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Lancet (London, England) Jul 2016Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome that seems to originate from disruption of brain development caused by genetic or... (Review)
Review
Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome that seems to originate from disruption of brain development caused by genetic or environmental factors, or both. Dysfunction of dopaminergic neurotransmission contributes to the genesis of psychotic symptoms, but evidence also points to a widespread and variable involvement of other brain areas and circuits. Disturbances of synaptic function might underlie abnormalities of neuronal connectivity that possibly involves interneurons, but the precise nature, location, and timing of these events are uncertain. At present, treatment mainly consists of antipsychotic drugs combined with psychological therapies, social support, and rehabilitation, but a pressing need for more effective treatments and delivery of services exists. Advances in genomics, epidemiology, and neuroscience have led to great progress in understanding the disorder, and the opportunities for further scientific breakthrough are numerous--but so are the challenges.
Topics: Antipsychotic Agents; Brain; Cognition Disorders; Environmental Exposure; Humans; Psychotherapy; Schizophrenia; Schizophrenic Psychology; Social Support; Social Work
PubMed: 26777917
DOI: 10.1016/S0140-6736(15)01121-6 -
Neurobiology of Disease Nov 2019Treatment resistant schizophrenia (TRS) refers to the significant proportion of schizophrenia patients who continue to have symptoms and poor outcomes despite treatment.... (Review)
Review
Treatment resistant schizophrenia (TRS) refers to the significant proportion of schizophrenia patients who continue to have symptoms and poor outcomes despite treatment. While many definitions of TRS include failure of two different antipsychotics as a minimum criterion, the wide variability in inclusion criteria has challenged the consistency and reproducibility of results from studies of TRS. We begin by reviewing the clinical, neuroimaging, and neurobiological characteristics of TRS. We further review the current treatment strategies available, addressing clozapine, the first-line pharmacological agent for TRS, as well as pharmacological and non-pharmacological augmentation of clozapine including medication combinations, electroconvulsive therapy, repetitive transcranial magnetic stimulation, deep brain stimulation, and psychotherapies. We conclude by highlighting the most recent consensus for defining TRS proposed by the Treatment Response and Resistance in Psychosis Working Group, and provide our overview of future perspectives and directions that could help advance the field of TRS research, including the concept of TRS as a potential subtype of schizophrenia.
Topics: Drug Resistance; Humans; Schizophrenia
PubMed: 30170114
DOI: 10.1016/j.nbd.2018.08.016 -
Canadian Journal of Psychiatry. Revue... Jan 2019Schizophrenia is a heterogeneous psychiatric disorder that is poorly treated with current therapies. In this brief review, we provide an update regarding the use of... (Review)
Review
Schizophrenia is a heterogeneous psychiatric disorder that is poorly treated with current therapies. In this brief review, we provide an update regarding the use of animal models to study schizophrenia in an attempt to understand its aetiology and develop novel therapeutic strategies. Tremendous progress has been made developing and validating rodent models that replicate the aetiologies, brain pathologies, and behavioural abnormalities associated with schizophrenia in humans. Here, models are grouped into 3 categories-developmental, drug induced, and genetic-to reflect the heterogeneous risk factors associated with schizophrenia. Each of these models is associated with varied but overlapping pathophysiology, endophenotypes, behavioural abnormalities, and cognitive impairments. Studying schizophrenia using multiple models will permit an understanding of the core features of the disease, thereby facilitating preclinical research aimed at the development and validation of better pharmacotherapies to alter the progression of schizophrenia or alleviate its debilitating symptoms.
