Schizophrenia has historically been considered to be a deteriorating disease, a view reinforced by recent MRI findings of progressive brain tissue loss over the early years of illness. On the other hand, the notion that recovery from schizophrenia is possible is increasingly embraced by consumer and family groups. This review critically examines the evidence from longitudinal studies of (1) clinical outcomes, (2) MRI brain volumes, and (3) cognitive functioning. First, the evidence shows that although approximately 25% of people with schizophrenia have a poor long-term outcome, few of these show the incremental loss of function that is characteristic of neurodegenerative illnesses. Second, MRI studies demonstrate subtle developmental abnormalities at first onset of psychosis and then further decreases in brain tissue volumes; however, these latter decreases are explicable by the effects of antipsychotic medication, substance abuse, and other secondary factors. Third, while patients do show cognitive deficits compared with controls, cognitive functioning does not appear to deteriorate over time. The majority of people with schizophrenia have the potential to achieve long-term remission and functional recovery. The fact that some experience deterioration in functioning over time may reflect poor access, or adherence, to treatment, the effects of concurrent conditions, and social and financial impoverishment. Mental health professionals need to join with patients and their families in understanding that schizophrenia is not a malignant disease that inevitably deteriorates over time but rather one from which most people can achieve a substantial degree of recovery.
To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder.
Although antipsychotic drugs can reduce psychotic behavior within a few hours, full efficacy is not achieved for several weeks, implying that there may be rapid, short-term changes in neuronal function, which are consolidated into long-lasting changes. We showed that the antipsychotic drug haloperidol, a dopamine receptor type 2 (D2R) antagonist, stimulated the kinase Akt to activate the mRNA translation pathway mediated by the mammalian target of rapamycin complex 1 (mTORC1). In primary striatal D2R-positive neurons, haloperidol-mediated activation of mTORC1 resulted in increased phosphorylation of ribosomal protein S6 (S6) and eukaryotic translation initiation factor 4E-binding protein (4E-BP). Proteomic mass spectrometry revealed marked changes in the pattern of protein synthesis after acute exposure of cultured striatal neurons to haloperidol, including increased abundance of cytoskeletal proteins and proteins associated with translation machinery. These proteomic changes coincided with increased morphological complexity of neurons that was diminished by inhibition of downstream effectors of mTORC1, suggesting that mTORC1-dependent translation enhances neuronal complexity in response to haloperidol. In vivo, we observed rapid morphological changes with a concomitant increase in the abundance of cytoskeletal proteins in cortical neurons of haloperidol-injected mice. These results suggest a mechanism for both the acute and long-term actions of antipsychotics.
AIM. To compare the prevalence of cardiovascular risk factors (CVRF) and vascular events, between patients treated and untreated with antipsychotic drugs. SUBJECTS AND METHODS. A cross-sectional study was done in Barcelona. We compared patients attended in Primary Health Care Centres, treated with or without antipsychotics between 2008 and 2010. Anthropometric measurements, clinical variables, and CVRF were assessed. Adult and elderly patients, typical and atypical antipsychotics, were studied separately. RESULTS. 14,087 patients had been prescribed antipsychotics (63.4% atypical), the most common being risperidone. We selected 13,724 patients with the same age and gender but not treated (total of 27,811 patients). Patients receiving antipsychotic had higher prevalence of obesity (16.9% vs. 11.9%), smoking (22.2% vs. 11.1%), diabetes mellitus (16% vs. 11.9%), and dyslipidemia (32.8% vs. 25.8%) (p < 0.001). The prevalence of stroke was significantly higher in the treated patients, both in adults (odds ratio = 2.33) and the elderly (odds ratio = 1.64). The prevalence of coronary heart disease was similar in both groups (odds ratio = 0.97). Among patients treated with antipsychotic, differences were not observed depending typical or atypical ones. CONCLUSIONS. Patients treated with antipsychotic drugs had a greater prevalence of several CVRF (diabetes mellitus, obesity, and smoking). The presence of stroke was higher in those treated with antipsychotics. No relevant differences were observed between patients receiving typical or atypical antipsychotics.
To produce a practice guideline that includes a set of detailed consensus principles regarding the prescription of antipsychotics (APs) amongst people with dementia living in care homes.
Genetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS.
It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration.
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Published 8 months ago
Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models, which can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing datasets from ten studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders. All mice were drug-naïve with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder.Neuropsychopharmacology accepted article preview online, 04 August 2017. doi:10.1038/npp.2017.167.
To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP).
Joanna Moncrieff looks at the lack of long-term evidence for antipsychotic medication and considers what is needed to ensure we have the knowledge to maximize benefits and minimize harms.