Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life : A meta-analysis

Background: The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. Method: We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants). Results: The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19). Conclusions: CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.Peer reviewedFinal Published versio

The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations

N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study

N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p < 0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality

A leaky umbrella has little value:evidence clearly indicates the serotonin system is implicated in depression

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this