It has been suggested that (1) the clinical efficacy of the heterocyclic antidepressant trazodone in depression may, in part, be attributed to its metabolite meta-chlorophenylpiperazine (mCPP); and (2) the enhancement of the efficacy of trazodone by the addition of fluoxetine, a selective serotonin reuptake inhibitor, may, in part, be ascribed to fluoxetine-induced plasma concentrations of trazodone. After a washout period of 10 days, 27 inpatients with major depression were treated with trazodone 100 mg/day (orally). One week later (T0), fluoxetine 20 mg/day, placebo, or pindolol 7.5 mg/day was added. Plasma concentrations of mCPP and trazodone were determined at T0 and 2 and 4 weeks later. Although placebo and pindolol had no significant effect on the plasma concentrations of mCPP and trazodone, there was a significant increase of the concentrations of these compounds associated with the combination of trazodone + fluoxetine. The results suggest that fluoxetine-induced increases in plasma mCPP and trazodone concentrations contribute to the clinical efficacy of the combination of fluoxetine + trazodone. It is suggested that desensitization of 5-HT2C receptor function by mCPP as well as fluoxetine may contribute to the antidepressant effects of this combination. (J Clin Psychopharmacol 1997;17:358-364).
Abstract Background The Montreal Cognitive Assessment (MoCA) rating scale is frequently used to assess cognitive impairments in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Objectives The aims of this study are to a) evaluate the construct validity of the MoCA and its subdomains or whether the MoCA can be improved by feature reduction, and b) develop a short version of the MoCA (MoCA-Brief). Methods We recruited 181 participants, divided into 60 healthy controls, 61 aMCI, and 60 AD patients. Results The construct reliability of the original MoCA was not optimal and could be improved by deleting one subdomain (Naming) and five items, namely Clock Circle, Lion, Digit Forward, Repeat 2 nd Sentence, and Place, which showed inadequate loadings on the extracted latent vectors. To construct the MoCA-Brief, the reduced model underwent further reduction and feature selection based on model quality data of the outer models. We produced a MoCA-Brief rating scale comprising five items, namely Clock Time, Subtract 7, Fluency, Month, and Year. The first latent vector extracted from these five indicators showed adequate construct validity with an Average Variance Extracted of 0.599, composite reliability of 0.822, Cronbach’s alpha of 0.832 and rho_A of 0.833. The MoCA-Brief factor score showed a strong correlation with the total MoCA score (r=0.98, p<0.001) and shows adequate concurrent, test-retest, and inter-rater validity. Conclusion The construct validity of the MoCA may be improved by deleting five items. The new MoCA-Brief rating scale deserves validation in independent samples and especially in other countries.
Summary Recently, some investigators have reported blunted natural killer cell activity (NKCA) in patients with major depression. In addition, there were some reports on negative relationships between NKCA and the occurence of negative life events. In order to replicate the above findings, the present study investigates NKCA and negative life events in 11 normal and 35 unipolar (minor, simple major, melancholic) depressed subjects. NKCA has been determined by all subjects. They completed the Questionnaire on Recently Experienced Events with scores on number and impact factor of events related to a) illness, b) working conditions, c) social relationships, d) housing problems, e) loss of possession. Depressed subjects reported higher scores on number and/or impact factor of events related to illness, social relationships and housing problems. In our investigation NKCA was significantly blunted in depressed subjects and, particularly in melancholies. So NKCA is negative correlated to the severity of depression. We were unable to detect any significant relationship between NKCA, and life events ( number of impact factors ), Our results do not corroborate the thesis that life events may affect immune function, as assessed by NKCA.
Abstract Stable phase schizophrenia is characterized by altered patterning in tryptophan catabolites (TRYCATs) and memory impairments, which are associated with PHEMN (psychosis, hostility, excitation, mannerism and negative) and DAPS (depression, anxiety and physio-somatic) symptoms. This study was carried out to examine the association between TRYCAT patterning, memory impairments, psychopathological features and health-related quality of life (HR-QoL) in schizophrenia. The World Health Organization (WHO) QoL instrument-Abbreviated version (WHO-QoL-BREF), IgA/IgM responses to TRYCATs, cognitive tests, Scale for the Assessment of Negative Symptoms (SANS), Hamilton and Depression (HAMD) and Anxiety (HAMA) Rating Scales and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF) were measured in 80 schizophrenia patients and 40 controls. Neural Network analysis shows that the total HR-Qol score is best predicted by (in descending order) FF, HAMA and SANS scores, Mini Mental State examination, hostility, ratio noxious/protective TRYCATs and HAMD score. Partial least Squares (PLS) analysis shows that 55.1% of the variance in Domain1 (physical) is predicted by PHEMN and DAPS latent vector (LV) scores, while 57.9% of domain2 (psychological), 32.7% of domain3 (social) and 55.0% of domain4 (environment) are explained by DAPS LV scores. TRYCATs and episodic/semantic memory impairments have specific indirect effects on domains 2, 3 and 4, which are mediated by DAPS symptoms, while the effects of TRYCATs on domain1 are mediated by PHEMN and DAPS symptoms. Picolinic acid, xanthurenic acid and 3-hydroxy-kynurenine decrease WHO-QoL scores, whilst anthranilic acid is protective. The results show that lowered HR-Qol in schizophrenia is strongly predicted by noxious TRYCATs, impairments in episodic and semantic memory and DAPS symptoms, especially physio-somatic symptoms and anxiety. Neuro-immune pathways and the consequent cognitive impairments determine to a great extent lowered HR-QoL in schizophrenia.