Relationships between inflammatory markers and suicide risk status in major depression.

Pro-inflammatory status has been implicated in depression and suicidal behaviors. Polyunsaturated fatty acids (PUFAs) and cytokines, two types of inflammatory biomarkers, have been associated with suicide, independent of depression severity. How these biomarkers relate to each other is less clear. We measured plasma phospholipid levels of arachidonic acid (AA%), docosahexaenoic acid (DHA%), and eicosapentaenoic acid (EPA%) as a percentage of total phospholipids, as well as serum interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), in 80 patients with major depressive disorder (MDD) and 24 healthy controls (HC). Individual PUFA and cytokine species were compared using ANOVA across four suicide risk-stratified groups: 1) highest-risk, recent (within 5 years) suicide attempters (n = 20); 2) high-risk, severe current suicidal ideators (having intent or plan) with no recent attempt history (n = 22); 3) low-risk, current non-ideators who were also lifetime non-attempters (n = 38); and 4) HC (n = 24). None of the participants were enrolled following an acute suicide attempt. Of biomarkers studied, only DHA% (p = 0.012) and IL-1ß (p = 0.002) differed between groups. In post-hoc testing, DHA% was lower in attempters than ideators (p = 0.018) or MDD non-ideators (trend level, p = 0.073). IL-1ß was lowest in attempters, differentiating them from ideators (p = 0.009) and HC (p = 0.004). Recent suicide attempt, one of the most powerful predictors of suicide risk, was also most closely tied to inflammatory indices in this study. Low DHA% as an indicator of suicide risk is consistent with previous reports; however, lower IL-1ß was unexpected and may relate to acuity/chronicity of inflammation. There is a need for prospective studies of immune status with respect to suicidal behaviors.

Emotional Intelligence in a group of patients with first-episode psychosis in Iran.

This study was aimed to evaluate the Emotional Intelligence (EI) of a group of patients with first episode psychosis in Iran as compared with a healthy control group. A case-control design was used. EI was assessed using Persian version of Bar-On Emotional Quotient inventory (EQ-i) administered on 25 patients with history of a single psychotic episode in the last two years, as well as 64 healthy participants. The mean (±SD) of EI scores of patients' and healthy controls' group was 319.8 (±40.9) and 328.8 (±33.3), respectively. Two-independent sample t-test revealed no significant difference in the EI scores of two groups (P=0.29). In contrast with chronic schizophrenia, the patients with first-episode psychosis were not different from the healthy subjects in terms of emotional intelligence score. It might be implied that the low emotional intelligence of the patients with chronic psychotic disorders is an accumulative result of the underlying disease over time.

Tamoxifen disrupts consolidation and retrieval of morphine-associated contextual memory in male mice: interaction with estradiol.

RATIONALE: Tamoxifen (TMX), a selective estrogen receptor modulator, can affect cognitive functions of the brain. The conditioned place preference (CPP) paradigm involves memory for the association between contextual cues and the rewarding properties produced by a drug. OBJECTIVES: The effects of TMX alone and in combination with estradiol (E2) on reward-related memory of morphine were investigated in adult male mice. MATERIALS AND METHODS: Using an unbiased CPP paradigm, the ability of morphine sulfate (0.5-10 mg/kg, s.c.) to produce CPP was studied. Afterwards, the effects of TMX (1-10 mg/kg, s.c.) on the acquisition, consolidation, and expression of morphine-induced CPP were assessed. We have also evaluated the possible effects of s.c. E2 (10-200 mug/kg) and its co-administration with TMX (10 mg/kg, s.c.) on the consolidation and retrieval of morphine-associated contextual memory. RESULTS: (1) Morphine (0.5-10 mg/kg) significantly induced CPP in a dose-dependent manner. (2) TMX (10 mg/kg) significantly reduced the time spent by mice in the morphine compartment when given immediately after each conditioning session (consolidation) or 30 min before testing for place preference in the absence of morphine (expression), whereas it had no effect when administered 30 min before each training session (acquisition). (3) Post-training or pre-testing administration of E2 increased morphine-induced CPP in a dose-dependent manner. (4) In addition, concomitant administration of E2 with TMX appears to prevent the impairing effect produced by TMX. CONCLUSIONS: TMX appears to disrupt consolidation and retrieval of morphine-associated contextual memory and this impairing effect might be prevented by E2 treatment.

Antagonism of muscarinic M1 receptors by dicyclomine inhibits the consolidation of morphine-associated contextual memory.

M1 muscarinic receptor has been shown to be involved in cognitive functions of the brain. Conditioned place preference (CPP) paradigm involves memory for the association between environmental stimuli and the rewarding properties produced by a treatment. Using a balanced CPP design, we studied the possible involvement of M1 muscarinic receptors on the acquisition, expression and consolidation of morphine place conditioning in male mice. Subcutaneous administration of morphine sulphate-induced CPP in a dose-dependent manner. Using a 6-day schedule of conditioning, it was found that dicyclomine, an M1 muscarinic antagonist, significantly reduced the time spent by mice in the morphine compartment when given immediately, but not 6h, after each conditioning session (consolidation). It had no effect when administered 30 min before each conditioning session during CPP training period (acquisition) or 30 min before testing for place preference in the absence of morphine (expression). It is concluded that M1 muscarinic receptors may play a time-dependent role in the consolidation of reward-related memory of morphine.

Rewarding properties of sildenafil citrate in mice: role of the nitric oxide-cyclic GMP pathway.

RATIONALE: Sildenafil citrate is widely prescribed for erectile dysfunction and acts by inhibiting phosphodiesterase type-5, resulting in accumulation of cyclic-guanosine monophosphate (cGMP) via activation of nitric oxide synthase (NOS). The nitric oxide (NO) system is relevant to the rewarding effects of various drugs of abuse. Several epidemiologic studies indicate that sildenafil is abused in a recreational fashion. OBJECTIVES: In the present study, the rewarding properties of sildenafil and probable involvement of the NO-cGMP pathway were investigated in adult male NMRI mice. METHODS: The ability of sildenafil citrate (1-40 mg/kg) to produce conditioned place preference (CPP) was studied in an unbiased CPP paradigm. The effects of NO precursor L-arginine, nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the inhibitor of guanylyl cyclase methylene blue (MB) on sildenafil-induced CPP were assessed. RESULTS: Mice that received sildenafil (20 and 40 mg/kg) in one environment during conditioning phase displayed a preference for this environment. Both L-NAME (5 mg/kg) and MB (1 mg/kg) in combination with sildenafil (20 mg/kg) suppressed the acquisition of sildenafil-induced place preference. Lower and per se noneffective dose of sildenafil (10 mg/kg) and L-arginine (60 mg/kg), when coadministered, exerted a significant place conditioning. CONCLUSIONS: Sildenafil shows rewarding properties that may involve the NO-cGMP pathway.