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Neurobiology is the study of cells of the nervous system and the organization of these cells into functional circuits that process information and mediate behavior. As a subdiscipline of both biology and neuroscience, neurobiology has a significant impact of the development of schizophrenia.

Studies

Neurobiology of Schizophrenia

Journal Published
Neuron Volume 52, Issue 1, 5 October

Year Published
2006

Abstract
NeurobiologyZofZSchizophrenia.html.txt

Hypothesis

The review provides a definitive study of the neurobiology of schizophrenia is now possible.
The neurobiological study of schizophrenia may help illuminate the nature of normal thought, perception, and emotion.
Understanding schizophrenia may help us better understand human nature itself.

Background

Schizophrenia affects about 0.5 to 1.0 percent of the population worldwide with devastating consequences for affected individuals and their families, is the seventh most costly medical illness to our society
The available symptomatic treatment is only partially successful, and therefore the development of rational therapeutics, based on an understanding of the etiology and pathogenesis of schizophrenia, is imperative.
Until recently, progress in schizophrenia has been painfully slow and limited by a number of factors, including the heterogeneity of the schizophrenia phenotype and the lack of clear pathological lesions like those that have provided reference points in the study of Alzheimer's disease (AD), Parkinson's disease (PD), and other neurodegenerative disorders.
Investigation into the mechanism of action of the drugs used to treat schizophrenia has not provided clear understanding of the pathogenesis of the disease.
While schizophrenia is highly heritable (it has a heritability score of approximately 0.8), the genetics are complex and the interpretation of genetic data has proven difficult.
Now, however, advances in phenotypic analysis, neuroimaging, genetics, and molecular pathology provide the basis for optimism. Schizophrenia can be understood, at least in part, as a subtle disorder of brain development
Evidence now supports an etiologic role for mutations or polymorphisms in a number of genes as well as obstetrical and premorbid abnormalities of development and cognition.

Neurobiology of Schizophrenia Onset

School, Department or Faculty
Laboratory of Cellular Neuropathology (McLean Hospital); Department of Psychiatry (Beth Israel Deaconess Medical Center); Department of Psychiatry (Harvard Medical School).

Journal Published
Current Top Behaviour Neuroscience

Year Published
Tsung-Ung W. Woo

Abstract
NeurobiologyZofZSchizophreniaZOnset.pdf

Hypothesis

This review discusses the possible pathophysiological mechanisms that may contribute to the dysfunction of PV neurons in schizophrenia, focusing on:

Deficient glutamatergic innervation
Oxidative stress and
Impaired formation of ECM structures called perineuronal nets (PNNs).

