Cerebrospinal fluid gamma-aminobutyric acid in patients with panic disorder.

Cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels were measured in 11 patients with panic disorder (PD) prior to and following 7 months of treatment with alprazolam or imipramine and in six neurological control patients. Although a clear treatment response was observed in patients with PD, neither alprazolam nor imipramine significantly changed CSF GABA during the treatment period. A negative correlation was demonstrated between baseline CSF GABA and posttreatment overt psychopathology. Low pretreatment level of CSF GABA correlated significantly with poor therapeutic outcome, judged by the amount of anxiety and depression as well as by the frequency of panic attacks at the end of follow-up.

Elevated plasma vasopressin and normal cerebrospinal fluid angiotensin-converting enzyme in chronic pain disorder.

The study was performed proceeding from the hypothesis that pain proneness in chronic pain disorder (CPD) is a result of alterations in central mechanisms regulating pain sensations. To elucidate the function of the central renin-angiotensin system, the levels of angiotensin-converting enzyme (ACE) and arginine vasopressin (AVP) in cerebrospinal fluid (CSF) and peripheral blood were measured in 15 CPD patients and 19 healthy controls. Plasma AVP levels (p = .01) as well as the serum osmolality (p = .01) were significantly higher in the CPD group. No significant differences in CSF ACE levels were found. AVP is a stress-related peptide, but central antinociceptive effects have also been reported. Elevated plasma AVP levels possibly may constitute a response to chronic stress.

Electrophoretic pattern of red blood cell catechol-o-methyltransferase in schizophrenia and manic-depressive illness.

Human red blood cell (RBC) catechol-O-methyltransferase (COMT) was analyzed by polyacrylamide gel electrophoresis (PAGE). One major enzyme band (B) is observed after electrophoresis. In addition, a minor band (A) of COMT activity comprising no more than 25% of the total activity, is also detectable. The rate of migration during electrophoresis of both bands of RBC COMT was the same in manic depressive, schizophrenic, and normal individuals. These results did not reveal genetic variations in the COMT molecule among these three groups. Furthermore, when total RBC COMT was measured there were no statistically significant differences between schizophrenic, manic-depressive, and control individuals.

EEG and CT findings in patients with panic disorder.

Fifty-four patients with panic disorder were investigated using extensive electroencephalographic (EEG) recordings and computerized tomography (CT). Fifteen (28%) of these patients had previously been treated for temporal lobe epilepsy or were considered to have another neurological disorder. EEG recordings showed increased slow-wave activity in 13 (24%) patients and CT scan revealed incidental abnormalities in 6 (20%) of the 30 patients investigated. Taking into account the limitations of the methods applied, the present results indicate that clear-cut epileptic EEG patterns only rarely occur in panic disorder: the vast majority of panic patients exhibit normal EEG and CT findings.

Elevation of substance P-like peptides in the CSF of psychiatric patients.

Using a radioimmunoassay procedure substance P-like activity was measured in samples of human CSF obtained from 12 patients with major depressive disorder, 12 with schizophrenia, and 15 control cases diagnosed as psychiatrically normal. Levels were significantly higher in CSF of patients with depressive disorder as compared with schizophrenic patients or controls. Chemical characterization revealed that the measured activity was less basic than substance P itself and might be due to C-terminal fragments. A component reacting with an antiserum highly specific for the substance P[1-7]fragment was found in CSF of patients with depressive disorder. The results indicate that substance P-related peptides may be biological markers in psychoses, particularly in major depressive disorder.

Prolactin response to submaximal stimulation by TRH in nonaffective psychoses.

Nonaffective psychotic symptoms are heterogeneous and probably caused by mixed biopathology. A preliminary investigative tool to study pituitary dopamine activity, the prolactin response to submaximal stimulation by thyrotropin-releasing hormone (TRH) (mini-TRH test) was correlated in 20 subjects with nonaffective psychoses to positive psychotic symptoms as assessed by the Comprehensive Psychiatric Rating Scale psychosis subscale. A significant positive correlation was observed between the response and ratings of nonparanoid symptoms, especially nonparanoid delusions and disrupted thoughts. Because, in addition to pituitary dopamine activity, there is evidence to suggest that the response reflects extrapituitary dopamine activity as well, the results extend the evidence that nonparanoid acute productive psychotic symptoms may be associated with hypoactivity rather than with hyperactivity of brain dopaminergic systems.

Modified activity of the human auditory cortex during auditory hallucinations.

Previous reports have shown abnormalities in brain metabolism and evoked responses of schizophrenic patients with hallucinations. The authors recorded electric and magnetic auditory responses during transitory auditory hallucinations in two patients. Small but replicable response delays occurred during hallucinations. The results suggest that the effect of hallucinations on auditory cortex activity is similar to the effect of real sounds.

