L-thyroxine treatment in primary hypothyroidism does not increase the content of free triiodothyronine in cerebrospinal fluid: a pilot study.

The association between cerebrospinal fluid (CSF) and serum concentration of thyroid hormones and pituitary thyrotropin stimulating hormone (TSH) was studied in nine hypothyroid patients (HT) before and in seven after L-thyroxine treatment. With L-thyroxine, median free T4 increased 4-fold in serum (3.5 pmol/L vs 17.5 pmol/L) and 3-fold in CSF, (3.9 pmol/L vs 11.5 pmol/L). Correspondingly, total T3 in serum increased two-fold (0.9 nmol/L vs 2.2 nmol/L). Unexpectedly, free T3 concentration in CSF was similar (1.5 pmol/L vs.1.5 pmol/L) before and during treatment. In HT, TSH in serum correlated with TSH in CSF as did free T4 in serum and in CSF. During L-thyroxine, the correlation with TSH in serum and CSF remained. Likewise, the free T4 concentration in serum correlated with that in CSF. However, no correlation was found between T3 in serum and free T3 in CSF. It seems evident that free T4 in serum equilibrates with that in the CSF both in the HT and during L-thyroxine. Despite a two-fold increase in total serum T3, free T3 in CSF remained unchanged, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF. Alternatively, an accelerated conversion of T4 to T3 might have maintained the concentration of T3, due to strongly increased levels of TSH found in the hypothyroid state. The notion that free T4 in serum reflects the CSF concentration of free T4 is consistent with previous reports from studies in animals.

Cholecystokinin in plasma and cerebrospinal fluid--a study in healthy young women.

Cholecystokinin (CCK) is widely distributed in the brain and is known to affect behavioral and physiological functions including anxiety and pain. The expression of CCK has been shown to be regulated by estrogen and to vary during the estrous cycle in rat brain. In the present study CCK was determined in plasma from 25 healthy women (age 25.0+/-3.5) during the menstrual cycle, in the late luteal phase and in the follicular phase. In the follicular phase, a lumbar puncture was performed at the same time that a plasma sample was taken in 15 subjects. The participants had fasted and were nicotine-free for at least 8h preceding the sampling. We compared CCK-like immunoreactivity (CCK-LI) in plasma from 25 subjects in the late luteal phase (LLP) and the follicular phase (FP) and found that there was no difference during the menstrual cycle (n=25, R(2)=89.60%, p=n.s.). In the follicular phase no significant difference was found between CCK-LI in plasma and in cerebrospinal fluid (CSF) collected at the same time (n=15, R(2)=55.32%, p=n.s.).

Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder.

BACKGROUND: Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder. METHODS: We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography. RESULTS: Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers. LIMITATIONS: The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease. CONCLUSION: Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder.

Mobile phone computing for in-situ cognitive behavioral therapy.

Cognitive behavioral therapy (CBT) for psychological disorders is becoming increasingly popular on the Internet. However, when using this workstation approach, components such as training and learning relaxation skills, problem solving, exposure exercises, and sleep management guidance must be done in the domestic environment. This paper describes design concepts for providing spatially explicit CBT with mobile phones. We reviewed and analyzed a set of treatment manuals to distinguish elements of CBT that can be improved and supported using mobile phone applications. The key advantage of mobile computing support in CBT is that multimedia can be applied to record, scale, and label anxiety-provoking situations where the need arises, which helps the CBT clients formulate and convey their thoughts and feelings to relatives and friends, as well as to therapists at subsequent treatment sessions.

Temperament and character in pathological gambling.

