Evaluation of screening for drug use using postmortem prolactin levels in serum and cerebrospinal fluid.

Prolactin (PRL) levels can usually be controlled by PRL-inhibiting psychiatric drugs that include anti-dopamine agents. However, the use of dopamine (DA) antagonists may lead to hyperprolactinemia under certain clinical conditions. The aim of this study was to investigate postmortem PRL levels as potential markers of drug abuse, especially that of DA antagonists, in autopsy cases. We examined 121 autopsy cases, excluding cases involving acute hypoxia/ischemia, such as asphyxia, because PRL concentrations are reportedly increased under acute hypoxic conditions. Detected drugs were classified as either DA antagonists, stimulants, psychotropic drugs other than DA antagonists, or other non-psychotropic drugs, and many cases had no detected drugs. Samples comprised blood collected from the right heart chamber and cerebrospinal fluid (CSF). PRL protein level was measured by chemiluminescent immunoassay, and PRL gene expression in the anterior pituitary of autopsy cases was analyzed by reverse transcription-polymerase chain reaction. The PRL-positive cell ratio in the anterior pituitary gland was also measured by immunohistochemical analysis. The results indicated that PRL levels in the serum and CSF were higher in DA antagonist cases than in other cases. PRL levels in the serum and CSF also correlated with the PRL gene expression in cases with abuse of DA antagonists. However, no significant difference in the PRL-positive cell ratio in the anterior pituitary gland was evident between any of the classes of drug-detected and drug-undetected cases. These results suggest that postmortem measurements of PRL transcription levels may be useful for diagnosing cases of DA antagonist use.

Intrathecal Thyroid Autoantibody Synthesis in a Subgroup of Patients With Schizophreniform Syndromes.

Schizophreniform syndromes in combination with autoimmune thyroiditis and increased serum thyroid antibodies lead healthcare practitioners to consider a diagnosis of Hashimoto's encephalopathy. To detect specific biomarkers, the authors analyzed whether intrathecal antithyroid antibody synthesis occurred in a subgroup of schizophreniform patients. In doing so, the authors analyzed thyroid antibodies in paired cerebrospinal fluid and serum samples from 100 schizophreniform patients. Increased antibody indices (AIs) for antithyroid peroxidase or antithyroglobulin autoantibodies in 13 schizophreniform patients were found. AIs were increased in 68% of the seropositive patients. These findings support the hypothesis that autoimmune processes may contribute to the pathophysiology in these patients.

Glial cell line-derived neurotrophic factor and somatostatin levels in cerebrospinal fluid of patients affected by chronic migraine and fibromyalgia.

The aim of the present study was to verify cerebrospinal fluid (CSF) levels of glial cell line-derived neurotrophic factor (GDNF) and somatostatin, both measured by sensitive immunoassay, in: 16 chronic migraine (CM) patients, 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine (PCM) and probable analgesic-abuse headache (PAAH), 20 patients affected by primary fibromyalgia syndrome (PFMS), and 20 control subjects. Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls (GDNF =P < 0.001, P < 0.002; somatostatin = P < 0.002, P < 0.0003), without significant difference between the two groups. PFMS patients, with and without analgesic abuse, also had significantly lower levels of both somatostatin and GDNF (P < 0.0002, P < 0.001), which did not differ from those of CM and PCM + PAAH patients. A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM (r = 0.70, P < 0.02), PCM + PAAH (r = 0.78, P < 0.004), and PFMS patients (r = 0.68, P < 0.008). Based on experimental findings, it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain. The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated, which appear to be more strictly related to the chronic pain state, as demonstrated also for fibromyalgia.

Corticoliberin protects neurons from the negative influences of "dysfunctins" in living olfactory cortex slices.

The protective effects of corticoliberin on living rat olfactory cortex slices during perfusion with "dysfunctins" extracted from cerebrospinal fluid of drug addicts were studied. Isolated perfusion of slices with medium containing "dysfunctins" led to irreversible suppression of the amplitude of individual components of focal potentials induced by electrical stimulation of the lateral olfactory tract. The maximum level of depression was seen for the AMPA and NMDA components of EPSP. Preliminary perfusion of slices with medium containing corticoliberin (100 nM) for 15 min partially, and for 30 min completely protected processes mediated by activation of AMPA and NMDA receptor mechanisms from the negative influences of "dysfunctins." It is suggested that corticoliberin can induce its protective effects either via its own specific receptors or non-specifically via glutamate receptors. It is also possible that both of these mechanisms act in combination.

[Corticoliberin protects the olfactory cortex slices against the negative effect of "dysfunctins"]. / Kortikoliberin protektiruet neirony perezhivaiushchikh srezov oboniatel'noi kory ot negativnogo vliianiia "disfunktsinov".

Corticoliberin may induce protective effects via its specific receptors or unspecifically by means of the glutamate receptors. A combined action of these mechanisms is also possible.

Vasoactive intestinal polypeptide (VIP) in cerebrospinal fluid from men after long-term exposure to organic solvents.

Vasoactive intestinal polypeptide (VIP) is widely distributed within the central nervous system (CNS) and is thought to function as a neurotransmitter. VIP was measured in CSF from 14 men with psycho-organic syndrome occupationally exposed to organic solvents for 7-38 years and in CSF from 8 neurologically healthy male volunteers. The concentration of VIP in the exposed group, 28 +/- 15 (SD) pmol/l, did not significantly differ from that of controls, 38 +/- 14 pmol/l. Thus, determination of VIP in CSF appears to be of little value for detecting effects of long-term solvent exposure.

Cerebrospinal fluid proteins and cells in men subjected to long-term exposure to organic solvents.

Cerebrospinal fluid (CSF) was obtained from 17 men occupationally exposed to organic solvents and diagnosed as having a psycho-organic syndrome. Healthy volunteers and patients without neurological disorders were used as controls. The albumin ratio was increased in three heavily exposed men, indicating an increased passage of albumin over the blood-brain barrier. A slight monocytoid reaction was present in three of the subjects in the exposed group. Myelin basic protein and enolase activity were within normal limits. Isoelectric focusing of CSF-enriched proteins obtained by absorption chromatography showed alterations in nine out of 17 exposed individuals: The most prominent change was a relative increase of the protein band with Ip 4.7.

Cerebellar, cortical and functional impairment in toluene abusers.

24 solvent abusers (mean age 23 +/- 4.4 years +/- SD) were studied in hospital. They reported using substances containing a mean of 425 +/- 366 mg of toluene per day for 6.3 +/- 3.9 years. There was no laboratory evidence of under-nutrition. No withdrawal symptoms were observed. Marked impairment was observed in neurological and neuropsychological test performances in 65% of the sample. Cerebellar symptoms were particularly prominent. The impairment was significantly correlated with CT scan measurements of the cerebellum, ventricles and cortical sulci, all of which abnormal in comparison to age-matched controls. CSF abnormalities were elevated C1-, low PO2 and very low anion gap. The duration of abuse was only weakly correlated with neurological scores. After 2 weeks of abstinence, several liver function tests which were abnormal on admission had recovered, but only minimal changes in the CNS symptoms were observed.