PREDICT RELAPSE IN ALCOHOL-DEPENDENT PATIENTS

Advances in technology show that, with chronic alcoholism, the brain’s grey matter shrinks and  the volume is linked to relapse. Even newer cutting-edge research predicts the length of time it takes for recently-abstinent patients to relapse. Add this knowledge to your relapse-prevention techniques.

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Too many alcohol-dependent people who stop drinking relapse in months. But advances in technology allow us to identify ‘biomarkers’ in newly abstinent patients to measure susceptibility to relapse – which can then be compensated for during treatment to reduce the risk.

An increasing volume of research has already shown that, in chronic alcoholism, the brain’s grey matter shrinks in many cortical and subcortical areas and in the cerebellum, and that these deficits are more severe in alcoholics who relapse than in those who abstain.

Wrase and colleagues also recently reported smaller amygdala volumes in relapsed compared with abstinent alcoholics.

But no one assessed if brain volumes during sustained alcohol abstinence could predict length of time to relapse. Then a study led last year by Rajita Sinha for the departments of psychiatry and neurobiology at Yale University School of Medicine showed that low grey-matter volumes in the prefrontal cortex could do this.

Using high-resolution structural magnetic resonance imaging, researchers examined grey-matter volumes in specific brain areas of 35 male and 10 female hospitalised alcohol-dependent (they met DSM-IV diagnostic criteria) patients after one month of abstinence compared with 50 social-drinking healthy comparison subjects. All the alcohol-dependent patients were followed with face-to-face interviews at 14, 30 and 90 days after leaving inpatient treatment.

The researchers expected to find grey-matter volume deficits in alcohol dependents relative to the healthy comparison group, and a link between grey-matter deficits and prior history of chronic alcohol abuse. They also hypothesised that grey matter volume deficits in the medial frontal regions – which play an important role in behavioural control and decision making – would be independently predictive of shorter time to alcohol relapse. They were right.

To start, there were no differences between the alcohol-dependent and healthy comparison groups in sex, race and lifetime prevalence of mood and anxiety disorders. The patient group was older on average and had a lower mean IQ. Unexpectedly, the patient group also had a significantly higher mean number of days of alcohol use, a greater mean number of drinks per day and years of alcohol use.
The patients were followed for 90 days after discharge. After adjustments for age and IQ, they had lower grey-matter volumes than controls in three clusters: the lateral prefrontal cortex, medial frontal areas including regions in the cingulate gyrus, and parieto-occipital cortical areas. Alcohol use information – pooled from the Substance use Calendar, urine and breath test results and collateral information – indicated that relapse rates were 25% at day 14, 43% at day 30 and 68% at day 90.

Hazard ratios indicated that, for each 1ml reduction in grey-matter volume in the medial frontal cluster and in the parietal-occipital cluster, there was a 48% increase in risk of earlier relapse. After further adjustment for years of alcohol use and total alcohol consumed in the 90 days before treatment, smaller grey-matter volume in these two clusters predicted shorter time to relapse to heavy drinking, by 44% and 45% respectively.

This study did not establish a link with functional impairment, but the volume deficits in the medial frontal cortical cluster suggest disruption of cognitive control functions linked to atrophy in these regions. This could weaken a recovering alcohol-dependent patient’s ability to override strong, habitual responses to environmental cues, stress or otherwise cognitively challenging situations, and increase his/her susceptibility to relapse.

It is possible that overall grey-matter volume loss, as well as the degree of grey-matter recovery during abstinence, can effect impulse control and thus increase risk of relapse.

The impact of parietal-occipital areas on alcohol relapse is unclear. But tests suggest that male alcoholics invoked executive processes to perform at normal levels, while male control subjects used basic visuoperceptual processes. It might be that inefficient use of higher executive processes to perform low-level cognitive tasks could drain reserves of higher-level attentional capacity needed for recovery cognitive demands. The study found that reduced grey matter in visual-processing areas of alcohol-dependent subjects did predict shorter time to relapse.

In other analyses, researchers correctly identified 80% of relapsers by using cut-off values based on the medial frontal cluster volumes.

THREE CLINICAL IMPLICATIONS

There are important clinical implications to the findings. First, MRI volume assessment of medial frontal and posterior parietal-occipital brain regions could be developed as neural markers for identifying alcoholic patients at highest risk of relapse and treatment failure.

Second, use of such neural markers in clinical assessment could inform treatment planning by prescribing tailored interventions to improve brain atrophy and linked function early in abstinence in alcoholics at greatest risk of relapse.

Third, data in the study supports the development of pharmacological and other neural therapies which promote neurogenesis and cell proliferation to increase grey-matter volume in critical regions, to cut risk of relapse and promote recovery from alcoholism.

Addiction Today note: Castle Craig Hospital in Scotland is ahead of the game here in that it has installed an oxygen hyperbaric chamber as part of its “neurogenesis wellness programme”which it is now developing.

Association of frontal and posterior cortical gray matter volume with time to alcohol relapse is a 10-page research paper published in AJP in Advance (doi:10.1176/appi.ajp.2010.10020233).