Case-control study of the UCH-L1 S18Y variant in sporadic Parkinson’s disease in the Chinese population

The ubiquitin carboxy-terminal hydrolase L1 gene (UCH-L1) has been implicated in the etiology of Parkinson’s disease (PD). In several previous studies, an S18Y (C54A) polymorphism in exon 3 of the UCH-L1 gene has been found to be protective against PD. We performed polymerase chain reaction-restriction fragment length polymorphism analysis for DNA samples from 408 Chinese patients with PD and 398 Chinese healthy controls. For the S18Y variant, there was no significant difference either in the individual allele or genotype frequencies between cases and control subjects. Possession of the S18Y variant did not alter the risk of developing PD (odds ratio: 0.827; 95% confidence interval = 0.596-1.147). There was no statistically significant difference in terms of age or sex distribution between the patients and controls (p > 0.05). Overall, considering our present results together with those of our previous studies, we now have access to data from more than 1000 patients from different regions of China, supporting the conclusion that the S18Y polymorphism may not have a protective effect against PD in the Chinese population.     

Effects of computerized match-to-sample training on emergent fraction-decimal relations in individuals with fragile X syndrome

Individuals diagnosed with fragile X syndrome (FXS), the most common known form of inherited intellectual disability, are reported to exhibit considerable deficits in mathematical skills that are often attributed to brain-based abnormalities associated with the syndrome. We examined whether participants with FXS would display emergent fraction-decimal relations following brief, intensive match-to-sample training on baseline relations. The performance profiles on tests of symmetry and transitivity/equivalence of 11 participants with FXS, aged 10-23 years, following baseline match-to-sample training were compared to those of 11 age- and IQ-matched controls with idiopathic developmental disability. The results showed that both groups of participants showed significant improvements in the baseline (trained) relations, as expected. However, participants with FXS failed to show significant improvements in the (untrained) symmetry and transitivity/equivalence relations compared to those in the control group. A categorical analysis of the data indicated that five participants with FXS and eight controls showed at least “intermediate” emergence of symmetry relations, whereas one individual with FXS and three controls showed at least intermediate emergence of transitivity/equivalence relations. A correlation analysis of the data indicated that improvements in the symmetry relations were significantly associated with improvements in the transitivity/equivalence relations in the control group (r = .69, p = .018), but this was not the case in the FXS group (r = .34, p > .05). Participant IQ was significantly associated with improvements in the symmetry relations in individuals with FXS (r = .60, p = .049), but not in controls (r = .21, p > .05). Taken together, these results suggest that brief, computerized match-to-sample training may produce emergent mathematical relations for a subset of children with FXS and developmental disabilities. However, the ability of individuals with FXS to form transitivity/equivalence relations may be impaired relative to those with idiopathic developmental disabilities, which may be attributed to neurodevelopmental variables associated with the syndrome.     

Overcoming barriers to disseminating exposure therapies for anxiety disorders: a pilot randomized controlled trial of training methods

The present study evaluated methods for training mental health providers (N = 46) in exposure therapies (ETs) for anxiety disorders. A pilot randomized controlled trial compared: (1) an interactive, multimedia online training (ET OLT), (2) the ET OLT plus a brief Motivational Interviewing-based intervention (ET OLT + MI), and (3) a placebo control OLT. Assessments were completed at baseline, post-training, and one-week following training. Both ET OLT and ET OLT + MI received high satisfaction ratings and were comparably effective at increasing knowledge of ETs as well as clinicians’ overt efforts to learn and use the treatment. ET OLT + MI was the most effective method for improving clinicians’ attitudes toward ETs. Results indicate that OLT is effective for disseminating knowledge about ETs to clinicians, and suggest that supplementing OLT with a brief MI-based intervention may be a promising direction to address potential attitudinal barriers to adopting these highly efficacious treatments.     

Long-term outcome following Intensive Residential Treatment of Obsessive-Compulsive Disorder

Background

IRT has been demonstrated as an effective treatment for severe, refractory OCD.

Methods

Consecutive IRT subjects were ascertained over a 12 month period (female N = 26, male N = 35). Psychometric measures were completed at admission and discharge from the McLean/MGH OCD Institute IRT, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) and the Work and Social Adjustment Scale (WSA)(N = 61). These measures were repeated at one (N = 57), three (N = 42) and six months (N = 36) following discharge. This study was IRB approved.

