clinicalfeatures and cognitive impairments in methamphetamine use disorder clinical features and...

ClinicalClinical features and cognitive features and cognitive impairments in methamphetamine impairments in methamphetamine use disorderuse disorderMin Zhao, M.D & Ph.D., Prof. of Psychiatry

Shanghai Mental Health CenterShanghai Mental Health Center

Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong University School of Medicine

April 22-24, 2015, Hangzhou, ChinaApril 22-24, 2015, Hangzhou, China

MA recreational use have increased dramatically in recent yearsThe second most widely abused drugs 38% are ATS users in 2013 in China 90% new drug usersAnnual prevalence of drug use at the global level, by illicit drug category, 2009-2010

18%

6.6%

42.1%

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Background

NNCC, 2013 UNODC, 2013

Consequences of chronic MA useprolonged psychiatric symptoms (Scott, 2007)

Depression, anxiety and so on

Conginitive impairments

Poor quality of life, stress

HIV/AIDS risk, and other psychosocial consequences

Background

MA abuse associates with substantial neurotoxicityImpact multiple neurotransmitter systems,

e.g. Dopamine (DA), serotonin, glutamate (Volz, 2007)

Background

MA use relates with brain structural and functional abnormotiesStructural

frontal-striatum, limbic system, hippocampus, anterior cingulate cortex, amygdaloid (Sekine, 2001, 2006)

corpus callosum (Nakama, 2011)Functional

Frontal lobar, ventral inferior frontal gyrus (tobias 2010)

Background

MA addicts showes broad cognitive impairmentsE.g. verbal memory, visual spatial memory, prospective memory, working

memory, cognitive inhibition, attention networks, decision-making (Scott, 2007)Could these impairments improve after MA abstinence? (Iudicello 2010 )

Broad cognitive impairments

remain after 3-month abstinence improve partially

after 1-year abstinence

Background

MA executive function impairment and the Stroop Task

MA addicts suffer from executive function impairment, which might relate with relapse

The stroop task: test the congnitive controlCould predict drop-out treatment risk

(Lubman,2004)fMRI: prefrontal lobar hypoactivition (Chang

L,2007)

Background

Clinical features and psychosocial wellbeing of MA dependent individuals

Cogitive impairments and its changes after MA abstinence

Brain activity of abstinent MA users in word-color interference Stroop task

Hippocampal volume in recent abstinent MA users

Outline of the presentation

Part 1: The clinical features and psychosocial wellbeing of MA dependent individuals

Aims: Describe and understand the clinical features

and psychosocial wellbeing of chronic MA users

Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals

Methods

Cross-section survey, MA users were recruited from compulsory rehabilitation center in 2013

Interviewed by SCID-I for diagonsis (substance use disorder module), and diagnosed as ATS dependenc or abuse by DSM-IV were recruited

ASI, BIS, GAD, PSS and social support rating scale(SSRS), psychiatric symptom checklist were adminitrated to the participants

Approved by the Institutional Review

　　 Total (n=216)gender male, n(%) 76.2%　 female, n(%) 23.8%age, mean(SD) 37.05 (9.84）nation han, n(%) 97.1%　 minority, n(%) 2.9%education 1-9 years, n(%) 64.5%

>10 years, n(%) 35.5%marriage married , n(%) 63.0%　 unmarried, n(%) 37.0%employment unemployed, n(%) 50.6%　 employed, n(%) 49.4%

Demographic characteristics of the participants


The age of onset of MA, 32.14 ±10.10 years old

The average years of MA use, 4.49 ±3.93 years

The frequencies of MA use in last month, 9.1±20.5 days

The average dose, 0.39±0.35gram

61(28.2%) diagnosed as MA induced psychosis

167(77.3%) diagnosed as MA dependence, 49(22.7%) diagnosed as ATS abuse


Drug use and clinical diagonosis for the participants

49 (90.7%) 47 (87.1%)

30 (55.6%)25 (46.3%)

13 (24.1%)

