Long term course and outcome of first episode schizophrenia: a 27-to-31-year follow-up.

PURPOSE: To describe long term clinical and functional outcomes of schizophrenia in a developed country. METHOD: Long term longitudinal study of clinical and functional outcomes of incidence cohort of all consecutive admissions for a first hospitalization for schizophrenia between 1983 and 1987 in Montreal, Canada (n = 142). Data collection was conducted at admission, 5 years, 10-16 years and 27-31 years follow-up by reviewing hospital charts and government linked health administrative databases. RESULTS: One fifth of patients were never re-hospitalized and 35% were still in contact with the same catchment area psychiatric services. Thirty-four (24%) died on average at 45.5 years. Fourteen (9.9%) died by suicide; half of them did so 10 years after their first hospitalization. Over 20% were exposed to clozapine and nearly 50% to long-acting injectable antipsychotic medication. There were no inmates; an estimated one fifth might be inferred to be living in supervised residential settings and the rest lived alone or with family. Approximately three quarters of the patients under 65 were receiving social assistance benefits at study's end. From 15 to 25% might have been employed (supported or competitive employment). CONCLUSION: This study confirms that the long-term course of schizophrenia is heterogenous and mostly positive with most patients living in the community, although a significant proportion need long term support and an important proportion experience premature death. To mitigate the persistent suicide risk and to respond to their need for support, continuous mental health professional's involvement is required for many.

[Psychiatry in Quebec. Then and now]. / La psychiatrie au Québec : autrefois/maintenant.

This text narrates the evolution, since the 1960s, of different events that marked the history of psychiatry in the French-Canadian province of Quebec. From his personal experience, the author discusses. The evolution of the Départment de psychiatric de l'Université de Montréal fro where were issued more than 1000 psychiatrists who shaped clinical practice and research developments worthy of mention throughout the years. The evolution of diagnostic noselogy from the DSM-ii, very influenced by psychoanalysis, to the DSM-5 that is more atheortical, but that is still not based on objective data, which remains a challenge to the etiology of mental illness. The psychiatric drugs that we have learned to prescribe in the past 50 years in a more rational way thanks to a better understanding of their action mechanisms. In reality, there has been no discovery of new drug categories; rather it is the way we prescribe medication that evolved. The great adventure of the first textbook of Quebec psychiatry, which was first published in 1980, and is forthcoming in its 4th edition in 2015 in an improved and expanded format. The forthcoming version takes into consideration the developments in psychiatry. The creation of the Young Adults Clinic in 1988, providing treatment and rehabilitation to young adults in the early stages of schizophrenia, as well as psychoeducational support and information to heir family members. Through the years, this clinic had a considerable acknowledgement in Quebec and other French-speaking nations.

Clozapine and visuospatial processing in treatment-resistant schizophrenia.

INTRODUCTION: Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups. METHODS: Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5). RESULTS: Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Raven's Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance. CONCLUSION: Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.

Evidence review and clinical guidance for the use of ziprasidone in Canada.

While indicated for schizophrenia and acute mania, ziprasidone's evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success.

Schizophrenia, an illness with bad outcome: myth or reality?

OBJECTIVE: Different myths about schizophrenia endorsed by clinicians maintain the pessimism about outcome thus reducing chances of improvement. There are no recent North American studies on the long-term outcome of first-episode schizophrenia to clarify if these beliefs are myths or reality. Our study describes the long-term outcome (10 to 16 years) of a first-episode schizophrenia incidence cohort (n = 142) in a Canadian urban centre between 1983 and 1999. METHOD: Clinical and social functioning at different time points were assessed retrospectively from medical files of a catchment area hospital in Montreal. Service use and deaths were noted from provincial databases of physician billings, hospitalization, and vital statistics. RESULTS: Hospitalization days decreased considerably after the first year, with a small minority still needing it episodically after 4 years. Marital and occupational status were generally stable over time, but autonomy in living arrangements worsened. Thirty-three percent of subjects quit the Catchment Area Specialized Psychiatric Services. This group showed better social functioning while they were followed, were hospitalized less afterwards, and had fewer suicides, therefore indicating a better outcome for them. At the end of our study, 15% of the patients still alive were well enough to function without seeking medical help and 25% were not taking antipsychotic medication. Better outcome was predicted by older age at admission, being married, higher premorbid autonomy in living arrangements, and female sex. CONCLUSION: A significant proportion of first-episode schizophrenia patients achieve moderate long-term outcome, and the stability of global functioning is more frequent than deterioration, as shown in most industrialized countries.

