Gender Differences in Cognitive and Personality Functioning in Patients With Substance Use Disorder

Objectives: Substance abuse is associated with impairments in cognition and many serious physical and behavioral consequences both in men and women. Gender differences, however, are not clear. The aim of this study was to examine gender differences in specific neuropsychological measures and personality variables in a sample of single and polysubstance patients. Methods: A total of 164 hospitalized patients—97 men and 67 women—underwent neuropsychological tests of verbal capacity, attention, speed of processing, perceptual reasoning, memory and learning, executive functioning, and inhibitory capacity. Personality was measured using the Minnesota Multiphasic Personality Inventory. Associations between neuropsychological measures, personality variables, and gender differences were studied using multiway analysis of covariance controlled for regular substance use in years, onset age of regular substance use, polysubstance use, and education level. Results: After adjustment, all the differences between men and women disappeared in the neuropsychological tests. Men reported higher values of somatisation and emotions of depression and anxiety than women. Men were also more suspicious and elicited more disturbed thinking than women. Conclusions: Contrary to previous studies, women are not more vulnerable to the effects of substance use compared with men. Notably, men are more vulnerable to negative emotions than women.

T here is a growing general awareness of substance abuse in women and the importance of gender in medical research and treatment. Biological and psychological differences between men and women may manifest differently in the cognition and personality of those with substance use disorder (SUD). Women have been found to be more susceptible than men to alcohol's effects on behavioral and cognitive functions. 1 Evidence suggest that females are more impaired in tasks of executive functions, 2,3 visual memory, 3 and wechsler adult intelligence scale (WAIS) scores. 4 In contrast, gender does not appear to influence the impairment of cognitive functions in tests of memory, attention, visuospatial ability, and language in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). 5 In addition, men and women do not differ in the Montreal Cognitive Assessment (MoCA); there are no differences in visuospatial and executive functions, memory, attention, language, and delayed recall tests. 6 Differences in personality factors between males and females with alcohol and substance users have been marginally examined. Mulder reviewed personality-based explanations in alcoholism research, interest in which increased in the 1980s. It appeared that patients with alcohol use disorder who also abuse other substances have different personality characteristics from those who do not. 7 Individuals who abuse other substances are younger, more impulsive, disinhibited, and extroverted. Moreover, studies have shown that personality may be an important mediator of the genetic effects of alcoholism. The majority of studies have centered on antisocial personality disorder and conduct disorder, while others have focused on normally distributed personality disorders. Studies have found a clear association between antisocial behavior and alcoholism; From the *Doctoral Programme of Clinical Investigation; Departments of †Psychiatry; ‡Biostatistics, University of Turku, Turku, Finland.
The study was approved by the ethical committee of the A-Clinic Foundation. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation, institutional and national, and with the Helsinki Declaration of 1975, as revised in 2000 (5). Patients had informed consent of the aims of the study, and their participation was voluntary.
All authors have read and approved the manuscript for submission to, have made a substantial contribution to the conception and, design of the study, collection, analysis and interpretation of data, and the writing and intellectual content of the article; and acknowledge that they have exercised due care in ensuring the integrity of this work. measures of impulsivity or novelty seeking appeared less predictive. In women, high negative emotionality may predate alcoholism. Nevertheless, personality variables explain a small proportion of the risk of dependence. Vulnerability to alcoholism is increased by poorer educational achievement, deviant peers, and general disadvantage. 7 The results of a study of the Minnesota Multiphasic Personality Inventory (MMPI) profiles indicated that scale 4 (ie, psychopathic deviance) is likely to be elevated in individuals who abuse substances. 8 Scale 4 is typically not significantly elevated in medical patients. The 24/42 (ie, depressionpsychopathic) 2-point code type is found in men with alcohol use disorder. This same code type and the 46/64 (ie, psychopathic-paranoia) code type are often found in women with alcohol use disorder. Neither of these code types is common in other medical patients who do not abuse alcohol.
Gender differences in comorbidity are also important. The prevalence of personality disorders in alcoholism ranges from as low as 22% to 40% to as high as 58% to 78%. 9 Anxiety and mood disorders are the most prevalent comorbid disorders in women with alcohol use disorder, whereas substance abuse and antisocial personality disorders are most frequent in men with alcohol use disorder. In a large sample, women diagnosed with borderline personality disorder more often than men, whereas men had higher rates of antisocial and narcissistic personality disorders than women. 10 Previous studies have not ruled out the fact that the worst neuropsychological performance of men and women is limited to premorbid cognitive differences and education nor have they considered the impact of the onset age of regular substance use on differences in personality characteristics between men and women. The present study examined (1) the cognitive and personality differences between men and women; (2) the impact of education level, duration of regular substance use, and singlesubstance and polysubstance use on cognition; and (3) the impact of education level, onset age of regular substance use, and singlesubstance and polysubstance use on personality characteristics.

