Pathophysiology and Animal Models of Schizophrenia (original) (raw)
Related papers
2004
The devastating effects of schizophrenia on human persons have raised puzzling and overwhelming concern among mental health professionals and researchers. Due to the revenging and hallmark of this ailment, neuropsychologists, as well as psychiatrists are in continuous controversial debate as what may constitute the actual etiology of schizophrenia. Many of the researchers have unequivocally maintained that schizophrenia is a genetically transmitted mentaldisorder. They sustain the argument with the studies of the monozygotic twins and the experiment with amphetamine, chlorpromazine, and phenothiazines. They maintain that the dopamine receptor genes are the agents that perpetuate the genetic transmission of heritability of schizophrenia. The sequence of argument has been referred to as the dopamine hypothesis. The strong genetic component of this hypothesis has spilt neurobiologists into two camps, “lumpers” and “splitters.” The lumpers believe that the symptoms manifested by schizop...
Genetic aspects in schizophrenia. Receptoral theories. Metabolic theories
Romanian Journal of Morphology and Embryology, 2020
Ties between schizophrenia (SCZ) and genetics are undeniably significant issue prone to be discussed in the nowadays psychology. Recent research on this domain focuses more on specific genes and heredity (specifically monozygotic pairs of twins) for diagnosing SCZ, than on environmental influences. SCZ is considered a multifactorial disease, thought to convert from a merger of risk and biological genes and environmental factors that could alter and reshape the trajectory of brain development. On this regard, this review sums up recent and innovative methods of distinguishing schizophrenic features from other mental illnesses in patients, based on chromosomal and genes changes. The term "reverse genetics" is no longer up to date, being replaced with "genome scanning" and "positional cloning". For many researchers, genome scanning is continuing the reverse of the sensible strategy for detecting various important biological disorders, which may start from the discovery of a protein or any other molecule involved in a biological process, being followed by its gene cloning. Genes being discovered in this manner could become candidate genes for the disease. However, genome scanning occurs through testing each chromosomal segment (or mitochondrial genome) for the counter transmission of the disease.
Neurobiology of Schizophrenia: A Comprehensive Review
Cureus
Schizophrenia is a debilitating disease that presents with both positive and negative symptoms affecting cognition and emotions. Extensive studies have analyzed the different factors that contribute to the disorder. There is evidence of significant genetic etiology involving multiple genes such as dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1). There is no clear link between neurotransmitter changes and the pathophysiology of schizophrenia; however, studies have shown that subcortical dopamine dysfunction is the key mechanism. Specific regions of gray and white matter changes are observed in patients with schizophrenia; gray matter changes being more significant after the onset of psychosis. These pathological changes may be implicated in the impairment of executive functioning, attention, and working memory. The disease can be managed with pharmacological treatments based on individual patient profile, patient compliance, and disease severity. The challenge of disease management sometimes persists due to the side effects. A better understanding of the pathological processes in schizophrenia may lead to more specific and effective therapies.
Recent advances in the neurobiology of schizophrenia
Molecular interventions, 2003
Despite great progress in basic schizophrenia research, the conclusive identification of specific etiological factors or pathogenic processes in the illness has remained elusive. The convergence of modern neuroscientific studies in molecular genetics, molecular neuropathology, neurophysiology, in vivo brain imaging, and psychopharmacology, however, indicates that we may be coming much closer to understanding the molecular basis of schizophrenia. Schizophrenia may be a neurodevelopmental and progressive disorder with multiple biochemical abnormalities involving the dopaminergic, serotonin, glutamate, and gamma -aminobutyric acidergic systems. In the near future, biological markers for the illness may come from the combination of diverse assessment techniques. An understanding of the pathophysiology of schizophrenia will be essential to the discovery of preventive measures and therapeutic intervention. Rapidly advancing research into schizophrenia includes diverse etiological hypothes...
[Neurodevelopment and schizophrenia]
Vertex (Buenos Aires, Argentina)
The evidence of neuroleptics' antipsychotic action due to their antagonism of dopamine receptors led to the hyperdopaminergic theory of schizophrenia. But the functional disturbance of the dopamine neurons should explain the increase and the reduction of some symptoms at the same time through the D2 receptors blockade. The prodromical manifestations of schizophrenia include abnormal movements which precede and predict the beginning of the disease. They also suggest a dopamine deficit. An injury in the mesocortical dopamine projection during the neural development could result in a functional impairment of the prefrontal cortex which causes the cognitive deficit symptoms. It would result also in an excessive compensatory subcortical dopamine activity which would cause the psychotic symptoms. The evidence in behalf of this physiopathology is complex. The mechanism of the subcortical compensation of the prefrontal dopamine deficit remains unknown. It is necessary to find out which ...