Results

OCD mean severity did not significantly worsen from discharge to the one (17.4, SD 6.5), three (16.5, SD 7.4) or six month (16.2, SD 7.3) follow-up (p > 0.25). Furthermore, the significant improvement from admission was maintained at each of the one (17.4, SD 6.5), three (16.5, SD 7.4) and six month (16.2, SD SD 7.3) follow-up time points (p < 0.001). Relapsers were significantly more likely to be living alone following discharge (p = 0.01), and were less likely to have comorbid illnesses (p = 0.02). There were no significant differences found between study dropouts and completers with regards to YBOCS scores (P > 0.47).

Conclusion

In the first OCD IRT long-term follow-up study to date, findings have indicated that mean treatment gains were maintained at one, three, and six months post-discharge. This finding is important as it suggests that improvements of OCD severity were subsequently retained in home and work environments. Improvement of depression severity from admission was also maintained.     

Differences in myocardial sympathetic degeneration and the clinical features of the subtypes of Parkinson’s disease

Parkinson’s disease (PD) can be divided into the akinetic-rigid (ART), mixed (MT), and tremor-dominant (TDT) subtypes according to the clinically dominant symptoms. We analyzed the correlations between ¹²³I-meta-iodobenzylguanidine (MIBG) uptake and the clinical features of patients with various PD subtypes. In addition, we evaluated the relationship between MIBG uptake and the severity of the cardinal motor symptoms among patients with PD subtypes. The mean Unified Parkinson’s Disease Rating Scale motor scores differed significantly among patients with different PD subtypes (± standard deviation [SD]) (ART, 34.6 ± 18.28; MT, 24.63 ± 7.78; TDT, 16.22 ± 4.15, p = 0.002), especially between the ART and TDT subtypes (p = 0.022). The mean MIBG uptake (± SD) was decreased in the TDT (1.69 ± 0.39), MT (1.35 ± 0.32), and ART (1.35 ± 0.22) subtypes (p = 0.049). The MIBG uptake values differed significantly between the ART and TDT subtypes (p = 0.02). The MIBG uptake was inversely correlated with the severity of hypokinesia in the ART subtype (r = −0.75; p = 0.01) and the MT subtype (r = −0.8; p = 0.02), but it was not correlated with the severity of any of the parkinsonian motor symptoms in the TDT subtype. These results imply that hypokinesia is strongly associated with sympathetic myocardial degeneration and that sympathetic myocardial degeneration can reflect the progression of the disease in patients with the ART and mixed MT subtypes of PD.     

Barriers to the effective management of depression in general practice

OBJECTIVE: The aim of this study was to investigate the effects of prior general practice training in mental health and practice location on general practitioner (GP) attitudes toward depression, self-confidence in assessing and treating depressed patients, identification of doctor, patient and practice barriers to the effective care of depressed patients in general medical practice and GP-reported current clinical practice. METHOD: Fifty-two (out of 123) Divisions of General Practice that responded to an invitation to participate in the study distributed 608 anonymous surveys to a representative sample of GPs; 420 (69%) were returned. The questionnaire focused on current clinical practice, perceived barriers to care of depressed patients and doctors' self-efficacy for assessing and treating depressed patients. It also consisted of two scales, based upon previous research, designed to assess doctors' attitudes towards depression and depressed patients. RESULTS: General practitioners who had undertaken mental health education and training more often used non-pharmacological treatments (p=0.00), as did female GPs (p=0.00). Male GPs (p=0.00) and those in rural settings (p=0.01) more often prescribed medication for depression. Those without mental health training more often identified incomplete knowledge about depression as a barrier to its effective management (p=0.00). Urban-based GPs (p=0.04) and those with prior mental health training (p=0.00) were more confident in the use of non-pharmacological treatments. Female GPs without mental health training were the least confident in the use of these methods (p=0.01). Overall, GPs with mental health training were more positive in their attitudes toward depression and their treatment of these patients (p=0.00). Female GPs appeared more positive in their attitudes toward depression than male GPs (p=0.01), although the results were not entirely consistent. CONCLUSIONS: Participation in mental health training by GPs appears to be related to their attitudes toward depressed patients and to their confidence and abilities to diagnose and manage the common mental disorders effectively.     

