Subjective cognitive complaints in first episode psychosis: A focused follow-up on sex effect and alcohol usage.

A network of early psychosis-specific intervention programs at the University of Montreal in Montreal, Quebec, Canada, conducted a longitudinal naturalistic five-year study at two Urban Early Intervention Services (EIS). In this study, 198 patients were recruited based on inclusion/exclusion criteria and agreed to participate. Our objectives were to assess the subjective cognition complaints of schizophrenic patients assessed by Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) in their first-episode psychosis (FEP) in relation to their general characteristics. We also wanted to assess whether there are sex-based differences in the subjective cognitive complaints, as well as differences in cognitive complaints among patients who use alcohol in comparison to those who are abstainers. Additionally, we wanted to monitor the changes in the subjective complaints progress for a period of five years follow-up. Our findings showed that although women expressed more cognitive complaints than men [mean (SD) SSTICS, 28.2 (13.7) for women and 24.7 (13.2) for men], this difference was not statistically significant (r = -0.190, 95 % CI, -0. 435 to 0. 097). We also found that abstainers complained more about their cognition than alcohol consumers [mean (SD) SSTICS, 27.9 (13.4) for abstainers and 23.7 (12.9) for consumers], a difference which was statistically significant (r = -0.166, 95 % CI, -0. 307 to -0.014). Our findings showed a drop in the average score of SSTICS through study follow-up time among FEP patients. In conclusion, we suggest that if we want to set up a good cognitive remediation program, it is useful to start with the patients' demands. This demand can follow the patients' complaints. Further investigations are needed in order to propose different approaches between alcohol users and abstinent patients concerning responding to their cognitive complaints.

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study.

Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada.Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut.Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27-78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47-35.30).Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut.

Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study.

BACKGROUND: Cannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals. METHODS: Data from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16). After at least 72h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms. RESULTS: Cocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders. CONCLUSION: We could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.

Specific impact of stimulant, alcohol and cannabis use disorders on first-episode psychosis: 2-year functional and symptomatic outcomes.

BACKGROUND: Many studies have concluded that cannabis use disorder (CUD) negatively influences outcomes in first-episode psychosis (FEP). However, few have taken into account the impact of concurrent misuse of other substances. METHODS: This 2-year, prospective, longitudinal study of FEP patients, aged between 18 and 30 years, admitted to early intervention programs in Montreal, Quebec, Canada, examined the specific influence of different substance use disorders (SUD) (alcohol, cannabis, cocaine, amphetamines) on service utilization, symptomatic and functional outcomes in FEP. RESULTS: Drugs and alcohol were associated with lower functioning, but drugs had a greater negative impact on most measures at 2-year follow-up. Half of CUD patients and more than 65% of cocaine or amphetamine abusers presented polysubstance use disorder (poly-SUD). The only group that deteriorated from years 1 to 2 (symptoms and functioning) were patients with persistent CUD alone. Outcome was worse in CUD than in the no-SUD group at 2 years. Cocaine, amphetamines and poly-SUD were associated with worse symptomatic and functional outcomes from the 1st year of treatment, persisting over time with higher service utilization (hospitalization). CONCLUSION: The negative impact attributed to CUD in previous studies could be partly attributed to methodological flaws, like including polysubstance abusers among cannabis misusers. However, our investigation confirmed the negative effect of CUD on outcome. Attention should be paid to persistent cannabis misusers, since their condition seems to worsen over time, and to cocaine and amphetamine misusers, in view of their poorer outcome early during follow-up and high service utilization.

The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank.

In 2008, the National Institute of Mental Health (NIMH) announced that in the next few decades, it will be essential to study the various biological, psychological and social "signatures" of mental disorders. Along with this new "signature" approach to mental health disorders, modifications of DSM were introduced. One major modification consisted of incorporating a dimensional approach to mental disorders, which involved analyzing, using a transnosological approach, various factors that are commonly observed across different types of mental disorders. Although this new methodology led to interesting discussions of the DSM5 working groups, it has not been incorporated in the last version of the DSM5. Consequently, the NIMH launched the "Research Domain Criteria" (RDoC) framework in order to provide new ways of classifying mental illnesses based on dimensions of observable behavioral and neurobiological measures. The NIMH emphasizes that it is important to consider the benefits of dimensional measures from the perspective of psychopathology and environmental influences, and it is also important to build these dimensions on neurobiological data. The goal of this paper is to present the perspectives of DSM5 and RDoC to the science of mental health disorders and the impact of this debate on the future of human stress research. The second goal is to present the "Signature Bank" developed by the Institut Universitaire en Santé Mentale de Montréal (IUSMM) that has been developed in line with a dimensional and transnosological approach to mental illness.

