Increased glutamate levels in the medial prefrontal cortex in patients with postpartum depression.

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.

Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women.

OBJECTIVE: To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002. RESULTS: Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects. CONCLUSIONS: Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00620581.

Prevalence and relationship to delusions and hallucinations of anxiety disorders in schizophrenia.

We investigated the prevalence of anxiety disorders in a sample of individuals with chronic schizophrenia, controlling for anxiety symptoms that may be related to delusions and hallucinations, and the possible differences in clinical variables between the groups. Individuals with a diagnosis of schizophrenia and able to give informed consent were recruited from the community. The Mini International Neuropsychiatric Interview (MINI) was administered to both confirm the DSM-IV diagnosis of schizophrenia and screen for comorbid anxiety disorders. If a comorbid anxiety disorder was found, its relation to the individual's delusions and hallucinations was examined. Clinical rating scales for schizophrenia were administered as well as rating scales for specific anxiety disorders where appropriate. Overall, anxiety disorders ranged from 0% [ for Post Traumatic Stress Disorder (PTSD)] to 26.7% [ for generalized anxiety disorder (GAD) and agoraphobia without panic] with lower rates when controlled for anxiety symptoms related to delusions and hallucinations. In investigating clinical variables, the cohort was initially divided into schizophrenics with no anxiety disorders and those with an anxiety disorder; with further analyses including schizophrenics with anxiety disorders related to delusions and hallucinations and those with anxiety disorders not related to delusions and hallucinations. The most consistent difference between all the groups was on the PANSS-G subscale. No significant differences were found on the remaining clinical variables. Comorbid anxiety disorders in schizophrenia can be related to the individual's delusions and hallucinations, though anxiety disorders can occur exclusive of these positive symptoms. Clinicians must be aware that this comorbidity exists in order to optimize an individual's treatment.