Topics: Animals; Disease Models, Animal; Schizophrenia
PubMed: 29742910
DOI: 10.1177/0706743718773728 -
Psychopharmacology Bulletin Feb 2019Schizophrenia is a mental disorder that is characterized by progressive cognitive impairment in areas of attention, working memory, and executive functioning. Although... (Review)
Review
Schizophrenia is a mental disorder that is characterized by progressive cognitive impairment in areas of attention, working memory, and executive functioning. Although no clear etiology of schizophrenia has been discovered, many factors have been identified that contribute to the development of the disease, such as neurotransmitter alterations, decreased synaptic plasticity, and diminished hippocampal volume. Historically, antipsychotic medications have targeted biochemical alterations in the brains of patients with schizophrenia but have been ineffective in alleviating cognitive and hippocampal deficits. Other modalities, such as exercise therapy, have been proposed as adjuvant or primary therapy options. Exercise therapy has been shown to improve positive and negative symptoms, quality of life, cognition, and hippocampal plasticity, and to increase hippocampal volume in the brains of patients with schizophrenia. This article will briefly review the clinical signs, symptoms and proposed etiologies of schizophrenia, and describe the current understanding of exercise programs as an effective treatment in patients with the disease.
Topics: Cognition; Exercise; Humans; Neuronal Plasticity; Schizophrenia
PubMed: 30858639
DOI: No ID Found -
International Journal of Molecular... Apr 2013Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia's biological... (Review)
Review
Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia's biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.
Topics: Biomarkers; Humans; Melatonin; Schizophrenia
PubMed: 23698762
DOI: 10.3390/ijms14059037 -
Schizophrenia Bulletin Aug 2018This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal... (Review)
Review
This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal elicitation of the immune response may increase immune reactivity throughout life, and similar findings have been described in humans. Levels of pro-inflammatory markers, such as cytokines, have been found to be increased in the blood and cerebrospinal fluid of patients with schizophrenia. Numerous epidemiological and clinical studies have provided evidence that various infectious agents are risk factors for schizophrenia and other psychoses. For example, a large-scale epidemiological study performed in Denmark clearly showed that severe infections and autoimmune disorders are such risk factors. The vulnerability-stress-inflammation model may help to explain the role of inflammation in schizophrenia because stress can increase pro-inflammatory cytokines and may even contribute to a chronic pro-inflammatory state. Schizophrenia is characterized by risk genes that promote inflammation and by environmental stress factors and alterations of the immune system. Typical alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission described in schizophrenia have also been found in low-level neuroinflammation and consequently may be key factors in the generation of schizophrenia symptoms. Further support for the relevance of a low-level neuroinflammatory process in schizophrenia is provided by the loss of central nervous system volume and microglial activation demonstrated in neuroimaging studies. Last but not least, the benefit of anti-inflammatory medications found in some studies and the intrinsic anti-inflammatory and immunomodulatory effects of antipsychotics provide further support for the role of inflammation in this debilitating disease.
Topics: Animals; Anti-Inflammatory Agents; Humans; Inflammation; Schizophrenia
PubMed: 29648618
DOI: 10.1093/schbul/sby024 -
Schizophrenia Research May 2022Obsessive-compulsive symptoms are frequent in schizophrenia-spectrum disorders and often cause differential diagnostic challenges, especially in first-contact patients.... (Review)
Review
Obsessive-compulsive symptoms are frequent in schizophrenia-spectrum disorders and often cause differential diagnostic challenges, especially in first-contact patients. Drawing upon phenomenology of cognition, we critically review classic and contemporary psychopathological notions of obsessive-compulsive phenomena and discuss their relevance for differential diagnosis between obsessive-compulsive disorder (OCD) and schizophrenia-spectrum disorders. The classic psychopathological literature defines true obsession as intrusions with intact resistance and insight and regards these features as essential to the diagnosis of OCD. In schizophrenia, the classic literature describes pseudo-obsessive-compulsive phenomena characterized by lack of resistance and an affinity with other symptoms such as thought disorder and catatonia. By contrast, the notions of obsession and compulsion are broader and conceptually vague in current diagnostic systems and research instruments. Here, these phenomena overlap with delusions as well as various subjective and behavioral anomalies, which we discuss in detail. Furthermore, we examine a link between obsessive-compulsive phenomena and disturbances of basic structures of experience in schizophrenia-spectrum disorders addressed in contemporary psychopathological research. We suggest that these experiential alterations have relevance for differential diagnosis and early detection in this complex symptom domain.
