Bernard Ravitz

Cerebrospinal fluid monoamine metabolites in alcoholic patients who attempt suicide.

Reduced cerebrospinal fluid (CSF) levels of the serotonin metabolite 5‐hydroxyindoleacetic acid have been reported to be commonly associated with suicidal behaviour. Alcoholics are known to often manifest suicidal behaviour. Therefore, we compared cerebrospinal fluid levels of monoamine metabolites in alcoholics who had (n= 20) and had not (n= 108) attempted suicide and healthy volunteers (n= 30). There were no significant differences among the 3 groups for CSF levels of either 5‐hydroxyindoleacetic acid, the dopamine metabolite homovanillic acid, norepinephrine, or the norepinephrine metabolite 3‐methoxy‐4‐hydroxy‐phenylglycol.

A cerebrospinal fluid study of the pathophysiology of panic disorder associated with alcoholism

In order to investigate the neurochemistry of panic disorder in alcoholics, we measured various cerebrospinal fluid (CSF) parameters in subjects with both conditions and compared them with an age‐ and sex‐matched population of alcoholics and normal controls. When height, age and weight were covaried, subjects with panic disorder had higher levels of B‐endorphin in CSF. There were no differences in other CSF measures between the groups. Alcoholics with panic disorder had higher plasma MHPG concentrations compared with alcoholics without panic disorder but these were not statistically different from controls.

Cerebrospinal fluid thyrotropin-releasing hormone concentrations in alcoholics and normal controls

Alterations in hypothalamic-pituitary-thyroid axis function have been reported in alcoholism. Blunting of the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) occurs in approximately 25% of alcoholic patients. Using a sensitive radioimmunoassay that allows TRH itself to be measured in cerebrospinal fluid (CSF), CSF concentrations of TRH were measured in alcoholics and normal controls. There was no significant difference in TRH concentrations between the groups. However, among the controls there was a significant correlation between CSF concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and CSF concentrations of TRH. This correlation was lacking in the alcoholics. These findings are of interest because basic neurobiological studies have reported that TRH and serotonin are co-localized in certain neurons in the rat central nervous system.

Cerebrospinal fluid levels of somatostatin, corticotropin-releasing hormone and corticotropin in alcoholism

Reduced brain and cerebrospinal fluid (CSF) levels of somatostatin, corticotropin‐releasing hormone (CRH) and corticotropin (ACTH) have been reported among neuropsychiatric patients with cognitive dysfunction. Alcoholism is a disorder in which associated neuropsychiatric disorders occur. Therefore, we compared CSF levels of somatostatin, CRH and ACTH in alcoholics (n= 100) and normal controls (n= 30). There were no significant differences between the groups in concentrations of the 3 peptides. Moreover, there were no significant correlations between concentrations of the peptides in CSF and computed tomographic measures of the size of brain ventricles. There were, however, significant correlations between CSF concentrations of CRH and ACTH and between CSF concentrations of CRH and somatostatin in both the alcoholic and control groups.

CSF neuropeptide Y in alcoholics and normal controls

Neuropeptide Y is found in brain tissue. In dogs it has been shown to enhance activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone. It is localized in certain catecholamine neurons and to some extent colocalized with somatostatin. Disturbances of the central noradrenergic system may underlie some forms of alcoholism. Therefore, we compared male alcoholics and normal controls on cerebrospinal fluid (CSF) levels of neuropeptide Y. There was no significant difference between the two groups for neuropeptide Y. There was also no significant difference for CSF levels of growth hormone releasing hormone. However, there were significant positive correlations between CSF levels of neuropeptide Y and CSF levels of corticotropin-releasing hormone, somatostatin, and growth hormone releasing hormone.

Cerebro‐spinal Fluid Studies in Alcoholics and Violent Offenders

Firstly, the contribution that cerebro-spinal fluid (CSF) studies have made to our understanding of the pathophysiology of alcohol withdrawal is addressed. Secondly, the developing literature, from our own studies and those of others, on abnormal CSF measurements in alcoholics and violent offenders is reviewed, with particular regard to impulsive murderers and arsonists. It is concluded that there is CSF evidence for increased norepinephrine function in alcohol withdrawal and an underlying serotonin hypofunction in impulsive disorders including some forms of alcoholism. Finally we report that patients with Korsakoffs syndrome may have central serotonin dysfunction since they show memory improvements during treatment with the serotonin uptake blocker fluvoxamine. Furthermore, these improvements correlate with the magnitude of change that fluvoxamine produces in CSF concentrations of the serotonin metabolite 5-HIAA.