Deterioration of intelligence in methamphetamine-induced psychosis: Comparison with alcohol dependence on WAIS-III
*Shih-Ku Lin, MD, 309 Songde Road, Taipei City Psychiatric Center, Taipei 110, Taiwan. Email: firstname.lastname@example.org
Aims: Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration.
Methods: The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 ± 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 ± 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III).
Results: The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 ± 10.8, 84.3 ± 11.9, 81.9 ± 12.1, 85.5 ± 11.9, 84.7 ± 12.5, 85.4 ± 13.6, and 78.5 ± 12.7 in MIP patients and 90.5 ± 12.0, 95.2 ± 11.3, 86.0 ± 13.7, 95.5 ± 11.0, 87.1 ± 14.5, 96.2 ± 13.1, and 84.5 ± 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was <70 and 13 (38.2%) whose full-scale IQ was <85 and >70, while one AD patient had a full-scale IQ <70 (2.9%) and 10 (22%) had full-scale IQ <85 and >70.
Conclusions: Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients.
METHAMPHETAMINE ABUSE IS an increasingly serious problem in many countries. Chronic misuse of stimulants may damage brain cells, cause neurotoxicity and lead to long-lasting impairment in brain function.1–3 In animal studies, methamphetamine was demonstrated to cause damage to dopaminergic and serotonergic neurons,4,5 leading to permanent change in both systems in select areas of the brain.6,7 Long-term use of methamphetamine could also lead to the emergence of psychotic symptoms, such as paranoid ideation, persecutory delusion, auditory and visual hallucination and thereby to a diagnosis of methamphetamine-induced psychosis (MIP), which sometimes is difficult to differentiate from paranoid schizophrenia. Clinically, MIP is not an uncommon disorder in epidemic areas, and management is mainly focused on the amelioration of psychosis using antipsychotics, yet the complication of cognitive deterioration of the addicts is seldom noted. Previous reports of neuropsychological examination on methamphetamine-dependent individuals have shown a mild degree of impairment in the domains of attention and memory.8,9 In a well-designed study of the neuropsychological function of 78 amphetamine users, McKetin and Mattick reported that the severity of amphetamine dependence was found to be associated with poorer performance on both memory and attention/concentration indices of the Wechsler Memory Scale–Revised.10 In a comparison study, Ornstein et al. compared amphetamine and heroin abusers, together with age- and IQ-matched control subjects on a neuropsychological test battery that included both conventional tests and also computerized tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting.11 They found that chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card-Sorting Test); whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. The authors concluded that the two groups were profoundly but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of corticostriatal circuitry. Long-term use of methamphetamine can also result in psychosis and morphological change in certain areas of the brain.12
Alcohol is also a popular substance that has been widely used throughout the world. Long-term use of alcohol can also lead to numerous physical consequences including liver disease, gastrointestinal problems, neurological complications, and psychosocial function deterioration.13–15 In severe cases gross deficits may be evident, including Wernicke's encephalopathy,16 Korsakoff's syndrome and alcohol-related dementia.17 Chronic intake of ethanol both in human and rat results in a substantial impairment in memory function associated with a reduction in the number of cholinergic neurons in the basal forebrain that give rise to the cholinergic afferentation of the cortical mantle.18 Neuropsychological studies have demonstrated poor functioning on tests of visuospatial, executive, and memory functioning in alcohol-dependent (AD) adults compared with demographically matched controls.19
The Wechsler Adult Intelligence Scale (WAIS) is a tool to measure multiple aspects of cognitive function, and is widely used in clinical and educational settings. The third edition of the WAIS (WAIS-III) consists of 13 primary subtests (Object Assembly was excluded and three new subtests Matrix Reasoning, Symbol Search, and Letter–Number Sequencing were added),20 as compared with its predecessor, the Wechsler Adult Intelligence Scale–Revised (WAIS-R). The scoring is based on deviation from the norm. IQ score <1 SD (15, i.e. <85) is considered as borderline intelligence and 2 SD (30, i.e. <70) as mild mental retardation. The translation and standardization of the Chinese version (Taiwan) of the WAIS-III was carried out by its developers and revisers by examining 888 normal subjects aged between 16 and 84.21 The WAIS-R has been used for many drug abuses and chronic alcoholic subjects.22–26 Most of the studies showed that long-term use of substances or alcohol would result in impairment of their cognitive function to some degree. For WAIS-III, Ryan et al. tested 100 men in a treatment program for substance abuse disorders and found an average full-scale IQ (FSIQ) of 93.8 ± 14.0 with verbal IQ (VIQ) and performance IQ (PIQ) of 95.3 ± 13.6 and 93.0 ± 13.9, respectively.27 The aim of the present study was therefore to investigate the performance of MIP patients on the WAIS-III, and use AD patients as a comparison.
