Individuals with variations in gamma-amino butyric acid A (GABA_A) receptor genes may be more susceptible to the bipolar disorder phenotype schizoaffective disorder, bipolar type (SABP), study findings suggest.

Variation in these genes was not associated with any other bipolar disorder phenotype, however.

Nick Craddock, from Cardiff University in Wales, UK, and colleagues note that unknown biological validity of current bipolar disorder phenotypes makes it difficult to implicate specific genes or systems in the risk for bipolar disorder, despite compelling evidence for a substantial genetic contribution.

In the recent Wellcome Trust Case Control consortium genome-wide association analysis of bipolar disorder, comprising 1868 patients and 2938 controls, the polymorphisms most strongly associated with the condition lay within the gene encoding the GABA_A receptor ?1 subunit, or GABRB1.

The researchers investigated this association further to determine whether it is specific to certain diagnostic subsets and whether other GABA_A receptor genes are also involved.

Using logistic regression analysis they found that, of 11 clinical phenotypic subsets considered, a subset of 279 bipolar patients who met the Research Diagnostic Criteria for SABP showed the strongest evidence for an association with the GABRB1 risk allele, at the index single nucleotide polymorphism rs7680321, with an odds ratio of 1.80.

By contrast, the remaining 1589 patients with BD had an attenuated association signal for this polymorphism, at an odds ratio of 1.26.

Testing a further 18 genes from the GABA_A receptor gene family in the subset of patients with SABP, the researchers found that five ??” GABRB1, GABRA5, GABRB3, GABRA4, and GABRR3 ??” were significantly associated with the risk for SABP independent of the index signal.

“In our sample, estimates of population attributable fraction were in the range 10??”20% for several of these risk alleles,” note Craddock et al in the journal Molecular Psychiatry.

“This suggests that variation at GABA_A receptor genes make an important contribution to the burden of this disease phenotype in the population.”

The researchers conclude that patients with SABP seem to be more biologically homogenous than bipolar disorder patients as a whole.

Their findings also help explain some of the common comorbidity between bipolar disorder and alcohol abuse, anxiety states, and panic episodes, as GABAergic transmission is strongly implicated in all of them.

“Indeed, it may soon be possible to start developing diagnostic classifications that group disorders together according to underlying pathogenesis,” says the team. “Such a move is likely to be beneficial for etiological research as well as clinical management and would signal a shift from the current situation of a purely descriptive approach.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Patients with bipolar disorder have a worsening response to psychoeducation the more previous episodes they have, a proof-of-concept study suggests.

“Psychoeducation should be delivered as soon as possible in the illness course, supporting the idea of early intervention,” say Eduard Vieta, from the University of Barcelona in Spain, and colleagues.

The researchers analyzed data on 120 euthymic bipolar patients who participated in a 5-year study on the efficacy of psychoeducation in the prophylaxis of recurrences in bipolar disorder.

They determined the efficacy of psychoeducation, compared with no psychoeducation, on two outcome measures ??” recurrence and time spent ill.

The risk for recurrence was defined as the time elapsed between baseline and the emergence of a new acute episode (Young Mania Rating Scale [YMRS] score ?20 for manic recurrence; YMRS ?12 for hypomanic recurrence; Hamilton Depression Rating Scale [HDRS] score ?17 for depressive recurrence; HDRS ?12 and YMRS ?20 for mixed recurrence). Time spent ill was judged to be the number of days in which patients fulfilled criteria for a specific episode.

Patients with six or fewer episodes experienced a significant improvement in the time to recurrence compared with patients not receiving psychoeducation. However, there was no significant benefit in patients with seven or more previous episodes.

More than 14 previous episodes were needed before the benefit of psychoeducation was no longer significant with regard to time spent ill.

Patients with nine to 14 episodes showed a benefit in terms of fewer days spent in hypomania and depression but not in mixed states or mania, while patients with up to seven or eight episodes had a benefit in terms of fewer days spent in hypomania, depression, mixed episodes, or any episodes but not mania.

The researchers note that only patients presenting with up to six episodes showed a reduction in time spent in any episode polarity.

The team suggests that patients with more previous episodes may have greater difficulty in changing habits and so benefit less from psychoeducation. [sggn] Alternatively, and more positively, patients with more episodes may as a result have a longer experience in the management of their disorder and so benefit less from the therapy.

Vieta et al note in the journal Acta Neuropsychiatrica that their study had a number of limitations, including not being powered for the outcome tested and some retrospective data collection.

Nevertheless, they conclude that “the present data may have clinical relevance, pointing at the need to start psychoeducation promptly.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Patients with bipolar disorder who experience frequent mood episodes show a greater level of life disruption than their peers with less frequent episodes, results of a large community study show.

The investigators also found that only about half of those with recent bipolar disorder report treatment for depression or mania/hypomania.

“It seems that efforts to encourage access to treatment and maintenance of treatment could do much to ameliorate the course of disorder,” say J Elisabeth Wells (University of Otago, Christchurch, New Zealand) and colleagues in the Journal of Affective Disorders.

A number of cross-sectional epidemiological studies have examined the prevalence of bipolar disorder ??” with estimates ranging from 0.5% for euphoric-grandiose bipolar I disorder to 5.5% for generally defined bipolar disorder.

However, most such studies have not collected information on the frequency of mood episodes, and it remains unclear to what extent disability results from rapid cycling or from the severity of mood episodes regardless of frequency.

The New Zealand Mental Health Survey is a national cross-sectional survey with a multi-stage probability sample of individuals aged 16 years or more living in the community.

From a total sample size of 12,992, the lifetime prevalence of broadly defined bipolar disorder was 3.8% ??” with a prevalence of 1.0% for bipolar I disorder and 0.7% for bipolar II disorder.

When lifetime bipolar disorder cases were grouped by mood episode frequency in the past 12 months, the prevalence was 0.3% with frequent mood episodes (FME), 0.7% with 1??”3 episodes (no FME), and 0.7% with no episodes.

Patients with 12-month FME had earlier onset of bipolar disorder than 12-month cases without FME or those with lifetime bipolar disorder but with no episode in the past 12 months ((16.0 vs 19.5 and 20.1 years, respectively).

The number of weeks in episode, total days out of role, and role impairment in were all worse for the FME group. Both the FME and no-FME groups experienced severe and impairing depression, and lifetime suicidal behaviors and comorbidity were high in all three bipolar groups with little difference between them.

“In summary, these results indicate that predictors and correlates are similar in those with and without FME but that the burden of bipolar disorder is more for those with frequent episodes,” Wells and colleagues conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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