Neuroanatomy Of Schizophrenia Research Articles

Predictive Motor Timing and the Cerebellar Vermis in Schizophrenia: An fMRI Study.

Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia.

Optogenetic neuronal control in schizophrenia

Schizophrenia is a serious mental disorder characterized by a heterogonous spectrum of clinical manifestations. Schizophrenia is basically incurable. The discovery of antipsychotic medications in the late 1940s has helped control some of the symptoms but has not reversed the course of the disorder and has had limited effect on the debilitating symptoms of the illness. In recent years brain stimulation technologies have emerged in the bio-scientific scenery. Deep brain stimulation now plays an important role in the treatment of many neurological disorders, and seems promising in treating depression. Optogenetics is a new technology that offers control over neuronal activity by turning on and off distinct neuronal populations. It has a great advantage over previous brain stimulation technologies in that it is accurate and specific to the neurons intended for activation and control. There is no evidence that brain stimulation has been investigated in schizophrenia patients. This possibility was discussed in a single commentary that proposed the hippocampus and nucleus accumbence as targets for DBS in schizophrenia, however it was emphasized that the neurophysiology and neuroanatomy of schizophrenia have not been elucidated to the extent that brain stimulation can be planned. In light of new optogenetic technology time is ripe to seriously consider optional targets of intervention in the brain of schizophrenia patients. Any such target should involve neuronal circuits (1) known to be relevant for schizophrenia, (2) involved in cognitive and brain functions that are disturbed in schizophrenia, and (3) relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia. This paper reviews the relevant literature and proposes that optogenetic interventions in schizophrenia should begin in the prefrontal cortex and the Globus-Pallidus Subthalamic nuclei systems. In the protocol for the prefrontal cortex, wide-arbore and chandelier inhibitory interneurons should be targets for optogenetic intervention and in the Globus-Pallidus Subthalamic nuclei the fast spiking neurons should be targets for optogenetic intervention. These subsystems are critical modulators of neural complexity which is directly relevant to connectivity organization in the brain. Schizophrenia is described as a disturbance of connectivity organization in the brain treatable by the relevant optogenetic interventions promoted in this paper.

Abnormalities of cingulate gyrus neuroanatomy in schizophrenia

Objective and methods Abnormalities of the neuroanatomy of the gray matter of the cingulate gyrus, especially its anterior segment, have been suggested to be an important characteristic of schizophrenia. In this study, T1-weighted magnetic resonance scans were collected in 53 individuals with schizophrenia and 68 comparison subjects matched for age, gender, race and parental socioeconomic status. We applied Labeled Cortical Mantle Distance Mapping to assess the volume, surface area and thickness of the cortical mantle within the anterior (AC) and posterior (PC) segments of the cingulate gyrus, excluding the paracingulate gyrus, and related these anatomical measures to measures of psychopathology and illness duration. Results After covarying for total cerebral volume, individuals with schizophrenia showed smaller AC gray matter volume ( p = 0.024), thickness (trend, p = 0.081), but not surface area ( p = 0.16), than comparison subjects. Similar group differences were found for PC gray matter volume ( p = 0.0005) and thickness (trend, p = 0.055), but not surface area ( p = 0.15). Across both groups, there was a significant L > R asymmetry in thickness of the AC, and a significant L > R asymmetry in the surface area of the PC. However, there were no significant group-by-hemisphere interactions. In the individuals with schizophrenia, thinning of the AC, but not the PC, was correlated with a longer duration of illness and a greater severity of psychotic symptoms. Conclusions Individuals with schizophrenia showed smaller gray matter volumes across the entire cingulate gyrus, mostly due to a reduction in cortical mantle thickness. However, structural measures of the AC were more closely related to clinical features of the illness.

Are brain structural abnormalities useful as endophenotypes in schizophrenia?

Endophenotypes, which represent intermediate phenotypes on the causal pathway from the genotype to the phenotype, can help unravel the molecular etiopathology of complex psychiatric disorders such as schizophrenia. Several candidate endophenotypic markers have been proposed in schizophrenia, including neurocognitive and neurophysiological impairments. Over the past three decades, there has been an impressive body of literature in support of brain structural alterations in schizophrenia, but few studies have critically examined whether these abnormalities can be considered useful endophenotypic markers. We critically reviewed the extant literature on the neuroanatomy of schizophrenia in this paper to evaluate their candidacy as endophenotypes. Structural brain changes are robustly associated with schizophrenia, are state independent and may cut across the diagnostic boundaries of major psychotic illnesses. Brain morphometric measures are heritable, co-segregate with the broadly defined neurocognitive and behavioural phenotypes within the first degree relatives of schizophrenia patients and are present in unaffected family members more frequently than in the general population. Taken together, brain morphometric alterations appear largely to meet the criteria for endophenotypes in psychotic disorders. Further work is needed to examine how specific genes and their interactions with the environment may produce alterations in brain structure and function that accompany psychotic disorders.