OBJECTIVE: We have studied temperament and character in pathological gambling (PG). METHODS: Thirty-eight DSM-IV verified pathological gamblers (31 males and 7 females; mean age 35.4 +/- 10.4 years) were tested with Cloninger's Temperament and Character Inventory (TCI). Matched controls were chosen from the normal population. RESULTS: Pathological gamblers scored higher on the temperament factors novelty seeking (NS) and harm avoidance (HA). The most pronounced difference was found in the character factor self-directedness (SD). The pathological gamblers differed from controls in cooperativeness and self-transcendence. A personality disorder was found in 29% of the pathological gamblers 84% of whom scored either low on SD and high on impulsivity or had a more dishonest behaviour. Two-thirds of pathological gamblers showed immature character with or without high HA in temperament. The other third showed normal-character extravagant behaviour (86%), high impulsivity (36%) and less responsibility (50%) being the most common personality traits. CONCLUSION: HA and NS might be trait-like characteristics in PG.

Diurnal and seasonal variation of cholecystokinin peptides in humans.

Cholecystokinin (CCK) was determined in plasma obtained from 10 female (aged 23.4+/-SD 2.3 years) and nine male (aged 22.0+/-SD 1.4 years) healthy volunteers. Blood samples were drawn three times (8.00a.m., 12 noon and 8.00a.m.) on each of two sessions, one in the winter (November-December) and one in the summer (April-July). The participants had fasted (and were nicotine-free) since midnight preceding the sampling. A standardized breakfast was served after the first sampling. CCK was determined by radioimmunoassay. The area under the curve 0-24h (AUC)(CCK Winter) was lower than AUC(CCK Summer) (F(1:17)=4.73; P=0.0440) in the whole group of volunteers. On comparing the CCK concentrations within each session, there was an overall difference in winter (F(2:36)=14.81; P<0.0001) as well in summer (F(2:36)=18.39; P<0.0001). Post hoc comparisons yielded a difference between the 8.00a.m. and 12 noon concentrations on the first day in winter (t=-3.96; P=0.0009) as well as in summer (t=-4.64; P=0.0002). The difference between the summer and winter AUCs(CCK) correlated with the difference between AUCs for temperatures in summer and winter (r=0.58; P=0.0089). The correlation was accounted for by the females (r=0.73; P=0.0171). The results are in accord with a diurnal and a seasonal variation of CCK in human plasma.

Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with psychiatric complications including cognitive impairment, affective disorders, and psychosis. Previous studies have revealed a disturbed kynurenine metabolism in these patients leading to increased levels of neuroactive compounds acting at glutamatergic neurotransmission. Kynurenic acid (KYNA), one of these metabolites is a glutamate-receptor antagonist, preferentially blocking the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Increased levels of brain KYNA have been suggested to induce a NMDA receptor hypofunction that is associated with psychotic symptoms. In the present study, we analyze the concentration of KYNA in the cerebrospinal fluid (CSF) from HIV-1 infected patients (n=22), including HIV-1 infected patients with psychotic symptoms (n=8) and HIV-1 infected patients without psychiatric symptoms (n=14). We found that HIV-1 infected patients had significantly higher median concentration of CSF KYNA (3.02nM) compared to healthy controls (1.17nM). Furthermore, CSF KYNA levels were significantly elevated in HIV-1 infected patients with psychotic symptoms (4.54nM) compared to patients with HIV-1 without psychiatric symptoms (2.28nM). Present results indicate that increased levels of CSF KYNA may be associated with development of psychotic symptoms in HIV-1 infected patients.

Cerebrospinal fluid kynurenic acid in male and female controls - correlation with monoamine metabolites and influences of confounding factors.

The concentrations of the tryptophan metabolite kynurenic acid (KYNA) and the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in the cerebrospinal fluid (CSF) from 43 healthy volunteers (30 males and 13 females). Healthy female controls displayed higher CSF concentration of KYNA (1.91nM+/-0.20) compared to healthy male controls (1.06nM+/-0.07) and lower CSF levels of HMPG (39.2nM+/-2.0 and 43.4+/-1.2, respectively). CSF levels of HVA and 5-HIAA did not differ between females (181.3nM+/-21.9 and 93.7nM+/-11.4, respectively) and males (138.9nM+/-12.6 and 74.8nM+/-5.9, respectively). Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA while CSF content of HMPG did not correlate with KYNA or the other monoamine metabolites in CSF. A negative correlation was found between back length and CSF concentrations of KYNA, HVA and 5-HIAA and also between CSF KYNA levels and body height. The results of the present study suggest that concentrations of KYNA and the monoamine metabolites in CSF from healthy controls are dependent on gender and back length, which must be taken in consideration when analysing mixed groups of men and women. The higher KYNA concentration found in female controls compared to male might be attributed to a shorter back in women compared to men. Furthermore, these findings suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover.

