Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies.

Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: a prospective controlled study in a real-world setting.

BACKGROUND: Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients' functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia. OBJECTIVE: To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia. METHODS: Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment. RESULTS: The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes. CONCLUSIONS: The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.

Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies.

BACKGROUND: A number of meta-analytic reviews of structural brain imaging studies have shown that multiple subtle brain abnormalities are consistently found in schizophrenia. However, quantitative reviews till now published have included mainly studies performed on chronic schizophrenic patients but have failed to provide clear information on specific, possibly different, findings in first-episode schizophrenia. METHODS: We performed a systematic search for MRI studies that reported quantitative measurements of volumes of brain regions in first-episode schizophrenic patients and in healthy controls. Twelve meta-analyses were performed for 6 cerebral regions. RESULTS: Twenty-one studies were identified as suitable for analysis. Significant overall effect sizes were demonstrated for lateral and third ventricular volume increase, and for volume reduction of whole brain and hippocampus, but not for temporal lobe, amygdala and total intracranial volumes. CONCLUSIONS: The available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenic patients. However, unlike the results of published meta-analyses conducted primarily on samples of chronic schizophrenic patients, the present study did not confirm a significant reduction of temporal lobe or amygdala volumes in first-episode schizophrenia. These findings support the hypothesis of different patterns of involvement of various cerebral areas over the time course of schizophrenia.

In vivo serotonin 5HT(2A) receptor binding and personality traits in healthy subjects: a positron emission tomography study.

Using positron emission tomography (PET) and [(11)C]raclopride, an association between striatal D(2) dopamine receptors and emotional detachment has been recently reported. Several laboratory findings indicate a link between the serotoninergic system and harm avoidance. In this study we investigated, in a group of healthy volunteers, the relationship between the in vivo binding of 3-(2'-[(18)F]fluoroethyl)spiperone ([(18)F]FESP) to cortical 5HT(2) and striatal D(2) receptors and three personality dimensions, i.e., "novelty seeking," "reward dependence," and "harm avoidance." Eleven healthy volunteers were evaluated by means of the Tridimensional personality Questionnaire (C. R., Arch. Gen. Psychiatry 44: 573-588.) and underwent a PET scan with [(18)F]FESP. Harm avoidance showed a significant inverse correlation with [(18)F]FESP binding in the cerebral cortex, particularly in the frontal cortex (R(2) = -0.709, P = 0.0145) and left parietal cortex (R = -0.629, P = 0.038) but not in the basal ganglia (r = -0.176, P = 0.651). Similar results were obtained using SPM at a P threshold of 0.05. No significant correlation was observed with novelty seeking or reward dependence. In the cerebral cortex, high values of [(18)F]FESP binding values are associated with a high tendency to avoid danger, indicating involvement of the serotoninergic system and, in particular, 5HT(2A) receptors, in this trait of personality. The results of this as well as of previous studies on personality dimensions indicate the existence of a relationship between behavioral and neurobiological factors. In addition these results support the concept that the variability of PET data may be explained by neurochemical differences related to the prevalence of specific personality traits.