Schizophrenia, Neurobiology and the Methodology of Systemic Modeling

Tretter, Felix; Scherer, Josef

doi:10.1055/s-2006-931486

Cited by 26 publications

(31 citation statements)

References 31 publications

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“…It is thus getting clearer that the identity of each individual mesDA neuron is specifi ed during development at a unique " node " within a complex four-dimensional (space and time) network of interacting signaling and transcription factors. Systems biology (in the sense of " systems science " ) may help in identifying the unique properties of each of these nodes using approaches analogous to those previously suggested by Tretter et al [3,58] for the initial description and further characterization of neurochemical interactions in the adult human brain, under both normal and diseased (e.g. schizophrenia) conditions.…”

Section: Discussionmentioning

confidence: 99%

“…neurons that have not yet acquired their adult physiological properties. Non-linear equations with several variables and steady states, as described for the adult brain [3,58] , are not refl ecting the true situation in the developing embryo. The development of mesDA neurons is probably best described by binary " on / off " systems whose complexity is based on the multitude of interactions between its individual components.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Control of Rodent Midbrain Dopaminergic Neuron Development in the Light of Human Disease

Klafke¹,

Wurst²,

Prakash³

2008

Pharmacopsychiatry

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Dopamine-producing neurons in the mammalian midbrain have received considerable attention in recent years because of their involvement in diverse neurological and psychiatric human disorders such as Parkinson's Disease (PD), schizophrenia and addiction. Although the underlying pathogenic mechanisms of these disorders are far from being understood, it is meanwhile accepted that a combination of genetic predisposition and environmental factors lead to the disease state. More recent evidence also suggests that both neurological and psychiatric disorders result from early disturbances affecting the normal development of the mesencephalic dopaminergic (mesDA) neurons. Understanding the cues directing the generation of the different mesDA cell groups, the establishment of their proper connections within the brain and their maintenance in the adult are therefore also of great clinical interest. Rodents, and in particular the mouse, have served as the classical "surrogate" organism for these studies based on their phylogenetic relationship to humans, their relatively well characterized mesDA system on both the anatomical and physiological levels, and especially on the propensity of the mouse to genetic manipulation enabling the dissection of genetic pathways underlying the proper generation and maintenance of the mesDA system in this species. In the present review, we will summarize recent findings in the overall context of murine mesDA neuron development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Control of Rodent Midbrain Dopaminergic Neuron Development in the Light of Human Disease

Klafke¹,

Wurst²,

Prakash³

2008

Pharmacopsychiatry

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“…In fact we performed some kind of intuitive principal component analysis by assuming that relevant variance occurs in limited directions [13].…”

Section: Resultsmentioning

confidence: 99%

A Visual Metaphor Describing Neural Dynamics in Schizophrenia

Beveren

Haan

2008

PLoS ONE

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BackgroundIn many scientific disciplines the use of a metaphor as an heuristic aid is not uncommon. A well known example in somatic medicine is the ‘defense army metaphor’ used to characterize the immune system. In fact, probably a large part of the everyday work of doctors consists of ‘translating’ scientific and clinical information (i.e. causes of disease, percentage of succes versus risk of side-effects) into information tailored to the needs and capacities of the individual patient. The ability to do so in an effective way is at least partly what makes a clinician a good communicator. Schizophrenia is a severe psychiatric disorder which affects approximately 1% of the population. Over the last two decades a large amount of molecular-biological, imaging and genetic data have been accumulated regarding the biological underpinnings of schizophrenia. However, it remains difficult to understand how the characteristic symptoms of schizophrenia such as hallucinations and delusions are related to disturbances on the molecular-biological level. In general, psychiatry seems to lack a conceptual framework with sufficient explanatory power to link the mental- and molecular-biological domains.Methodology/Principal FindingsHere, we present an essay-like study in which we propose to use visualized concepts stemming from the theory on dynamical complex systems as a ‘visual metaphor’ to bridge the mental- and molecular-biological domains in schizophrenia. We first describe a computer model of neural information processing; we show how the information processing in this model can be visualized, using concepts from the theory on complex systems. We then describe two computer models which have been used to investigate the primary theory on schizophrenia, the neurodevelopmental model, and show how disturbed information processing in these two computer models can be presented in terms of the visual metaphor previously described. Finally, we describe the effects of dopamine neuromodulation, of which disturbances have been frequently described in schizophrenia, in terms of the same visualized metaphor.Conclusions/SignificanceThe conceptual framework and metaphor described offers a heuristic tool to understand the relationship between the mental- and molecular-biological domains in an intuitive way. The concepts we present may serve to facilitate communication between researchers, clinicians and patients.

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“…This theory employs antipsychotics treatment, the most widely used method to manage schizophrenia. Psychopharmacology based on the understanding of the neurophysiology and neurochemistry, especially focusing on neurotransmitters, can guide effective treatment methods for patients who have schizophrenia [23]. Although genetic theory employs treatment methods such as gene therapy or consultation approaches, these methods may have pitfalls because of their being highly technical and expensive.…”

Section: Utility In Guiding Treatmentmentioning

confidence: 99%

Understanding the Etiology and Treatment Approaches of Schizophrenia: Theoretical Perspectives and Their Critique

Kim¹

2016

OJPsych

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This paper reviewed genetic, neurodevelopmental, and neurobiological perspectives to understand the etiology and relevant treatment approaches of schizophrenia. Although genetic and neurodevelopmental theories provide a substantial contribution to the etiology of schizophrenia, neurobiological one has its dominant stance in which it can explain causative mechanisms of schizophrenia, identify targets for treatment, and predict outcomes well. According to the neurobiology, onset and course of schizophrenia are well supported by the alterations in neurotransmitters such as dopamine or serotonin. Based on this mechanism, antipsychotics have been widely used as one of the treatment approaches for schizophrenia. By following up the degree of patients' responses to antipsychotics, treatment outcomes could be evaluated or predicted. Although neurobiology seldom provides information about identification or prevention of risk factors about schizophrenia compared to genetic and neurodevelopmental approaches, it has well-established scientific foundations, ability to guide treatment, applicability across age and culture, and usefulness as a research framework.

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Schizophrenia, Neurobiology and the Methodology of Systemic Modeling

Cited by 26 publications

References 31 publications

Genetic Control of Rodent Midbrain Dopaminergic Neuron Development in the Light of Human Disease

Genetic Control of Rodent Midbrain Dopaminergic Neuron Development in the Light of Human Disease

A Visual Metaphor Describing Neural Dynamics in Schizophrenia

Understanding the Etiology and Treatment Approaches of Schizophrenia: Theoretical Perspectives and Their Critique

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