Cerebrospinal fluid amino acids in pathological gamblers and healthy controls.

Amino acids, such as valine, isoleucine and leucine compete with tyrosine and tryptophan for transport into the brain and might thus affect the central serotonin and catecholamine patterns. Furthermore, the excitatory amino acids glutamic acid, aspartic acid and glycine are known to act on the N-methyl-D-aspartate receptor, which is part of the reward system. Based on these facts, we have explored the role of cerebrospinal fluid (CSF) amino acids in pathological gambling. Concentrations of amino acids were determined in CSF obtained from one female and 11 pathological male gamblers and 11 healthy male controls. In an ANCOVA with best subset regression, pathological male gamblers had higher CSF levels of the excitatory glutamic and aspartic acids, as well as of phenylalanine, isoleucine, citrulline and glycine. A negative contribution of glycine in interaction with the neuraxis distance might mirror a reduced spinal supply or an altered elimination of glycine in pathological gamblers. A decreasing CSF gradient from the first (0-6 ml) to the third (13-18 ml) CSF fraction was found for glutamic acid, glycine, leucine, isoleucine, lysine, ornithine and glutamine in both pathological gamblers and healthy controls. A decreasing gradient was found, however, for aspartic acid and phenylalanine in pathological male gamblers. The altered pattern of CSF amino acids in pathological gamblers might exert an influence on central monoamines as well as on N-methyl-D-aspartate receptor function.

Cerebrospinal fluid kynurenic acid in male patients with schizophrenia - correlation with monoamine metabolites.

BACKGROUND: The tryptophan metabolite kynurenic acid (KYNA) is an endogenous glutamate/nicotinic receptor antagonist. Previous studies have shown that the concentration of the compound is increased in cerebrospinal fluid (CSF) of patients with schizophrenia. Furthermore, it has been found that the CSF concentration of KYNA is positively correlated to CSF concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) in healthy control subjects. OBJECTIVES: To study the correlations between KYNA and the monoamine metabolites HVA, 5-HIAA and 4-hydroxy-3-methoxyphenylglycol (HMPG) in CSF of male patients (n= 53, ranging from 20 to 48 years of age) with verified schizophrenia. METHODS: CSF was obtained by lumbar puncture, and KYNA analysis was performed with an isocratic reversed-phase high-performance liquid chromatography system connected to a fluorescence detector. HVA, 5-HIAA and HMPG concentrations were measured by mass fragmentography with deuterium-labelled internal standards. RESULTS: Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA, while CSF content of HMPG did not correlate to KYNA or any of the monoamine metabolites in CSF. CONCLUSION: The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia.

CSF monoamine patterns in pathological gamblers and healthy controls.

Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological gamblers have focused on disturbed NA, DA and 5-HT function in the central nervous system. We have analysed precursors, transmitters and transmitter metabolites in 3 x 6 ml of CSF obtained from one female and 11 male pathological gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8 h of fasting without preceding strict bedrest. Pathological gamblers displayed lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5-HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA level did not differ between pathological gamblers and healthy controls. A disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and HMPG, but only in pathological gamblers. A disrupted gradient was found for 5-HIAA in both pathological gamblers and healthy controls. The results are in line with the presence of altered indoleamine and catecholamine function in pathological gamblers as well as an altered CSF transport from the brain to the lumbar compartment in such gamblers.

Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients.

