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OBJECTIVE Several studies have investigated possible biological correlates of mental disorders. Although some studies have consistently reported elevated levels of serum inflammatory markers in depression, very few have evaluated cytokine levels in patients with lifetime panic disorder (PD). METHODS Seventy-eight adults (75% women) from an anxiety disorders outpatient unit were categorized according to their PD status: current or in remission. Serum levels of interleukin (IL)-6, tumor necrosis factor α, and IL-10 were evaluated using flow cytometry with enhanced sensitivity flex sets. Data on clinical comorbidity, lipid profile, fasting blood glucose, C-reactive protein, and PD severity were also obtained. RESULTS Significantly higher mean levels of serum IL-6 (0.83 vs 0.60 pg/mL [95% confidence interval {CI}for the log-transformed mean difference, -0.41 to -0.57], p = .008) but not of tumor necrosis factor-α (0.18 vs 0.14 pg/mL [95% CI, -1.12 to 0.11]; p = 0.53) or IL-10 (0.21 vs 0.26 [95% CI, -0.20 to 0.44]; p = 0.16), were associated with current PD compared to remitted PD. Higher Panic Disorder Severity Scale (standardized β = 0.36; p = .013), body mass index (standardized β = 0.53, p < .001) and fasting blood glucose 5.6 mmol/L or greater (standardized β = 0.23, p = .038) were significantly associated with higher levels of IL-6 in the multivariate linear regression model. CONCLUSIONS Our findings support a proinflammatory state in patients with current PD that is independent of possible confounders. Although there are important implications of these findings, replication is required.

Oxidative damage and inflammation occur early in the brain after sepsis and are resolved when long-term cognitive impairment occurs. There is no information of a direct relation between acute levels of brain inflammation and oxidative damage and long-term cognitive deficits. We hypothesized that higher levels of early oxidative damage and inflammation are followed by long-term cognitive deficits, and this is related to a decrease in the levels of brain-derived neurotropic factor (BDNF). Wistar rats were subjected to sham operation or cecal ligation and perforation and the cerebrospinal fluid (CSF) was obtained 6 and 24 h after the determination of thiobarbituric acid-reactive species, interleukin 1 (IL-1), IL-10, and tumor necrosis factor α (TNF-α). Animals were followed until 30 days after surgery and were subjected to the step-down inhibitory avoidance (IA) task, and the hippocampus levels of BDNF were determined. At 6 h, higher CSF levels of thiobarbituric acid-reactive species and TNF-α were observed in septic animals that had a better performance in the IA task and presented higher BDNF levels in the hippocampus. At 24 h, higher CSF levels of IL-1β and TNF-α were observed in septic animals that had a worse performance in the IA task, and this was associated with lower BDNF levels. The persistence of brain inflammation during the acute phase of sepsis is associated with long-term hippocampus levels of BDNF and memory impairment in sepsis survivors.

Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.

An increasing debate exists about the potential of early exposure to methylphenidate to increase the risk for drug abuse. In addition, little is known about the neurobiological effects of early exposure to methylphenidate. This study was designed to investigate whether chronic treatment with methylphenidate induces behavioral sensitization to subsequent methylphenidate and D-amphetamine challenge in adolescent Wistar rats. Young Wistar rats (P25) were treated with either methylphenidate (1, 2, or 10 mg/kg, intraperitoneally) or saline for 28 days. After 14 days of washout, animals were challenged with methylphenidate 2.5 mg/kg intraperitoneally or D-amphetamine 2 mg/kg intraperitoneally (P67). Locomotor behavior was assessed using the open field test. Rats chronically treated with methylphenidate in the adolescent period showed augmented locomotor sensitization to D-amphetamine but not to methylphenidate in the adult phase. These findings suggest that early exposure do methylphenidate might increase the risk for subsequent D-amphetamine abuse. Further studies focusing on the neurobiological effects of early exposure to methylphenidate are warranted.

The aim of this study was to evaluate the effects of interactions between memory modulatory systems on inhibitory avoidance retention in rats. Adult female Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.3 mA footshock). The training-test interval was 24 h. The animals received an intraperitoneal injection of saline or midazolam (1 mg/kg) 15 min before training, and saline, adrenaline (25 microg/kg), naloxone (0.4 mg/kg), dexamethasone (0.3 mg/kg) or glucose (320 mg/kg) immediately after training. In saline-pretreated rats, adrenaline, naloxone, dexamethasone and glucose enhanced memory retention. Pretreatment with midazolam prevented the facilitatory effects of those treatments. These findings suggest that the facilitation of learning by post-training memory-enhancing treatments is prevented by midazolam.

To the Editor: We read with interest the article by Schwartz et al.1 on the enhancing effect of d-cycloserine on implicit memory in Alzheimer patients. The findings reported add a note of optimism to the management of memory impairment in Alzheimer's disease (AD). In fact, the N -methyl-D-aspartate (NMDA) type of glutamate receptor channel has been implicated in learning and memory …