5 (9.3%)

0%

25%

50%

75%

100%

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Distributions of psychiatric Symptoms among participants who reported psychaitric symtoms



Psychological wellbings(M±q ， n （ %）项目 Total(n=216) Male(n=159) Femal(n=57 ） Z 值 / 2值 p

Depression 　　　 6.802 0.009

BDI 分 <20 119 （ 55%） 96 （ 60.4%) 23(40.4%)

BDI分≥ 20 97 （ 45%） 63(39.6%) 34(59.6%)

Anxity 4.362 0.037

GAD 分 <5 107 （ 49.5%） 87(54.7%) 22(38.6%)

GAD分≥ 5 109 （ 50.5%） 72(45.3%) 35(61.4%)

PSS* 16.7±8 16±8 19±8 -2.692 0.007

SSRS* 26.95±8.06 26.5±11.2 27±9 -0.363 0.717

注： * 数据非正态分布，采用秩和检验；其余采用卡方检验


ASI scores among MA induced psychoses （ M±q)

项目 MA induces psychoses(n=61）

Without MA induced psychoses

（ n=155 ）Z p

ASI total scores 2.01±0.88 1.61±1.03 -3.709 <0.001

Physical health 0±0.24 0±0.23 -0.57 0.568

Employment 0.67±0.52 0.67±0.41 -1.055 0.291

Alcohol ues 0.085±0.24 0.059±0.3 -0.37 0.711

Drug use 0.16±0.152 0.13±0.153 -2.297 0.022

Legal problems 0.2±0.37 0.2±0.35 -0.346 0.729

Family and social support

0.27±0.49 0.2±0.27 -2.642 0.008

Mental health 0.4±0.41 0.14±0.34 -5.427 <0.001


Pschological wellbings among ATS induced psychoses （ M±q ， n（ % ） )

项目ATS induces

psychoses（ n=61）

Without ATS induces psychoses

（ n=155 ）Z 值 /2值 p

Depression 　　 12.44 <0.001

BDI评分 <20 22(36.1%) 97(62.6%)

BDI ≥评分 20 39(63.9%) 58(37.4%)

Anxity 10.625 0.001

GAD评分 <5 20(32.8%) 89(57.4%)

GAD ≥评分 5 41(67.2%) 66(42.6%)

SSRS* 25±9.5 27±10 -0.898 0.369

PSS* 20±7.5 16±8 -4.373 <0.001



ASI between ATS dependence and abuse （ M±q)

Dependence(n=167)

Abuse （ n=49 ） Z p

ASI total scores 1.88±0.94 1.31±0.6 -4.501 <0.001

Physical health 0±0.27 0±0.11 -1.433 0.152

Employment 0.67±0.52 0.67±0.32 -0.071 0.944

Alcohol ues 0.089±0.3 0.028±0.24 -1.786 0.074

Drug use 0.15±0.16 0.082±0.115 -4.999 <0.001

Legal problems 0.2±0.4 0.05±0.225 -2.492 0.013

Family and social support 0.22±0.35 0.19±0.13 -2.181 0.029

Mental health 0.27±0.41 0.09±0.21 -4.702 <0.001


Pschological wellbings betweem ATS dependence and abuse （ M±q ， n（ % ） )

dependence （ n=167)

Abuse(n=49 ） Z/ 2 p

Depression 2.672 0.102

BDI评分 <20 87(52.1%) 32(65.3%)

BDI ≥评分 20 80(47.9%) 17(34.7%)

Anxity 9.08 0.003

GAD评分 <5 75(44.9%) 34(69.4%)

GAD ≥评分 5 92(55.1%) 15(30.6%)

SSRS* 27±10 27±12 -0.242 0.808

PSS* 17±7 14±10.5 -2.803 0.005


Part 2. Cognitive functions among ATS dependent patients

Aim: to understand the cognitive function and its

changes after MA abstinence for 6 months

Case control and longitudinal study Subjects: MA=54, HC=58 Inclusion criteria:

(1) more than 9 years of education; (2) aged between 18 and 45 years old; (3) Han nationality and proficient at Chinese (4) normal or corrected-to-normal vision and hearing.

