Cue-exposure treatment influences resting-state functional connectivity-a randomized controlled fMRI study in alcohol use disorder.

RATIONALE: Cue-exposure therapy (CET) consists of exposing patients to the cause of their affliction in a controlled environment and after psychological preparation. Ever since it was conceived, it has been suggested as a treatment for different types of behavioural impairments, from anxiety disorders to substance abuse. In the field of addictive behaviour, many different findings have been shown regarding the effectiveness of this therapy. OBJECTIVES: This study aims to examine the underlying neurobiological mechanisms of the effects of CET in patients with alcohol use disorder using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In a randomized, controlled study, we examined patients after inpatient detoxification as well as healthy controls. Patients underwent nine sessions of CET spaced over 3 weeks. Rs-fMRI was conducted before treatment and 3 weeks after treatment onset in patients, healthy controls received only one rs-fMRI measurement. The final participant sample with complete data included 35 patients in the CET group, 17 patients in the treatment-as-usual group, and 43 HCs. RESULTS: Our results show differences in the Salience Network when comparing the CET group to the treatment-as-usual group (TAU). Functional connectivity between the anterior cingulate Cortex (ACC) and the insula was increased after CET, whereas it was decreased from ACC to the putamen and globus pallidus. Further, increased connectivity with the precuneus was found in the dorsal attention network after cue exposure treatment. CONCLUSIONS: These findings suggest that cue exposure therapy changes the resting-state brain connectivity with additional effects to the standard psychotherapy treatment. Hence, our study results suggest why including CET in standard therapies might improve the preparation of patients in front of daily situations.

The Role of Unawareness, Volition, and Neural Hyperconnectivity in Alcohol Use Disorder: A Functional Magnetic Resonance Imaging Study.

BACKGROUND: Automated alcohol craving and habitual alcohol consumption characterize the later stages of alcohol use disorder (AUD). This study reanalyzed previously collected functional neuroimaging data in combination with the Craving Automated Scale for Alcohol (CAS-A) questionnaire to investigate the neural correlates and brain networks underlying automated drinking characterized by unawareness and nonvolition. METHODS: We assessed 49 abstinent male patients with AUD and 36 male healthy control participants during a functional magnetic resonance imaging-based alcohol cue-reactivity task. We performed whole-brain analyses examining the associations between CAS-A scores and other clinical instruments and neural activation patterns in the alcohol versus neutral contrast. Furthermore, we performed psychophysiological interaction analyses to assess the functional connectivity between predefined seed regions and other brain areas. RESULTS: In patients with AUD, higher CAS-A scores correlated with greater activation in dorsal striatal, pallidal, and prefrontal regions, including frontal white matter, and with lower activation in visual and motor processing regions. Between-group psychophysiological interaction analyses showed extensive connectivity between the seed regions inferior frontal gyrus and angular gyrus and several frontal, parietal, and temporal brain regions in AUD versus healthy control participants. CONCLUSIONS: The present study applied a new lens to previously acquired alcohol cue-reactivity functional magnetic resonance imaging data by correlating neural activation patterns with clinical CAS-A scores to elucidate potential neural correlates of automated alcohol craving and habitual alcohol consumption. Our results support previous findings showing that alcohol addiction is associated with hyperactivation in habit-processing regions, with hypoactivation in areas mediating motor and attention processing, and with general hyperconnectivity.

Decoding fMRI alcohol cue reactivity and its association with drinking behaviour.