[Implementation in Quebec of the Integrated Psychological Treatment (IPT) for people with schizophrenia: five years later]. / L'implantation au Québec de l'Integrated Psychological Treatment (IPT) auprès des personnes atteintes de schizophrénie : cinq ans après.

This article examines the adoption in Québec of the evidence-based practice, Integrated Psychological Treatment (IPT) of people with schizophrenia and the longevity of this practice within nine clinical milieus in a context of transformation of services. A team of researchers of the Centre de recherche Fernand Seguin has closely followed the implementation and the maintenance of the IPT in nine clinical milieus. More specifically, this article presents the factors that have contributed, on a five year period, to the maintenance (or not) of the IPT in these settings. It raises the important question of longevity of an approach that is specialized and specific to a clientele in contexts of transformation of services.

Preserved awareness of their cognitive deficits in patients with schizophrenia: convergent validity of the SSTICS.

This study aimed to examine the convergent validity of the SSTICS. The association between the SSTICS and the five-factor model of the PANSS was also examined. One hundred and seventy-six schizophrenia-spectrum disorder patients were recruited. A correlation analysis was performed. The SSTICS score correlated with the score on the FPSES. The SSTICS score also correlated with the cognition factor of the PANSS. Our results demonstrate that the SSTICS is a good instrument for evaluating the subjective complaints of patients with schizophrenia. They also reveal good concordance between cognitive impairments experienced by patients and cognitive disorders assessed by a clinical rater.

Reward-related decision-making in schizophrenia: A multimodal neuroimaging study.

Schizophrenia is a severe psychiatric disorder characterized by important cognitive deficits, which ultimately compromise the patients' ability to make optimal decisions. Unfortunately, the neurobiological bases of impaired reward-related decision-making in schizophrenia have rarely been studied. The objective of this study is to examine the neural mechanisms involved in reward-related decision-making in schizophrenia, using functional magnetic resonance imaging (fMRI). Forty-seven schizophrenia patients (DSM-IV criteria) and 23 healthy subjects with no psychiatric disorders were scanned using fMRI while performing the Balloon Analogue Risk Task (BART). A rapid event-related fMRI paradigm was used, separating decision and outcome events. Between-group differences in grey matter volumes were assessed with voxel-based morphometry. During the reward outcomes, increased activations were observed in schizophrenia in the left anterior insula, the putamen, and frontal sub-regions. Reduced grey matter volumes were observed in the left anterior insula in schizophrenia which spatially overlapped with functional alterations. Finally, schizophrenia patients made fewer gains on the BART. The fact that schizophrenia patients had increased activations in sub-cortical regions such as the striatum and insula in response to reward events suggests that the impaired decision-making abilities of these patients are mostly driven by an overvaluation of outcome stimuli.

Benefits and risks of antipsychotic polypharmacy: an evidence-based review of the literature.

Combination antipsychotic prescription is an increasingly common practice in clinical psychiatry. This clinical practice is at odds with clinical guidelines promoting antipsychotic monotherapy. Moreover, there has been increased concern over the safety profile of atypical antipsychotics in the last 10-15 years. We reviewed the literature on antipsychotic combinations with a focus on safety and efficacy. Multiple electronic database searches were complemented by relevant bibliography cross-checking and expert discussions. The review showed a literature that is dominated by case reports and uncontrolled studies. Polypharmacy was unequally studied, with some recent combinations (i.e. clozapine and risperidone) being extensively, albeit inconclusively, studied and other more commonly used combinations (first- with second-generation agents) receiving little attention. From an evidence-based perspective, further trials of antipsychotic association of sufficient power to address safety issues are needed before recommending any antipsychotic combination. Particular weaknesses of the present literature are low number of participants, lack of adequate control of confounding variables, short duration of experimental follow-up and inadequate monitoring of potential adverse effects.

Pain perception in schizophrenia: no changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization.

BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both excitatory (e.g. sensitization) and inhibitory endogenous modulation systems. Preliminary experimental studies have shown diminished pain sensitivity in schizophrenia patients. The objective of the study was to investigate the role of excitatory and inhibitory systems on pain perception in schizophrenia. METHODS: Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity. Excitatory and inhibitory systems were elicited using a temporal summation test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time was a significant predictor of pain scores in controls, but not in patients. That is, pain ratings increased during the tonic thermal stimulation among controls but not in schizophrenia patients. When correlation coefficients (between time and pain ratings) for patients and controls were compared, the correlation coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04; p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar in magnitude in both patients and controls. CONCLUSIONS: Diminished pain sensitivity in schizophrenia may be related to abnormal excitatory mechanisms, but not to DNIC. More studies are needed to better characterize the neurophysiological and neurochemical mechanisms involved in the lack of sensitization in schizophrenia.

Working memory and depressive symptoms in patients with schizophrenia and substance use disorders.

BACKGROUND: Substance abuse is highly prevalent in schizophrenia and it has been associated with negative consequences on the course of the pathology. Regarding cognition, the prevailing literature has produced mixed results. Some groups have reported greater cognitive impairments in dual diagnosis schizophrenia, while other groups have described the reverse. OBJECTIVE: The current cross-sectional study sought to investigate the potential differences in psychiatric symptoms and cognition between schizophrenia patients with and without substance use disorders. METHODS: Fifty-three schizophrenia patients were divided into two groups: with (n=30) and without (n=23) a substance use disorder (DSM-IV criteria). Psychiatric symptoms were measured with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). Psychomotor speed and spatial working memory were measured using Cambridge Neuropsychological Tests Automated Battery (CANTAB). RESULTS: Patients in the dual diagnosis group displayed more severe depressive symptoms and poorer strategy during the working memory task. CONCLUSIONS: These results are in keeping with the prevailing literature describing negative consequences of substance abuse in schizophrenia. Substance abuse may exacerbate depressive symptoms and interfere with metacognition in schizophrenia.

Avatar Therapy for Persistent Auditory Verbal Hallucinations in an Ultra-Resistant Schizophrenia Patient: A Case Report.

Effective treatment strategies for schizophrenia remain very challenging and many treatment-resistant patients will suffer from persistent auditory verbal hallucinations (AVH). While clozapine is the gold-standard medication for this complex population, many will not respond to this molecule. For these ultra-resistant patients, limited options are available. Cognitive-behavioral therapy (CBT) is the most widely used psychological intervention, though it offers modest effects. With the interpersonal dimension of AVH being recognized, Avatar Therapy (AT), a novel experiential treatment enabling patients to create an avatar of their persecutor and allowing them to gain control over their symptoms, was developed and tested. Results have shown significant improvements in AVH symptomatology. This paper details a case report showcasing the beneficial results of AT for even the most severe and symptomatic cases of schizophrenia. Mr. Smith has been afflicted with the persistency of all his voices for almost 20 years. To our knowledge, this patient tried almost all possible treatments with little efficacy. This case highlights the difficulty of finding an adequate treatment for ultra-resistant patients. Mr. Smith first followed CBT before initiating AT. With AT, he significantly improved in a way that was not observed with any other intervention and these improvements remained afterward. The severity of his positive symptoms as well as his depressive symptoms diminished, and his most distressing persecutory voice disappeared. He was able to regain a life. The effects of AT went well beyond the patient, the morale of the entire family improved. This ultra-resistant case suggests that AT may be a promising intervention for refractory AVH in schizophrenia.

Reduced dorsolateral prefrontal cortex activation during affective Go/NoGo in violent schizophrenia patients: An fMRI study.

We investigated the influence of anger processing on cognitive control in male schizophrenia patients presenting violent behaviors. We recruited 23 patients without and 24 patients with (SCZ+V) a history of violent behaviors, as well as 22 healthy non-violent men. Participants were administered an affective (angry-neutral faces) Go/NoGo task while undergoing functional magnetic resonance imaging. We found a reduced activation in the dorsolateral prefrontal cortex in SCZ+V patients specifically when inhibiting a response while viewing angry faces. These results show an inability of SCZ+V to recruit a core region of the (inhibitory) cognitive control network in the context of anger.

Virtual reality therapy for refractory auditory verbal hallucinations in schizophrenia: A pilot clinical trial.