Exclusive criteria: (1) physical or neurological illnesses affecting cognitive

function (e.g., stroke, seizure, or a severe head injury);(2) other Axis I disorder of DSM-IV criteria; (3) use of cognitive enhancing drugs within 6 months of

study enrollment; and (4) substance dependence other than nicotine, within the

past 5 years.


Measurements:The cognitive assessments: the CogState

batteryWHO-quality of life instrument (WHOQOL-BREF) Social Adaptation Self-evaluation Scale (SASS) Beck depression scale-II CogState Battery: 8 dimensions, baseline, 3, 6

months afterInternational shopping list task (ISL, verbal memory)Detection Task (DET, processing speed) Identification Task (IDN, tapping attention/vigilance)One Card Learning Task (OCL, visual memory)Two Back Task (TWOB, working memory)Social Emotional Cognition Task (SEC, social cognition)Continuous Paired Association Learning Task (CPAL,

spatial working) The Groton Maze Learning Task (GML, memoryproblem

solving and error monitoring)


Demographics data and drug use history

　 MA group (n=54)HC group (n=58)

χ2 or t P

Male$, n (%) 40 (74.1%) 37 (63.8%) 1.37 0.503Age#(years), mean (SD) 33.89 (7.47) 30.52 (6.55) 2,54 0.12

Years of Education#, mean (SD) 9.80 (1.83)*** 14.26 (3.70) 8.18 <0.001

Married$, n (%) 16(29.63%) *** 36 (62.07%) 11.83 <0.001

Smoking$, n (%) 5 (90.74%) *** 36 (62.07%) 12.56 <0.001

Employed within the last year, n (%) 24 (44.4%)

MA onset age (years), mean (SD) 28.78 (8.59)Years of MA use, mean (SD) 4.14 (3.42)Days of abstinence, mean (SD) 44.85 (20.65)Heroin users 5 years ago before study entry, n (%)

22 (40.7%) 　　　


The psychological wellbeing of MA addicts

　 MA group (n =54) HC group (n=58) t value P

SASS 31.98 (6.95) 35.97(6.51) 3.13 0.002

WHO-QOL

Physical health 24.46 (3.54) 26.40 (3.21) 3.03 0.003

Psychological health 18.48 (4.18) 21.67 (3.40) 4.44 <0.001

Social relationships 10.50 (2.16) 11.60 (2.66) 2.04 0.018

Environment 25.41 (5.50) 28.52 (9.04) 2.18 0.031

Total score 78.81 (12.30) 86.77 (10.30) 3.7 <0.001


Cognitive function of MA addicts

MA group HC group

Baseline 3m later 6m later Baseline 3m later 6m later

DET 2.54 (0.15) 2.58 (0.10) 2.61 (0.09) 2.59 (0.11) 2.60 (0.09) 2.55 (0.09)

IDN 2.71 (0.08) 2.73 (0.08) 2.75 (0.08) 2.73 (0.06) 2.73 (0.09) 2.73 (0.07)

OCL 1.01 (0.10) 1.01 (0.11) 1.05 (0.12) 1.01 (0.12) 1.11 (0.37) 1.05 (0.10)

TWOB 1.17 (0.18) 1.21 (0.22) 1.25 (0.17) 1.27 (0.16) 1.27 (0.17) 1.29 (0.17)

GML 72.3 (25.9)62.39 (23.5)

51.41 (25.5) 55.16 (27.6)43.12 (13.5)

46.16 (19.6)

ISL 19.62 (4.3)22.52 (4.26)

23.44 (3.93) 24.36 (4.0)24.84 (4.70)

26.00 (4.14)

SEC 1.06 (0.16) 1.14 (0.11) 1.16 (0.14) 1.22 (0.12) 1.16 (0.10) 1.15 (0.08)

CPAL 114.62 (54.26)