Current Perspectives on the Pathophysiology of Schizophrenia, Depression, and Anxiety Disorders
Medical Clinics of North America, 2001
In the 1990s, significant advances in basic and clinical neuroscience yielded new perspectives on the neurobiology and treatment of major psychiatric disorders. Insights into the pathophysiology of psychiatric disorders have been associated with the introduction of new medication classes, such as the atypical neuroleptics or serotonin reuptake inhibitors, that largely have supplanted older pharmacotherapies that had poorer efficacy or tolerability. This article reviews advances in the neurobiology of three major psychiatric disorders: schizophrenia, major depressive disorder, and panic disorder. These three disorders have been the focus Supported by NIAAA (KO2 AA 00261-01) and the Department of Veterans Affairs 559 560 KRYSTAL et a1 of a great deal of research, and advances in the current understanding of their neurobiology have occurred. Schizophrenia, major depression, and panic disorder illustrate the classes of thought disorder, affective disorder, and anxiety disorder. The phenomenology and neurobiology of each disorder are introduced briefly. Although the genetics of these disorders are not clear, progress in this area also is addressed, when relevant. The relevance of the current understanding of the neurobiology of each disorder for treatment is considered briefly. Interested readers seeking an introduction of greater depth are referred to reviews on these SCHIZOPHRENIA Schizophrenia is a profoundly disabling chronic illness with insidious onset in adolescence or early adulthood, variable course, and a growing array of treatment^.^^ Signs and symptoms of this disorder include hallucinations and delusions and encompass many aspects of cognitive and emotional function. Schizophrenia frequently produces social isolation and vocational impairment. In 1990, the economic burden of schizophrenia was greater than $30 million, and it exceeded the economic impact of cancer.lo6 Genetic, neurochemical, and neural circuitry insights into the neurobiology of this disorder are highlighted in this section.
Studies of biological factors associated with the inheritance of schizophrenia: A selective review
Journal of Psychiatric Research, 1987
Although a familial component to schizophrenia has been established through several family, twin and adoption studies, an inherited biological factor has yet to be established. Efforts to define clinical familial subtypes of schizophrenia have generally been unsuccessful, although recent data from our study population of pairs of siblings with schizophrenia suggests that schizophrenia with recurrent episodes of major depression may define one such group. There have only been a few biological traits consistently found to be associated with schizophrenia and also found to be heritable. These findings (e.g. measures of monoamine metabolism, brain structural morphology, neurophysiological markers, and protein polymorphisms) are reviewed in the present chapter. The proportion of patients with any of the noted abnormalities never approaches 100o/0, nor have any been found to be specific to schizophrenia. Research into the biogenetics of schizophrenia is clearly just beginning.
Schizophrenia: pathophysiological mechanisms — a synthesis
Brain Research Reviews, 2000
A Nobel Symposium, 'Schizophrenia: Pathophysiological Mechanisms' was held in Stockholm, October 1-3, 1998. The topics ranged from etiology, genetics, neuropathology, neurotransmitter, brain imaging, to integrative aspects including cognition and language. The collective amount of information is already enormous and will rapidly increase with advances in molecular pathology, gene transcript profiling and non-invasive imaging techniques. Probably reflecting the complexity is the absence of a disease model that can accommodate the data and explain its roots. In the process of moving from simplistic mechanisms involving single or a few interacting neurotransmitters or circuits and turning to more complex interactive models, there is a need for improved data storage and retrieval. Stochastic search in chemical libraries for potential new drug candidates coupled with rational approaches in their final design may improve therapeutic efficacy.
Schizophrenia: Unraveling the Labyrinth of Etiology and Epidemiology
International Journal of Pharmacy and Biological Sciences
Schizophrenia mental disorder is the combination of psychotic and neurotic disorder where the clinical symptoms and signs, duration and cognitive adjectives are well defined. In this, pharmacological treatments are existing successfully, even though they are likely relieving pain without dealing with the cause of the condition. The most risky constituents for schizophrenia are genetics and formational and operative abnormalities of brain. These factors are precautionable by the scientists by innovating new genetic information in the human genome and brain imaging techniques which direct inquiries the structural functionality of neurochemistry. Dopamine role does not ignore in current assumption of pathophysiology but it emphasizes the integration of neural systems in the expression of illness and symptoms generating in limbic system. Advanced observations for futuristic discovery are arising from the combination of molecular genetics and brain imaging techniques.