Family history of alcoholism and cognitive recovery in subacute withdrawal

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1 Blackwell Publishing AsiaMelbourne, AustraliaPCNPsychiatry and Clinical Neurosciences Blackwell Science Pty LtdFebruary Original ArticleFamily alcoholismy. Moriyama et al. Psychiatry and Clinical Neurosciences (2006), 60, Regular Article Family history of alcoholism and cognitive recovery in subacute withdrawal YASUSHI MORIYAMA, md, 1 TARO MURAMATSU, md, 2 MOTOICHIRO KATO, md, 2 MASARU MIMURA, md 3 AND HARUO KASHIMA, md 2 1 Department of Psychiatry, Komagino Hospital, 2 Department of Neuropsychiatry, Keio University School of Medicine, and 3 Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan Abstract A family history of alcoholism has been demonstrated to be an important factor affecting cognitive function. However, no studies have yet been conducted to compare cognitive recovery of family history-positive (FH+) and family history-negative (FH ) alcoholics in the subacute withdrawal period. To tackle this problem, a neuropsychological test battery consisting of six computerized tests was administered to 19 FH+ and 20 FH alcoholics at 2 and 7 weeks after abstinence. At 2 weeks after abstinence, overall performance of both FH+ and FH groups was significantly poorer than that of healthy controls. At 7 weeks, these performances tended to recover, but in Trail Making A and Figure Position, performances of FH+ alcoholics remained worse than those of controls, while those of FH alcoholics did not. Thus cognitive recovery during the subacute withdrawal period was worse among FH+ alcoholics than FH alcoholics, and this finding should be considered when planning alcohol rehabilitation programs. Key words alcoholics, cognitive recovery, executive function, family history, withdrawal. INTRODUCTION Excessive, chronic alcohol consumption damages the structure and function of the brain, leading to deficiencies in problem-solving, visuospatial and visuomotor skills, and working memory. These impairments are known to be ameliorated by abstinence. Brandt et al. indicated that the greatest return of function takes place in the first week of abstinence. 1 The rate of return slows down rapidly thereafter, leveling off at 3 6 weeks. These impairments are considered to primarily reflect the neurotoxic effects of alcohol on the brain, but investigators pointed out that other factors such as psychiatric comorbidities, neurochemical abnormalities and medical complications also play a role in the cognitive impairment of alcoholics. Accordingly, patterns of cognitive recovery after abstinence are probably influenced by numerous etiological factors and hence could be highly variable. Correspondence address: Yasushi Moriyama, MD, Department of Psychiatry, Komagino Hospital, 273 Uratakao, Hachioji, Tokyo , Japan. yamori@rg7.so-net.ne.jp Received 23 May 2005; revised 27 June 2005; accepted 24 July One factor that may influence cognitive function in alcoholics and has been of great interest to many researchers is genetic predisposition to alcoholism. There has been a substantial body of studies on this topic, comparing alcoholics or healthy subjects with a positive family history of alcoholism (FH+) with those with a negative family history (FH ). 2 4 In general, FH+ alcoholics perform more poorly on a variety of neuropsychological tests than FH alcoholics 4 and even healthy subjects with FH+ exhibit certain subtle neuropsychological or neurophysiological abnormalities. 5 7 Such findings suggest that the unknown genetic factors associated with alcoholism are also associated with vulnerabilities to the neurotoxic effects of alcohol, and/or premorbid deficits in central nervous system function, which could lead to neurocognitive deficits. 3 Although some controversy remains on this topic, family history of alcoholism is conceivably one of the most important factors influencing cognitive performance in any stage of alcoholism, including recovery with abstinence. However, to our knowledge, no studies have compared the cognitive recovery of FH+ and FH alcoholics in the subacute withdrawal period, prompting us to perform the present investigation.