Schizophrenia is a chronic and severe mental illness that poses significant challenges. While many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, notably auditory verbal hallucinations (AVH), which are highly disabling. This unmet clinical need requires new innovative treatment options. Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a computerized representation of their voices. These very promising results have been extended by our team using immersive virtual reality (VR). Our study was a 7-week phase-II, randomized, partial cross-over trial. Nineteen schizophrenia patients with refractory AVH were recruited and randomly allocated to either VR-assisted therapy (VRT) or treatment-as-usual (TAU). The group allocated to TAU consisted of antipsychotic treatment and usual meetings with clinicians. The TAU group then received a delayed 7weeks of VRT. A follow-up was ensured 3months after the last VRT therapy session. Changes in psychiatric symptoms, before and after TAU or VRT, were assessed using a linear mixed-effects model. Our findings showed that VRT produced significant improvements in AVH severity, depressive symptoms and quality of life that lasted at the 3-month follow-up period. Consistent with previous research, our results suggest that VRT might be efficacious in reducing AVH related distress. The therapeutic effects of VRT on the distress associated with the voices were particularly prominent (d=1.2). VRT is a highly novel and promising intervention for refractory AVH in schizophrenia.

Use of the process dissociation procedure to study the contextual effects on face recognition in schizophrenia: familiarity, associative recollection and discriminative recollection.

Contextual effects were explored in schizophrenia patients and paired comparison subjects during a long-term face recognition task. The objective was to investigate the contextual effects on face recognition by manipulating, in the same experiment, the perceptual context of the face (intrinsic vs. extrinsic) and the task context (inclusion vs. exclusion instructions). The situation was derived from the Jacoby's [Jacoby, L.L., 1991. A process dissociation framework: separating automatic from intentional uses of memory. Journal of Memory and Language 30, 513-541] process dissociation procedure. The results showed that schizophrenia patients (N=20) presented lower performances than healthy controls (N=20) in the inclusion but not in the exclusion task. This observation emphasizes the heterogeneity of recollection and suggests that the memory impairment in schizophrenia reflects an imbalance between two mechanisms. The first is a deficit in "associative recollection", i.e., the failure to use efficiently associative information. The other is an enhanced "discriminative recollection" that impedes their capacity to process information separately from its perceptual context. In addition, correlation with symptoms suggest that the former is expressed in the loosening of associations characteristic of disorganization symptoms, whereas the latter reflects the lack of flexibility or the contextualization bias related to psychotic symptoms, i.e., delusions and hallucinations.

[Study of the follow-up of early psychosis at the Université de Montréal (L'Etude de Suivi des Psychoses Emergentes de l'Université de Montréal (ESPEUM): context, objectives and methodology]. / L'Etude de Suivi des Psychoses Emergentes de l'Université de Montréal (ESPEUM): contexte, buts et méthodologie.

In this article, the authors examine specialized programs and services in the treatment and rehabilitation of people with an early psychosis. The authors realized that various programs have multiplied in the course of the last decade and many have shown benefits in comparison with the usual treatments delivered in general psychiatry. Thus these programs are composed of the following elements : family intervention, intensive community treatment, employment support, cognitive behavioural therapy and social skills training.

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images.

BACKGROUND: Cigarette smoking is highly prevalent in schizophrenia and is one of the main factors contributing to the significantly decreased life expectancy in this population. Schizophrenia smokers, compared to their counterparts with no comorbid psychiatric disorder, are largely unaware and indifferent to the long-term negative consequences of cigarette smoking. The objective of this study was to determine, for the first time, if these meta-cognitive deficits are associated with neuro-functional alterations in schizophrenia smokers. METHODS: Twenty-four smokers with no psychiatric disorder and 21 smokers with schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging and exposed to anti-smoking images. Granger causality analyses were used to examine the effective connectivity between brain regions found to be significantly activated. RESULTS: Across groups, potent activations were observed in the left ventro-lateral prefrontal cortex, the left amygdala (AMG), and the dorsomedial prefrontal cortex (dmPFC). Using the dmPFC as a seed region, we found an abnormal negative connectivity from the dmPFC to the AMG in schizophrenia smokers during the viewing of anti-smoking stimuli. This abnormal connectivity was not present during the viewing of aversive stimuli unrelated to tobacco. DISCUSSION: Given the well-established roles of the dmPFC in social cognition and of the AMG in emotional processing, our results suggest that the relative indifference of schizophrenia smokers regarding the negative consequences of tobacco smoking could be explained by a cognitive-affective dissonance.

