Neuroimaging studies of cognitive remediation in schizophrenia:A systematic and critical review

AIM To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia.METHODS A systematic, computerised literature search was conducted in the PubM ed/Medline and PsychI nfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [("cogniti*" and "remediation" or "training" or "enhancement") and("fMRI" or "MRI" or "PET" or "SPECT") and(schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included.RESULTS A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimaging studies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless,great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of wholebrain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive, functional and structural improvements tended to be positively correlated.CONCLUSION Neuroimaging studies of cognitive remediation in patients with schizophrenia suggest a positive effect on brain functioning in terms of the functional reorganisation of neural networks.

Brain-derived neurotrophic factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor(BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature.

Moderators and mediators of antipsychotic response in delusional disorder:Further steps are needed

Delusional disorder(DD)has been traditionally considered a relatively rare and treatment-resistant psychotic disorder.In the last decade,increasing attention has focused on therapeutic outcomes of individuals affected by this disorder.The aim of this paper is to provide a synthesis of the literature addressing two very important questions arising from DD research:(1)For which patients with DD do antipsychotic medications work best(the moderators of response);and(2)What variables best explain the relationship between such treatments and their effectiveness(the mediators of response).We searched PubMed and Google Scholar databases for English,German,French and Spanish language papers published since 2000.We also included a few classic earlier papers addressing this topic.Variables potentially moderating antipsychotic response in DD are gender,reproductive status,age,duration of illness,the presence of comorbidity(especially psychiatric comorbidity)and its treatment,brain structure,and genetics of neurochemical receptors and drug metabolizing enzymes.Antipsychotic and hormonal blood levels during treatment,as well as functional brain changes,are potential mediating variables.Some,but not all,patients with DD benefit from antipsychotic treatment.Understanding the circumstances under which treatment works best can serve to guide optimal management.

Differences between delusional disorder and schizophrenia:A mini narrative review

Psychotic syndromes are divided into affective and non-affective forms.Even among the non-affective forms,substantial differences exist.The aim of this relatively brief review is to synthesize what is known about the differences between two non-affective psychoses,schizophrenia and delusional disorder(DD),with respect to clinical,epidemiological,sociodemographic,and treatment response characteristics.A PubMed literature search revealed the following:in schizophrenia,hallucinations,negative symptoms and cognitive symptoms are prominent.They are rare in DD.Compared to schizophrenia patients,individuals with DD maintain relatively good function,and their delusions are believable;many are beliefs that are widely held in the general population.Treatments are generally similar in these two forms of psychosis,with the exception that antidepressants are used more frequently in DD and,for acute treatment,effective antipsychotic doses are lower in DD than in schizophrenia.It is with the hope that the contrasts between these two conditions will aid in the provision of safe and effective treatment for both that this review has been conducted.