Conny Nordin

Prevalence of depressive symptoms in late pregnancy and postpartum.

Background. Postnatal depression refers to a non‐psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology.

Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia

Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl D-aspartate-receptor. Mounting evidence indicate that the compound is significantly involved in basal neurophysiological processes in the brain. In the present investigation, cerebrospinal fluid (CSF) level of kynurenic acid was analyzed in 28 male schizophrenic patients and 17 male healthy controls by means of high pressure liquid chromatography and fluorescence detection. Schizophrenic patients showed elevated CSF levels of kynurenic acid (1.67+/-0.27 nM) compared to the control group (0.97+/-0.07 nM). Furthermore, CSF levels of kynurenic acid in schizophrenic patients were also found to correlate with age. The present finding is indicative of a contribution of kynurenic acid in the pathogenesis of schizophrenia.

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.

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.

Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia

Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n=49) and male patients with schizophrenia (n=90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM+/-0.10 vs. 1.06 nM+/-0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM+/-0.19, n=37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM+/-0.17, n=34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM+/-0.10, n=19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.

Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in luman beings

The pharmacokinetics of a single oral dose of 6 mg perphenazine was studied in a group of six slow and six rapid hydroxylators of debrisoquin. Peak serum concentrations of perphenazine were significantly higher in slow hydroxylators than they were in rapid hydroxylators (2.4 ± 0.6 versus 0.7 ± 0.3 nmol/L, p < 0.001). The AUC(0–12) was also higher in slow hydroxylators than it was in rapid hydroxylators (18.5 ± 6.2 versus 4.5 ± 2.5 nmol · L−1 · hr, p < 0.001). The data suggest that the disposition of the antipsychotic drug perphenazine covaries with polymorphic debrisoquin hydroxylation.

Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype.

The pharmacokinetics of thioridazine and its metabolites were studied in 19 healthy male subjects: 6 slow and 13 rapid hydroxylators of debrisoquin. The subjects received a single 25 mg oral dose of thioridazine, and blood samples were collected during 48 hours. Concentrations of thioridazine and metabolites in serum were measured by HPLC. Slow hydroxylators of debrisoquin obtained higher serum levels of thioridazine with a 2.4‐fold higher Cmax and a 4.5‐fold larger AUC(0‐∞) associated with a twofold longer half‐life compared with that of rapid hydroxylators. The side‐chain sulphoxide (mesoridazine) and sulphone (sulphoridazine), which are active metabolites, appeared more slowly in serum and had lower Cmax values, but comparable AUC. The thioridazine ring‐sulphoxide attained higher Cmax and 3.3‐fold higher AUC in slow hydroxylators than in rapid hydroxylators of debrisoquin. Thus the formation of mesoridazine from thioridazine and the 4‐hydroxylation of debrisoquin seem to be catalyzed by the same enzyme, whereas the formation of thioridazine ring‐sulphoxide is probably formed mainly by another enzyme.

Attempted suicide predicts suicide risk in mood disorders

Suicide risk was studied in a sample of 346 mood disorder inpatients, 92 of whom were admitted after a current suicide attempt. The overall suicide mortality after a mean observation period of 6 years was 8%. The potential of attempted suicide to predict suicide risk in hospitalized patients with mood disorders was studied by survival analysis after subgrouping on the basis of whether a current suicide attempt had occurred or not. The suicide risk the first year after attempting suicide was 12% (11/92), compared with 2% (4/254) in the mood disorder subgroup with no current suicide attempt. The long‐range suicide risk after a current suicide attempt in depression was 15% (14/92) as compared with 5% (13/254) among those without a current suicide attempt. It is concluded that a current suicide attempt in mood disorder inpatients predicts suicide risk particularly within the first year and should be taken very seriously.

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients

Objective: This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients.

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

BackgroundRecent 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.MethodLevels 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.ResultsThe 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.ConclusionOur data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia.