Biomedical subjects
Publications and source records attributed to A Roy.
Depression and suicidal behavior are commonly found among schizophrenic patients and schizophrenia is associated with an increased risk of suicide; the reasons for this are reviewed.
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Diagnosis and prognosis are critical issues confronting psychiatry. In order to answer the fundamental questions concerning the origin and development of schizophrenia, we must first be clear about what it is. We must be able to separate the illness of schizophrenia from other disorders (see Fig. 1). We have attempted in this article to examine some of the illnesses that may resemble schizophrenia and make its discrimination difficult. We hope that by discussing these disorders and their similarities to schizophrenia the important issues and dilemmas have become clearer and more readily understood by the clinician. Future studies assessing the validity of diagnostic systems for schizophrenia may have to rely on features other than cross-sectional symptoms and longitudinal course. Such characteristics as pharmacologic responsivity and genetic transmission and the development of biologic markers may be the prospective cornerstones for validating the diagnosis of schizophrenia.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy.
In a comparison with 300 matched controls, significantly more of 300 patients with nonendogenous depression had experienced permanent separation (not due to death) from their mother before both 11 and 17 years of age and significantly more had experienced permanent separation from their father (not due to death) before both 11 and 17 years of age. The results suggest that early permanent separation from mother is a risk factor for nonendogenous depression but occurs in only about 6.7% of these patients before 11 years of age and in about 10% before 17 years of age and early permanent separation from father is also a risk factor for nonendogenous depression and occurs in about 9.3% of these patients before 11 years of age and in about 16.7% before 17 years of age.
The plasma norepinephrine (NE) level was measured in 45 depressed patients and in 41 normal control subjects. Patients who met DSM-III criteria for a major depressive episode with melancholia (MDE-MEL; N = 16), and those with MDE but with melancholia in a previous episode (MDE-PMEL; N = 8), had significantly higher levels of plasma NE than normal control subjects while lying and standing and a greater change in the levels; whereas, patients with MDE alone (N = 10) and patients with dysthymic disorder (N = 11) had levels of NE comparable with control levels. Bipolar patients (N = 7), all with current melancholia or a history of it, had significantly lower levels of NE while lying down or standing than depressed unipolar patients with similar histories of melancholia. Among unipolar patients with melancholia, nonsuppressors on the dexamethasone suppression test had significantly higher lying-down NE values than did suppressors, suggesting that dysregulation of both the hypothalamic-pituitary-adrenal axis and the peripheral sympathetic nervous system occur together in this subgroup of depressed patients.
Life events that had occurred in the 6 months before the onset of depression were recorded in 40 depressed patients and 41 normal controls. The depressed patients had experienced significantly more life events and significantly more undesirable life events than the controls. The 20 patients with a DSM-III diagnosed major depressive episode (MDE) without melancholia had experienced significantly more life events in the 6 months before the onset of depression than the 20 patients with a major depressive episode with melancholia. The patients with MDE without melancholia, but not the MDE with melancholia patients, had also experienced significantly more life events than a group of age- and sex-matched normal controls.
Several recent studies in animals and man indicate that corticosteroids may alter catecholaminergic activity in both the peripheral and central nervous systems. We administered 1 mg of the synthetic glucocorticoid, dexamethasone, to 12 drug-free healthy volunteers and measured plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Dexamethasone was administered at 11 p.m. and blood was collected at 4 p.m. on the preceding and subsequent days. Dexamethasone administration resulted in a significant increase in plasma HVA but did not consistently affect MHPG. All subjects showed a suppression of serum cortisol to values less than 5 micrograms/dl while prolactin levels were unaltered. In an additional group of nine volunteers, we administered 2 mg of dexamethasone and observed a similar increase in plasma HVA without change in plasma MHPG, indicating a selective effect on dopamine metabolism. Implications of these findings for an understanding of the neurochemical and behavioral changes seen with steroid administration and in explaining previous results on plasma MHPG/HVA ratios in delusional depression are discussed.
Cerebrospinal fluid levels of norepinephrine and six monoamine metabolites were measured in 28 medication-free depressed patients. Patients with a major depressive episode with melancholia (n = 15) had significantly lower levels of the three dopamine metabolites: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and conjugated dihydroxyphenylacetic (CONJDOPAC), when compared with a combined group of patients with a major depressive episode or dysthymic disorder (n = 13). In patients with major depressive episode with melancholia, levels of HVA and of the serotonin metabolite 5-hydroxyindoleacetic acid significantly correlated with the severity of depression. In the total group of 28 depressed patients, cerebrospinal fluid (CSF) levels of norepinephrine significantly correlated with symptoms of anxiety. In both patients with major depressive episode and major depressive episode with melancholia, those who were non-suppressors on the dexamethasone suppression test had significantly higher CSF levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol compared to those who were suppressors.
The nucleotide sequence of an Escherichia coli DNA segment containing the ptsH gene and the first 162 nucleotides of the ptsI gene encoding, respectively, Hpr and enzyme I of the phosphoenolpyruvate-dependent glycose phosphotransferase system (PTS), was determined. The ptsH promoter was localized using the S1 mapping technique. A nucleotide sequence very similar to the consensus binding site for cAMP receptor protein was found in the -35 region of the ptsH promoter. The ptsH gene is transcribed in the same direction as the ptsI gene and the crr gene (encoding enzyme IIIGlc of the PTS). Analysis of the nucleotide sequence substantiates the notion that the ptsH-ptsI-crr genes constitute a polycistronic operon.
The monoamine metabolites 5-hydroxindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were measured in the lumbar cerebrospinal fluid (CSF) of 27 chronic schizophrenic patients who at some time had attempted suicide, and were compared with values from 27 chronic schizophrenic patients without a history of attempted suicide. There were no significant differences between either the violent or non-violent attempters and those without a history of attempted suicide in the mean lumbar CSF concentrations of the serotonin metabolite 5-HIAA, the dopamine metabolite HVA, or the norepinephrine metabolite MHPG. Significantly more of the suicide attempters had a previous major depressive episode, had received a course of ECT, and had significantly more psychiatric admissions than those who had never attempted suicide.