Are cholinergic enhancers beneficial for memory in schizophrenia? An event-related potentials (ERPs) study of rivastigmine add-on therapy in a crossover trial.

Studies have reported beneficial effects of cholinergic enhancers, e.g., rivastigmine, on memory in schizophrenia but others have not. Possibly, these discrepancies are related to the lack of specificity of the tests used. This study investigated the effect of rivastigmine on memory in schizophrenia using event-related potentials (ERPs). Eighteen patients treated with atypical antipsychotic received rivastigmine adjuvant therapy in a randomized, crossover design. They were assessed at baseline (T1) and on two subsequent occasions (T2 and T3), where one half of the subjects were taken rivastigmine and the other half not. ERPs were recorded during a recognition memory task on each session. Behavioral and ERP data were analyzed using mixed ANOVA models first at T1 to detect potential group differences and for the trial (T1-T2) to determine the influence of rivastigmine, i.e., sessionxgroup interactions. The results showed no group difference at T1 except a trend for one group to be less efficient than the other on RT measures. When controlling for this difference the results on the trial data showed a trend for a benefit of rivastigmine on the RT memory effect. ERP analysis revealed that rivastigmine affects the amplitudes of two components elicited within 150-300 ms over posterior (reduced N2b) and frontal sites (enhanced P2a). It also enhances the magnitude of the memory (old/new) effect on two later components over posterior (N400) and frontal sites (F-N400). These results suggest that rivastigmine improves selective attention by enhancing interference inhibition processes (P2a) and lowering the reactivity to incoming stimulus (N2b). It also improves the integration of information with knowledge (N400) and with its context (F-N400). Generally, this study showed that the beneficial effect of rivastigmine on memory is not unitary but rather comes from its action at different time points within information processing cascade.

Health care resource use associated with integrated psychological treatment.

BACKGROUND: Mental health policies, advocating outpatient as well as community mental health care for the severely mentally ill, are aiming towards health system cost containment and patient quality of life. Programs with cognitive behavioral therapy, such as the Integrated Psychological Therapy (IPT), added to standard medical therapy for patients with schizophrenia have been associated with improved outcomes. A Quebec version of the IPT program was integrated in outpatient clinics and improvements were observed in overall symptoms, subjective experiences, cognitive and social functioning, and quality of life. In light of these results we deemed it relevant to describe the health system cost and patient resource use associated with the program. The costs related to IPT have not been previously reported and this study will elucidate on effective health services and budget allocation needed to include IPT. AIMS: To describe health care resource use and related costs associated with participating in an IPT program included as standard medical therapy in nine clinical settings. METHODS: A cohort of patients with schizophrenia participating in the IPT program were followed up to one year preceding the start of the program and concurrently until the end to compare the resource use and costs incurred by patients with schizophrenia during their participation. A health and social service system and patient perspective was adopted, and the medical and non-medical costs associated with the IPT program were measured. Valuation (2001 CDN dollars) was based on information provided by provincial billing systems. Statistical differences were assessed using the Wilcoxon signed-rank test. RESULTS: The IPT program induced a one time fixed cost (2347 dollars) for the training of mental health professionals and costs related to patient participation (1350 dollars). Our results show that there was an average decrease in health care system resource use per patient during the IPT program (26,133 dollars) as opposed to the preceding year (26,750 dollars). There was a significant decrease in the number of visits and in physician fees paid out to psychiatrists, the number of hospitalizations and related costs, and visits to the emergency department per patient during the IPT program as compared to the preceding year. No significant difference was observed in patient related costs which averaged 7295 dollars and 7537 dollars, before and during the IPT program, respectively. DISCUSSION: Although the IPT program induces a one time fixed cost for training, the integration of IPT, as part of an individualized standard medical therapy, is associated with a change from inpatient towards outpatient resource use with no significant increase in health system related costs. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Given clinical and quality of life improvements, the findings suggest that offering IPT to more patients with severe mental illness may prove more cost beneficial by decreasing the health system related costs per user in the long term. IMPLICATIONS FOR FURTHER RESEARCH: Additional research is needed to examine in parallel the long-term clinical and cost impact of the IPT program in different clinical settings (young adults to long term mentally ill). This will elucidate to which patient population IPT is most cost-effective.