Several lines of evidence suggest that D-serine, an endogenous agonist of the glycine site on the NMDA receptors, might play a role in the pathophysiology of schizophrenia. The purpose of this study was to determine whether levels of D- and L-serine or D-serine ratio (D-serine/total serine) in cerebrospinal fluid (CSF) were altered in first episode and drug-naive schizophrenic patients. The CSF levels of D- and L-serine in 25 male first episode and drug-naive schizophrenic patients and 17 age-matched male healthy subjects were measured using a column-switching high performance liquid chromatography system. The percentage of D-serine in the total serine of patients was significantly (z = -2.01, p = 0.044) lower than that of controls. This study suggests that synthetic or metabolic pathways of D-serine may be abnormal in the brain of drug-naive schizophrenic patients, supporting the NMDA receptor dysfunction hypothesis of schizophrenia.

Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients.

BACKGROUND: Recent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients. METHOD: Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography. RESULTS: The ratio (126.1 (median), 117.7 +/- 27.4 (mean +/- S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 +/- 22.5 (mean +/- S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls. CONCLUSION: Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia.

CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartum.

The aim of this exploratory was to investigate the theory of a relation between cytochrome P450 2D6 (CYP2D6) genotype and depressive symptoms in late pregnancy and/or postpartum. We studied 145 women with depressive symptoms. CYP2D6 genotype was analysed in leukocyte DNA by polymerase chain reaction (PCR). There were no significant differences in CYP2D6 genotypes between the groups of women being depressed during and/or after pregnancy. The frequencies of CYP2D6 genotypes did not differ from other European studies. This study cannot confirm that depressive symptoms in late pregnancy and postpartum are connected with CYP2D6 genotype. It is, however, noteworthy that the frequency of ultrarapid metabolizers was higher than in a general Caucasian population. This warrants further exploration in a greater study sample, but should also be investigated in a general population with major depression.

CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype.

Eight healthy male volunteers, lumbar-punctured before and during simvastatin treatment, were phenotyped for CYP2D6 analysis of the debrisoquine metabolic ratio (the ratio between the urinary recovery of debrisoquine and its 4-hydroxy metabolite) after a single oral dose of debrisoquine. The mean cerebrospinal fluid concentrations of cholesterol and taurine did not differ before and during treatment. During (but not before) treatment taurine in the CSF correlated with the debrisoquine metabolic ratio (r=-0.93; P=0.0007) Our results might indicate an influence of CYP2D6 on the level of taurine in the CSF that was secondary to the change in plasma cholesterol.

Clinical and biochemical observations during treatment of depression with electroacupuncture: a pilot study.

Six patients suffering from major depression were treated with electroacupuncture. During 4 weeks of treatment, the total CPRS-S-A score decreased from 23.8 to 13.4 (p=0.0095). A decrease of neuropeptide Y (NPY) in plasma during the first 2 weeks of treatment was noted in five of the patients, all being women (p=0.0431). The decrease was negatively correlated with age (rs=-0.29; p=0.046). The results are in line with a putative antidepressive effect of electroacupuncture, along with an influence on NPY in plasma.

Obstetric, somatic, and demographic risk factors for postpartum depressive symptoms.

OBJECTIVE: To identify and test the predictive power of potential independent risk factors of postpartum depressive symptoms during pregnancy and the perinatal period. METHODS: We conducted a case-control study where 132 women with postpartum depressive symptoms were selected as an index group and 264 women without depressive symptoms as a control group. Data related to sociodemographic status, medical, gynecologic, and obstetric history, pregnancy, and perinatal events were collected from standardized medical records. RESULTS: The strongest risk factors for postpartum depressive symptoms were sick leave during pregnancy and a high number of visits to the antenatal care clinic. Complications during pregnancy, such as hyperemesis, premature contractions, and psychiatric disorder were more common in the postpartum depressed group of women. No association was found between parity, sociodemographic data, or mode of delivery and postpartum depressive symptoms. CONCLUSION: Women at risk for postpartum depression can be identified during pregnancy. The strongest risk factors, sick leave during pregnancy and many visits to the antenatal care clinic, are not etiologic and might be of either behavioral or biologic origin. The possibilities of genetic vulnerability and hormonal changes warrant further investigation to reach a more thorough understanding.