Participants
This research is a retrospective cross-sectional study. Data was collected from patients of Järvenpää Addiction Hospital who underwent neuropsychological examination in 2004 to 2012. An abstinence period of one month was required before testing, given the longer-lasting, subacute cognitive, and neural effects of cannabis.
The inclusion criteria were as follows: (1) aged 18 to 65 years, (2) native Finnish speakers with a substance use diagnosis, and (3) minimum of one month of abstinence. Meanwhile, the exclusion criteria were as follows: (1) younger than 18 years old; (2) human immunovirus-positive patients or those having other chronic diseases possibly affecting the central nervous system; and (3) history of neurological disorder, opioid substitution treatment, or epileptic seizures.
The study group consisted of 164 hospitalized patients with SUD, both men (n = 97) and women (n = 67). No gender differences were found in age, level of education, learning difficulties, or polysubstance use. Duration of regular substance use was significantly longer in men than in women. This variable was controlled in later statistical analyses ( Table 1).
The majority of subjects used alcohol as a singlesubstance, with (89.4% among men and 80.0% among women). About half of the men (48%) and more than half of the women (55%) were polysubstance users. The majority of polysubstance users abused alcohol (ie, 80.0% among men and 62.2% among women) in addition to sedatives, cannabis, opioids, and stimulants.
Experienced psychiatrists made the diagnoses following the criteria of ICD-10 based on all available information at the time of discharge. SUD diagnoses also included alcohol overuse or dependence. Data on the years of regular substance use was obtained from medical records, medical examinations, and interviews with a nurse and a social worker.
The study was approved by the ethical committee of the A-Clinic Foundation (23.1.2013). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation, both institutional and national, and the Helsinki Declaration of 1975, as revised in 2000 (5). Patients had informed consent of the aims of the study, and their participation was voluntary.

MEASURES Neuropsychological Assessments
Neuropsychological testing was conducted as part of a work clinical assessment and a treatment plan assessment by the first author who is experienced in using the methods. Table 2 presents all neuropsychological measures.
The computerized CogniSpeed tasks 11 were used to measure simple reaction time and automatic and conscious information processing. The Simple Reaction Time subtest of the computerized CogniSpeed test battery was performed first. Inhibitory capacity was assessed by the CogniSpeed version of the Stroop Color-Word Test. 12 The test has 3 subtests: (1) Neutral Condition (COL), (2) Congruous Word Condition CON, and (3) Incongruous Word Condition (IN). COL and CON are related to more automatic information processing, while IN involves more conscious and effort-intensive processing. The Total Stroop Effect is the difference between reaction times in CON and IN, whereas Stroop Interference is the difference between reaction times in IN and COL.
Studies have confirmed that the CogniSpeed software is a sensitive instrument for measuring the performance of healthy participants and patients with brain disease. 11,13,14 Personality Assessment Personality variables were measured using the subscales of the MMPI, namely hypochondriasis, depression, hysteria, psychopathic deviate, masculinity-femininity, paranoia, psychasthenia, schizophrenia, and hypomania scales. 8,15 Statistical Analyses The sociodemographic data of the 2 patient groups were compared using the Student t test and Mann-Whitney U test for continuous measurements and the χ 2 test or the Fisher exact test for categorical variables. For statistical comparisons, P < 0.05 was considered statistically significant.
Analysis of covariance was used to study associations between

