NEUROPSYCHOLOGICAL PERFORMANCE IN PATIENTS WITH SUD WITH AND

NEUROPSYCHOLOGICAL PERFORMANCE IN PATIENTS WITH SUD WITH AND WITHOUT MOOD DISORDERS Irma Höijer, M. Sc. , Doctoral Student Doctoral Programme of Clinical Investigation University of Turku Tuula Ilonen, Ph. D. University of Turku, Department of psychiatry Eliisa Löyttyniemi, M. Sc. Department of Biostatistics University of Turku Raimo Salokangas, Ph. D. Turku University Hospital Psychiatry

BACKGROUND AIMS • Substance abuse as well as mood disorder has been consistently associated with neuropsychological impairment in many cognitive domains. • SUD may create a “double deficit” in cognitive functions in those with mood disorder and have an adverse impact on their course of illness and functional outcome. • The aim of the study was to examine the effects of mood and substance use disorders on specific neuropsychological measures in a sample of single and multidrug patients with and without mood disorders.

. METHOD • Participants • 164 hospitalised patients, • 88 with (SUD+MD) and • 76 (SUD-MD) without mood disorders

PARTICIPANTS • Diagnoses were made according to the criteria of ICD-10 by experienced psychiatrists. • Substance use disorder (SUD) diagnoses also consisted of alcohol overuse or dependence. • No significant differences were cited between SUD-MD and SUD+MD groups in the use of intoxicating substances (see table 1).

TABLE 1. SUBSTANCE USED IN PATIENTS. SUD-MD SUD+MD N=76 N=88 Only one drug 39 (51%) 52 (59%) Alcohol 29 (38%) 39 (44%) Sedatives 3 (3%) 8 (9%) Stimulants 3 (3%) Opioids 3 (3%) 2 (1%) Multidrug 37 (48%) 36 (40%) Alcohol, sedatives 5 (7%) 20 (23%) Alcohol, cannabis 1 (1 %) 0 (0%) Alcohol, stimulants 0 (0%) 1 (1%) Alcohol, other psychoactives 12 (16%) 10 (11%) Opioids, other psychoactives 9 (11%) 0 (0%)

DIAGNOSTIC DISTRIBUTION OF SUD+MD SAMPLE • Bipolar Disorder: severe with psychotic features (F 32. 3; 3%), • major depressive disorder, single episode, bipolar disorder (F 31; 21%), • Major depressive disorder, single episode, mild (F 32. 0; 3%), • major depressive disorder, single episode, moderate (F 32. 1; 23%), • major depressive disorder, single episode, severe without psychotic features (F 32. 2. ; 11%), • major depressive disorder, single episodeunspecified (F 32. 9; 6%), • recurrent major depressive disorder, mild (F 33. 0; 2%), • recurrent major depressive disorder, moderate (F 33. 1; 6%), • recurrent major depressive disorder, severe without psychotic symptoms (F 33. 2; 3%) • recurrent major depressive disorder, in remission (F 33. 4; 3%), • Persistent mood (affective) disorders (F 34. 1; 3% ) and • Mixed anxiety and depressive disorder (F 41. 2; 13%).

SOSIODEMOGRAPHICS Age (mean, SD) Sex Male Female Level of Education No Primary School Vocational Training College-level Education Higher Education Marital status Married Stable Partner Single Separate/Divorced Unemployed Military Service (only males) Exemption Completed Unknown Prison ruling None Parole Prison Pending Judgment Unknown SUD-MD N = 76 37. 8 (11. 9) 42 (43. 3%) 34 (50. 7%) SUD+MD N = 88 39. 1 (10. 3) 55 (56. 7%) 33 (49. 3%) Statistical analysis t-test Chi. Square p value 0 (0. 0%) 35 (53. 0%) 23 (43. 4%) 10 (35. 7%) 8 (47. 1%) 0 (0. 0%) 31 (47. 0%) 32 (56. 6%) 18 (64. 3%) 9 (52. 9%) Chi. Square . 45 12 (48. 0%) 6 (50. 0 %) 36 (55. 4%) 22 (35. 5%) 47 (50. 5%) 13 (52. 0%) 6 (50. 0%) 29 (44. 6%) 40 (64. 5%) Chi. Square . 16 46 (49. 5%) Chi. Square . 23 . 26 17 (53. 1%) 20 (35. 7%) 2 (33. 3%) 15 (46. 9%) 36(64. 3%) 4 (66. 7%) 54 (50. 0%) 8 (50. 0%) 10 (47. 6%) 4 (100. 0%) 54 (50. 0%) 8 (50. 0%) 11 (52. 4) 0 (0. 0%) Chi. Square . 29 . 42 . 35

