Psychiatry and Clinical Neurosciences (2006), 60, 85–89
Blackwell Publishing AsiaMelbourne, AustraliaPCNPsychiatry and Clinical Neurosciences1323-13162005 Blackwell Science Pty LtdFebruary 20066018589Original ArticleFamily alcoholismY. Moriyama et al.
Correspondence address: Yasushi Moriyama, MD, Department of Psychiatry, Komagino Hospital, 273 Uratakao, Hachioji, Tokyo 193-8505, Japan. Email: yamori@rg7.so-net.ne.jp
Received 23 May 2005; revised 27 June 2005; accepted 24 July 2005.
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, md3 AND HARUO KASHIMA, md2
1Department of Psychiatry, Komagino Hospital, 2Department of Neuropsychiatry, Keio University School of Medicine, and 3Department 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
con-trols, while those of FH– alcoholics did not. Thus cognitive recovery during the subacute
with-drawal 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 deficien-cies 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 abnormali-ties and medical complications also play a role in the cognitive impairment of alcoholics. Accordingly, pat-terns of cognitive recovery after abstinence are proba-bly influenced by numerous etiological factors and hence could be highly variable.
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– alcoholics4 and
even healthy subjects with FH+ exhibit certain subtle
neuropsychological or neurophysiological
abnormali-ties.5–7 Such findings suggest that the unknown genetic
factors associated with alcoholism are also associated with vulnerabilities to the neurotoxic effects of alco-hol, 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 perfor-mance in any stage of alcoholism, including recovery with abstinence. However, to our knowledge, no
stud-ies have compared the cognitive recovery of FH+ and
FH– alcoholics in the subacute withdrawal period, prompting us to perform the present investigation.
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
clin-ical interview from DSM-III-R8 was used to diagnose
alcohol dependence. Age at onset of alcohol depen-dence 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 dis-ease 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 evalu-ated using the Family History Research Diagnostic
Criteria (FH-RDC);10 Subjects were administered
sec-tions 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
study11 (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.
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
alter-nating between the two sequences.13 Time of
comple-tion 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 work-ing 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 ver-sion) was calculated. A maximum of 40 questions were asked. This test is considered to reflect visual-motor processing and divided attention.
Table 1. Demographic variables of alcoholics
FH+ FH– P
Age 49.8 ± 5.8 50.1 ± 5.7 n.s.
Education 11.8 ± 2.9 12.5 ± 2.9 n.s. Age at onset of alcohol
dependence
35.4 ± 7.2 37.3 ± 6.2 n.s. Duration of alcohol
dependence
14.4 ± 8.6 12.5 ± 8.1 n.s. Duration of daily drinking 27.5 ± 6.6 26.6 ± 7.0 n.s. Data are expressed as mean ± SD. The unpaired t-test was used.
Family alcoholism 87
Block Design
This task was identical to the WAIS-R16 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 visuo-constructional 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 pre-sentation of red circles only; (ii) random prepre-sentation of red, yellow, and blue circles; subjects press a button when a red circle appeared; and (iii) random presenta-tion of red, yellow and blue circles; with subjects hav-ing to press a button only when a red circle followed a yellow circle. Each version lasted for 60 s, and the aver-age time of correct reactions was computed. The reac-tion 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< 0.05.
RESULTS
Table 2 shows the neuropsychological test perfor-mances of each group at the second and seventh week after abstinence and those of healthy controls. As expected, at 2 weeks after abstinence, overall
perfor-mances of both FH+ and FH– groups were
signifi-cantly poorer than those of controls, other than those for Reaction Time tests. At 7 weeks, these perfor-mances 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 princi-ple 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 con-trols, 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 func-tions 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 Controls FH+ FH– FH+ FH– Trail Making A (s) 51.2 ± 21.0** 36.7 ± 7.3** 39.0 ± 13.2** 32.8 ± 11.2 30.2 ± 6.8 Trail Making B (s) 100.4 ± 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 ± 4.4 14.2 ± 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) 114.7 ± 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 ± 0.21 0.47 ± 0.22* 0.44 ± 0.14 0.37 ± 0.05 -ii (s) 0.42 ± 0.10 0.43 ± 0.13* 0.44 ± 0.13 0.40 ± 0.07 0.37 ± 0.04 -iii (s) 0.46 ± 0.20 0.53 ± 0.20 0.48 ± 0.14* 0.47 ± 0.14 0.44 ± 0.04 Significantly impaired as compared with controls: *P< 0.05; **P< 0.01.