Analyses of Covariance of Neuropsychological Tests
The primary differences between men and women in the neuropsychological tests are presented in Table 3.
There were significant differences between men and women in a test of Vocabulary of WAIS-R, the Digit Symbol test, and the Raven test. Women performed better in the Vocabulary test and were faster in the Digit Symbol test, while men performed better in the Raven test indicating better skills in perceptual reasoning. Performance in the Digit Symbol test was, however, below normal average for both men and women. Tests of visual memory and learning and delayed memory were also below average in both men and women. Men were clinically below average in tests of Visual Memory Index. Both men and women were as slow as 63-year and 64-year olds in tasks of Stroop Congruence and Incongruence. 12 Neuropsychological tests were separately tested, adjusting for calendar age, education level, polysubstance use, and years of regular substance use. Calendar age was adjusted with neuropsychological test without age correction as CogniSpeed tasks of simple reaction time, COL, CON, and IN. In addition, age was adjusted with tests of WAIS-R using original data of raw scores (ie, Digit Span Forward and Backward tests, and Block Design test).
After adjustment, all the differences between men and women disappeared, and there were no correlations nor interactions with substance use variables (ie, duration of regular substance use and multidrug use) or background variables (ie, education level).

Analyses of Covariance of the Personality Test of MMPI
Personality tests were separately tested, adjusting for education level, polysubstance use, and onset age of regular substance use. Men and women differed in almost all scales. Table 4 outlines the primary differences between men and women and the results of multiway analysis of covariance.
The interpretations of the score levels of scales are based on Graham. 8 Both men and women scored moderately high (T = 60-80) on all clinical scales. Only women scored below 60 in the masculinity-femininity scale. The elevation of the F scale, combined with the normal range scores on L and K, may suggest overreporting, but significant pathology may still be present.
Gender was significantly associated with depression, psychasthenia, hysteria, schizophrenia, hypochondriasis, and masculinity-femininity. Using education level, onset age of regular substance use, and polysubstance use as covariables, significant differences between men and women remained. With education level as a covariable, significant differences were found in hypomania. With onset age of regular substance use as a covariable, significant differences were found in masculinity-femininity. Accordingly, earlier onset of regular substance use was associated with both lower and higher scores, while T-score values tended to diminish with later onset age. With polysubstance use as covariable, significant differences were found in paranoia, psychasthenia, and hypomania. Polysubstance use was also associated with higher paranoia, psychasthenia, and hypomania.
The Validity Scale of K-correction correlated significantly with gender. Women scored higher than men. Using onset age of regular use as a covariable, significant differences were found in the validity Scale of Lie. Later onset age of regular use was associated with the higher T-score, while the Validity Scale of Infrequency correlated significantly with polysubstance use. Polysubstance users scored higher than patients without polysubstance use.