CLINICAL VARIABLES (1) Onset substance SUD-MD N=76 SUD+MD N=88 Statistical analysis p value 16. 2 (7. 6) 16. 3 (5. 9) T-test 0. 97 21. 2 (11. 3) 23. 5 (1. 0) T-test 0. 17 16. 1 (9. 4) 15. 7 (8. 8) T-test 0. 78 18. 6 (9. 5) 24. 2 (1. 0) T-test 0. 01˟˟ of use age Onset of regular substance use Substance use duration (years) Onset of multidrug use

CLINICAL VARIABLES (2) Multidrug use in years Onset of injection SUD-MD N=76 SUD+MD N=88 Statistical analysis 8. 2 (8. 0) 10. 7 (7. 1) T-test 0. 07 19. 9 (5. 3) 23. 3 (6. 6) T-test 0. 12 4. 5 (6. 0) 5. 7 (3. 7) T-test 0. 55 33. 1 (12. 3) 36. 2 (10. 3) T-test 0. 09 p value drug abuse Duration of injection abuse Treatment onset age

CLINICAL VARIABLES (3) Depression score SUD-MD N=76 SUD+MD N=88 Statistical analysis 79. 2 (17. 7) 91. 5 (18. 4) T-test 0. 001˟˟˟ 4. 4 (4. 5) p value (MMPI) Affection disorder data (only males) Duration disorder of

TABLE 2. 1 NEUROPSYCHOLOGICAL MEASURES Cognitive Domain Test Score units Premorbid IQ Vocabulary (WAIS-R; Wechsler, 1975) Standard Score Attention Digit Span Forward Digit Span Backward Total raw score, max 12 Speed of Processing Digit Symbol (WAIS-R; Wechsler, 1975) Standard Score Simple reaction time (Cogni. Speed; Revonsuo et al. , 1993) Time to complete (ms) Perceptual Reasoning Block Design (WAIS-R; Wechsler, 1975) Raven Standard Matrices (Raven, 2004) Standard Score

TABLE 2. 2 NEUROPSYCHOLOGICAL MEASURES Cognitive Domain Test Score units Verbal Memory Verbal subtests of the WMS-R (Wechsler, 1987) and Learning Verbal Memory Index Total raw score, max 50 Total raw score, max 24 Total raw score, max 8 Visual Memory and Learning Visual Memory Index Total raw score, max 18 Total raw score, max 6 Total raw score, max 41 Delayed Memory Immediate Logical Memory Delayed recall of Logical Memory Immediate Associate Learning Delayed recall of Associate Learning Visual subtests of (WMS-R (Wechsler, 1987) Immediate Visual Learning Delayed recall of Visual Learning Immediate Visual Reproduction Delayed recall of Visual Reproduction (WMS-R (Wechsler, 1987) Delayed Memory Index

TABLE 2. 3 NEUROPSYCHOLOGICAL MEASURES Cognitive Test Score units Domain Inhibitory Capacity Executive Function Total Stroop (IN 2 -CON) Stroop Cogni. Speed version of the Stroop Color-Word Test (Stroop, 1935) Neutral Condition, COL Congruous Word Condition, CON Incongruous Word Condition, IN 2 Cogni. Speed version of the Stroop Color-Word Test (Stroop, 1935) Time to complete (ms), and number of errors Time to complete (ms)

COGNISPEED COLOR REACTION TIME -TASKS Neutral Condition COL nnnnnnnn Right index finger push the Congruous Word Condition CON Red Incongruous Word Condition IN 2 reaction key red or blue as soon as possible Blue Right index finger push the reaction key red or blue as soon as possible Blue Red Pay attention only the color, Ignore the possible word and its meaning (semantic content) Congruous Condition STIN nnnnnnnn Red Blue Same instructions than above Incongruous Condition STIR nnnnnnnn Red Blue Same instructions than above

RESULTS • Compared with normative, memory, learning and processing speed were impaired in both SUD+MD and SUD -MD groups. • Processing speed (p <0. 01), perceptual reasoning (p<0. 05) and susceptibility to interference (p=0. 03) were more impaired in the SUD+MD group than in the SUD-MD group. • The SUD+MD and SUD-MD were most powerfully separated by the Digit Symbol and Block Design tests. • Cognitive interference in the SUD+MD group was significantly correlated with slowing the speed of processing.