Emerging insights on the neuroanatomy of schizophrenia

Emerging research continues to advance our understanding of the neuroanatomy of schizophrenia. Studies have identified neurobiologic alterations during the lifespan of the illness, from its premorbid precursors to its course following illness onset. Attention is also being focused on the relationship between neuropathology and cognitive function, and to populations that may be at risk for schizophrenia. Recent references on the cutting edge of schizophrenia research are sampled and summarized in the following major areas: 1) studies documenting premorbid neuroanatomic alterations; 2) understanding the anatomic bases of impaired cognition; 3) longitudinal studies of dysfunctional neuroanatomy; and 4) applications of newer techniques in white matter imaging. This article provides a brief synthesis of the major trends in the basic science of schizophrenia research, and how the present trends may shape future understanding of aspects of the illness.

Functional neuroanatomy of schizophrenia

Functional neuroanatomy of schizophrenia

Mesopontine cholinergic and non-cholinergic neurons in schizophrenia

Mesopontine cholinergic neurons influence midbrain dopaminergic neurons, and thalamic and cerebellar structures which have been implicated in the neuroanatomy of schizophrenia. It has been reported that there are approximately twice as many mesopontine cholinergic neurons in schizophrenics than in normals, using nicotinomide adenosine dinucleotide phosphate-diaphorase histochemistry to identify the cholinergic neurons. The present study sought to replicate this finding by analysing mesopontine cholinergic neurons using an antibody against choline acetyltransferase. The mesopontine cholinergic neurons are located in the pars compacta and pars dissipata of the pedunculopontine nucleus, and in the laterodorsal tegmental nucleus. Quantitative computer imaging techniques were used to map the distribution of mesopontine cholinergic neurons. In addition, all medium-sized and large neurons in a region of interest containing the middle portion of the pedunculopontine nucleus pars compacta were counted in Nissl-stained sections. There was no difference between schizophrenic and normal brains in terms of: (i) the rostral–caudal length of the cholinergic cell complex, ∼10 mm; (ii) the estimated total number of cholinergic neurons in the combined pedunculopontine nucleus and laterodorsal tegmental nucleus, ∼20,000 cells unilaterally; and (iii) the combined number of cholinergic and non-cholinergic Nissl-stained neurons in the middle portion of the pedunculopontine nucleus. The present data do not support the previous observation of increased numbers of mesopontine cholinergic neurons in schizophrenia.

New insights on the neuroanatomy of schizophrenia.

Recent ideas and research evidence about the neuroanatomy of schizophrenia come to us from diverse sources. These include 1) conventional (magnetic resonance imaging morphometry); 2) novel (diffusion tensor imaging) structural anatomic techniques; 3) information on patterns of anatomic changes from longitudinal anatomic studies; 4) illumination of functional connectivity and pathway anomalies associated with the disorder; 5) family studies on the distribution of anatomic abnormalities within affected and unaffected family members; and 6) anatomic distributions of neurotransmitters and their receptors, as well as their response to drugs used to treat the disorder. Taken together, these new data provide an exciting look at the direction in which the field is headed.

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Variability of functional neuroanatomy in schizophrenia: implications for group analyses

Variability of functional neuroanatomy in schizophrenia: implications for group analyses

27-3 - Functional correlates of temporal lobe neuroanatomy in schizophrenia

27-3 - Functional correlates of temporal lobe neuroanatomy in schizophrenia

Sex differences in schizophrenia: epidemiology, genetics and the brain

The identification of sex differences in schizophrenia is not new, since even Kraepelin described dementia praecox as a disorder primarily afflicting young men (Kraepelin, 1893). Since then, the literature has shown that schizophrenic men and women differ in terms of age at onset, symptom expression, neurobiological factors, course, treatment response, incidence and familial transmission. More controversial is the literature on sex differences in cognition and structural brain abnormalities in schizophrenia. However, many investigators would now agree that sex modifies the phenotypic expression of schizophrenia. It remains a testable hypothesis whether sex is a risk factor, i.e. has etiological consequences for the illness. This review will summarize the literature on sex differences in the epidemiology, genetics and the brain in schizophrenia. That is, what are the differences in the phenomenology of the disorder? Do they impact the incidence and/or prevalence? How have investigators attempted to explain sex differences in terms of genetic transmission and the neuroanatomy of schizophrenia?

The Neuroanatomy of Schizophrenia: Editors' Introduction

In the past 20 years there has been a marked increase in the number of studies examining the neuroanatomy of schizophrenia . This increase has been paralleled by even greater advances in our understanding of the structure and function of neurons and the brain. These advances in our knowledge of schizophrenia and the brain, in combination with the development of more sophisticated structural and functional imaging and postmortem analytic techniques, promise a more decisive study of the neuropathology of schizophrenia in the future. This issue of Schizophrenia Bulletin provides a review of the status of research on the neuroanatomy of schizophrenia, the nature of the evidence implicating specific brain regions, and which brain regions are best candidates for hypothesis-testing studies.

Landmark analysis of the neuroanatomy of schizophrenia

Landmark analysis of the neuroanatomy of schizophrenia

Strong Inference, Theory Testing, and the Neuroanatomy of Schizophrenia

Failure to address the putative etiologic and pathophysiologic heterogeneity of the schizophrenia syndrome and problems in definitive assessment of human brain function have impaired progress in schizophrenia research. New approaches to psychopathology and converging evidence from antemortem and postmortem study can now result in more decisive study of the neuroanatomy and neuropathology of schizophrenia.