77.36 (43.06)

70.09 (47.24)

48.00 (29.45)

24.16 (12.79)

30.72 (16.81)


-0.10 OCL

IDN0.19

DET0.22

-0.40 TWOB* -0.57

GML**

-1.28 ISL***

-0.62 SEC**

-0.96 CPAL***

-0.44 COMP***

-1.50

-1.20

-0.90

-0.60

-0.30

0.00

0.30

Healthy control means

Z-s

core

s

Figure 3. Magnitude of impairment of relative to healthy controls in the CogState Battery. Abbreviation: ISLT International Shopping List Task, DET Detection Task, IDN Identification Task, OCL One Card Learning Task, ONB One Back Task, CPAL Continuous Paired Association Task, GML Groton Maze Learning Task, SEC social emotional cognition, COMP composite score. Numbers of the figure are Z score. *P<0.05, **P<0.01, ***P<0.001


Figure 4. Follow-up assessment of cognitive function in the MA and HC groups *P<0.05. Abbreviation: GML Groton Maze Learning Task. ISL International Shopping, SEC social emotional cognition, List Task

** * *

*

Hoffman (2006) √ Morgan (2012) √ Hoffman (2006) ×

Verbal memory Visual memory

Salo (2009a) √ van der Plas (2009) √

Salo (2009b) ×

Working memory

Error monitoring

Attention

Processing speed

Social cognition Kim (2011) √ Payer (2008) √

•MA addicts endure broad cognitive impairments

Verbal memory

• longitudinal ： Indicelllo (2010)

• Cross sectional: no improvement in 3 month abstinence

Error monitoring

• longitudinal ： Indicelllo (2010)

• Cross sectional ： Van der Plas (2010), IGT 、 WCST 、 Stroop

Social cognition • Henry (2009),6-month

abstinence ， MA<HC

•MA addcits cognitive impariments could partially improve

MethodsSubjects: MA group (n=28):

over 1 year MA useTotal lifetime MA consumption > 50 g

Health control (n=26): age, sex matched

Inform consent

• fMRI scan• stroop task simultaneously

•Demorgraphic data•Abuse history•Clinical data

•Stroop task training•8min

Part 3. Brain activity of abstinent MA users in word-color interference Stroop task

The words-color interference Stroop taskE-prime 2.0 Block design, psudo-random

congruency incongruency rest

red red/red/red +

•Stimulus presented 2 s •Rest 2-12 s

•Mean 5875ms• reaction time, total errors

•（ RTincon—RTcon ） / RTcon

Methods


fMRI: Simens 3.0T, event related fMRI

EPIT1

AC-PC lineLocalizing

Scans

TR=2530msTE=2.34ms1*1*1plane resolution192 layer

TR=2000msTE=30ms90°flip angle31 layer ， 4.5mm thickness64*64 matrix3*3*4.5 plane resolution


Mean (SD)MA group （ n=28）

HC group (n=26）

Age 32.81 （ 6.62） 32.80 （ 7.15）Male % 18 （ 66.7%） 16 （ 61.5%）Years of education* 9.65 （ 1.83） 11.52 （ 2.40）Marriage % 5 （ 18.5%）

MA onset age 26.05 （ 7.23）

Lifetime MA use 6.76 （ 3.82）

Days of MA abstinent 168.48 （ 46.08）

•Demographic and clinical data


•Stroop effects

•No main effects in group or interaction无

•（ RTincon—RTcon ） / RTcon （ t=1.43,P=0.16 ）

MA group HC group

congruent In-- congruent In--

RT a 932.17 (158.68)

1088.93 (150.30)

908.28 (138.86)

1038.56 (192.12)

error 29.98 (3.17) 29.63 (2.57) 30.69 (1.69) 29.96 (2.32)

•The performance of the Stroop task


whole brain one-sample t-test for brain activity in both groups

• robust activations in whole brain, mainly in anterior cingulated cortex (ACC), parietal lobe, insula, precuneus, prefrontal, temporal, occipital lobes ， cerebellum


