Cortisol dysregulation and cognitive impairment in abstinent male alcoholics

Background: Alcoholics have impaired cortisol response to stress, indicating dysregulation in the extra-hypothalamic systems responsible for activating cortisol secretion in response to stressor exposure. There is a growing literature indicating a relationship between hypothalamic-pituitary-adrenocortical axis activity and neurocognitive functioning. This study examined the hypothesis that dysregulation of the hypothalamic-pituitary-adrenocortical axis may be associated with some neuropsychological impairments in alcoholics. Methods: Serum cortisol was obtained during cognitive testing and after exposure to cold pressor and mental arithmetic stress in 48 male alcoholics abstinent for 32 +/- 6.7 days and in 30 controls; cortisol was also obtained from 18 of the alcoholic patients during withdrawal. Neurocognitive tasks included the Wechsler Memory Scale and Wisconsin Card Sorting Test. Relationships among alcoholics' cognitive test scores, cortisol levels, and drinking practices were examined by correlation and regression analyses. Results: Verbal memory deficits were more severe in alcoholics who had more withdrawals and ingested a higher typical quantity of alcohol during the prior year (p < 0.05). Higher levels of cortisol during withdrawal, an index of withdrawal severity, were associated with more errors on the Wisconsin Card Sorting Test (p < 0.005). As previously reported, the alcoholics had lower cortisol levels after stress compared with controls. Lower poststress cortisol levels were associated with poorer logical memory on the Wechsler Memory Scale and more errors on the Wisconsin Card Sorting Test (P < 0.05). Among controls, memory deficits occurred only in relation to higher poststress cortisol levels. Conclusions: Poorer cognitive performance in alcoholics was related to more withdrawals, heavier alcohol consumption, and higher cortisol levels during a recent withdrawal. Alcoholics' cognitive impairment was also related to attenuated stress cortisol responses. Altered stress regulation of the hypothalamic-pituitary-adrenal axis should be studied further as a potential factor related to impaired cognitive function in recovering alcoholics.