Thirty-four DSM-IV diagnosed MIP patients and 34 AD patients hospitalized in Taipei City Psychiatric Center were recruited and each provided informed consent. The main reasons for hospitalization were to treat psychotic symptoms such as auditory hallucination, delusion of persecution, and disturbed behaviors for MIP patients; and alcohol withdrawal syndrome for AD patients. Patients who had comorbid non-nicotine substance abuse or dependence; had significant physical illnesses, had other major psychiatric disorders, such as schizophrenia, bipolar disorder, or major depressive disorder were excluded. We collected the subjects' sociodemographic data (age, gender, educational level, marital and occupational status), as well as methamphetamine (exclusively by vapor sniffing) or alcohol use history, including age at first use and duration of regular use. MIP patients were treated with antipsychotics (mostly second generation) and AD patients received a fixed-dose schedule of alcohol detoxification treatment with oral lorazepam 8 mg/day in four divided doses, with gradual tapering off in 1 week. Table 1 lists the demographic data. The mean age in the MIP group was 28.7 ± 6.1 years, much younger than the AD group (40.7 ± 7.3 years). Both groups of patients began to use substances from adolescence. The mean duration of regular use of methamphetamine was 6.1 ± 3.5 years, significantly shorter than the regular drinking in the AD group (13.3 ± 7.7 years). The mean duration of years of education was not different between the two groups.
Table 1. Subject characteristics
|n (M/F)||34 (28/6)||34 (32/2)|
|Age (years)||28.0 ± 5.9||40.2 ± 7.2*|
|Years of education||10.4 ± 1.8||11.1 ± 2.8|
|Age at onset (years)||18.6 ± 4.6||18.6 ± 4.9|
|Duration of regular use (years)||6.1 ± 3.5||13.6 ± 7.4*|
Chinese version of the WAIS-III was administered to all subjects by a trained clinical psychologist. In the MIP group, patients received examination after psychotic symptoms had subsided for at least 2 weeks. The mean dose of haloperidol-equivalent antipsychotics was 3.9 ± 2.9 mg/day while performing the test. In the AD group they received the test after detoxification for at least 2 weeks. The mean dose of lorazepam-equivalent benzodiazepines was 3.9 ± 2.1 mg/day during the test.
Due to the unavailability of pre-morbid IQ data for clinical subjects, the demographic information estimation formula index (DI) developed by Barona et al. was applied.28 This method provided a quick and accurate estimation of premorbid abilities for the majority of subjects. In this method individual demographic variables such as age, sex, race, education, occupation, rural–urban residence, geographic residence, and handedness were used in predicting premorbid IQ on the WAIS-R. Because all subjects were Han-Chinese and lived in a northern metropolitan area in Taiwan, we set 2 for race score and 3 for region score, respectively, in the estimation formula.
Categorical variables were analyzed on χ2 test or Fisher's exact test. Independent-sample t-tests were used for comparison of continuous variables. The significant threshold was set at P < 0.05. Data were analyzed using SPSS for Windows (version 10.0, SPSS, Chicago, IL, USA).
