Schizophrenia has often been conceived as a disorder of connectivity between components of large-scale brain networks. We tested this hypothesis by measuring aspects of both functional connectivity and functional network topology derived from resting-state fMRI time series acquired at 72 cerebral regions over 17 min from 15 healthy volunteers (14 male, 1 female) and 12 people diagnosed with schizophrenia (10 male, 2 female). We investigated between-group differences in strength and diversity of functional connectivity in the 0.06 -0.125 Hz frequency interval, and some topological properties of undirected graphs constructed from thresholded interregional correlation matrices. In people with schizophrenia, strength of functional connectivity was significantly decreased, whereas diversity of functional connections was increased. Topologically, functional brain networks had reduced clustering and small-worldness, reduced probability of high-degree hubs, and increased robustness in the schizophrenic group. Reduced degree and clustering were locally significant in medial parietal, premotor and cingulate, and right orbitofrontal cortical nodes of functional networks in schizophrenia. Functional connectivity and topological metrics were correlated with each other and with behavioral performance on a verbal fluency task. We conclude that people with schizophrenia tend to have a less strongly integrated, more diverse profile of brain functional connectivity, associated with a less hub-dominated configuration of complex brain functional networks. Alongside these behaviorally disadvantageous differences, however, brain networks in the schizophrenic group also showed a greater robustness to random attack, pointing to a possible benefit of the schizophrenia connectome, if less extremely expressed.

Cognitive-behavioural therapy has a therapeutic effect on schizophrenic symptoms in the 'small' range. This reduces further when sources of bias, particularly masking, are controlled for.

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These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.

All of the tasks impaired following sulpiride are known to be sensitive to frontal lobe damage and the precise pattern of deficits seen is consistent with the anatomical distribution of central dopamine receptors. The results are discussed with particular reference to their close simulation of the impairments seen in idiopathic Parkinson's disease.

Modafinil, a novel cognitive enhancer, selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder (ADHD). It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission. The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia. Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind, randomized, placebo-controlled crossover study using a 200 mg dose of modafinil. Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. Improvement was seen on short-term verbal memory span, with trends towards improved visual memory and spatial planning. This was accompanied by slowed response latency on the spatial planning task. No effect on stop-signal performance was seen. Importantly, significant improvement in attentional set shifting was seen, despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.

Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.

Background. Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and meta-analyses have not fully considered the potential influence of blindness or the use of control interventions.Method. We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non-specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor.Results. CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder.Conclusions. CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder. Key words : Bipolar disorder, cognitive therapy, depression, schizophrenia. IntroductionCognitive behavioural therapy (CBT) has been widely adopted by psychiatry in recent years, but its increase in use in the severe disorders of schizophrenia, major depression and bipolar disorder is particularly noteworthy. This is because it challenges what has, until recently, been a dominance of biological approaches to these disorders. Thus, although contemporary accounts of schizophrenia (e.g. Picchioni & Murray, 2007) emphasize biological factors in its aetiology and consider neuroleptic drugs to be the mainstay of treatment, official UK treatment guidelines from the National Institute for Clinical Excellence (NICE) also state that psychological interventions are indispensable and that CBT should be offered to all patients (NICE, 2003(NICE, , 2009. Psychological factors may loom larger in the aetiology of major affective disorder, but when it comes to treatment, the emphasis in the literature, particularly in bipolar disorder, has once again been firmly on pharmacotherapy. Attitudes may be changing here too, however. References to the effectiveness of CBT are pervasive in the UK depression treatment guideline (NICE, 2004) ; a government initiative is under way in the UK to provide CBT for depression and anxiety in 250 dedicated therapy centres (Layard, 2006) ; and CBT is being advocated for relapse prevention in bipolar disorder (e.g. Scott & Colom, 2005 ;Basco & Rush, 2007).Nevertheless, a cursory look at the literature reveals well-conducted trials where CBT has had negative findings in all three disorders. For example, large-scale trials of CBT in schizophrenia have failed to find significant advantages over befriending (Sensky et al. 2000) or supportive counselling (L...