant differences in performance between people deemed to be treatment-resistant or ultra-treatment-resistant, and those who responded well to first-line antipsychotic medication were observed. There was no significant relationship between antipsychotic dose and scores on any of the neuropsychological tests. Cognitive impairment is a central feature of schizophrenia, but our results suggest that treatment-resistance may not be associated with more severe deficits.

Do psychological factors influence recovery from complex regional pain syndrome type 1? A prospective study.

Previous studies have shown that the outcomes of complex regional pain syndrome (CRPS) vary significantly between patients, but few studies have identified prognostic indicators. The aim of this study was to determine whether psychological factors are associated with recovery from recently onset CRPS amongst patients followed prospectively for 1 year. Sixty-six patients with CRPS (type 1) were recruited within 12 weeks of symptom onset and assessed immediately and at 6 and 12 months, during which time they received treatment as usual. At each assessment, the following were measured: signs and symptoms of CRPS, pain, disability, depression, anxiety, stress, pain-related fear, pain catastrophising, laterality task performance, body perception disturbance, and perceived ownership of the limb. Mixed-effects models for repeated measures were conducted to identify baseline variables associated with CRPS severity, pain, and disability over the 12 months. Results showed that scores for all 3 outcome variables improved over the study period. Males and those with lower levels of baseline pain and disability experienced the lowest CRPS severity scores over 12 months. Those with lower baseline anxiety and disability had the lowest pain intensity over the study period, and those with lower baseline pain and pain-related fear experienced the least disability over the 12 months. This suggests that anxiety, pain-related fear, and disability are associated with poorer outcomes in CRPS and could be considered as target variables for early treatment. The findings support the theory that CRPS represents an aberrant protective response to perceived threat of tissue injury.

Extensive gray matter volume reduction in treatment-resistant schizophrenia.

BACKGROUND: Approximately one-third of people with schizophrenia are treatment-resistant and some do not achieve remission with clozapine, the gold-standard antipsychotic medication for treatment-resistant schizophrenia. This study compared global and regional brain volumes between treatment-respondent and treatment-resistant patients with schizophrenia, including a group of patients who were clozapine-resistant. METHODS: T1-weighted brain MRIs were obtained on a 3T scanner in 20 controls and 52 people with schizophrenia who were selected based on their symptomatic responses to antipsychotic medication: 18 responded well to first-line atypical antipsychotics (FLR), 19 were treatment-resistant but responsive to clozapine monotherapy (TR), and 15 were ultra-treatment-resistant and did not respond to clozapine (UTR). Treatment groups were matched for disease duration and current psychopathology. SIENAX and FSL-VBM were used to investigate differences in the global brain, gray matter (GM), white matter, ventricular cerebrospinal fluid volumes, and regional GM volumes. RESULTS: GM volume was significantly reduced in the TR and UTR groups compared with controls and the FLR group (p < 0.05). GM volume was significantly reduced in TR patients compared with FLRs in the superior, middle, and inferior temporal gyri, pre- and post-central gyri, middle and superior frontal gyri, right supramarginal gyrus, and right lateral occipital cortex. UTR patients showed reduced GM compared with FLRs in their right parietal operculum and left cerebellum. No significant volume differences were observed between TR and UTR groups. CONCLUSIONS: These differences are unlikely to be solely due to medication effects, and reduced GM volume in treatment-resistant schizophrenia may represent an accelerated disease course or a different underlying pathology.

Glutamatergic neurometabolites in clozapine-responsive and -resistant schizophrenia.

BACKGROUND: According to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated. METHODS: Proton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects. RESULTS: Group differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η(2) = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η(2) = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected). CONCLUSIONS: Total glutamate + glutamine levels scaled to creatine in the putamen may represent a marker of response to clozapine. Future studies should investigate glutamatergic anomalies prior to clozapine initiation and following successful treatment.

The outcome of complex regional pain syndrome type 1: a systematic review.

UNLABELLED: The purpose of this systematic review was to examine the outcome of complex regional pain syndrome (CRPS) type 1. We searched MEDLINE, Embase, and PsycINFO for relevant studies and included 18 studies, with 3,991 participants, in this review. The following data were extracted: study details, measurement tools used, and rates or severity scores for the symptoms/signs of CRPS at baseline and follow-up, or in groups of patients with different disease durations. A quality assessment revealed significant limitations in the literature, with many studies using different diagnostic criteria. The 3 prospective studies demonstrated that for many patients, symptoms improve markedly within 6 to 13 months of onset. The 12 retrospective studies had highly heterogeneous findings, documenting lasting impairments in many patients. The 3 cross-sectional studies showed that rates of pain and sensory symptoms were highest among those with the longest duration of CRPS. Additionally, most studies showed that motor symptoms (stiffness and weakness) were the most likely to persist whereas sudomotor and vasomotor symptoms were the most likely to improve. Overall, this suggests that some CRPS patients make a good early recovery whereas others develop lasting pain and disability. As yet little is known about the prognostic factors that might differentiate between these groups. PERSPECTIVE: We found evidence that many CRPS patients recover within 6 to 13 months, but a significant number experience some lasting symptoms, and some experience chronic pain and disability. The quality of the evidence was poor. Future research should examine the factors associated with recovery and identify those at risk of poor outcomes.