Atrial fibrillation predicts good functional outcome following intravenous tissue plasminogen activator in patients with severe stroke

Objective

Atrial fibrillation (AF) is associated with poor outcome after intravenous thrombolysis probably due to greater pretreatment stroke severity. We conducted this retrospective study to determine whether AF is an independent predictor for clinical outcome in patients stratified by initial stroke severity.

Methods

A total of 143 acute ischemic stroke patients who received intravenous thrombolysis within 3 h after onset were enrolled. The patients were categorized according to the baseline stroke severity by National Institute of Health Stroke Scale (NIHSS) score (≤10 vs. >10) and the presence of AF or not. Favorable 90-day outcome was defined as a modified Rankin Scale (mRS) score < 2.

Results

Among the 100 patients with severe stroke (NIHSS > 10), those with AF (n = 52) had a higher proportion of favorable 90-day outcome than those without AF (31% vs. 8%, P = 0.005). After adjustment for age, baseline glucose level, and onset to treatment time, the difference remained significant (odds ratio 5.80, 95% confidence interval 1.63–20.68). In patients with mild stroke (NIHSS ≤ 10), no difference in clinical outcome was found between AF (n = 20) and non-AF (n = 23) groups.

Conclusion

Presence of AF was associated with favorable 90-day outcome following intravenous thrombolysis in patients with severe stroke at baseline, while the association did not exist in patients with mild stroke.     

Axial kinesthesia is impaired in Parkinson's disease: Effects of levodopa

Integration of sensory and motor inputs has been shown to be impaired in appendicular muscles and joints of Parkinson's disease (PD) patients. As PD advances, axial symptoms such as gait and balance impairments appear, which often progresses to complete inability stand or walk unaided. The current study evaluates kinesthesia in the axial musculature of PD patients during active postural control to determine whether impairments similar to those found in the appendages are also present in the hip and trunk. Using axial twisting, we quantified the detection threshold and directional accuracy of the hip relative to the feet (i.e. Hip Kinesthesia) and the hip relative to the shoulders (i.e. Trunk Kinesthesia). The relation of kinesthetic threshold to disease progression as measured by UPDRS and the effect of levodopa treatment on kinesthesia were assessed in 12 PD compared to age-matched controls. Subjects stood unaided while passively twisted at a very low constant rotational velocity (1°/s). The results showed that accuracy in determining the direction of axial twisting was reduced in PD relative to healthy control subjects in the hip (PD-ON: 81%; PD-OFF: 91%; CTL = 96%) and trunk (PD-ON: 81%; PD-OFF: 88%; CTL = 95%). Thresholds for perception of axial twisting were increased when PD subjects were ON levodopa versus OFF in both the hip (p < 0.01) and the trunk (p < 0.05). The magnitude of decrease in sensitivity due to being ON levodopa was significantly correlated with the increase in UPDRS motor scores (Hip: r = 0.90, p < 0.01 and Trunk: r = 0.60, p < 0.05). This effect was not significantly correlated with equivalent levodopa dosage. PD subjects with disease onset on the left side of their body showed significantly higher axial thresholds than subjects with right PD onset (p < 0.05). In conclusion, deficits in axial kinesthesia seem to contribute to the functional impairments of posture and locomotion in PD. Although levodopa has been shown to improve appendicular kinesthesia, we observed the opposite in the body axis. These findings underscore the dissociable neurophysiological circuits and dopaminergic pathways that are known to innervate these functionally distinct muscle groups.     

Knowledge of TIA among general practitioners and emergency department physicians. A questionnaire survey in a French semi-rural area

Background and objective

Management of transient ischemic attacks (TIAs) is of vital importance in an attempt to prevent stroke. However, suboptimal management still raise concern among general practitioners (GPs) and emergency department (ED) physicians—the first medical contact of most TIA patients. This may relate to their poorly updated knowledge about TIA. The study was designed to assess knowledge of TIA among these non-neurologists.

Methods

The study was a post-mailed questionnaire survey among GPs and ED physicians. The questionnaire related to selective clinical aspects on TIA.