THE DIGIT SYMBOL OF WAIS-R STANDARD SCORES FOR THE SUDMD GROUP AND THE SUD+MD GROUP. The significant differences within each diagnostic group are shown by an asterisk (P <. 01). The data shown are 95% Confidence Interval for median, Lower Bound 7. 5 and Upper Bound 9. 0 for the SUD-MD group; Lower Bound 6. 4 and Upper Bound 7. 7 for the SUD+MD group.

SIMPLE REACTION TIME OF COGNISPEED TASKS REACTION TIME (MS) FOR THE SUD-MD GROUP AND SUD+MD GROUP. The significant differences within each diagnostic group are shown by asterisk (P < . 01). The Data shown are 95% Confidence Interval for median, Lower Bound 369. 7 and Upper Bound 456. 5 for SUD-MD Group; Lower Bound 407. 2 and Upper Bound 503. 2 for SUD+MD group.

THE BLOCK DESIGN TEST OF WAIS-R STANDARD SCORES FOR THE SUD-MD GROUP AND THE SUD+MD GROUP. The significant differences within each diagnostic group are shown by asterisk (P < . 01). The Data shown are 95% Confidence Interval for median, Lower Bound 369. 7 and Upper Bound 456. 5 for SUD-MD Group; Lower Bound 407. 2 and Upper Bound 503. 2 for SUD+MD group.

INCONGRUOUS WORD CONDITION OF COGNISPEED TASKS REACTION TIME (MS) FOR THE SUD-MD GROUP AND THE SUD+MD GROUP. The significant differences within each diagnostic group are shown by asterisks (P < . 01). The Data shown are 95% Confidence Interval for median, Lower Bound 635. 0 and Upper Bound 752. 3 for the SUD Group; Lower Bound 710. 7 and Upper Bound 836. 8 for the SUD+MD group.

CONCLUSIONS • SUD+MD patients may suffer from more severe cognitive deficits than SUDMD patients. • In this study processing speed was also measured by Cogni. Speed tasks (simple reaction time, COL, IN 2). Both groups -SUD-MD and SUD+MD - had deficits in processing speed compared to healthy controls, but mood disorders further enhanced slowing down. • Mental speed was partially modulated by age in Cogni. Speed tasks. Elderly patients were slower, but their higher education level was a compensatory factor diminishing the impact of ageing. • The single substance used (mostly alcohol) was probably involved in test performance deterioration. The mean age of the SUD+MD patients was 38, but their processing speed was at the same level as normal 67 year olds have.

CONCLUSIONS • In the SUD+MD group of this study, Stroop interference significantly slowed down information processing, both in automatic and more conscious, effortful processing. The wrong or irrelevant word slowed ink-naming performance (e. g. , the blue colored letters formed the word ‘red’) significantly independently of age, education level, multiple substance use and learning difficulties. • The role of Total Stroop is less researched in mood disorders and substance abuse disorders. The Total Stroop effect is a combined effect of facilitation and interference (Revonsuo, 1995). • In SUD+MD patients the increased Total Stroop was related significantly with the slowing of processing speed. It seems that patients could not use congruent and facilitative and relevant conditions (the right word ‘red’ in red ink) to speed performance.

CONCLUSIONS • As a quantitative measure of selective attention and executive function, Stroop tasks require future research in order to clarify what mechanisms are involved in Stroop effects in individuals with substance abuse and mood disorders. • It is possible that Stroop effects are cognitive markers of comorbidity and are worthy of inclusion in future studies. The tasks may have prognostic utility among drugdependent patients (Carpenter et al. , 2006).