DISCUSSION
The present study examined cognitive and personality differences between   Men and women did not differ in any of the sociodemographic variables studied. Moreover, they did differ in clinical variables. The duration of regular substance use among men was longer than that of women. The effect of this variable was controlled in the statistical analyses.
Significant differences between men and women in the primary neuropsychological tests were observed. Women had better vocabulary, and they were faster than men in the test of psychomotor speed. In contrast, men performed better than women in perceptual reasoning. After controlling the effects of education level, duration of regular substance use, polysubstance use, and calendar age, all the differences between men and women disappeared, and there were no correlations nor interactions with substance use variables. The results do not support the findings of previous studies that women's cognitive functions are more susceptible to the effects of alcohol and substance use than men's.
Several differences were noted between men and women in personality variables. Controlling for the impact of education level, onset age of regular substance use, and polysubstance use, men reported more severe personality and emotional problems than women in the scale values of depression, psychasthenia, hysteria, schizophrenia, hypochondriasis, and masculinity-femininity. Men also had higher scores than women in the depression scale. In the psychasthenia scale, men tended to be more anxious, tense, and agitated than women. In the hypochondriasis and hysteria scales, men perceived themselves more often than women as physically ill, and they tended to lack insight into the somatic symptoms or indications of the psychological components of their conditions. Similarly, men's schizophrenia scale values were significantly higher than women's values, suggesting the possibility of psychotic disorder, confusion, disorganization, and disorientation. In the masculinity-femininity scale, men had higher values than women, indicating a lack of stereotypically masculine interests. Women's values were indicative of interests that tended to be stereotypically more masculine than feminine. K-correction scale values (ie, a validity scale) were higher in women, suggesting that women denied symptoms and problems more than men do.
Personality differences between male and female participants in this study did not support previous findings concerning negative emotionality. Previous studies have found that women with high negative emotionality, anxiety, and depression are more susceptible to alcoholism than men. 7,9,16 In this  study, men had more characteristics of negative emotionality, such as depression, anxiety, tension, and disorganized thinking. Expectations of men in their roles as the main breadwinner of the family remained strong. Failure in these expectations caused more anxiety and depression in men than in women. Similarly, personality differences between male and female participants in this study did not align with previous findings concerning paranoia and psychopathic personality characteristics. There was no significant difference between men and women in scales of psychopathic deviate and paranoia. The result of the paranoia scale was unlike previous findings, that women are more paranoid than men. 8 In fact, both genders were equal in their scores of psychopathic deviances, and this finding differs from that in previous studies. 9 Polysubstance users had more serious problems in the paranoia and hypomania scales irrespective of gender differences. The values of the paranoia scale were extremely high in the polysubstance group. Moreover, the values of the hypomania scale correlated with polysubstance use, diminishing with higher education levels. Notably, subjects with higher education levels had moderately higher scores compared with the overall average. Findings from the present study revealed that men have more serious problems regulating emotions, although women also had moderately high values in most scales. Both groups produced higher than normal values on the depression, psychopathic deviate, paranoia, anxiety, thinking disturbances, and hypomania scales. Their profiles were interpreted as indicating increased tendencies toward acting-out behavior, high levels of stress and psychological discomfort, interpersonal guardedness, and hostility. Both genders had difficulties regulating their emotions and behaviors, although men found it more difficult to do so.
The personality factors in this study appeared independent of education level except the hypomania scale. The values of the hypomania scale diminished with higher education levels. Subjects with higher education levels had moderately higher values compared with the average level. Patients tended to be bored and restless easily. Moreover, their frustration tolerance was low, suggesting that both genders have features of hyperactivity and short attention span.
The personality factors also appeared independent of onset age of regular substance use, except the masculinity-femininity scale. Participant groups with early onset of regular substance use had both lower and higher values, which tended to diminish with later onset age. The results suggest that deviance from traditional masculinity and femininity interests may be a risk factor for substance abuse.
The present study demonstrated qualitative differences in emotion regulation between male and female substance-dependent individuals. However, knowledge of gender differences in emotional brain development is still limited. Emotional and personality disturbances associated with substance use are suggested to be based on earlier proneness to negative emotionality and social deviance in men and women. 7,17,18 Regarding treatment, prognosis is unfavorable for both men and women because of their lack of insight into and resistance to the psychological components of their condition. As such, it may be useful to combine self-report inventory tests with more advanced methods for personality research, for example, the schema-focused approach 18 and the Rorschach Comprehensive System. 17 These methods can help patients to recognize persistent, maladaptive patterns of thinking, feeling, and behaving. It is also important to openly discuss and evaluate affect dysregulation and impulse control problems targeting relapse of substance use. Although personality disorders are said to explain only a small proportion of the use of intoxicants, it is essential to identify related disturbances in regulating feelings and behaviors during treatment. Moreover, our findings of personality and emotional variables enable to develop cost-effective screening procedures for clinical use in SUDs.

Limitations and Advantages
One limitation of this study is that we were unable to investigate the effects of specific substances, as nearly half of the participants abused multiple substances. Each substance of abuse presents