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+
alcohol-ics 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
generali-zation 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 respon-sible for this impairment of cognitive recovery in the subacute withdrawal stage. Other factors such as psy-chiatric 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
per-sonality profile than sons of non-alcoholics.20
There-fore, it cannot be ruled out that the anxiety due to
the FH+ alcoholic’s psycho-economic factors or
comorbidity21 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
perfor-mance 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 with-drawal syndrome appears to be terminated, cognitive function of each participant is a crucial factor for deter-mining the timing and content of the education pro-gram. 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: 435–442.
2. Schaeffer KW, Parsons OA, Yohman JR. Neuropsycho-logical differences between male familial and nonfamilial alcoholics and nonalcoholics. Alcohol. Clin. Exp. Res. 1984; 8: 347–351.
3. Alterman AI, Gerstley LJ, Goldstein G, Tarter RE. Comparisons of the cognitive functioning of familial and nonfamilial alcoholics. J. Stud. Alcohol 1987; 48: 425– 429.
4. Schaeffer KW, Parsons OA, Errico AL. Abstracting def-icits and childhood conduct disorder as a function of familial alcoholism. Alcohol. Clin. Exp. Res. 1988; 12: 617–618.
5. Drejer K, Theilgaard A, Teasdale TW, Schulsinger F, Goodwin DW. A prospective study of young men at high risk for alcoholism: neuropsychological assessment. Alcohol. Clin. Exp. Res. 1985; 9: 498–502.
6. Tarter RE, Jacob T, Bremer DL. Specific cognitive impairment in sons of early onset alcoholics. Alcohol. Clin. Exp. Res. 1989; 13: 786–789.
7. Corral M, Holguín SR, Cadaveira F. Neuropsychological characteristics of young children from high-density alco-holism families: a three-year follow-up. J. Stud. Alcohol 2002; 64: 195–199.
8. Spitzer RL, Williams JBW, Gibbon M, First MB. Struc-tured Clinical Interview for DSMIII-R (SCID): User’s Guide. American Psychiatric Press Inc., Washington, DC, 1990.
9. Yoshino A, Kato M. Prediction of 3-year outcome of treated alcoholics by an empirically derived multivariate typology. Am. J. Psychiatry 1996; 153: 829–830.
10. Endicott J, Andreasen NC, Spitzer RL. Family History-Research Diagnostic Criteria (FH-RDC), 3rd edn. New York State Psychiatric Institute, New York, 1978. 11. Kato A, Kato M, Ishii H et al. Development of
quantita-tive neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria – multicenter collab-orative study. Hepatol. Res. 2004; 30: 71–78.
12. Reitan R. Trail Making Test: Manual for Administration, Scoring, and Interpretation. Indiana University, Bloom-ington, 1956.
13. Trannel D, Anderson SW, Benton A. Development of the concept of executive function and its relationship to the frontal lobes. In: Boller F, Grafman J (eds). Hand-book of Neuropsychology, Vol. 9. Elsevier, New York, 1994; 125–148.
14. Smith A. Symbol Digit Modalities Test. Manual. Western Psychological Services, Los Angeles, 1973.
15. Wechsler D. WAIS-R Manual: Wechsler Adult Intelli-gence Scale-Revised. Harcourt Brace & Jovanovich, New York, 1981.
16. Moriyama Y, Mimura M, Kato M et al. Executive dys-function and clinical outcome in chronic alcoholics. Alco-hol. Clin. Exp. Res. 2002; 26: 1239–1244.
17. Zinn S, Stein R, Swartzwelder S. Executive functioning early in abstinence from alcohol. Alcohol. Clin. Exp. Res. 2004; 28: 1338–1346.
18. Mann K, Günther A, Stetter F, Ackermann K. Rapid recovery from cognitive deficits in abstinent alcoholics: a
Family alcoholism 89
controlled test–retest study. Alcohol. Alcohol 1999; 34: 567–574.
19. Schafer K, Butters N, Smith T et al. Cognitive perfor-mance of alcoholics: a longitudinal evaluation of the role of drinking history, depression, liver function, nutrition, and family history. Alcohol. Clin. Exp. Res. 1991; 15: 653–660.
20. Tarter RE, Andrea M, Hegedus MPA et al. Adolescent sons of alcoholics: neuropsychological and personality characteristics. Alcohol. Clin. Exp. Res. 1984; 8: 216–222.
21. Nurnberger JI, Wiegand R, Bucholz K et al. A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands. Arch. Gen. Psychiatry 2004; 61: 1246–1256.
22. Parsons OA, Nixon SJ. Neurobehavioral sequelae of alcoholism. Neurol. Clin. 1993; 11: 205–218.
23. Yohman JR, Parsons OA, Leber WR. Lack of recovery in male alcoholic’s neuropsychological performance one year after treatment. Alcohol. Clin. Exp. Res. 1985; 9: 114–117.