[Subjective cognition in schizophrenia]. / L'insight neurocognitif dans la schizophrénie.

OBJECTIVES: Given the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients' self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables. METHODS: Eighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients' subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed. RESULTS: For the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance. Visual learning performance was the most consistent predictor of most SSTICS subscores (e.g. episodic memory, attention, executive functioning, language and praxis). Modest associations were found between the PANSS cognitive factor and objective cognition (e.g. Stroop interference, visual learning, and working memory). Finally, the factor analysis revealed a 6-factor solution that echoes the classification of the items of the SSTICS based on the neuropsychological literature. CONCLUSIONS: Using a scale having good internal validity, as shown by the factor analysis, the current study highlighted modest associations between subjective and objective cognitive performance, which suggests that schizophrenia patients are only partially aware of their own cognitive deficits. The results also showed a lack of correspondence between the impaired cognitive domain and the domain of cognitive awareness. It should be noted that clinicians were not better than patients at evaluating their cognitive deficits. Future research will need to determine if the observations reported here are schizophrenia-specific or not.

Meta-analysis of rates of drop-out from psychosocial treatment among persons with schizophrenia spectrum disorder.

UNLABELLED: Non-compliance with pharmacotherapy among persons suffering from schizophrenia disorders stands at an average rate of 42% and is the subject of numerous studies. However, no studies to date have addressed the specific question of non-compliance with psychosocial treatment. The present study therefore aimed to determine the rate of drop-out from psychosocial treatment and to assess the influence of factors on this rate. METHOD: A meta-analysis was conducted based on 74 studies of randomized clinical trials on psychosocial treatment among persons suffering from schizophrenia spectrum disorder. RESULTS: A drop-out rate of 13% was obtained. Age, gender, duration of illness, duration of treatment, treatment setting and study quality affected drop-out rates. CONCLUSION: The 13% rate of drop-out from psychosocial treatment is markedly lower than the drop-out rate from pharmacotherapy studies. This finding supports the feasibility of evidence-based psychosocial treatment - which has, moreover, clearly been shown to be clinically effective - as part of a complete care program for schizophrenia.

Validation of insulin secretion indices in cystic fibrosis patients.

BACKGROUND AND AIMS: Impaired insulin secretion plays a key role in the development of cystic fibrosis-related diabetes (CFDR). Numerous indices to evaluate insulin secretion have been proposed, but their validity has not been explored in cystic fibrosis (CF). The aim of the present study was to validate surrogate indices of insulin secretion in CF patients against the gold standard, the intravenous glucose tolerance test (IVGTT). METHODS: 32 subjects were enrolled: 16 controls, 10 cystic fibrosis-normal glucose tolerant (CF-NGT) and 6 CFRD patients. All subjects underwent a 2-h oral glucose tolerance test (OGTT) and an IVGTT. Insulin secretion was estimated using three indices: the HOMA-beta cell, the Stumvoll's early insulin secretion, and the insulin secretion rate (ISR). RESULTS: In control subjects, all insulin secretion indices correlated significantly with the IVGTT. In CF-NGT patients, the HOMA-beta cell correlated significantly with the IVGTT at shorter time points but not over longer time-period. On the other hand, both OGTT-derived indices (Stumvoll and IRS) correlated significantly with the IVGTT for the CF-NGT and CFRD groups. CONCLUSION: Since the OGTT is required on a regular basis in CF patients to screen for CFRD, OGTT-derived indices appear to be suitable for evaluating insulin secretion.

Dichotomy between postprandial glucose and lipid profiles in adults with cystic fibrosis: a pilot study.