Accumulation of macrophages in the CSF of schizophrenic patients during acute psychotic episodes.

OBJECTIVE: There have been numerous reports of organic or structural abnormalities in the central nervous system (CNS) of patients with schizophrenia. Given that pathological conditions in the CNS are frequently reflected in the cell profiles of CSF, the authors compared the cytology of CSF from schizophrenic patients with that from a reference population in order to find out trails of elementary pathogenetic events in this serious psychiatric disease. METHOD: CSF samples from 35 patients with acute schizophrenia and 46 comparison subjects were prepared by Millipore filtration. The total and differential counts of CSF mononuclear cells were performed by light microscopy. RESULTS: At the beginning of treatment, the proportion of mononuclear phagocytes/macrophages in the patients' CSF was significantly higher than that in the comparison subjects. During treatment with conventional neuroleptic medication, the cytology returned to normal in several patients. CONCLUSIONS: The high proportion of macrophages in schizophrenia without a significantly higher total cell count may reflect neurodevelopmental disorder, a neurodegenerative process, or subtle CNS immunoactivation with mobilization of microglia.

Positive treatment effect of estradiol in postpartum psychosis: a pilot study.

BACKGROUND: Postpartum illnesses with psychiatric symptoms and serious adverse sequelae are highly prevalent during the childbearing years. Despite multiple medical contacts, these illnesses often remain unidentified and untreated. To study the association between estradiol and puerperal psychosis, we measured serum concentration of estradiol and performed an open-label trial of physiologic 17beta-estradiol in women with this disorder. METHOD: Ten women with ICD-10 psychosis with postpartum onset consecutively recruited from a psychiatric duty unit were studied. Serum estradiol concentration was measured at baseline and weekly during sublingual 17beta-estradiol treatment for 6 weeks. The treatment effect was evaluated by a clinician-rated psychiatric symptom scale (the Brief Psychiatric Rating Scale [BPRS]). RESULTS: The baseline serum estradiol levels (mean = 49.5 pmol/L; range, 13-90 pmol/L) were even lower than the threshold value of gonadal failure, and the patients exhibited high scores on the psychiatric symptom scale (mean BPRS total score = 78.3; range, 65-87). During the first week of 17beta-estradiol treatment, psychiatric symptoms diminished significantly (BPRS score decreased to a mean of 18.8, p < .001). Until the end of the second week of treatment, serum estradiol concentrations rose to near the values normally found during the follicular phase, and the patients became almost free of psychiatric symptoms. CONCLUSION: The reversal of psychiatric symptoms in all patients by treating documented estradiol deficiency suggests that estradiol plays a role in the pathophysiology and may have a role in the treatment of this condition. There was a rebound of psychotic symptoms in the 1 patient who discontinued estradiol treatment. Given the small number of patients, this area deserves further study.

Neuroleptic malignant syndrome due to depot fluphenazine.

The parenteral long-acting phenothiazines are drugs frequently used in the treatment of hospitalized and ambulatory psychiatric patients. The usual side effects of these drugs are familiar to psychiatrists. However, the "Neuroleptic malignant syndrome" reported in this paper can give rise to considerable diagnostic difficulty. The clinical characteristics and differential diagnosis of this syndrome are described with a care report. The need for prompt initiation of adequate therapy is stressed.

Myelin basic protein antibodies in catatonic schizophrenia.

Myelin basic protein (MBP) antibodies were determined by solid-phase radioimmunoassay in the serum and cerebrospinal fluid of 10 patients with catatonia, 10 patients with other forms of schizophrenia, and 10 psychiatrically healthy controls. The mean counts per minute (cpm) value of serum anti-MBP antibody of the catatonia group was significantly higher than that of the patients with other forms of schizophrenic psychoses (p less than .05). No significant differences were observed among the cpm values of the CSF specimens from the three patient groups. The hypothesis of a central virus-induced immunologic aberration in catatonic schizophrenia is discussed.

Viral antibodies and interferon in acute psychiatric disorders.

In a prospective study of 54 patients with acute psychiatric disorders, interferon and antibodies in serum and CSF were measured to 19 microbes by the complement fixation (CF) test and to 7 viruses by enzyme immunoassay (EIA). The CF test revealed a fourfold or greater change (p less than .001) in serum antibody titers in 20 patients, and EIA showed a twofold or greater change in CSF titers in 7 patients. Pathological serum/CSF antibody ratio by EIA was observed in 8 patients. The results suggest that viral infections and inflammatory processes have significance in the etiopathogenesis of acute psychiatric disorders.