Relationships between psychological factors, pain, and disability in complex regional pain syndrome and low back pain.

OBJECTIVE: Cognitive and emotional factors are known to influence peoples' pain experiences in many conditions, including low back pain. However, in complex regional pain syndrome (CRPS), their role is unclear. This study aimed to assess the relationships between psychological factors, pain, and disability in CRPS, compared with low back pain. This could help to identify target variables for psychological treatment. MATERIALS AND METHODS: A total of 88 CRPS patients and 88 low back pain patients completed measures of pain, disability, depression, anxiety, and fear of movement and reinjury (kinesiophobia). Mean scores between the 2 groups were compared, and correlations between psychological factors, pain, and disability were compared between the 2 groups. Predictors of pain and disability were assessed using multiple regression analyses. RESULTS: The 2 groups had remarkably similar scores on measures of pain, disability, depression, anxiety, and kinesiophobia. In both groups, those who were more depressed, anxious, and kinesiophobic were more disabled. For the CRPS group (but not the low back pain group), pain intensity significantly correlated with distress. Multivariate analyses showed that the unique predictors of disability for the 2 groups were pain and depression, and that depression had a stronger relationship with disability for the CRPS group. For both groups, pain intensity was predicted by kinesiophobia, and anxiety was a unique predictor in the CRPS group only. DISCUSSION: In CRPS, disability and pain severity were more strongly associated with psychological factors than they were in low back pain. Cause and effect relationships could not be established by this cross-sectional study.

Differential responses to anticipation of reward after an acute dose of the designer drugs benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) alone and in combination using functional magnetic resonance imaging (fMRI).

RATIONALE: Functional magnetic resonance imaging (fMRI) studies have reported increased activation of the mesolimbic system in response to anticipation of rewarding stimuli. The anticipation of uncertain outcomes evokes activation in the amygdala, orbitofrontal cortex, inferior frontal gyrus and insula. Drugs known to effect dopaminergic and serotonergic neurons also alter regional activation. OBJECTIVES: Benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been recreationally used worldwide for more than a decade. BZP affects mainly dopaminergic neurons, while TFMPP has serotonergic effects. METHODS: We investigated the effects of an acute dose of BZP, TFMPP or a combination of BZP and TFMPP on the anticipation of reward in a double-blind, placebo-controlled, crossover study using fMRI. An event-related gambling paradigm was completed by healthy controls 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. RESULTS: After giving BZP, the anticipation of a $4 reward decreased the activation of the inferior frontal gyrus, insula and occipital regions in comparison to placebo. TFMPP increased the activation of the putamen but decreased the activity in the insula relative to placebo. When BZP and TFMPP were given in combination, activation of the rolandic operculum occurred. The magnitude of reward also affected neural correlates. CONCLUSION: We propose that the effects of BZP and TFMPP on dopaminergic and serotonergic circuitry, respectively, reflect regional changes. The dopaminergic effects of BZP appear to increase positive arousal and subsequently reduce the response to uncertainty, while TFMPP appears to alter the response to uncertainty by increasing emotional responses.

Compulsory community mental health treatment: literature review.

Following their introduction in the United States in the 1970s various forms of compulsory treatment in the community have been introduced internationally. Compulsory treatment in the community involves a statutory framework that mandates enforceable treatment in a community setting. Such frameworks can be categorized as preventative, least restrictive, or as having both preventative and least restrictive features. Research falls into two categories; descriptive, naturalistic studies and controlled and uncontrolled comparative studies. The research has produced equivocal results, and presents numerous methodological challenges. Where programmes have demonstrated improved outcomes debate continues as to whether these outcomes are associated with legal compulsion or enhanced service provision. Service user, family and clinician perspectives demonstrate a divergence of views within and across groups, with clinicians more strongly in support than service users. The issue of compulsory community treatment is an important one for nurses, who are often at the forefront of clinical service provision, in some cases in statutory roles. Critical reflection on the issue of compulsory community treatment requires understanding of the limitations of empirical investigations and of the various ethical and social policy issues involved. There is a need for further research into compulsory community treatment and possible alternatives.

Caregivers' stresses when living together or apart from patients with chronic schizophrenia.

Ratings of stress and burden and mental symptoms which were screened by the General Health Questionnaire (GHQ) caseness were collected from two types of primary caregivers either living with (n = 37) or separately from (n = 48) a patient with a chronic schizophrenic disorder. The stress levels and burden of caregivers living apart were similar to those who were living together with patients and around 25 percent of both groups met GHQ criterion for having a mental disorder. Multiple regression analyses of all subjects identified stress with the patient's disorder and strain in their own marital relationships as most predictive of their subjective global stress ratings. These results suggest that mental health services should aim to assist key caregivers of people with chronic schizophrenic disorders to manage stress whether or not the patient lives in the same household as the caregiver.