More male patients in both groups were recruited. Table 2 lists the results of WAIS-III from both groups. All patients completed the full examination subsets except for Letter–Number Sequencing (15 patients in MIP group and 18 in AD group received this subset test). The mean FSIQ was 82.3 ± 10.8 in MIP patients, significantly lower than that of AD patients. VIQ, but not PIQ was significantly lower in MIP patients. In the subsets, the difference of vocabulary, arithmetic, digit span, information, comprehension and symbol search all reached a significant level. In indexes, verbal comprehension and working memory reached a significant level. Table 3 lists the comparison of current and estimated premorbid IQ scores (DI method) between the two groups. Premorbid FSIQ and PIQ were significantly higher than the current scores for both groups, while for VIQ, MIP but not AD subjects had significant decrease.
Table 2. Wechsler Adult Intelligence Scale scores
|Vocabulary||6.4 ± 2.2||8.5 ± 2.5||0.00|
|Similarities||7.8 ± 2.4||8.8 ± 1.9||0.07|
|Arithmetic||6.9 ± 2.0||8.6 ± 2.7||0.00|
|Digit Span||8.1 ± 3.0||10.1 ± 2.9||0.01|
|Information||7.7 ± 2.4||10.1 ± 2.7||0.00|
|Comprehension||7.1 ± 2.5||9.0 ± 2.4||0.00|
|Letter–Number Sequencing||8.7 ± 3.2 (n = 15)||10.5 ± 2.4 (n = 18)||0.09|
|Picture Completion||7.6 ± 2.6||7.1 ± 2.9||0.51|
|Digit Symbol-Coding||5.4 ± 2.6||6.2 ± 3.3||0.29|
|Block Design||6.7 ± 3.0||7.2 ± 2.8||0.53|
|Arithmetic||7.8 ± 2.8||9.0 ± 3.0||0.08|
|Picture Arrangement||7.9 ± 3.0||9.1 ± 3.0||0.09|
|Symbol Search||6.4 ± 2.9||7.9 ± 2.9||0.03|
|Verbal Comprehension Index||85.5 ± 11.9||95.5 ± 11.0||0.00|
|Perceptual Organization Index||84.7 ± 12.5||87.1 ± 14.5||0.48|
|Working Memory Index||85.4 ± 13.6||96.2 ± 13.1||0.00|
|Processing Speed Index||78.5 ± 12.7||84.5 ± 15.0||0.08|
|Verbal Scale IQ||84.3 ± 11.8||95.1 ± 11.3||0.00|
|Performance Scale IQ||81.9 ± 12.1||86.0 ± 13.7||0.19|
|Full Scale IQ||82.3 ± 10.8||90.5 ± 12.0||0.00|
Table 3. Current vs estimated premorbid IQ scores
|Full-scale IQ||MIP (n = 34)||82.3 ± 10.8||91.5 ± 4.4||−9.2 ± 10.4||0.00|
|AD (n = 34)||90.5 ± 12.0||96.4 ± 8.2||−5.9 ± 9.9||0.001|
|Verbal IQ||MIP (n = 34)||84.3 ± 11.8||90.9 ± 4.7||−6.6 ± 11.4||0.002|
|AD (n = 34)||95.1 ± 11.3||95.9 ± 8.5||−0.8 ± 9.4||0.64|
|Performance IQ||MIP (n = 34)||81.9 ± 12.1||92.6 ± 3.3||−10.7 ± 11.8||0.00|
|AD (n = 34)||86.0 ± 13.7||96.3 ± 6.3||−10.3 ± 11.9||0.00|
There were 13 patients (38.3%) in the MIP group and 10 (29.4%) in AD group whose FSIQ were <85 (<1 SD) and >70, and six (17.6%) in the MIP group and one in the AD group whose FSIQ were <70 (<2 SD), respectively (Table 4).
