Objective: Although there have been case reports suggesting a relationship between treatment with the acne medication isotretinoin and the development of depression and suicide, this topic remains controversial. In order for isotretinoin to cause depression, it must have an effect on the brain; however, the effects of isotretinoin on brain functioning in acne patients have not been established. The purpose of this study was to assess the effects of isotretinoin on brain functioning in acne patients. Results: Isotretinoin but not antibiotic treatment was associated with decreased brain metabolism in the orbitofrontal cortex (-21% change versus 2% change for antibiotic), a brain area known to mediate symptoms of depression. There were no differences in the severity of depressive symptoms between the isotretinoin and antibiotic treatment groups before or after treatment. Conclusions:This study suggests that isotretinoin treatment is associated with changes in brain functioning.

Objective To clarify the relationship between depression and heart rate variability (HRV) in a sample of twins. Reduced HRV, a measure of autonomic dysfunction, has been linked to depression but many studies have inadequately controlled for familial and environmental factors. Furthermore, little is known about whether depression and HRV share common genetic pathways. Methods We performed power spectral analysis on 24-hour ambulatory electrocardiograms in 288 middle-aged male twins. Log-normalized ultra low, very low, low, high frequency, and total power were calculated. A lifetime history of major depressive disorder (MDD) was determined, using the Structured Clinical Interview for Psychiatry Disorders, and current depressive symptoms were measured with the Beck Depression Inventory. Mixed-effect regression models were used to account for intrapair variability and estimate within-pair effects at the same time controlling for potential confounders. Results Both current depressive symptoms and a history of MDD were significantly associated with lower HRV. There was a graded effect, and power in each frequency band was 29% to 36% lower in the lowest band compared with the highest BDI category. All HRV measures except high frequency remained significantly associated with current depressive symptoms in multivariable analysis, but not with lifetime history of MDD. When analyses were stratified by zygosity, a significant within-pair association between BDI score and HRV was found in the dizygotic but not in the monozygotic twins, suggesting a genetic influence on the association. Conclusions A shared, genetically influenced biological pathway underlies the association between depression and lower HRV. These two phenotypes may be the expression of a generalized neurobiological perturbation.

Introduction One possible mechanism of higher cardiovascular mortality associated with the metabolic syndrome (MetS) may be through abnormal modulation in autonomic tone. Methods and Results We examined the association between the MetS and autonomic tone as measured by heart rate variability (HRV) among 288 twins from the Twins Heart Study. Of the 288 participants, 151 (52%) had the MetS. The MetS was associated with decreased HRV across all frequency ranges, and each additional MetS risk factor was associated with lower HRV. After adjustment for several potential confounders, very-low frequency (p<0.001), low frequency (p<0.001), and total power (p=.02) spectra of HRV remained significantly lower in twins with a progressively higher number of MetS components (18-50% decrease comparing twins with 5 risk factors to those with no risk factors). Among 87 twin pairs who were discordant for the number of MetS components, a one-unit increment in MetS components was associated with an 8% smaller very-low frequency (p=0.03) and a 15% smaller low frequency spectrum (p=0.002) comparing each twin with his brother. Conclusion MetS was associated with lower HRV in a well-characterized sample of middle-aged male twins. This association persisted even after controlling for genetic and shared environmental factors accounted for by comparison within twin pairs. Abnormalities of autonomic tone, as evidenced by lower HRV, may be partly responsible for the higher rate of atrial fibrillation, coronary heart disease, cardiac death, and overall mortality seen in patients with the MetS.

Neuroimaging studies of individuals with posttraumatic stress disorder (PTSD) have revealed altered patterns of activity in medial prefrontal brain regions, including the anterior cingulate cortex (ACC), an area implicated in affect regulation. Selective serotonin reuptake inhibitors (SSRIs) have been shown to effectively treat PTSD symptoms, but there remains a lack of functional neuroimaging research examining the effects of psychopharmacological treatment on brain function in PTSD. The purpose of this pilot study was to assess the effects of the SSRI paroxetine on neural responses to traumatic memories in a small sample of patients with PTSD, as measured with PET imaging; we hypothesized that paroxetine treatment would be associated with increased regional cerebral blood flow (rCBF) in the medial prefrontal cortex. Thirteen participants with PTSD were given controlled-release paroxetine (paroxetine CR) or placebo in a randomized, double-blind fashion for 12 weeks. Participants underwent brain imaging using positron emission tomography (PET) before and at the end of treatment in conjunction with exposure to neutral scripts and personalized trauma scripts. Participants treated with paroxetine CR and placebo both exhibited significantly increased rCBF in the ACC during trauma versus neutral script presentations; however, we noted an increase in function in the orbitofrontal cortex (OFC) in paroxetine-treated (but not placebo-treated) participants. Participants in both groups showed decreases in overall PTSD symptomatology following treatment; paroxetine-treated participants showed a slightly greater percentage decrease in symptoms. These preliminary findings indicate that increased ACC function represents a nonspecific response to treatment, whereas increased OFC function is specifically associated with paroxetine treatment in PTSD. These pilot data reveal putative mechanisms for SSRI treatment in PTSD and substantiate the need for large-scale placebo-controlled studies investigating these effects.

Background Why do some patients suffer acute myocardial ( ) infarction MI despite angiographically normal coronary arteries ( ) NL+ MI whereas others enjoy an acute MI-free life despite ( ) extensive three-vessel disease 3VD-MI ? The present study contrasts these two groups to identify some differences in the risk profile. MethodsIn 10 000 patients admitted to the cardiology service, a first MI was confirmed in 2356 patients, of whom 1609 underwent coronary angiography. In 77 patients with MI, ( coronary angiography was found to be entirely normal NL+ MI, ) 77/ 1609, 4.1% . These were contrasted to 123 patients with ( ) severe three-vessel coronary disease but no MI 3VD-MI .( Results Patients with NL+ MI were 13 years younger 42" 8.3 ) ( ) vs 55" 10.5, P -0.05 , with 33 patients 43% under the ( ) age 40 years, in contrast to only 9 patients 7.3% in the 3VD group being this age. Patients with NC + MI were more often ( ) current smokers 80.5% vs 29% in the 3VD group; P -0.01 . Patients with 3VD-MI were, on the other hand, more often ( ) diabetic 54% vs 9% in the NL+ MI group; P -0.01 and had ( a higher cholesterol level 5.6" 1.1 vs 4.9" 1.0 Mmol / l, ) P -0.01 as well as a higher incidence of chronic stable ( ) ( angina 52% vs 22%; P -0.01 and heart failure 6% ) compared with 0% in the NL+ MI group . Sixty-one out of 77 ( ) 79% NL+ MI patients had a single risk factor, and in 87%, this was smoking alone. Diabetes mellitus was rare and never occurred alone in this group. ConclusionIn patients who suffer MI despite normal coronary angiography, smoking is a major risk factor: In contrast, in patients with extensive coronary artery disease on angiography but no MI, diabetes rather than smoking is the dominant risk factor. The findings of this study support the view that the risk factors for stable and unstable coronary artery disease are different, as reflected by the contrast of the above groups at the extremes of the spectrum. Smoking appears to be a major ( risk factor for acute MI even with normal coronary ) angiography , whereas diabetes is a major risk factor for more severe but more stable coronary artery disease.