BACKGROUND: Cystic fibrosis (CF) patients present a high incidence of glucose tolerance abnormalities. Altered insulin secretion combined with recommended high-fat intake could be associated with dysregulation of glucose and lipid metabolism. We examined postprandial glucose and lipid profiles during an oral glucose tolerance test (OGTT) and following a standardized high-fat test meal (TM). METHODS: Sixteen CF patients with normal glucose tolerance (NGT) or CF-related diabetes (CFRD) and 16 controls underwent a 4 h OGTT and a TM. We then measured plasma glucose, insulin, free fatty acid (FFA) and triglyceride (TG) concentrations. RESULTS: CF patients presented higher glucose excursion compared to controls after the OGTT and TM. However, in CF patients, this excursion was significantly reduced in both amplitude and length after the TM. The TM provoked a comparable increase in TG levels in both groups whereas they remained stable during the OGTT. FFAs were suppressed similarly in both groups after both challenges. CONCLUSION: CF is associated with abnormal glucose excursion in the presence of relatively normal lipid excursion. The rapid normalization of glucose values after a mixed meal should be further explored and, if confirmed, might have significant implications for CFRD diagnostic.

No relationship between mean plasma glucose and glycated haemoglobin in patients with cystic fibrosis-related diabetes.

AIM: Cystic fibrosis-related diabetes (CFRD) prevalence has increased dramatically with the improved life expectancy of patients with cystic fibrosis (CF). Glycated haemoglobin (HbA(1c)) is an important tool for monitoring blood glucose control but, unlike in type 1 and type 2 diabetes, a correlation between HbA(1c), fructosamine and mean plasma glucose has not been clearly established in CF. This study aimed to examine the relationship between mean plasma glucose and HbA(1c) or fructosamine in stable patients with CFRD. METHODS: Fifteen type 1 diabetes and 13 CFRD patients (HbA(1c)<9.0%; no anaemia), matched for age and body mass index (BMI), provided 72 capillary blood glucose profiles taken 3days/month for three months. At the end of this time, HbA(1c) and fructosamine were measured. Mean plasma glucose was estimated using the Diabetes Control and Complications Trial (DCCT) conversion formula, and linear regressions carried out to establish its relationship with HbA(1c) and fructosamine. RESULTS: In type 1 diabetes patients, mean plasma glucose correlated significantly with HbA(1c) (r=0.68; P=0.005). In CFRD patients, no correlation was found between mean plasma glucose and HbA(1c) (r=0.24; P=0.460). Also, no association was found between mean plasma glucose, representing the month before blood sampling, and fructosamine in either group. CONCLUSION: Unlike in type 1 diabetes, HbA(1c) did not correlate with mean plasma glucose in CFRD subjects. Thus, having a normal HbA(1c) may not be sufficient to indicate a low risk of diabetes complications in CFRD. Further studies are required to explain such a discrepancy.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

RATIONALE: Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. AIM: To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). METHODS: Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. RESULTS: CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CONCLUSION: CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Increased extrapyramidal symptoms in patients with schizophrenia and a comorbid substance use disorder.

Few data have been gathered about the impact of psychoactive substances on extrapyramidal symptoms (EPS) in schizophrenia, and so far, inconsistent results have been reported. We studied 41 outpatients with schizophrenia (based on DSM-IV criteria), who were divided into two groups: with (n = 17) and without (n = 24) a substance use disorder (alcohol, cannabis, and/or cocaine). Both groups were matched for sociodemographic data and psychiatric symptoms (Positive and Negative Syndrome Scale). EPS were evaluated with the Extrapyramidal Symptoms Rating Scale and the Barnes Akathisia Scale, and all patients were stable on either quetiapine or clozapine. Patients receiving anticholinergic drugs were excluded. Analyses of variance were conducted on both groups and showed that schizophrenia patients with a comorbid substance use disorder (especially cocaine) displayed more EPS compared with non-abusing patients.