Results

There were a total of 85 respondents for analysis, mostly GPs (n = 64; 75.3%), out of 177 mailed physicians. Response rate was 52.7%. Many of these respondents were unaware of the newly proposed TIA definition (59%), unfamiliar with TIA mimics and predictors of post-TIA early stroke recurrence and therefore with the rationales underlying the need of emergency management of TIA. More than one third (39%) were unaware of the relevant national guidelines. Guidelines-aware respondents performed better in most part of the mailed questionnaire.

Conclusion

Our results show that poorly updated knowledge about TIA among non-neurologists represents a potential contributing factor to the persisting sub-optimal management of the disorder. Although further studies are needed to confirm this, improved continuous medical education of this group of health care professionals appears warranted.     

Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study

A mild to moderate reduction in dopamine, noradrenaline and serotonin levels alongside a progressive loss of hypocretin cells and melanin hormone concentrating cells has been reported in the hypothalamus of PD at postmortem. Hypothalamic uptake of ¹⁸F-dopa PET, an in vivo marker of dysfunction of monoaminergic neurons, is also significantly reduced in these patients. These data indicate a general impairment of hypothalamic function in PD. Dopamine receptors play an important role in the regulation of hypothalamic pathways. To date, possible changes in hypothalamic D₂ receptor availability have not been investigated in PD. The objective in this study was to assess dopamine D₂ receptor availability in hypothalamus of patients with idiopathic Parkinson's disease (PD) using positron emission tomography (PET) with ¹¹C-raclopride (RAC). We evaluated D₂ binding in RAC PET images of 14 PD patients using both region of interest (ROI) analysis and a voxel based approach. ROIs for the hypothalamus were traced on the subject's MRI co-registered to the PET image. ¹¹C-raclopride binding potentials (BP) for hypothalamus were obtained by applying ROIs onto parametric images. Findings were compared with those of 9 normal controls. We found a significant reduction in the mean hypothalamic RAC BP of the PD patients compared with the normal controls (0.2714 ± 0.06 vs. 0.3861 ± 0.04; mean ± SD; p = 0.0005). ROI results were confirmed with statistical parametric mapping (SPM). Individual hypothalamic BP values of PD patients did not correlate with age, disease duration, disease severity and levodopa equivalent dose. It remains to be ascertained whether the reductions in hypothalamic D₂ receptor availability seen in PD are disease related, the results of chronic exposure to levodopa or both. Our results provide further evidence of dopaminergic dysfunction in the hypothalamus in PD, and this may contribute to the development of sleep, endocrine and autonomic disorders.     

The impact of and the factors associated with drooling in Parkinson's disease

We administered a 7-question survey on drooling to PD patients and age-matched controls. Each subject was assigned a drooling severity score and categorized as a “drooler” or a “non-drooler”. The age, disease duration, motor scores, quality of life (PDQ-39), and levodopa equivalent daily dosage (LEDD) were compared between PD droolers vs. PD non-droolers.58 PD patients and 51 age-matched controls participated. In PD patients, the mean: disease duration was 10.96 years (SD 8.66) and UPDRS on motor score was 30.76 (SD 10.57). The drooling severity score was significantly different between patients vs. controls (3.41 vs. .58; p < .01). 14% of controls vs. 59% of patients were droolers (p < .01). PD droolers scored worse on the ADL subscale of the PDQ-39 (p = .031). Furthermore, PD droolers had significant difficulty speaking (7.27% vs. 0%; p < .01); eating (3.64% vs. 0%; p = .01); and socially interacting (12.73% vs. 0%; p < .01) compared to PD non-droolers. Interestingly, the hallucination component of the UPDRS Part I was significantly correlated with being a drooler (p = .016). None of the other variables have significant effect on drooling severity scores. There is a high prevalence of drooling among PD patients compared to controls.PD droolers had worse quality of life and had more difficulty speaking, eating and socially interacting compared to PD non-droolers. Experiencing hallucinations was the only factor that correlated with being a drooler and it may be confounded by medications.     

Anti-cholinergics for axial symptoms in Parkinson's disease after subthalamic stimulation

Objective

We studied the effect of anti-cholinergic therapy on axial symptoms that show a tendency to worsen over time after deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD).

Patients and methods

We conducted a prospective study of 20 consecutive patients treated with the anti-cholinergic agent trihexyphenidyl after bilateral STN-DBS and assessed the effect of anti-cholinergic therapy on parkinsonism 1 month after its initiation using the Unified Parkinson's Disease Rating Scale (UPDRS).

