Circulating Cortisol-Associated Signature of Glucocorticoid-Related Gene Expression in Subcutaneous Fat of Obese Subjects.

Circulating cortisol-associated signature of glucocorticoid-related gene expression in subcutaneous fat of obese subjects.

Obesity (Silver Spring). 2013 May; 21(5): 960-7
Pavlatou MG, Vickers KC, Varma S, Malek R, Sampson M, Remaley AT, Gold PW, Skarulis MC, Kino T

Serum cortisol concentrations fluctuate in a circadian fashion, and glucocorticoids exert strong effects on adipose tissue and induce obesity through the glucocorticoid receptor.To examine the impact of physiologic levels of circulating cortisol on subcutaneous adipose tissue, 25 overweight and obese subjects were employed, and their serum levels of morning (AM) and evening (PM) cortisol, AM/PM cortisol ratios, and 24-h urinary-free cortisol (UFC) were compared with their clinical parameters, serum cytokine levels, and mRNA expression of 93 receptor action-regulating and 93 glucocorticoid-responsive genes in abdominal subcutaneous fat.AM cortisol levels did not correlate with mRNA expression of the all genes examined, whereas PM cortisol levels, AM/PM cortisol ratios, and 24-h UFC were associated with distinct sets of these genes. Body mass index did not significantly correlate with the four cortisol parameters employed. These results suggest that physiologic levels of AM serum cortisol do not solely represent biological effects of circulating cortisol on the expression of glucocorticoid-related genes in subcutaneous adipose tissue, whereas PM levels, amplitude, and net amounts of the diurnally fluctuating serum cortisol have distinct effects. Through the genes identified in this study, glucocorticoids appear to influence intermediary metabolism, energy balance, inflammation, and local circadian rythmicity in subcutaneous fat. Our results may also explain in part the development of metabolic abnormality and obesity in subjects under stress or patients with melancholic/atypical depression who demonstrate elevated levels of PM serum cortisol. HubMed – depression

Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders.

J Psychopharmacol. 2013 Jun 19;
Carhart-Harris R, Brugger S, Nutt D, Stone J

Despite the widespread application of drug modelling in psychiatric research, the relative value of different models has never been formally compared in the same analysis. Here we compared the effects of five drugs (cannabis, psilocybin, amphetamine, ketamine and alcohol) in relation to psychiatric symptoms in a two-part subjective analysis. In the first part, mental health professionals associated statements referring to specific experiences, for example ‘I don’t bother to get out of bed’, to one or more psychiatric symptom clusters, for example depression and negative psychotic symptoms. This measured the specificity of an experience for a particular disorder. In the second part, individuals with personal experience with each of the above-listed drugs were asked how reliably each drug produced the experiences listed in part 1, both acutely and sub-acutely. Part 1 failed to find any experiences that were specific for negative or cognitive psychotic symptoms over depression. The best model of positive symptoms was psilocybin and the best models overall were the acute alcohol and amphetamine models of mania. These results challenge current assumptions about drug models and motivate further research on this understudied area. HubMed – depression

Lamotrigine for attention deficit-hyperactivity disorder comorbid with mood disorders: a case series.

J Psychopharmacol. 2013 Jun 19;
Oncü B, Er O, Colak B, Nutt DJ

Attention de?cit-hyperactivity disorder (ADHD) is frequently comorbid with mood disorders in both children and adults. Comorbidity is shown to have negative consequences and it needs to be treated effectively. Lamotrigine, an anticonvulsant indicated for the maintenance treatment of bipolar depression is reported to be effective in adult ADHD comorbid with bipolar II disorder. We conducted a retrospective chart review to identify patients with adult ADHD and comorbid mood disorders on lamotrigine, along with ADHD medications, and/or antidepressants and antipsychotics. We identified 40 patients (17 women, 42.5%; age range 16 – 55 yrs), 50% with bipolar II and 50% with recurrent depression. Their treatment response was evaluated by Clinical Global Impression scales. We found that 31 patients (77.5%) improved with lamotrigine, there was no change in 7 patients (17.5%) and 2 patients got worse, with a mean lamotrigine dose of 125.6 ± 47.8 mg (25 – 250 mg). To our knowledge, this is the first study to report that lamotrigine might be a safe and effective treatment option for adult ADHD comorbid with bipolar and recurrent depression. HubMed – depression

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