Immunoglobulin G antibodies to herpes simplex type 1 virus detected by radioimmunoassay in serum and cerebrospinal fluid of patients with schizophrenia.

Serum and CSF specimens from 16 schizophrenic patients and 18 nonpsychiatric controls were tested by radioimmunoassay for immunoglobulin G antibody of capsid, envelope and excreted antigens of herpes simplex type 1 virus. There were no significant differences in the antibody levels between the schizophrenic patients and the controls. The etiological role of viruses and virus-like agents in schizophrenia and some methodological aspects are discussed.

The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans.

Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the beta-adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits beta-adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a druh also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.

Cyclic GMP in the CSF of patients with schizophrenia before and after neuroleptic treatment.

Cerebrospinal fluid (CSF) cyclic GMP may derive from central cholinergic neurotransmission. Measurement of CSF cyclic GMP may allow evaluation of possible implications of the dopaminergic hyperactivity in schizophrenia proposed by the dopamine hypothesis. The CSF cyclic GMP levels in 27 drug-free schizophrenic patients was measured and compared to that in 9 psychiatrically-healthy individuals. The mean CSF cyclic GMP level of the schizophrenic patients was 23 per cent lower than that of the control group, but this difference did not attain statistical significance. In addition the CSF cyclic GMP levels in a group of 10 schizophrenic patients were compared before and after 2 months of neuroleptic treatment. The mean level of cyclic GMP rose 50 per cent after treatment with phenothiazines (P less than 0.05). These results could indicate some tendency for decreased activity of central cholinergic neurons in schizophrenia as well as a restored dopaminergic-cholinergic balance after neuroleptic treatment.

Serum and CSF levels of haloperidol by radioimmunoassay and radioreceptor assay during high-dose therapy of resistant schizophrenic patients.

Serum and cerebrospinal fluid (CSF) levels of haloperidol were measured in 12 chronic neuroleptic-nonresponsive schizophrenic patients after 1 month on 60 mg haloperidol daily and then again after 1 month on 120 mg haloperidol daily. Serum haloperidol and CSF haloperidol rose with increasing dose. Serum and CSF levels were significantly correlated. No clinical improvement was achieved despite the high serum and CSF drug levels.

Elevated angiotensin-converting enzyme (kininase II) in the cerebrospinal fluid of neuroleptic-treated schizophrenic patients.

Disturbances of water homeostasis have frequently been reported in schizophrenia. Water homeostasis is regulated by arginine vasopressin (AVP), the renin-angiotensin system and natriuretic hormones. The aim of this study was to determine the activity of the central renin-angiotensin system in schizophrenia by measuring levels of angiotensin-converting enzyme (ACE) in the cerebrospinal fluid (CSF) and blood in 14 in-patients with schizophrenia on neuroleptic medication and in 9 healthy volunteers. The levels of CSF ACE were significantly higher in the schizophrenia group. There were no correlations between CSF ACE and gender, age, age at first episode, duration of illness, term of hospitalization or neuroleptic dosage. No correlations between CSF ACE and serum ACE were found in either group. The authors suggest an activated central renin-angiotensin system in schizophrenia at least during antipsychotic drug treatment, which may cause 'psychogenic' polydipsia in some patients. ACE and the brain renin-angiotensin system may also play a role in the regulation of neuron growth and differentiation in schizophrenia.

Inverse correlation between hallucinations and serum prolactin in patients with non-affective psychoses.

Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation was observed between clinical measures (total CPRS score, schizophrenia subscale score or depression and anxiety subscale score) and serum PRL.

No differences in phospholipase-A2 activity between acute psychiatric patients and controls.

The phospholipase-A2 activity in plasma from 62 psychiatric patients admitted in an acute state to psychiatric hospital was determined by a fluorometric assay and compared to that of age- and sex-matched controls. Contrary to earlier findings, no significant differences were found between patients and controls.

Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders.

Plasma levels of interleukin (IL)-1 beta and IL-6 were measured in 60 acutely hospitalized psychiatric patients and in 60 healthy controls by enzyme-linked immunosorbent assay (ELISA). Almost no IL-6 was detected in the plasma of the patients or controls. The mean level of IL-1 beta was found to be significantly higher in schizophrenic patients than in their corresponding controls (P = 0.03). The acute schizophrenics, but not the group of chronic schizophrenics, contributed to this increase. No correlation with age, duration of illness or overt psychopathology was found. The neuroleptic medication did not prove to have a significant effect on the plasma IL-1 beta levels. There was no difference between non-psychotic affective disorder patients (N = 17) and the controls.