BACKGROUND: Cue reactivity, the enhanced sensitivity to conditioned cues, is associated with habitual and compulsive alcohol consumption. However, most previous studies in alcohol use disorder (AUD) compared brain activity between alcohol and neutral conditions, solely as cue-triggered neural reactivity. OBJECTIVE: This study aims to find the neural subprocesses during the processing of visual alcohol cues in AUD individuals, and how these neural patterns are predictive for relapse. METHODS: Using cue reactivity and rating tasks, we separately modelled the patterns decoding the processes of visual object recognition and reward appraisal of alcohol cues with representational similarity analysis, and compared the decoding involvements (ie, distance between neural responses and hypothesised decoding models) between AUD and healthy individuals. We further explored connectivity between the identified neural systems and the whole brain and predicted relapse within 6 months using decoding involvements of the neural patterns. FINDINGS: AUD individuals, compared with healthy individuals, showed higher involvement of motor-related brain regions in decoding visual features, and their reward, habit and executive networks were more engaged in appraising reward values. Connectivity analyses showed the involved neural systems were widely connected with higher cognitive networks during alcohol cue processing in AUD individuals, and decoding involvements of frontal eye fields and dorsolateral prefrontal cortex could contribute to relapse prediction. CONCLUSIONS: These findings provide insight into how AUD individuals differently decode alcohol cues compared with healthy participants, from the componential processes of visual object recognition and reward appraisal. CLINICAL IMPLICATIONS: The identified patterns are suggested as biomarkers and potential therapeutic targets in AUD.

Association between iron accumulation in the dorsal striatum and compulsive drinking in alcohol use disorder.

RATIONALE: Brain iron accumulation has been observed in neuropsychiatric disorders and shown to be related to neurodegeneration. OBJECTIVES: In this study, we used quantitative susceptibility mapping (QSM), an emerging MRI technique developed for quantifying tissue magnetic susceptibility, to examine brain iron accumulation in individuals with alcohol use disorder (AUD) and its relation to compulsive drinking. METHODS: Based on our previous projects, QSM was performed as a secondary analysis with gradient echo sequence images, in 186 individuals with AUD and 274 healthy participants. Whole-brain susceptibility values were calculated with morphology-enabled dipole inversion and referenced to the cerebrospinal fluid. Then, the susceptibility maps were compared between AUD individuals and healthy participants. The relationship between drinking patterns and susceptibility was explored. RESULTS: Whole-brain analyses showed that the susceptibility in the dorsal striatum (putamen and caudate) among AUD individuals was higher than healthy participants and was positively related to the Obsessive Compulsive Drinking Scale (OCDS) scores and the amount of drinking in the past three months. CONCLUSIONS: Increased susceptibility suggests higher iron accumulation in the dorsal striatum in AUD. This surrogate for the brain iron level was linearly associated with the compulsive drinking pattern and the recent amount of drinking, which provides us a new clinical perspective in relation to brain iron accumulation, and also might indicate an association of AUD with neuroinflammation as a consequence of brain iron accumulation. The iron accumulation in the striatum is further relevant for functional imaging studies in AUD by potentially producing signal dropout and artefacts in fMRI images.

Neural cue reactivity is not stronger in male than in female patients with alcohol use disorder.

Background: Males consume more alcohol than females, and alcohol use disorder (AUD) is more prevalent in males than females. However, females progress faster to AUD. Sex differences in neural alcohol cue reactivity were previously observed in young social drinkers, indicating a role of hypersensitivity to alcohol-related cues in very early stages of addiction. To our knowledge, this is the first study on patients diagnosed with AUD to test sex differences in neural reactivity to alcohol cues in order to widen previous findings. Methods: We analyzed data from previous studies, using a well-established functional magnetic resonance imaging (fMRI) paradigm to compare neural reactivity to alcohol cues between 42 female and 124 male patients with AUD (mean age 45 and 46 years) in predefined regions of interest that were implicated by previous studies (ventral and dorsal striatum as well as caudate, putamen, amygdala, hippocampus, insula, anterior cingulate cortex, and medial prefrontal cortex) using independent samples t-tests. Post-hoc, effect size calculations were performed. Results: Throughout all nine regions of interest, we found no statistically significant sex differences in neural reactivity toward alcoholic pictures alone or in comparison to neutral pictures (p > 0.05, FDR-corrected). Post-hoc effect size estimates indicated a magnitude between 0.137 and 0.418 (Hedge's g) on alcohol reactivity to alcohol cues compared to neutral cues and indicate very small to less than medium effect sizes in the direction of higher cue reactivity in female patients. Conclusion: Previous studies showed sex differences in neural alcohol cue reactivity in younger social and problematic alcohol drinkers, i.e., stronger striatal cue-reactivity in males. After correction for multiple comparisons, we did not observe significant sex differences in a cohort of middle-aged females and males with AUD. Sex differences that are present during early phases of addiction development might disappear at later stages of AUD and might thus be considered as clinically less relevant in patients with more severe AUD.