2 86 Y. Moriyama et al. METHODS Subjects Thirty-nine male alcoholic inpatients were recruited for this study from the Alcohol Treatment Unit of Komagino Hospital, Tokyo, Japan. The structured clinical interview from DSM-III-R 8 was used to diagnose alcohol dependence. Age at onset of alcohol dependence was defined as the age when a subject first met DSM-III-R criteria for this. 9 Furthermore, duration of alcohol dependence was defined as the interval between the onset of alcohol dependence and the date of the evaluation. Patients were excluded from the study if they had a history of liver cirrhosis, diabetes mellitus, coronary artery disease, cerebrovascular disease or head injury. Those with a history of other drug dependence or of major psychiatric illness were also excluded. Family histories of alcohol dependence among all biological first-degree relatives were evaluated using the Family History Research Diagnostic Criteria (FH-RDC); 10 Subjects were administered sections of the FH-RDC interview and were classified as family history-positive for alcoholism (FH+) if they met both of the following: (i) a problem with drinking not limited to isolated incidents; and (ii) at least one alcohol-related problem in the following areas: legal, health, marital or family, work, social, and treatment for alcoholism. Thus 19 subjects were classified as FH+ and 20 as FH. Age, education, age at onset of alcohol dependence, duration of alcohol dependence, and duration of daily drinking of FH+ and FH alcoholics did not differ statistically between these two groups (Table 1). The controls were the same as the former study 11 (15-non-alcoholic age- and education- matched male cohorts). Their mean age was 50.4 ± 5.5 years and mean length of education 12.8 ± 3.1 years. Informed consent to participate in this study was obtained from all participants. This study protocol was approved by the local ethics committee of the hospital. Table 1. Demographic variables of alcoholics FH+ FH P Age 49.8 ± ± 5.7 n.s. Education 11.8 ± ± 2.9 n.s. Age at onset of alcohol 35.4 ± ± 6.2 n.s. dependence Duration of alcohol 14.4 ± ± 8.1 n.s. dependence Duration of daily drinking 27.5 ± ± 7.0 n.s. Data are expressed as mean ± SD. The unpaired t-test was used. Neuropsychological tests At approximately 2 and 7 weeks after detoxification (13.4 ± 2.9 days and 48.5 ± 3.8 days, respectively), the six neuropsychological tests were administrated to each subject. This was done in an independent test room between 15:00 and 17:00 hours in order to exclude environmental effects as far as possible. Instruction and stimulus presentation were given by a computer and subjects responded using a touch panel monitor. 12 To exclude the effects of drugs, the first test was administrated after psychotropics had been discontinued for at least 4 days, and no subjects received psychotropic supplementation at the second test. Brief descriptions of each test are provided below. Trail Making A The subject was requested to draw lines to connect 25 consecutively numbered circles that were randomly distributed on the screen. 13 Time of completion was computed. This test is thought to reflect visuomotor and attentional processing. Trail Making B The subject was requested to draw lines to connect 25 consecutively numbered and lettered circles by alternating between the two sequences. 13 Time of completion was computed. As well as testing visuomotor and attentional processing, Trail Making B in particular requires executive functioning with alternating or dividing attention. 14 Figure Position Test The subject was requested to memorize two to four figures (e.g. a triangle and a square) together with their positions among six possible arrangements. The subject was instructed to recall the figures and their positions after 15 s intervals. The summed time for completion was calculated. This test is thought to reflect non-verbal short-term memory or spatial working memory. Symbol Digit Modalities The subject was requested to match a symbol to a digit. 15 The number of correct responses achieved within 60 s (instead of the 90 s used in the original version) was calculated. A maximum of 40 questions were asked. This test is considered to reflect visual-motor processing and divided attention.

3 Family alcoholism 87 Block Design This task was identical to the WAIS-R 16 subtest. The subject was requested to copy a model with four red/ white cards. The summed time for completion was computed. This test is considered to may reflect visuoconstructional ability. Reaction Time The subject was requested to press a button as soon as a red circle appeared on the touch panel monitor. The test included three versions: (i) consecutive brief presentation of red circles only; (ii) random presentation of red, yellow, and blue circles; subjects press a button when a red circle appeared; and (iii) random presentation of red, yellow and blue circles; with subjects having to press a button only when a red circle followed a yellow circle. Each version lasted for 60 s, and the average time of correct reactions was computed. The reaction times in this test are considered to reflect higher attention. Statistical analysis Using an unpaired t-test, test performance of FH+ and FH alcoholics at 2 and 7 weeks was compared to those of healthy controls. The level of statistical significance was set at P < RESULTS Table 2 shows the neuropsychological test