Diabetes: a major co-morbidity of cystic fibrosis.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis, its prevalence increases with age of patient and is close to 30% at the age of 30 years. As life expectancy greatly increases, the number of cystic fibrosis patients developing diabetes will increase too. CFRD shares some features with type 1 and type 2 diabetes, initial phase is characterised by postprandial hyperglycaemia followed by a progression toward insulin deficiency. Insulin deficiency is an essential factor in the development of diabetes with an additional contribution of insulin resistance. Systematic screening with an oral glucose tolerance test is recommended from the age of 14 years because clinical signs of CFRD are often confused with signs of pulmonary infection and CFRD occurrence is associated with weight and pulmonary function deterioration. In observational studies CFRD diagnosis is associated with a significant increase in mortality, while treatment allow correction of weight and lung deterioration suggesting that CFRD has a significant impact on CF evolution. Microvascular complications are recognised, although paucity of data does not permit a clear description of their natural history. Annual screening for microvascular complication is recommended. There is no evidence by now that CF patients develop macrovascular complications. The only recommended pharmacological treatment is insulin therapy.

[Schizophrenia and addiction: An evaluation of the self-medication hypothesis]. / Schizophrénie et toxicomanie: une relecture du concept d'automédication.

Despite the fact that most researchers acknowledge the high prevalence of comorbid substance abuse among schizophrenic patients, there is no common agreement regarding the etiology of this serious public health problem. At the center of this debate though, Khantzian's self-medication hypothesis has captured most of the attention. In the present literature review, the authors evaluate this hypothesis in the light of our current knowledge. Formulated in a clinical context, in reaction to the psychoanalytic interpretation of addiction as a pleasure seeking pathology, Khantzian's hypothesis holds that schizophrenic patients use psychoactive substances to relieve their symptoms. Properly understood, this conjecture presupposes that, with the relief of certain target symptoms, substance use would no more be a necessity. But in reality, the use of psychoactive substances usually leads to a general deterioration of the patients' condition. Pharmacodependent schizophrenic patients relapse more often, they are more frequently hospitalized, they show more violent behaviors, and they are more frequently homeless. In particular, the positive symptoms of these patients are generally exacerbated by the psychoactive drugs--with the possible exception of opiates. This observation is in lign with the fact that psychostimulants (cocaine, amphetamines), anesthesic dissociatives (PCP, ketamine) as well as hallucinogens (cannabis, LSD) are all known to exert psychotomimetic effects. As for negative symptoms, the reality is more complex. Preliminary results certainly suggest that stimulants (minor or major) relieve these symptoms, but in the case of the other psychoactive substances, empirical evidence remains fragmentary. Still, the properties of psychoactive substances invite to pay close attention, among the negative symptoms, to the cognitive deficits, the social inaptitudes and the hedonic deficits of these patients. Unsatisfied with the self-medication hypothesis, an increasing number of researchers hypothesize that schizophrenic patients abuse drugs in hope to relieve the negative affects (stress, depression) that commonly accompany their symptomatology. Interestingly, increasing data link these negative manifestations and substance abuse among schizophrenic patients. But these same data do not elucidate whether these manifestations are primary or secondary to drug abuse. For the moment, these findings must be replicated. Furthermore, it remains to be clarified what negative affect is involved here. Is it stress, anxiety or, as commonly thought, depression? Other paths aim in the direction of personality traits and dissociation. The first path is suggested by recent studies demonstrating that pharmacodependent schizophrenic patients differ from non-abusing schizophrenics in that their personality is characterized by traits such as sensation seeking and impulsivity. As for the second path, it is suggested by a recurrent observation in addictive medicine practice, that is: alcohol, cannabis, ketamine, LSD, opiates, PCP, all these substances can induce dissociative states (depersonalization, derealization, etc.). Surprisingly, most of the hypotheses advanced so far have been formulated without reference to neuroscience. However, from a biological perspective, substance abuse among schizophrenic patients appears paradoxical: while the positive symptoms of schizophrenia might involve an hyperactivity of the reward system, the drugs of abuse all seem to increase dopamine release in that same system. That very paradox further casts some doubt on the self-medication hypothesis. And it opens an alternative: schizophrenic patients might be biologically vulnerable to the rewarding effects of drugs abuse. On the therapeutic level finally, the authors argue that polypharmacy medications such as clozapine and quetiapine, known to act on the reward system preferentially to the extrapyramidal system and known to dissociate fastly from the dopamine-D2 receptor, could simplify clinical intervention.