Vulnerability for alcohol use disorder after adverse childhood experiences (AUDACE): protocol for a longitudinal fMRI study assessing neuropsychobiological risk factors for relapse.

BACKGROUND: Adverse childhood experiences (ACE) are common and may predispose affected individuals to various health problems, including alcohol use disorder (AUD). Although a relationship between ACE and AUD has been well-established, potential mechanisms that may underlie this relationship remain to be elucidated. The importance of these mechanisms with respect to relapse risk is of particular interest, given the clinical relevance of relapse in addictions. Thus, the aim of this study is to longitudinally assess the role of clinically relevant variables in the relationship between ACE and AUD, namely stress sensitivity, emotion processing, cue reactivity and cognitive functioning (response inhibition and working memory), in relation to relapse risk. METHODS AND ANALYSIS: In this observational, longitudinal case-control study, 36 patients with AUD and heavy drinkers with varying degrees of ACE from a previous project (NCT03758053) as well as newly recruited participants from the same study population will be assessed. Besides measuring long-term relapse in AUD by re-examining these 36 previous participants after 2-2.5 years, factors contributing to short-term relapse will be examined by reassessing all participants on a 3-month follow-up. Furthermore, participants with no or mild ACE will be compared with participants with moderate to severe ACE to assess between-subject differences in risk factors for AUD. Questionnaires and interviews will thus be used to cover individuals' drinking behaviour and ACE. Emotion processing, stress sensitivity, cue reactivity and cognitive functioning will be assessed using task-based functional MRI (fMRI). Additionally, saliva cortisol and blood samples will be taken to measure hormonal stress response and to perform genome wide association analyses, respectively. The general linear model will be applied on the first level fMRI analyses, whereas for the second level analyses and analyses of behavioural data, t-tests, regression analyses, repeated-measures and one-way analysis of variances will be used. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of the Medical Faculty Mannheim of Heidelberg University (ethics approval number: 2018-560N-MA with amendment from 29 June 2021). The findings of this study will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05048758; Pre-results, clinicaltrials.gov.

The reliability and validity of a screening scale for online gaming disorder among Chinese adolescents and young adults.

BACKGROUND: In recent years, there have been frequent reports of gaming disorder in China, with more focus on young people. We developed and psychometrically tested a Gaming Disorder screening scale (i.e., Gaming Disorder Screening Scale - GDSS) for Chinese adolescents and young adults, based on the existing scales and diagnostic criteria, but also considering the development status of China. METHODS: For testing content and criterion validity, 1747 participants competed the GDSS and the Internet Addiction Test (IAT). After 15 days, 400 participants were retested with the scales for to assess test-retest reliability. Besides, 200 game players were interviewed for a diagnosis of gaming disorder. RESULTS: The Cronbach's alpha coefficient on the GDSS was 0.93. The test-retest coefficient of 0.79. Principal components analysis identified three factors accounting for 62.4% of the variance; behavior, functioning, cognition and emotion. Confirmatory factor analysis showed a good model fit to the data (χ2 /df = 5.581; RMSEA =0.074; TLI = 0.916, CFI = 0.928). The overall model fit was significantly good in the measurement invariance tested across genders and different age groups. Based on the clinical interview, the screening cut-off point was determined to be ≥47 (sensitivity 41.4%, specificity 82.3%). CONCLUSIONS: The GDSS demonstrated good reliability and validity aspects for screening online gaming disorder among Chinese adolescents and young adults.

