A review of MRI findings in schizophrenia

This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.

Background While depression is known to involve a disturbance of mood, movement and cognition, its associated cognitive deficits are frequently viewed as simple epiphenomena of the disorder.

Aims To review the status of cognitive deficits in depression and their putative neurobiological underpinnings.

Method Selective computerised review of the literature examining cognitive deficits in depression and their brain correlates.

Results Recent studies report both mnemonic deficits and the presence of executive impairment — possibly selective for set-shifting tasks — in depression. Many studies suggest that these occur independent of age, depression severity and subtype, task ‘difficulty’, motivation and response bias: some persist upon clinical ‘ recovery’.

Conclusions Mnemonic and executive deficits do no appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key aspects of the dorsal and ventral aspects of the prefrontal cortex in depression.

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Cognitive deficits in depression: possible implications for functional neuropathology.

OBJECTIVE: Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. METHOD: Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. RESULTS: Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less t...

Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

There is a substantive literature on the behavioral effects of psychosocial stressors on schizophrenia. More recently, research has been conducted on neurohormonal indicators of stress responsivity, particularly cortisol release resulting from activation of the hypothalamic-pituitary-adrenal (HPA) axis. This article integrates the psychosocial and biological literatures on stress in schizophrenia, and it offers specific hypotheses about the neural mechanisms involved in the effects of stressors on the diathesis. Both the behavioral and biological data indicate that stress worsens symptoms and that the diathesis is associated with a heightened response to stressors. A neural mechanism for these phenomena is suggested by the augmenting effect of the HPA axis on dopamine (DA) synthesis and receptors. Assuming the diathesis for schizophrenia involves an abnormality in DA receptors, it is proposed that the HPA axis acts as a potentiating system by means of its effects on DA. At the same time, DA receptor abnormality and hippocampal damage render the patient hypersensitive to stress. This neural diathesis-stress model is consistent with findings on prenatal factors and brain abnormalities in schizophrenia, and it provides a framework for explaining some key features of the developmental course and clinical presentation.

Schizophrenia: A neural diathesis-stress model.

Objective As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals. Method Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated. Results Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects. Conclusions These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.

White matter hyperintensity signals in psychiatric and nonpsychiatric subjects.

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Objective: Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia

Lateral Ventricle-Brain Ratio and Balance Between CSF HVA and 5-HIAA in Schizophrenia

Ensuring the normalcy of "normal" volunteers.

MRI findings as a predictor of clozapine response

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