Table 4. IQ vs group
|MIP n (%)||13 (38.3)||6 (17.6)|
|Mean IQ (±SD)||79.5 ± 3.4||64.5 ± 4.0|
|AD n (%)||10 (29.4)||1 (2.9)|
|Mean IQ (±SD)||78.4 ± 3.8||67|
The present study investigated the intelligence of MIP patients compared with AD patients on the WAIS-III. This test is widely used in psychiatric clinical practice and is easy for clinicians to interpret. Although MIP patients were younger, with shorter duration of substance misuse than alcoholic patients, their mentality had more severe deterioration. The mean average FSIQ was 82.3 in MIP patients, showing that long-term use of methamphetamine not only resulted in psychosis, but also in the deterioration of general intelligence. Most previous neuropsychological studies regarding amphetamine or methamphetamine abusers used non-psychotic subjects. In clinical practice, however, the management of MIP patients includes not only treating the psychotic and withdrawal symptoms, but also the evaluation of their functional status and implementation of rehabilitative programs. Ujike and Sato observed three core characteristics of methamphetamine abusers, namely progressive qualitative alteration in mental symptoms from a non-psychotic to a pre-psychotic to a severely psychotic state; enhanced vulnerability to relapse of psychosis; and a very long duration of vulnerability to relapse.29 The clinical course of MIP seems to be chronic in certain patients. In the present MIP patient group there were six patients (17.6%) whose FSIQ was <70, reaching the diagnostic criteria of mild mental retardation, and 13 (38.2%) whose FSIQ was <85, rated as borderline intelligence. This result indicates that more than half (55.9%) of MIP patients have intelligence problems besides their psychotic symptoms. It is not clear whether the IQ would be restored to premorbid levels after a certain duration of substance abstinence. This issue needs further investigation.
Most of the MIP patients had poor socioeconomic status, were jobless, and needed social support. The evaluation of present mental function is necessary for patients themselves, clinicians and their families to plan a rehabilitative program or to assist patients who wish to resume work. The WAIS-III is widely applied in clinical psychiatric practice and familiar in the public, so the assessed results would be easily understood and accepted by patients and their family.
It is well documented that chronic use of alcohol, sedatives and inhalants induces persisting dementia. The consequences of mentality or intelligence impairment and deterioration induced by the use of other substances has been seldom mentioned. In clinical practice the psychosis induced by stimulants is the major focus and concern. Also in public education or propaganda material for drug use prevention, this aspect of unwanted sequels of methamphetamine abuse is very often omitted. Only a few studies have been reported from Western countries.9,10 There are also very few studies regarding the chronic users of other stimulants. Rosselli et al. reported that neuropsychological test performance scores of chronic cocaine users were within the low average or borderline range.25 The most abnormal scores were observed in attention, memory, and executive functioning tests. In the present MIP patients the four indexes including verbal comprehension, perceptual organization, working memory and processing speed were all impaired (approx. 1 SD lower than average), while in AD patients, two indexes including perceptual organization and processing speed were impaired.
The shortcoming of the present study was the lack of a normal control group. Because WAIS-III is an assessment tool of cognitive function derived from the calculation of normal distribution, the scores reflected the actual function of an individual. Here we used the DI method28 to make the premorbid IQ estimations (Table 3). Only VIQ in the AD group did not reach a significant level of deterioration (P = 0.64). The MIP patients had significantly lower premorbid score on FSIQ, VIQ and PIQ compared to AD patients. These results imply that MIP patients might have lower premorbid IQ, or that they have poorer professional and technical occupation. In the comparison of differences of deteriorated scores, only VIQ was significant (P = 0.024). These results suggest that after long-term use of alcohol, PIQ was more affected than VIQ. This phenomenon needs further investigation.
Another drawback of the present study was that these patients all received antipsychotic treatment during their evaluation. The mean haloperidol-equivalent dose of antipsychotics was 3.9 ± 2.9 mg/day. This is low as compared to the general dosage used for schizophrenia patients. In addition, a significant proportion of second-generation antipsychotics was prescribed, which have fewer side-effects and interfere with performance less.
The literature on the application of WAIS-III in substance abuse patients is still scarce. So far there are no publications from countries in Asia such as Japan, Korea or Taiwan regarding this field. The present results indicate that long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration, which is even more severe than in long-term alcohol use.
This study was supported by NSC- 93-2314-B-532-005. The authors thank Mr Yan-Lung Chui for assistance in examination of WAIS-III and statistical analysis.