Schizophrenia, Depressive Symptoms, and Antipsychotic Drug Treatment.
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ABSTRACT:
SUBMITTER: Reynolds GP
PROVIDER: S-EPMC8059489 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and hypothesisComplex schizophrenia symptoms were recently conceptualized as interactive symptoms within a network system. However, it remains unknown how a schizophrenia network changed during acute antipsychotic treatment. The present study aimed to evaluate the interactive change of schizophrenia symptoms under seven antipsychotics from individual time series.Study designData on 3030 schizophrenia patients were taken from a multicenter randomized clinical trial and used to estimate the partial correlation cross-sectional networks and longitudinal random slope networks based on multivariate multilevel model. Thirty symptoms assessed by The Positive and Negative Syndrome Scale clustered the networks.Study resultsFive stable communities were detected in cross-sectional networks and random slope networks that describe symptoms change over time. Delusions, emotional withdrawal, and lack of spontaneity and flow of conversation featured as central symptoms, and conceptual disorganization, hostility, uncooperativeness, and difficulty in abstract thinking featured as bridge symptoms, all showing high centrality in the random slope network. Acute antipsychotic treatment changed the network structure (M-test = 0.116, P < .001) compared to baseline, and responsive subjects showed lower global strength after treatment (11.68 vs 14.18, S-test = 2.503, P < .001) compared to resistant subjects. Central symptoms and bridge symptoms kept higher centrality across random slope networks of different antipsychotics. Quetiapine treatment network showed improvement in excitement symptoms, the one featured as both central and bridge symptom.ConclusionOur findings revealed the central symptoms, bridge symptoms, cochanging features, and individualized features under different antipsychotics of schizophrenia. This brings implications for future targeted drug development and search for pathophysiological mechanisms.
| S-EPMC9810008 | biostudies-literature
Project description:BackgroundSchizophrenia involves alterations in hippocampal function. The implications of these alterations for memory function in the illness remain poorly understood. Furthermore, it remains unknown how memory is impacted by drug treatments for schizophrenia. The goal of this study was to delineate specific memory processes that are disrupted in schizophrenia and explore how they are affected by medication. We specifically focus on memory generalization--the ability to flexibly generalize memories in novel situations.MethodsIndividuals with schizophrenia (n = 56) and healthy control subjects (n = 20) were tested on a computerized memory generalization paradigm. Participants first engaged in trial-by-error associative learning. They were then asked to generalize what they learned by responding to novel stimulus combinations. Individuals with schizophrenia were tested on or off antipsychotic medication, using a between-subject design in order to eliminate concerns about learning-set effects.ResultsIndividuals with schizophrenia were selectively impaired in their ability to generalize knowledge, despite having intact learning and memory accuracy. This impairment was found only in individuals tested off medication. Individuals tested on medication generalized almost as well as healthy control subjects. This between-group difference was selective to memory generalization.ConclusionsThese findings suggest that individuals with schizophrenia have a selective alteration in the ability to flexibly generalize past experience toward novel learning environments. This alteration is unaccompanied by global memory impairments. Additionally, the results indicate a robust generalization difference on the basis of medication status. These results suggest that hippocampal abnormalities in schizophrenia might be alleviated with antipsychotic medication, with important implications for understanding adaptive memory-guided behavior.
| S-EPMC4023678 | biostudies-literature
Project description:Trials of novel compounds for the treatment of schizophrenia are typically tested in patients following brief withdrawal of ongoing medication despite known long-term changes in the dopamine (DA) system following chronic antipsychotic drug therapy. The present study explored the impact of withdrawal from repeated haloperidol (HAL) treatment, as well as the response to a novel ?5 gamma-aminobutyric acid (GABA(A)) receptor positive allosteric modulator (?5PAM), on the activity of the DA system in the methylazoxymethanol acetate (MAM) neurodevelopmental model of schizophrenia. Electrophysiological recordings were conducted from DA neurons in the ventral tegmental area of MAM and saline (SAL) rats following 7-day withdrawal from repeated HAL (21 d, 0.6 mg/kg, orally). In separate animals, amphetamine-induced locomotion was measured to assess changes in DA behavioral sensitivity. SAL rats withdrawn from HAL demonstrated reduced spontaneous DA neuron activity along with an enhanced locomotor response to amphetamine, indicative of the development of DA supersensitivity. Both ?5PAM treatment and ventral hippocampal (vHPC) inactivation reversed the DA neuron depolarization block following HAL withdrawal in SAL rats. In contrast, MAM rats withdrawn from HAL exhibited reduced spontaneous DA activity and enhanced locomotor response to amphetamine compared with untreated SAL rats; however, this condition was unresponsive to ?5PAM treatment or vHPC inactivation. Withdrawal from prior HAL treatment interferes with the therapeutic actions of this novel treatment in the MAM model of schizophrenia. Consequently, testing novel compounds on chronically treated schizophrenia patients may be ineffective.
| S-EPMC3932102 | biostudies-literature
Project description:BackgroundThis meta-analysis was conducted to evaluate whether HTR1A gene polymorphisms impact the efficacy of antipsychotic drugs in patients with schizophrenia.MethodsCandidate gene studies that were published in English up to August 6, 2015 were identified by a literature search of PubMed, Web of Science, and Google scholar. Data were pooled from individual clinical trials considering overall symptoms, positive symptoms and negative symptoms, and standard mean differences were calculated by applying a random-effects model.ResultsThe present meta-analysis included a total of 1281 patients from 10 studies. Three polymorphisms of HTR1A (rs6295, rs878567, and rs1423691) were selected for the analysis. In the pooled data from all studies, none of these HTR1A polymorphisms correlated significantly with either overall symptoms or positive symptoms. However, C allele carriers of the rs6295 polymorphism showed a significantly greater negative symptoms improvement than G allele carriers (P=.04, standardized mean difference =-0.14, 95％CI = 0.01 to 0.28).ConclusionsThe results of our present analysis indicate that the HTR1A rs6295 polymorphism may impact negative symptoms improvement but not on either overall symptoms or positive symptoms improvement. However, this meta-analysis was based on a small number of studies and patients, and the effect size on negative symptoms was small. Given this limitation, the results should be confirmed by further investigations.
| S-EPMC4886666 | biostudies-literature
Project description:Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis.
| S-EPMC3652172 | biostudies-literature
Project description:BackgroundNeuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1β1 levels following antipsychotic treatment and the relationship between NRG1β1 levels and improvements in psychotic symptoms among first-episode drug-naïve (FEDN) patients and patients with chronic schizophrenia.MethodsA total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1β1 levels and positive and negative syndrome scale (PANSS) scores were measured at baseline and after four weeks. Serum NRG1β1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISAs).ResultsBaseline NRG1β1 levels were significantly lower in patients with schizophrenia than in healthy controls. NRG1β1 levels increased significantly following antipsychotic treatment. NRG1β1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1β1 increased significantly in responders after four weeks of treatment, although nonresponders showed no such effect. Correlation analyses showed that the levels of NRG1β1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.ConclusionThe levels of serum NRG1β1 and the therapeutic effects gradually increased following treatment, indicating that NRG1β1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation.
| S-EPMC8957169 | biostudies-literature
Project description:BackgroundOur previous study has shown the cingulate cortex abnormalities in first-episode drug naïve (FEDN) schizophrenia patients with comorbid depressive symptoms. However, it remains largely unknown whether antipsychotics may induce morphometric change in cingulate cortex and its relationship with depressive symptoms. The purpose of this study was to further clarify the important role of cingulate cortex in the treatment on depressive symptoms in FEDN schizophrenia patients.MethodIn this study, 42 FEDN schizophrenia patients were assigned into depressed patients group (DP, n = 24) and non-depressed patients group (NDP, n = 18) measured by the 24-item Hamilton Depression Rating Scale (HAMD). Clinical assessments and anatomical images were obtained from all patients before and after 12-week treatment with risperidone.ResultsAlthough risperidone alleviated psychotic symptoms in all patients, depressive symptoms were decreased only in DP. Significant group by time interaction effects were found in the right rostral anterior cingulate cortex (rACC) and other subcortical regions in the left hemisphere. After risperidone treatment, the right rACC were increased in DP. Further, the increasing volume of right rACC was negatively associated with improvement in depressive symptoms.ConclusionThese findings suggested that the abnormality of the rACC is the typical characteristics in schizophrenia with depressive symptoms. It's likely key region contributing to the neural mechanisms underlying the effects of risperidone treatment on depressive symptoms in schizophrenia.
| S-EPMC9922813 | biostudies-literature
Project description:For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs) which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.
| S-EPMC5532378 | biostudies-literature
Project description:Schizophrenia is, in part, a cognitive illness. There are no approved medications for cognitive impairments associated with schizophrenia (CIAS) and primary negative symptoms. Cholinergic and glutamatergic systems, alpha-7 nicotinic acetylcholine (α-7nACh) and N-methyl-D-aspartate (NMDA) receptors, kynurenic acid (KYNA), and mismatch negativity have been implicated in the pathophysiology of CIAS and negative symptoms. Galantamine is an acetylcholinesterase inhibitor that is also a positive allosteric modulator at the α4β2 and α7nACh receptors. Memantine is a noncompetitive NMDA receptor antagonist. Galantamine and memantine alone and in combination were effective for cognition in animals and people with Alzheimer's disease. The objective of this article is to critically dissect the published randomized controlled trials with galantamine and memantine for CIAS to highlight the efficacy signal. These studies may have failed to detect a clinically meaningful efficacy signal due to limitations, methodological issues, and possible medication nonadherence. There is evidence from a small open-label study that the galantamine-memantine combination may be effective for CIAS with kynurenine pathway metabolites as biomarkers to detect the severity of cognitive impairments. Given that there are no available treatments for cognitive impairments and primary negative symptoms in schizophrenia, testing of this "five-pronged strategy" (quintuple hypotheses: dopamine, nicotinic-cholinergic, glutamatergic/NMDA, GABA, and KYNA) is a "low-risk high-gain" approach that could be a major breakthrough in the field. The galantamine-memantine combination has the potential to treat positive, cognitive, and negative symptoms, and targeting the quintuple hypotheses concurrently may lead to a major scientific advancement - from antipsychotic treatment to antischizophrenia treatment.
| S-EPMC6323397 | biostudies-literature
Project description:The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment response. Because of the rapid and exciting developments in the field, we reviewed the recent studies of the molecular genetic basis of treatment response in schizophrenia. The accumulating data suggest that DNA information in the pathways for drug metabolism and drug target sites may be an important predictor of treatment response in schizophrenia. The data suggest that clinicians may soon be using a patient's genotype to decide initial choice of antipsychotic drug treatment in schizophrenia. The pharmacogenetics of schizophrenia can improve the prospects of individualized treatment and drug discovery. Pharmacogenetic investigations of schizophrenia susceptibility loci, and genes controlling drug target site receptors, drug-metabolizing enzymes, the blood-brain barrier systems, and epigenetic mechanisms could lead to a molecular classification of treatment response and adverse events of psychotropic drugs.
| S-EPMC2276697 | biostudies-literature