Results

After a mean post-operative follow-up period of 22.3 months, the scores of axial symptoms on UPDRS part II (ADL score) and part III (motor score) deteriorated by 87% and 54% (baseline), respectively, compared with the pre-operative scores (P < 0.001 for both comparisons). After adding trihexyphenidyl to dopaminergic medication with stimulation, the scores of axial symptoms on UPDRS part II and part III improved from baseline by 33% and 39%, respectively (P < 0.001 for both comparisons).

Conclusions

Our findings demonstrated that the anti-cholinergic agent trihexyphenidyl shows positive effect for a patient population developing deterioration of axial symptoms after STN-DBS. The results in the present study may provide insights into the mechanism of emergence or progression of axial symptoms in patients with PD after STN-DBS.     

Affective reactivity of speech disturbances in schizotypy

Speech disturbances (SD) are a pernicious symptom of schizophrenia that increase when negative emotion is elicited. This increase is referred to as affective reactivity (AR). Although considerable research has examined SD in schizophrenia, few studies have investigated this symptom in individuals at risk for the disorder, who demonstrate schizophrenia-like, or schizotypic, traits. In the present study, we examined: (1) SD severity in schizotypy, (2) how SD varies as a function of stress reactivity in schizotypy, and (3) the relationship between SD/AR with Quality of Life (QOL). Individuals with psychometrically-defined schizotypy (n = 83) and controls (n = 22) completed a laboratory procedure in which they produced speech while viewing pleasant and stressful photographs. This speech was analyzed for subtle speech disorder using a well-validated measure. We found that the schizotypy group demonstrated significant increases in SD across both baseline and stressful conditions compared to the control group. AR was not significantly different between the groups. Within the schizotypy group, severity of disorganized schizotypy symptoms was associated with high levels of SD and AR while interpersonal schizotypy was associated with low levels of SD and AR. AR was also related to increased objective QOL in the schizotypy group. This study highlights the role of stress reactivity across the schizophrenia-spectrum. Moreover, the incongruous relationships between disorganized and interpersonal symptoms with SD underscore the marked heterogeneity in processes across schizotypy.     

Parkinson's patients cope with daylight saving time

Disturbances of the circadian timing system following daylight saving time (DST) may influence the symptoms of Parkinson's disease (PD). To address this question, we compared the severity of motor fluctuations and non-motor symptoms both before and after the time change. Total daily “off-time” based on diaries, excessive daytime sleepiness (Epworth Sleepiness Scale), depressive symptoms (Beck Depression Inventory), and psychosis associated with PD were assessed both before and after the DST. Eighty-three PD patients (mean age, 67 ± 7.7 years; mean disease duration, 10.4 ± 6.4 years) were included. Thirty-six patients had motor fluctuations (mean daily “off-time”, 4.8 ± 2.4 h/day). There was no significant variation of the total daily “off-time” (2.5 ± 2.6 h/day versus 2.5 ± 2.7 h/day), ESS (8.3 ± 4.8 versus 8.1 ± 4.9), BDI (10.4 ± 6.2 versus 10.0 ± 6.9), or PAPD (1.4 ± 1.6 versus 1.1 ± 1.6) scores (P > 0.05) after DST. Our results suggest that PD patients cope relatively well with DST.     

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline

Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p ≤ 0.04), a 1-back task (p ≤ 0.01), and a 2-back task (p ≤ 0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing neurocognitive impairment.     

A population-based longitudinal study of risk factors for suicide attempts in major depressive disorder

