Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

BACKGROUND: Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS: A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS: The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS: We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study.

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

Factors associated with dropout at 2 years post-initiation of treatment in the first episode of schizophrenia.

BACKGROUND: Prevention of new episodes during the first 2 years after a first episode of schizophrenia (FES) may delay treatment refractoriness and brain morphological changes over time. However, adherence to treatment is characteristically poor in these patients. AIM: The aim of this study was to examine clinical and sociodemographic factors associated with patient dropout in patients with FES. SETTING: This study was set at inpatient and outpatient services at a psychiatric hospital in the Western Cape, between 2007 and 2011. METHODS: Data were collected as part of a prospective longitudinal study, which followed up patients with FES treated with flupenthixol decanoate. We examined the relationship between treatment adherence and sociodemographic and clinical factors at baseline and at 24 months. Unadjusted and adjusted logistic regression models were used to determine adherence variables. RESULTS: A total of 62% of patients completed the 24 months of treatment. Participants with FES and a substance use disorder (dual diagnosis) were at greater risk of dropout (p = 0.01). On univariate analysis, dual diagnosis participants who dropped out were older (p = 0.04) had completed more years of schooling (p = 0.001), older age of onset (p = 0.02) and higher baseline positive symptoms (p = 0.05). On regression analysis, non-completer substance users achieved a higher level of education (odds ratio [OR]: 3.87, confidence interval [CI]: 1.34-11.11, p = 0.01). CONCLUSION: Substance use disorder was associated with non-adherence to follow up in a cohort of FES patients treated with flupenthixol decanoate. Interventions that take into account age, education and baseline positive symptoms may afford the opportunity to influence adherence and patient outcome.

Prolactin, flupenthixol decanoate and first episode schizophrenia - clinical and laboratory correlates.

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12 months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91 ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12 months more women than men had hyperprolactinemia (defined as more than 20 ng/ml for males, and as more than 25 ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12 months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.

Race trouble: experiences of Black medical specialist trainees in South Africa.

BACKGROUND: This research aimed to identify and explore the experiences of Black registrars in their training in the Western Cape's academic hospitals in order to identify structures, practices, attitudes and ideologies that may promote or impede the advancement of Black doctors into specialist medicine. This is justified by the requirement for universities to work towards monitoring and evaluating efforts to create non-discriminatory and inclusive training environments. METHODS: This study employed qualitative research methods. Ten Black African medical specialists were interviewed about their training experiences in two university training hospitals in the Western Cape Province, South Africa. Interview data was collected using open-ended questions and coded and analysed using thematic and critical discursive analysis techniques. RESULTS: Four experiential themes emerged from the interview data, they included: 1) experiences of everyday racism during work hours, 2) the physical and psychological effects of tokenism and an increased need to perform, 3) institutional racism as a result of inconsistent and unclear methods of promotion and clinical competence building, and 4) an organisational culture that was experienced as having a race and gender bias. CONCLUSION: This is a pilot study and there are limits on the generalizability of the data due to the small sample. What is clear from our participants, though, is the strong experiential component of finding it challenging to be a Black trainee in a White-dominated profession. We are undertaking further research to explore the issues raised in more detail.

Rate and predictors of non-response to first-line antipsychotic treatment in first-episode schizophrenia.

OBJECTIVE: The goals of this study were to (i) estimate the rate of non-response to first-line treatment in first-episode schizophrenia, (ii) evaluate other outcomes associated with symptom non-response and (iii) identify demographic, baseline clinical and early treatment response predictors of non-response. METHODS: This was a single-site, longitudinal cohort study assessing the effects of treatment with flupenthixol decanoate according to a standardised protocol over 12 months in patients with schizophrenia, schizophreniform and schizo-affective disorders. RESULTS: Of 126 patients who received at least one dose of study medication, 84 (67%) completed the study. Fifteen (12%) met our predefined criteria for non-response. Non-responders were younger and at baseline had more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS) and lower body mass index. At endpoint, the non-responders were characterised by higher levels of symptomatology in all domains, poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and lower body mass index. The strongest predictors of non-response were more prominent baseline NSS and poor early (7 weeks) treatment response. CONCLUSIONS: Results are consistent with a lower rate of refractoriness to treatment in first-episode schizophrenia compared with multi-episode samples.

Two Neuroanatomical Signatures in Schizophrenia: Expression Strengths Over the First 2 Years of Treatment and Their Relationships to Neurodevelopmental Compromise and Antipsychotic Treatment.

BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively. STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 months. Ninety-six matched healthy case-controls were included. STUDY RESULTS: Linear mixed effect repeated measures models indicated that the patients had stronger expression of signature 1 than controls that remained stable over time and was not related to treatment. Stronger signature 1 expression showed trend associations with lower educational attainment, poorer sensory integration, and worse cognitive performance for working memory, verbal learning and reasoning and problem solving. The most striking finding was that signature 2 expression was similar for patients and controls at baseline but increased significantly with treatment in the patients. Greater increase in signature 2 expression was associated with larger reductions in PANSS total score and increases in BMI and not associated with neurodevelopmental indices. CONCLUSIONS: These findings provide supporting evidence for two distinct neuroanatomical signatures representing the neurodevelopmental and treatment-responsive components of schizophrenia.

Sex and gender associations with indicators of neurodevelopmental compromise in schizophrenia spectrum disorders.

BACKGROUND: It has been proposed that sex and gender differences described in schizophrenia can be explained from a neurodevelopmental perspective. AIM: In this study, we examined the associations of biological sex and gender role endorsement with putative indicators of neurodevelopmental compromise. METHODS: We used the Bem Sex Role Inventory to calculate masculinity scores in 77 patients with a first episode of a schizophrenia spectrum disorder, and selected the following indicators of neurodevelopmental compromise: family history of schizophrenia, obstetric complications, premorbid functioning, neurological soft signs, and cognitive function. Secondary objectives included the moderating effects of age of onset of illness, substance use and negative symptoms on these associations. RESULTS: There were no significant sex differences across any of the indicators of neurodevelopmental compromise. However, lower masculinity scores correlated significantly with poorer premorbid adjustment, sensory integration deficits and worse overall cognitive performance. Stepwise linear regression identified poorer premorbid adjustment in early adolescence and lower verbal learning scores as independent predictors of lower masculinity scores. In contrast to sex, gender showed several associations with indicators of neurodevelopmental compromise. CONCLUSIONS: Lower masculinity scores may represent part of a phenotype for a neurodevelopmental anomaly that places some individuals on a pathway to schizophrenia.

The trajectories and correlates of two negative symptom subdomains in first-episode schizophrenia.

BACKGROUND: Recent studies suggest a two-factor structure for negative symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) in schizophrenia, namely experiential and expressive subdomains. Little is known about their clinical correlates and treatment trajectories. OBJECTIVES: We sought to replicate the two factor-analysis derived subdomains for PANSS negative symptoms in schizophrenia and to assess their independent demographic, premorbid and treatment-related characteristics. METHODS: This was a longitudinal study of 106 minimally treated participants with a first episode of a schizophrenia spectrum disorder who received treatment with flupenthixol decanoate 2-weekly injections over two years. Factor analysis was used to characterize the PANSS negative symptom subdomains and linear mixed-effect models for continuous repeated measures were constructed to assess the temporal relations between the negative symptom subdomains and premorbid and treatment related variables. RESULTS: Factor analysis confirmed a two-factor solution for experiential and expressive subdomains of negative symptoms, although they were strongly correlated. The treatment response trajectories for the two subdomains did not differ significantly, and neither subdomain was significantly associated with our premorbid variables. We found significant main effects for disorganised symptoms and extrapyramidal symptoms on the expressive subdomain, and for disorganised symptoms and depressive symptoms on the experiential subdomain. Post-hoc testing indicated that reductions in HDL-cholesterol levels were associated with less improvement in both expressive and experiential subdomain scores. CONCLUSION: The two negative symptom subdomains are closely related, have similar premorbid correlates and respond similarly to antipsychotic treatment. Depression affects the experiential subdomain, whereas extrapyramidal symptoms affect the expressive subdomain.

The associations of cannabis and methamphetamine use with cognitive performance over the first 2 years of treatment in schizophrenia spectrum disorders.

AIM: Cognitive deficits are a core feature of schizophrenia, and comorbid substance use may be a contributory factor. Methamphetamine use has been associated with cognitive impairment in schizophrenia, while associations with cannabis use are less clear-cut. This study aimed to investigate the associations of cannabis and methamphetamine use with cognitive performance in first-episode schizophrenia spectrum disorders over the first 2 years of treatment. METHODS: This was a longitudinal cohort study in 81 patients treated with flupenthixol decanoate according to a standardized protocol over 24 months. Cognitive performance was assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Cognitive Consensus Battery at four time points, and urine testing for cannabis and methamphetamine was conducted at six time points. We used linear mixed-effect models for repeated measures to assess visit-wise changes in composite cognitive scores in patients (n = 91) compared to matched controls without psychiatric or medical disorders (n = 100). Linear regression models were constructed to examine pre-treatment and end-point effects in patients. RESULTS: Compared to controls, patients exhibited greater cognitive impairments at baseline, which improved with treatment, but remained significantly lower throughout. The number of positive methamphetamine, but not cannabis, tests predicted less cognitive improvement in patients. CONCLUSIONS: Our findings suggest a negative association between methamphetamine and cognition, but not cannabis.

Differences in white matter microstructure in first-episode schizophrenia spectrum disorders vs healthy volunteers and their association with cognition.

OBJECTIVE: Both cognitive impairment and alterations in white matter tissue microstructure are well recognised in schizophrenia. We investigated whether differences in white matter microstructure underpin cognitive impairments in patients with first-episode schizophrenia spectrum disorders when controlling for multiple confounding factors. METHODS: We employed a cross-sectional study design and compared fractional anisotropy (FA) between individuals diagnosed with first- episode schizophrenia spectrum disorders (FES) (n = 68) and matched healthy controls (n = 120). We conducted multiple analyses of covariance (ANCOVAs) to compare the mean FA values for patients and controls across 27 white matter tracts. We conducted exploratory correlation analyses to determine if white matter tract differences were associated with global cognitive impairment as well as deficits across seven cognitive domains. RESULTS: We found widespread reductions in FA in patients compared to controls, after controlling for confounding variables, such as age, biological sex, education, substances, and childhood adversities. We found a significant positive correlation between the attention/vigilance domain and the splenium of the corpus collosum and external capsule after correction for multiple comparisons. In the control group we found no significant correlations between FA and cognition. CONCLUSION: Our findings provide a neurobiological basis for attentional cognitive deficits in schizophrenia, highlighting a potential role for the splenium of the corpus collosum and external capsule.

The course and concomitants of depression in first-episode schizophrenia spectrum disorders: A 24-month longitudinal study.

Depressive symptoms are common in schizophrenia and have been associated with both favourable and unfavourable outcomes. We studied the longitudinal course of depressive symptoms and explored their temporal relationships with other manifestations of the illness and its treatment. This longitudinal cohort study included 126 antipsychotic naïve or only briefly treated patients with first-episode schizophrenia spectrum disorders treated with a long-acting antipsychotic over 24 months. Depressive symptoms were assessed at three monthly intervals using the Calgary Depression Scale for Schizophrenia and changes over time were assessed using linear mixed-effect models for continuous repeated measures. Depressive symptoms were most prominent at baseline with highly significant reductions during the first three months of treatment and maintenance of improvement thereafter. Most improvement occurred with antipsychotic treatment alone, with few patients requiring additional antidepressants. We also found that depressive symptoms were associated with positive symptoms, better insight and poorer quality of life, but not with negative symptoms, extrapyramidal symptoms, substance use or cumulative antipsychotic dose.There were few differences between patients who met criteria for depression during the acute phase of treatment and those in the post-acute phase.

Cannabis use and clinical outcome in people with first-episode schizophrenia spectrum disorders over 24 months of treatment.

Cannabis use is associated with an unfavourable course of illness in schizophrenia, although several factors may confound this association. In this longitudinal study, we explored the influence of cannabis use on baseline symptom severity and treatment outcomes in 98 patients with first-episode schizophrenia spectrum disorders treated with a long acting injectable antipsychotic over 24 months. Using mixed models for repeated measures, we compared visit-wise changes in psychopathology, social and occupational functioning and quality of life between recent/current cannabis users (n=45) and non-users (n=53). There were no significant group by time interactions for any of our outcomes, and with the exception of poorer functionality in cannabis users at baseline, no significant differences in these domains at baseline or month 24. Also, remission rates were similar. However, more cannabis users met our operationally defined relapse criteria compared to non-users, and more frequent cannabis use over the course of treatment, as assessed by positive urine toxicology testing, predicted relapse. Our results suggest that cannabis users do not have poorer treatment response than non-users in terms of symptom reduction over the 24 months of treatment. However, dose-related risk of relapse remains with ongoing cannabis use, possibly by directly reducing the threshold for psychotic breakthrough.

The association between childhood trauma and treatment outcomes in schizophrenia spectrum disorders.

Childhood trauma exposure has been associated with poorer treatment outcomes in schizophrenia. Most studies to date have been conducted in naturalistic settings in which the outcome may have been mediated by factors such as poor adherence and substance abuse. We compared the effects of high vs low childhood trauma exposure on the treatment response over 24 months in 78 patients with first-episode schizophrenia spectrum disorders who received standardised treatment with a long acting injectable antipsychotic. Compared to the low childhood trauma group (n = 37), the high childhood trauma group (n = 41) received higher doses of antipsychotic medication and were less likely to achieve remission. When age, sex and cannabis use were controlled for, patients with high levels of childhood trauma had a slower treatment response for positive and disorganized symptom domains, although differences did not differ significantly at 24 months. While there were no differences in functional outcomes, self-rated quality of life was the domain that most clearly differentiated the high and low childhood trauma groups. High childhood trauma exposure was associated with lower quality of life scores at baseline, a lesser degree of improvement with treatment, and lower quality of life scores at 24 months.

Early recovery in the first 24 months of treatment in first-episode schizophrenia-spectrum disorders.

Studies assessing the treatment outcomes in first-episode schizophrenia have reported mixed results. While symptom improvement is frequently robust, when other domains are considered outcomes are generally poorer. We explored response trajectories, rates and predictors of recovery in the domains of core psychopathology, clinician-rated social and occupational functioning and patient-rated quality of life over 24 months of treatment in 98 patients with first-episode schizophrenia spectrum disorders who were treated with a long-acting antipsychotic medication. There was robust improvement in core psychopathology (effect size d = 3.36) and functionality (d = 1.78), with most improvement occurring within the first six months of treatment. In contrast, improvement in subjective quality of life was less marked (d = 0.37) and slower, only reaching significance after 12 months of treatment. Symptom remission was achieved by 70% of patients and over half met our criteria for functional remission and good quality of life. However, only 29% met the full criteria for recovery. Patients who met the recovery criteria had better premorbid adjustment, were less likely to be of mixed ethnicity and substance use emerged as the only modifiable predictor of recovery. Only 9% of our sample achieved both functional remission and good quality of life despite not being in symptom remission. We found high rates of symptom remission, functional remission and good quality of life in patients, although relatively few achieved recovery by meeting all three of the outcome criteria. Symptom remission is not a necessary prerequisite for functional remission and good quality of life, although few non-remitters achieve other recovery criteria.

Childhood trauma and hippocampal subfield volumes in first-episode schizophrenia and healthy controls.

Childhood trauma and schizophrenia are both associated with neuroanatomical abnormalities in the hippocampus, a stress-sensitive structure vulnerable to developmental insults. However, few studies have evaluated the effects of childhood trauma exposure on hippocampal morphometry in minimally treated first-episode schizophrenia patients. Here we aim to investigate the associations of childhood trauma with hippocampal subfield volumes in a cohort of antipsychotic-naive or minimally treated first-episode schizophrenia spectrum disorder patients and matched controls. 79 patients with first-episode schizophrenia spectrum disorder and 82 matched controls completed the childhood trauma questionnaire and underwent MRI assessment. Hippocampal subfields were reconstructed using FreeSurfer 6.0. We considered inter-correlations between the various subfields, by entering them as dependent variables into a multivariate analysis of co-variance (MANCOVA), modeling for interactions between diagnosis, childhood trauma total score and gender while controlling for substance use, scanner sequence and age. MANCOVA revealed a significant interaction between sex, childhood trauma total scores and diagnosis across hippocampal sub-regions (p = 0.012). Bonferroni corrected post-hoc analysis revealed a significant sex*diagnosis*childhood trauma score interaction for the hippocampal fissure (F(1,161) = 9.485,p = .002). Hippocampal fissure size showed a positive relationship with CA structures as well as whole hippocampal size in the larger sample. Findings from the present study suggest that childhood trauma exposure exerts illness-specific effects on hippocampal structures in female patients with first-episode schizophrenia, consistent with increased stress sensitivity in this group.