Background

Schizophrenia is a complex, prevalent, and extremely debilitating brain disorder affecting approximately 1% of the population worldwide.
It is defined by a constellation of positive (i.e., delusions and hallucinations) and negative (i.e., affective flattening, avolition, alogia, anergia, and anhedonia) symptoms.
In addition, patients exhibit prominent cognitive deficits (such as disturbances in executive functions), working memory, and attention.
Together, these symptoms and cognitive deficits render the individuals inflicted with the illness a life-long course of intellectual, vocational, interpersonal and social impairment.
At present, antipsychotic medications provide some symptomatic relief in some but not all patients, but they do not appear to impact the course or the long-term outcome of the illness in any meaningful fashion.
The current lack of truly effective treatment, in no small part, is because after decades of research the pathophysiological basis of schizophrenia remains poorly understood.
It has long been known that the onset of schizophrenia typically occurs during the period of late adolescence and early adulthood. In recent years, there has been growing emphasis in the field in identifying the clinical characteristics that immediately precede the onset of full-blown illness
The clinical symptoms and cognitive and functional deficits of schizophrenia typically begin to gradually emerge during late adolescence and early adulthood.
The underlying concept is that timely intervention during this critical phase of the pathogenetic process could attenuate or perhaps even prevent the onset of overt symptoms and deficits.
Although this line of research has evoked significant optimism and enormous excitement, reliable methods to faithfully predict who will ultimately develop symptoms and deficits do not yet exist.
Perhaps more importantly, it is far from clear as to what preventative or early intervention strategies would be effective.
The single most significant impediment is that the neurobiological mechanisms that mediate the onset of illness are at present virtually unknown.
The period of adolescence is a time of profound changes, when the highest-order cognitive functions, such as reasoning, abstract thinking, and planning, gradually achieve maturation.
This maturational process is thought to reflect the coming online of the executive brain system of the cerebral cortex, orchestrated in large part by the maturation of the prefrontal cortex (PFC) via extensive pruning of excitatory synapses, dendritic spines on pyramidal neurons on which these synapses form, and axon terminals of pyramidal neurons that are presynaptic to these synapses.
This connectional pruning process is associated with the maturation of the capacity of PFC pyramidal neuronal networks to oscillate and synchronize, especially in the gamma (i.e., 30–80 Hz) frequency band
In addition, gamma band oscillation appears to be an electrophysiological correlate of working memory, a core PFC function that is required for the integrity of executive functioning.
Interestingly, in patients with schizophrenia, working memory and executive functioning are compromised and gamma band oscillation has repeatedly been shown to be impaired.
The fact that many of the symptoms and cognitive deficits of schizophrenia typically begin to emerge during late adolescence and early adulthood has long led to the hypothesis that disturbances of the synaptic pruning process that occurs in the PFC during this period may play a role in triggering the onset of illness, although the specific neurobiological mechanisms that underlie the presumed synaptic pruning disturbances have not been systematically formulated. T
his is in large part due to the fact that, for a long time, the biological determinants of this synaptic pruning process were completely unknown. However, recent studies in rodents have identified the maturation of intracortical inhibition subserved by the parvalbumin (PV)-containing inhibitory neurons and the formation of extracellular matrix (ECM) environment as two important mechanisms that regulate the time course of the critical period for developmental synaptic plasticity in the cerebral cortex
Interpretation of these findings in the context of our current understanding of neuronal type-specific regulation of gamma band oscillation and PFC circuit dysfunction in schizophrenia allows us to begin to develop specific, experimentally testable hypotheses of the neurobiology of developmental synaptic pruning in the human PFC and the possible pathophysiological mechanisms of schizophrenia onset.
Specifically, it is postulated that the inhibitory neurons that contain PV may play a central role in regulating the time course of PFC synaptic pruning during late adolescence and arly adulthood and that disturbances of PV neurons may lead to aberrant loss of synapses and thereby cortical circuitry instability, hence triggering the onset of schizophrenia

Neurobiology of schizophrenia: search for the elusive correlation with symptoms

School, Department or Faculty
Psychiatry Service (San Francisco VA Medical Center); Department of Psychiatry (University of California)

Journal Published
Frontiers in Human Neuroscience

Year Published
2012

Authors / Collaborators
Daniel H. Mathalon and Judith M. Ford

Abstract
NeurobiologyZofZSchizophreniaZZSearchZforZtheZElusiveZCorrelationZWithZSymptoms.pdf

Full Article
NeurobiologyZofZSchizophrenia_1.html.txt

Hypothesis

This paper provides an overview of the myriad conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures, obstacles that ultimately impede progress toward elucidating the neurobiological mechanisms underlying these symptoms.

Background

Advances in neuroscience methods over the past 50 years have provided the means to study complex psychiatric disorders in vivo, firmly establishing that disorders once viewed as psychological reactions to stressful environments (particularly family environments) are associated with subtle abnormalities in brain structure and function.
This historical transition toward reconceptualizing psychiatric disorders as brain disorders is exemplified by the paradigm shift that gave primacy to neurobiological and neurodevelopmental perspectives in understanding the etiopathology of schizophrenia.
Despite the clinical heterogeneity of schizophrenia, a wide variety of neurobiological abnormalities have been replicated across clinical samples and research laboratories, providing some support for the neurobiological validity of the clinical criteria used to diagnose patients.
Efforts to understand the neurobiological bases of the clinical heterogeneity that schizophrenia comprises, mainly by correlating neurobiological measures with specific symptoms, have been largely unsuccessful.
Inconsistency” has been the most consistent finding to emerge from such efforts.

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Neurodevelopment of Schizophrenia - Neuroscience

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Neuroethics in Schizophrenia - Neuroscience

Neuroethics is an interdisciplinary research area that focuses on ethical issues raised by our increased and constantly improving understanding of the brain and our ability to monitor and influence it, as well as on ethical issues that emerge from our concomitant deepening understanding of the biological bases.

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Neuroethics in Schizophrenia - Neuroscience

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Neuroinflammation in Schizophrenia - Neuroscience

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Neuronal Excitability in Schizophrenia - Neuroscience

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Neuronal Interactions in Schizophrenia - Neuroscience

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Neuroplasticity In Schizophrenia - Neuroscience

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Neuropsychology Profile of Schizophrenia - Neuroscience

The neuropsychological profile is typically characterized by prominent specific deficits in memory and learning, working memory, executive functions, attention, and processing speed, which are evident on a background of a generalized cognitive deficit.

Research Questions

Studies

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