No longitudinal study has examined risk factors for future suicide attempts in major depressive disorder in a nationally representative sample. The objective of this study was to investigate baseline sociodemographic characteristics, comorbid mental disorders, specific depressive symptoms, and previous suicidal behavior as potential risk factors for suicide attempts at 3 years follow-up. Data came from the national epidemiologic survey on alcohol and related conditions (NESARC), a large nationally representative longitudinal survey of mental illness in adults [Wave 1 (2001-2002); Wave 2 (2004-2005) n = 34,653]. Logistic regression examined associations between risk factors present at Wave 1 and suicide attempts at Wave 2 (n = 169) among individuals with major depressive disorder at baseline assessment (n = 6004). Risk factors for incident suicide attempts at Wave 2 (n = 63) were identified among those with major depressive disorder at Wave 1 and no lifetime history of suicide attempts (n = 5170). Results revealed specific comorbid anxiety, personality, and substance use disorders to be associated with incident suicide attempts at Wave 2. Comorbid borderline personality disorder was strongly associated with suicide attempts in all models. Several comorbid disorders were strongly associated with suicide attempts at Wave 2 even after adjusting for previous suicidal behavior, notably posttraumatic stress disorder (adjusted odds ratio (AOR) = 2.20; 95% confidence interval (95% CI) 1.27-3.83) and dependent personality disorder (AOR = 4.43; 95% CI 1.93-10.18). These findings suggest that mental illness comorbidity confers an increased risk of future suicide attempts in major depressive disorder that is not solely accounted for by past suicidal behavior.     

Association study of PDE4B with panic disorder in the Japanese population

Background

Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population.

Methods

We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared.

Results

We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P = 0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P = 0.042, genotype P = 0.0034; haplotype C-T-T-A, permutation P = 0.028).

Conclusion

Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions.     

Social dysfunction predicts two years clinical outcome in people at ultra high risk for psychosis

The experience of a first psychotic episode is associated with a marked impairment in psychosocial functioning. However, the decline may be already evident in the pre-psychotic phases and play a significant role in the etiopathology of the disease onset. A sample of subjects at ultra high clinical risk for psychosis (“At Risk Mental State”, ARMS, n = 152) was compared with a demographically-matched general population (n = 98,072) on different measures of psychosocial functioning. The proportion of subjects with an ARMS living in communal establishments or living at home with their parents was significantly higher than that of the local population (p < 0.001). Subjects with an ARMS showed also higher rates of unemployment as compared to the general population (p < 0.001). GAF scores at baseline were significantly lower in unemployed ARMS as compared to students and employed ARMS (p = 0.002). ARMS subjects living in communal establishments presented higher rates of co-morbid psychiatric conditions (p = 0.007) and lower GAF scores at baseline (p = 0.017). Finally, baseline unemployment and living in a communal establishment were associated with an increased risk of developing a psychotic episode within the following two years (p < 0.05). We concluded that the “At Risk Mental State” is a clinical condition which is characterized by marked psychosocial impairment and by an increased vulnerability to psychosis. Unemployment at the first contact with the prodromal service may be a risk factor for the development of a psychotic episode.     

Diagnostic impact of baseline cerebral blood flow in patients with acute ischemic stroke prior to intravenous recombinant tissue plasminogen activator therapy

Objective

To determine whether severe cerebral perfusion defects measured by SPECT prior to rt-PA therapy attribute to severe intracerebral hemorrhage (SICH).

Methods

We measured baseline cerebral blood flow (CBF) using technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT qualitatively prior to rt-PA therapy, in 52 consecutive patients (range 38–93 years). The degree and extent of the asymmetry of local CBF were analyzed semi-quantitatively. We did not administrate rt-PA in patients with severe perfusion defects. Clinical outcome and the incidence of SICH were studied.

Results

Three (5.8%) patients had severe perfusion defects that were undetected by CT and/or DWI. The other 49 (94.2%) patients had mild perfusion defects. The asymmetry of local CBF was 0.08 ± 0.08 (n = 3) and 0.3 ± 0.15 (n = 49) in the two groups, respectively. The percentages of the ipsilateral hemisphere in which perfusion was impaired severely were 17.5 ± 9.5% (n = 3) and 0.43 ± 0.87% (n = 49). Two patients were found petechial hemorrhage, but there was no patient who developed SICH in the former group following conventional antithrombotic therapy. In the latter group, SICH occurred in 1/49 (2.0%) patient following rt-PA therapy.

Conclusion

These results suggest that rt-PA therapy for patients with severe cerebral perfusion defects may cause SICH and baseline CBF may contribute to identify patients at high risk for SICH after intravenous rt-PA therapy.     

Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue

Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 h for 12 h following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFN-alpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery-Asberg Depression Rating Scale (MADRS) score ? 15] during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38-positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r = 0.85, p = 0.001) and 12 (r = 0.70, p = 0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r = 0.82, p = 0.002) and cortisol responses to the initial injection of IFN-alpha (r = 0.91, p = 0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment.