Matteo Cella

Randomized-controlled trials in people at ultra high risk of psychosis: A review of treatment effectiveness

As an extension of the early intervention in psychosis paradigm, different focused treatments are now offered to individuals at ultra high risk of psychosis (UHR) to prevent transition to schizophrenia, however the effectiveness of these treatments is unclear. A systematic literature search in PubMed/Medline and PsycINFO was performed to derive information on randomized control trials (RCTs) in UHR samples. Seven reports were identified detailing results from five independent RCT studies. Two studies used antipsychotic drugs (one in combination with cognitive behavior therapy); one study employed cognitive therapy; one study used a two-year program of intensive community care with family psychoeducation; one study assessed the effectiveness of 3-months omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) supplementation. Intensive community care and the Omega-3 PUFAs supplementation were effective in reducing the transition to psychosis at 12 months. Overall, rates of transition to psychosis at 1 year were 11% for focused treatment groups (n=180) and 31.6% for control UHR groups (n=157). Receiving any of the focused treatment was associated with a lower risk of developing psychosis if compared with no treatment or treatment as usual (Relative Risk=0.36; 95%CI: 0.22-0.59). The available evidence at 2/3 years follow-up indicates that the effects of focused treatments are not stable after intervention cessation and when treatment is delivered over a restricted time (e.g. 6 months or less), it may achieve only a delay in psychosis onset. Due to the heterogeneity in the interventions considered, the current results do not allow recommendation for any specific treatment.

Impaired flexible decision-making in major depressive disorder

BACKGROUND Depression is associated with dysfunctional affective states, neuropsychological impairment and altered sensitivity to reward and punishment. These impairments can influence complex decision-making in changing environments. METHODS The contingency shifting variant Iowa Gambling Task (IGT) was used to assess flexible decision-making performance in a group of medicated unipolar Major Depressive Disorder (MDD) patients (n=19) and a group of healthy control volunteers (n=20). The task comprised the standard IGT followed by a contingency-shift phase where decks progressively changed reward and punishment schedule. RESULTS Patients with MDD showed impaired performance compared to controls during both the standard and the contingency-shift phases of the IGT. Analysis of the contingency-shift phase demonstrated that individuals with depression had difficulties perceiving when a previously bad contingency became good. LIMITATIONS The present findings have several limitations including small sample size, the possible confounding role of medication and absence of other neuropsychological tests (i.e., executive function). CONCLUSION Depressed patients show impaired decision-making behaviour in static and dynamic environments. Altered sensitivity to reward and punishment is proposed as the mechanism responsible for the lack of advantageous choices and poor adjustment to a changing environment.

Measuring fatigue in clinical and community settings

OBJECTIVE The Chalder Fatigue Scale (CFQ) is a widely used instrument to assess fatigue in both clinical and nonclinical settings. Psychometric properties of the scale and discriminative abilities were examined. METHODS A total of 361 patients with CFS and 1615 individuals in the community were assessed with the CFQ. Principal component analysis (PCA) was used to explore the structure of the scale. Receiver-operating characteristic curve (ROC) was used to investigate the discriminative properties. RESULTS Two components, physical and mental fatigue, were identified in the CFS patient group and in the general population samples. Area under the curve for ROC was .91. The fatigue scale effectively discriminates, at high scores, between CFS patients and the general population. CONCLUSION Physical and mental fatigue are clearly separable components of fatigue. The CFQ can discriminate reliably between clinical and nonclinical conditions.

Auditory verbal hallucinations in persons with and without a need for care

Auditory verbal hallucinations (AVH) are complex experiences that occur in the context of various clinical disorders. AVH also occur in individuals from the general population who have no identifiable psychiatric or neurological diagnoses. This article reviews research on AVH in nonclinical individuals and provides a cross-disciplinary view of the clinical relevance of these experiences in defining the risk of mental illness and need for care. Prevalence rates of AVH vary according to measurement tool and indicate a continuum of experience in the general population. Cross-sectional comparisons of individuals with AVH with and without need for care reveal similarities in phenomenology and some underlying mechanisms but also highlight key differences in emotional valence of AVH, appraisals, and behavioral response. Longitudinal studies suggest that AVH are an antecedent of clinical disorders when combined with negative emotional states, specific cognitive difficulties and poor coping, plus family history of psychosis, and environmental exposures such as childhood adversity. However, their predictive value for specific psychiatric disorders is not entirely clear. The theoretical and clinical implications of the reviewed findings are discussed, together with directions for future research.

Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale.

BACKGROUND Disability is a defining feature of chronic conditions, and it is an increasingly used measure of therapy effectiveness. The Work and Social Adjustment Scale (WSAS) is a simple and clear measure of disability. Although the scale is widely used, no study has yet investigated its psychometric properties in patients with chronic fatigue syndrome (CFS). METHODS Data from two samples of patients were used, one from a multicenter randomized controlled clinical trial of treatments for CFS (n =639) and the other from a clinic that specializes in CFS (n=384). All patients completed the WSAS as well as other measures. RESULTS Internal consistency and the Spearman-Brown split-half coefficient values indicated that the scale is reliable. CFS patients who had comorbid diagnoses of depression, anxiety or fibromyalgia had higher WSAS scores. High levels of disability were associated with high number of physical symptoms, severe fatigue, depression, anxiety, poor sleep quality and poor physical fitness, with correlation coefficients ranging between 0.41 and 0.11. Lower scores on the WSAS were modestly associated with better physical functioning as well as higher levels of physical capacity as assessed by a walking test. Sensitivity to change was evaluated in a subgroup of patients who had undergone a course of cognitive behavioral therapy. Disability significantly decreased after therapy and remained stable at follow-ups. CONCLUSION The WSAS is a reliable and valid assessment tool for disability in patients with CFS.

Gender and duration of untreated psychosis: a systematic review and meta‐analysis

Aim: Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta‐analysis on the role of gender in influencing DUP in first‐episode psychosis.

The relationship between dysphoria and proneness to hallucination and delusions among young adults

Previous research suggests that measures of dysphoria relate to positive schizophrenic symptoms. These relationships have rarely been studied within the dimensionality of psychopathology framework. The present study examined the relationship between 3 distinct aspects of dysphoria (depression and state and trait anxiety) and delusion and hallucination proneness in a nonclinical sample of young adults. A total of 472 participants were assessed on measures of dysphoria and delusion and hallucination proneness. Correlation analyses revealed significant associations between both anxiety and depression and hallucination and delusion proneness, suggesting that the association between dysphoria and positive symptoms is also present at a nonclinical level. Partial correlations, and hierarchical regression models, suggest an independent contribution of depression, over anxiety, in influencing hallucination and delusional proneness. The results are discussed in the framework of the cognitive account of schizophrenia and the dimensional model of psychopathology.

Does the Heterogeneity of Chronic Fatigue Syndrome Moderate the Response to Cognitive Behaviour Therapy? An Exploratory Study

Background: Chronic fatigue syndrome (CFS) is a heterogeneous condition. A few studies have shown that some independent factors predict outcomes after cognitive behaviour therapy (CBT). Two recent systematic reviews suggest that heterogeneity may moderate treatment outcomes. However, no study has explored whether subgroups of CFS predict response to treatment. Methods: We used both latent class analysis (LCA) and latent class regression (LCR) to clarify the relationship between subgroups of CFS patients (n = 236), diagnosed using the Oxford diagnostic criteria, and the response to CBT. We measured symptoms, demographics, mood, and cognitive and behavioural responses to illness to define subgroups. Results: We found 5 latent classes by LCA, which did not differ in the direction of their response to CBT, with all classes showing improvement. In contrast, an exploratory LCR identified 4 latent classes, 1 of which predicted a poor response to CBT, whereas the other 3 predicted a good outcome, accounting for more than 70% of the patients. The negative outcome class was defined by weight fluctuations and physical shakiness, anxiety, pain and being focused on symptoms. Conclusions: CBT should be offered to all classes of patients with CFS, when defined by these measures. It may be possible to predict a minority group with a negative outcome, but this exploratory work needs replication.

Cognitions, behaviours and co-morbid psychiatric diagnoses in patients with chronic fatigue syndrome.

BACKGROUND Specific cognitions and behaviours are hypothesized to be important in maintaining chronic fatigue syndrome (CFS). Previous research has shown that a substantial proportion of CFS patients have co-morbid anxiety and/or depression. This study aims to measure the prevalence of specific cognitions and behaviours in patients with CFS and to determine their association with co-morbid anxiety or depression disorders. METHOD A total of 640 patients meeting Oxford criteria for CFS were recruited into a treatment trial (i.e. the PACE trial). Measures analysed were: the Cognitive Behavioural Response Questionnaire, the Chalder Fatigue Scale and the Work and Social Adjustment Scale. Anxiety and depression diagnoses were from the Structured Clinical Interview for DSM-IV. Multivariate analysis of variance was used to explore the associations between cognitive-behavioural factors in patients with and without co-morbid anxiety and/or depression. RESULTS Of the total sample, 54% had a diagnosis of CFS and no depression or anxiety disorder, 14% had CFS and one anxiety disorder, 14% had CFS and depressive disorder and 18% had CFS and both depression and anxiety disorders. Cognitive and behavioural factors were associated with co-morbid diagnoses; however, some of the mean differences between groups were small. Beliefs about damage and symptom focussing were more frequent in patients with anxiety disorders while embarrassment and behavioural avoidance were more common in patients with depressive disorder. CONCLUSIONS Cognitions and behaviours hypothesized to perpetuate CFS differed in patients with concomitant depression and anxiety. Cognitive behavioural treatments should be tailored appropriately.

Cognitive remediation for negative symptoms of schizophrenia: A network meta-analysis.

Cognitive remediation (CR) is a treatment targeting cognitive difficulties in people with schizophrenia. Recent research suggested that CR may also have a positive effect on negative symptoms. This meta-analysis investigates the effect of CR on negative symptoms. A systematic search was used to identify all randomized-controlled trials of CR in people with schizophrenia reporting negative symptoms outcomes. Levels of negative symptoms at baseline, post-therapy and follow-up, sample demographics and treatment length were extracted. Study methodological quality and heterogeneity were addressed. Negative symptoms standardized mean change was calculated using Hedgess g and used as the main outcome. The search identified 45 studies reporting results for 2511 participants; 15 studies reported follow-up outcomes. CR was associated with a reduction of negative symptoms (most conservative model g=-0.30; 95% CI: -0.36, -0.22) at post-therapy compared with treatment as usual and this effect was larger at follow-up (g=-0.36; 95% CI: -0.51, -0.21). Drop-out rate was comparable between conditions. Network meta-analysis confirmed CR was superior to TAU and TAU plus active control or adjunctive treatment. No evidence of publication bias was found. Studies with more rigorous methodology were associated with larger negative symptom reduction (g=-0.40; 95% CI: -0.51 to -0.30). Although negative symptoms have not been considered a primary target for CR, this intervention can have small to moderate beneficial effects on this symptom cluster. Future research should explore in detail the active mechanisms responsible for negative symptom reduction and the relationship between cognitive and negative symptoms in schizophrenia.