performances of each group at the second and seventh week after abstinence and those of healthy controls. As expected, at 2 weeks after abstinence, overall performances of both FH+ and FH groups were significantly poorer than those of controls, other than those for Reaction Time tests. At 7 weeks, these performances tended to recover, but some scores were still worse than those of the controls. Notably by this stage, a significant difference between FH+ and FH alcoholics was found in terms of recovery; in Trail Making A, Figure Position, and Reaction Time (i and iii), performances of FH+ alcoholics remained worse than those of controls, while those of FH alcoholics did not. DISCUSSION The present study examined the relationship between family history of alcoholism and cognitive recovery in alcoholics in the subacute withdrawal stage. Our hypothesis that FH+ alcoholics would perform poorly on neuropsychological tests in this stage was in principle supported. Specifically, at 7 weeks after abstinence, for Trail Making A, Figure Position tests and Reaction Time (i and iii), the performance of FH+ alcoholics remained significantly worse than that of healthy controls, while that of FH alcoholics did not. The tests for which performance was impaired for FH+ alcoholics are thought to reflect working memory or higher attention. These cognitive functions are closely related to executive function. Executive function includes cognitive processes such as planning, response inhibition, working memory, and flexibility of thought and action. In addition, higher attention might be a byproduct of the executive functions of set maintenance and goal-directed activity. Impairment of executive function in alcoholics has been reported in several studies. 17,18 Furthermore, some studies have demonstrated that this deficit is greater in FH+ alcoholics than in FH alcoholics. 4 Table 2. Neuropsychological test performances of FH+ and FH alcoholics 2 weeks 7 weeks FH+ FH FH+ FH Controls Trail Making A (s) 51.2 ± 21.0** 36.7 ± 7.3** 39.0 ± 13.2** 32.8 ± ± 6.8 Trail Making B (s) ± 48.9** 77.3 ± 41.4** 54.8 ± 27.8** 58.1 ± 32.6** 42.7 ± 11.9 Figure Position (s) 26.1 ± 18.1** 18.5 ± 7.6* 19.8 ± 9.8* 14.9 ± ± 4.7 Symbol Digit Modalities (number) 14.8 ± 7.0** 16.5 ± 7.4** 19.9 ± 6.2** 21.4 ± 6.1** 26.2 ± 4.8 Block Design (s) ± 66.8** 92.1 ± 28.1* 73.0 ± 27.8** 67.9 ± 17.9* 55.5 ± 16.7 Reaction Time-i (s) 0.53 ± 0.18** 0.48 ± ± 0.22* 0.44 ± ± ii (s) 0.42 ± ± 0.13* 0.44 ± ± ± iii (s) 0.46 ± ± ± 0.14* 0.47 ± ± 0.04 Significantly impaired as compared with controls: *P < 0.05; ** P < Data are expressed as mean ± SD. The unpaired t-test was used.

4 88 Y. Moriyama et al. However, to our knowledge, our study is the first to tackle this issue in the subacute withdrawal stage. Our results suggest that cognitive recovery of FH+ alcoholics in the subacute withdrawal stage was worse than that of FH alcoholics in the domain of executive function. It is important to emphasize the pilot nature of our report. First, the small sample size precludes generalization of the results. Nonetheless, the FH+ and FH alcoholics included in this study were well matched in terms of age, education, and drinking history. Hence, further studies on this topic using larger samples are warranted. Second, it is unlikely that a single factor such as genetic predisposition to alcoholism is responsible for this impairment of cognitive recovery in the subacute withdrawal stage. Other factors such as psychiatric comorbidities and medical complications should also be investigated. 19 In our study, a history of other drug dependence or major psychiatric illness were excluded. However, earlier study has shown that the sons of alcoholics presented a more neurotic personality profile than sons of non-alcoholics. 20 Therefore, it cannot be ruled out that the anxiety due to the FH+ alcoholic s psycho-economic factors or comorbidity 21 might have influenced the results of the neuropsychological tests. Again, a larger sample is needed. Third, a longer follow-up period will be required to elucidate the nature of the poor performance observed in FH+ alcoholics in this study. Indeed, certain skills have been reported to recover much slower than others. 1,22,23 Among the tests in the present study, performance of Symbol Digit Modalities was demonstrated to be impaired after more than 1 year of abstinence. However, from our study design, it is not clear whether the differences found between FH+ and FH alcoholics are restricted to the subacute withdrawal stage or continue for longer, and if so, for how long. Notwithstanding these limitations, our findings have important implications for the clinical management of alcoholism. In many alcoholic rehabilitation programs, where education is planned to start after the withdrawal syndrome appears to be terminated, cognitive function of each participant is a crucial factor for determining the timing and content of the education program. Our findings suggest that, for alcoholics with a family history of alcoholism, special attention should be paid to this issue. REFERENCES 1. Brandt J, Butters N, Ryan C, Bayog R. Cognitive loss and recovery in long-term alcohol abusers. Arch. Gen. Psychiatry 1983; 40: Schaeffer KW, Parsons OA, Yohman JR. Neuropsychological differences between male familial and nonfamilial alcoholics and nonalcoholics. Alcohol. 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