The comparison of brain activity in MA addicts and health controls

BrodmannX

(mm)Y

(mm)Z

(mm)Z P

Incongruent and congruent condition （ MA<HC）

precuneus 7 -21 -42 48 3.35 0.000

Cingulated gyrus 32 -21 9 36 2.89 0.001

Postcentral gyrus 2 -36 -30 30 3.14 0.001

Left anterior lobe -- -12 -45 -27 3.14 0.001

Right anterior lobe -- 24 -30 -27 2.97 0.001

Congruent condition （ MA>HC）

Right insula 13 42 15 -9 3.66 0.000

Left insula 13 -45 -9 0 3.50 0.000


precuneus

Postcentral gyrus

Cingulated gyrus

anterior lobe

Right insula Left insula

Precuneus sensormotor anterior region

Relates with memory, executive function, attention

ACC (BA24、 32、 33): solving conflicts e.g. Kerns 2009; Salo 2009

PCC(BA23)： AD

anterior lobe

Relates with attention, language

MA addicts showed hypofunction in areas related with cognitive function


•within lateral sulcus

•elated with interoceptive awareness, emotion, motor, social cognition

•craving

• Some studies revealed that insular may have relationship with cocaine, alcohol, heroin and nicotine addictio

MA addcits showed heperfunction in areas related with craving


a cross-sectional study to examine hippocampal volume, and its relationship with cognitive function

29 healthy controls and 32 patients

Part 4. Hippocampal volume in recent abstinent MA users

CharacteristicsControls (N=29) Patients(N=30)

t / F P(Mean±SD) (Mean±SD)

Gender (Male/Female) 　　 Fisher’s exact

test 0.779

　 Male Female Male Female F 　Age (years) 33.42±6.45 32.00±8.23 34.00±4.87 30.30±8.71 0.772 0.515

Education (years) 10.95±2.39 13.00±2.58 9.48±1.87 10.40±2.22 5.684 0.002

　　 Total Male Female t 　

Duration of abstinence (months) N/A 5.52±1.59 6.41±1.03 3.75±0.82 7.084 <0.001

Age of onseta N/A 26.10±7.15 27.40±6.60 23.50±7.85 1.434 0.163

Duration of drug use (months) N/A 75.93±43.28 74.75±31.04 78.30±63.19 -0.208 0.836

Duration of continuous drug useb (months)

N/A 7.98±13.69 7.53±14.18 8.89±13.32 -0.254 0.802

Average number of grams of MA used per occasionc (gram)

N/A 0.66±0.48 0.55±0.35 0.87±0.64 -1.467 0.169

Part 4.Hippocampal volume in recent abstinent MA users

• No group or gender main effect, group*gender interaction for the

right (p=0.020) but not left (p=0.249) relative hippocampal

volume

• female patients and female controls (t(18) =-1.984, p=0.063), male

patients and male controls (t(37) = 0.802, p=0.427)


• male controls and female controls (t(27) = -4.443, p<0.001) ， male patients and female patients (t(28) = -1.303, p=0.203)

• a smaller volume of right hippocampus in female but not in male abstinent MA users compared to healthy controls.


Summery and conclusions

ATS dependent individuals experience high rates of psychaitric symtoms and had poor psychosocial wellbeing (such as depression, anxity, stress, quality of life, social adaption)

ATS dependent individuals show broad cognitive impairments (e.g. memory, working memory, executive function, social cognition) , some cognitive domain(executive function, verbal memory, social cognition) improve after abstinence

ATS dependent individuals appear to have hypo-activity in some brain regions related to cognitive function, and hyper-activity in region related with craving

Hippocampal volume reduction in female but not male recent abstinent MA users

Thanks for your attention

Min ZhaoMin Zhao

[email protected]@gmail.com

Look forward to collaborating with you in futureLook forward to collaborating with you in future

clinicalfeatures and cognitive impairments in methamphetamine use disorder clinical features and...

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