Changes in insight over the first 24 months of treatment in schizophrenia spectrum disorders.

BACKGROUND: While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised. AIMS: We assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic. METHOD: This single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models. RESULTS: There was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight. CONCLUSIONS: Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

Neurological soft signs in first-episode schizophrenia: State- and trait-related relationships to psychopathology, cognition and antipsychotic medication effects.

BACKGROUND: Neurological soft signs (NSS) are proposed to represent both state- and trait-related features of schizophrenia. METHOD: We assessed the course of NSS with the Neurological Evaluation Scale (NES) over 12months of standardised treatment in 126 patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder, and evaluated their state- and trait-related associations with psychopathology, functionality, cognition and antipsychotic treatment. We considered change scores from baseline to be state-related and endpoint scores to be trait-related. RESULTS: Significant effects for time were recorded for all NSS domains. For state-related change-scores greater improvements in sensory integration were predicted by more improvement in working memory (p=0.01); greater improvements in motor sequencing scores were predicted by more improvement in working memory (p=0.005) and functionality (p=0.005); and greater improvements in NES Total score were predicted by more improvement in disorganised symptoms (p=0.02). There were more substantial associations between trait-related endpoint scores than for state-related change scores. For endpoint scores lower composite cognitive score predicted poorer sensory integration (p=0.001); higher Parkinsonism score predicted poorer motor co-ordination (p=0.0001); lower composite cognitive score (p=0.001) and higher Parkinsonism score (p=0.005) predicted poorer motor sequencing; higher Parkinsonism score (p=0.0001) and disorganised symptoms (p=0.04), and lower composite cognitive score (p=0.0007) predicted higher NES total score. CONCLUSIONS: NSS improved with treatment, but were weakly associated with improvements in psychopathology. Studies investigating NSS as trait-markers should ensure that patients have been optimally treated at the time of testing, and should take possible effects of extrapyramidal symptoms into account.

How long should antipsychotic treatment be continued after a single episode of schizophrenia?

PURPOSE OF REVIEW: In this article, recent publications addressing the pros and cons of antipsychotic maintenance treatment are reviewed and some recommendations formulated. RECENT FINDINGS: On one hand, relapse rates are extremely high when antipsychotic treatment is discontinued, even after a single episode of psychosis; there are no reliable predictors of relapse; and there are serious psychosocial and biological consequences of relapse. On the other hand, in addition to the well recognised side-effect burden of antipsychotics, a few recent publications suggest an association between greater exposure to antipsychotic treatment and poorer long-term outcome. SUMMARY: There is more evidence in favour of maintaining patients on antipsychotics than on stopping them. There is an urgent need for more and better research before the question of duration of maintenance after a single episode of schizophrenia can be answered with confidence. Until such studies have been conducted, clinicians should prioritize relapse prevention, particularly in the early years of illness, by encouraging indefinite, continuous antipsychotic treatment, and avoid unnecessary side-effects by using the lowest possible effective dose and selecting the best tolerated antipsychotic.

Instruments measuring blunted affect in schizophrenia: a systematic review.

Blunted affect, also referred to as emotional blunting, is a prominent symptom of schizophrenia. Patients with blunted affect have difficulty in expressing their emotions. The work of Abrams and Taylor and their development of the Rating Scale for Emotional Blunting in the late 1970's was an early indicator that blunted affect could indeed be assessed reliably. Since then, several new instruments assessing negative symptoms with subscales measuring blunted affect have been developed. In light of this, we aim to provide researchers and clinicians with a systematic review of the different instruments used to assess blunted affect by providing a comparison of the type, characteristics, administration and psychometric properties of these instruments. Studies reporting on the psychometric properties of instruments assessing blunted affect in patients with schizophrenia were included. Reviews and case studies were excluded. We reviewed 30 full-text articles and included 15 articles and 10 instruments in this systematic review. On average the instruments take 15-30 minutes to administer. We found that blunted affect items common across all instruments assess: gestures, facial expressions and vocal expressions. The CAINS Self-report Expression Subscale, had a low internal consistency score. This suggests that this sub-scale does not reliably assess patients' self-reported blunted affect symptoms and is likely due to the nature of blunted affect. Instruments correlated minimally with instruments measuring positive symptoms and more importantly with depression suggesting that the instruments distinguish between seemingly similar symptoms.