Topics: Diagnosis, Differential; Humans; Obsessive Behavior; Obsessive-Compulsive Disorder; Psychopathology; Schizophrenia
PubMed: 35219003
DOI: 10.1016/j.schres.2022.02.014 -
Child and Adolescent Psychiatric... Apr 2017This article reviews the current state of diagnosis and treatment of schizophrenia, describing the recent proliferation of research in high-risk psychosis spectrum... (Review)
Review
This article reviews the current state of diagnosis and treatment of schizophrenia, describing the recent proliferation of research in high-risk psychosis spectrum conditions, which are different from childhood-onset and early onset schizophrenia, and findings of psychotic-like experiences in the normal population. Taken from adult and childhood literature, clinical quandaries in accurate diagnosis, and treatment gaps in co-occurring, or sometimes confounding, conditions are discussed. Thoughts on the impact of schizophrenia on an emerging adulthood trajectory are offered. Recent best practices in the treatment of schizophrenia are consistent with a recovery-oriented model of mental health services for transitional age youth.
Topics: Adolescent; Adult; Humans; Psychotic Disorders; Schizophrenia; Young Adult
PubMed: 28314460
DOI: 10.1016/j.chc.2016.12.014 -
Biological Psychiatry Feb 2021Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia and other psychiatric disorders with... (Review)
Review
Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia and other psychiatric disorders with developmental origins. Here, we summarize clinical and preclinical findings of epigenetic alterations in schizophrenia and relevant disease models and discuss their putative origin. Recent findings suggest that certain schizophrenia risk loci can influence stochastic variation in gene expression through epigenetic processes, highlighting the intricate interaction between genetic and epigenetic control of neurodevelopmental trajectories. In addition, a substantial portion of epigenetic alterations in schizophrenia and related disorders may be acquired through environmental factors and may be manifested as molecular "scars." Some of these scars can influence brain functions throughout the entire lifespan and may even be transmitted across generations via epigenetic germline inheritance. Epigenetic modifications, whether caused by genetic or environmental factors, are plausible molecular sources of phenotypic heterogeneity and offer a target for therapeutic interventions. The further elucidation of epigenetic modifications thus may increase our knowledge regarding schizophrenia's heterogeneous etiology and pathophysiology and, in the long term, may advance personalized treatments through the use of biomarker-guided epigenetic interventions.
Topics: Biological Variation, Population; Cicatrix; DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Humans; Schizophrenia
PubMed: 32381277
DOI: 10.1016/j.biopsych.2020.03.008 -
Psychiatry and Clinical Neurosciences Nov 2015Schizophrenia research is providing an increasing number of studies and important insights into the condition's etiopathogenesis based on genetic, neuropsychological and... (Review)
Review
Schizophrenia research is providing an increasing number of studies and important insights into the condition's etiopathogenesis based on genetic, neuropsychological and cranial neuroimaging studies. However, research progress has not yet led to the incorporation of such findings into the revised classification criteria of mental disorders or everyday clinical practice. By 2020, schizophrenia will most likely still be a clinically defined primary psychotic disorder. While there is some hope that treatment will be improved with new antipsychotic drugs, drugs addressing negative symptoms, more refined psychotherapy approaches and the introduction of new treatment modalities like transcranial magnetic stimulation, an additional hope is to improve early detection and prevention. As the results of new research into the etiopathogenesis of schizophrenia are promising to improve diagnosis, classification and therapy in the future, a picture of complex brain dysfunction is currently emerging requiring sophisticated mathematical methods of analysis. The imminent clinical challenge will be to develop comprehensive diagnostic and treatment modules individually tailored to the time-variable needs of patients and their families.
Topics: Antipsychotic Agents; Humans; Psychotherapy; Schizophrenia
PubMed: 26011091
DOI: 10.1111/pcn.12322