JAMA Psychiatry Online First

Neurosteroids as Therapeutic Leads in Psychiatry Neurosteroids as Therapeutic Leads in Psychiatry

Zorumski CF, Mennerick S. — Wed, 22 May 2013 00:00:00 GMT

Considerable progress has been made in understanding how neural circuits contribute to mental processing and psychiatric disorders. This research has highlighted the importance of network dysfunction, particularly changes in the balance between excitatory and inhibitory transmission within and across brain regions that underlie cognition, emotion, and motivation. Despite progress, the development of new and more effective treatments for psychiatric disorders has lagged considerably, and present pharmacological treatments represent incremental advances over agents introduced decades ago. One approach for identifying novel treatments has involved studies of neuronal stress responses and how these responses are modulated based on the role that stress plays in psychiatric disorders. In this overview, we describe cholesterol-derived agents (called neurosteroids) that are generated endogenously in the brain and that are important modulators of neuronal stress reactions. We highlight the potential of these agents as targets for therapeutic drug development in several neuropsychiatric illnesses.

Population-Based, Multigenerational Family Clustering Study of Obsessive-Compulsive Disorder Family Clustering in OCD

Mataix-Cols D, Boman M, Monzani B, et al. — Wed, 22 May 2013 00:00:00 GMT

Importance

Controlled family studies have consistently found that obsessive-compulsive disorder (OCD) aggregates in families but have typically relied on samples recruited from specialist clinics. Furthermore, previous studies could not disentangle genetic from environmental factors contributing to the observed familiality.

Objective

To provide unbiased estimates of familial risk for and heritability of OCD at the population level.

Design and Setting

Population-based, multigenerational, case-control family and twin studies using the Swedish National Patient Register, Multi-Generation Register, and Twin Register.

Participants

All individuals diagnosed as having OCD between January 1, 1969, and December 31, 2009 (n = 24 768) and all their available first-, second-, and third-degree relatives, as well as nonbiological relatives and matched general population control subjects. Twins (n = 16 383) were included from the population-based Twin Register.

Main Outcome and Measure

The risk for OCD among relatives of OCD probands.

Results

The risk for OCD among relatives of OCD probands increased proportionally to the degree of genetic relatedness. The risk for first-degree relatives was significantly higher than that for second- and third-degree and nonbiological relatives. Second-degree relatives had higher risk for OCD than third-degree relatives. Relatives at similar genetic distances had similar risks for OCD, despite different degrees of shared environment. Separate twin modeling analyses confirmed that familial risk for OCD was largely attributable to additive genetic factors (47%; 95% CI, 42%-52%), with no significant effect of shared environment. Nonbiological relatives (spouses or partners who have at least 1 child together) also had an elevated risk for OCD (odds ratio, 2.61; 95% CI, 1.99-3.42). Early-onset probands (3907 individuals; mean age, 13.7 years) had slightly (nonsignificantly) higher familial risk than the total sample, although this was substantially lower than previously reported. There were no significant sex differences in the familial pattern or heritability estimates.

Conclusions and Relevance

Obsessive-compulsive disorder clusters in families primarily due to genetic factors. Nonshared environmental factors are at least as important. The finding of possible assortative mating in OCD is intriguing and should be investigated further.

Noncancer Pain Conditions and Risk of Suicide Noncancer Pain Conditions and Risk of Suicide

Ilgen MA, Kleinberg F, Ignacio RV, et al. — Wed, 22 May 2013 00:00:00 GMT

Importance

There are limited data on the extent to which suicide mortality is associated with specific pain conditions.

Objective

To examine the associations between clinical diagnoses of noncancer pain conditions and suicide among individuals receiving services in the Department of Veterans Affairs Healthcare System.

Design

Retrospective data analysis.

Setting

Data were extracted from National Death Index and treatment records from the Department of Veterans Healthcare System.

Participants

Individuals receiving services in fiscal year 2005 who remained alive at the start of fiscal year 2006 (N = 4 863 086).

Main Outcomes and Measures

Analyses examined the association between baseline clinical diagnoses of pain-related conditions (arthritis, back pain, migraine, neuropathy, headache or tension headache, fibromyalgia, and psychogenic pain) and subsequent suicide death (assessed in fiscal years 2006-2008).

Results

Controlling for demographic and contextual factors (age, sex, and Charlson score), elevated suicide risks were observed for each pain condition except arthritis and neuropathy (hazard ratios ranging from 1.33 [99% CI, 1.22-1.45] for back pain to 2.61 [1.82-3.74] for psychogenic pain). When analyses controlled for concomitant psychiatric conditions, the associations between pain conditions and suicide death were reduced; however, significant associations remained for back pain (hazard ratio, 1.13 [99% CI, 1.03-1.24]), migraine (1.34 [1.02-1.77]), and psychogenic pain (1.58 [1.11-2.26]).

Conclusions and Relevance

There is a need for increased awareness of suicide risk in individuals with certain noncancer pain diagnoses, in particular back pain, migraine, and psychogenic pain.