A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

Reliability and validity of DSM-IV and DSM-5 methamphetamine use disorder diagnoses using the Chinese Version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

BACKGROUND: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) was developed to assess substance-use disorders and other psychiatric traits. We translated the SSADDA into Chinese and evaluated its inter-rater reliability and concurrent validity in diagnosing DSM-IV methamphetamine (MA) dependence and DSM-5 MA-use disorder (MUD). METHODS: The sample comprised 231 participants who were interviewed using the Chinese SSADDA and the Mini-International Neuropsychiatric Interview (Chinese MINI) for concurrent validation. Of the 231 participants, 191 were interviewed by two different interviewers two weeks apart. We evaluated the inter-rater reliability and concurrent validity of the diagnoses using percent agreement and Cohen's kappa coefficient (κ). Cohen's linear weighted kappa was used to assess the reliability of DSM-5 MUD severity. RESULTS: It showed good inter-rater reliability and no significant differences among the DSM-5 MUD (κ = 0.71), DSM-IV MA abuse or dependence (κ = 0.72), and the DSM-IV diagnoses of MA dependence (κ = 0.66) and abuse (κ = 0.68) tested separately. The weighted kappa was 0.67 across the three DSM-5 MUD severity levels. The reliability of each individual diagnostic criterion for DSM-5 MUD ranged from fair to excellent (κ = 0.41-0.80), except for "repeated attempts to quit/control use" (κ = 0.38). The concurrent validity based on MINI-derived diagnoses ranged from good to excellent (κ = 0.65-0.78). CONCLUSIONS: This study shows that the Chinese version of SSADDA has good reliability and validity among Chinese MA users.

Nature of glutamate alterations in substance dependence: A systematic review and meta-analysis of proton magnetic resonance spectroscopy studies.

Animal studies have reported the brain glutamatergic dysfunction in substance dependence. However, proton magnetic resonance spectroscopy (1H-MRS) studies of glutamate in substance-dependent patients published contradicting results. In order to investigate the characteristics of brain glutamatergic alterations in substance-dependent patients, we conducted systematic reviews and meta-analyses of 1H-MRS studies that have investigated the glutamate, glutamine, and Glx (glutamate + glutamine) concentration in substance-dependent patients. Multiple databases were searched until Sep 10, 2020. Twenty-nine studies comprising 982 patients and 787 controls were included. There was significantly decreased glutamate level in dorsolateral prefrontal cortex in patients compared with controls. Higher glutamate levels in medial prefrontal cortex and basal ganglia region were also demonstrated in patients compared with controls. Subgroup analyses based on the substance type and abstinence period (short vs medium-term abstinence period) were performed. The results revealed Glx and glutamate concentrations in all investigated brain regions were not different in patients with any types of substance dependence compared with controls. The abstinence period had no effect on the glutamate levels. In summary, substance dependence is associated with glutamatergic dysfunction of prefrontal cortex and basal ganglia. Present findings partially support the hypothesis that addiction is associated with abnormal brain glutamatergic neurotransmission.

The exploration of optimized protocol for repetitive transcranial magnetic stimulation in the treatment of methamphetamine use disorder: A randomized sham-controlled study.

BACKGROUND: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. METHODS: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). FINDINGS: The three real TBS groups had more craving decrease effect than the sham group (p<0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A (p = 0.03). Group C was effective in improve depression symptoms (p = 0.04) and withdrawal symptom (p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality (p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response. INTERPRETATION: The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients. FUNDING: This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100).

Disrupted brain network dynamics and cognitive functions in methamphetamine use disorder: insights from EEG microstates.

BACKGROUND: Dysfunction in brain network dynamics has been found to correlate with many psychiatric disorders. However, there is limited research regarding resting electroencephalogram (EEG) brain network and its association with cognitive process for patients with methamphetamine use disorder (MUD). This study aimed at using EEG microstate analysis to determine whether brain network dynamics in patients with MUD differ from those of healthy controls (HC). METHODS: A total of 55 MUD patients and 27 matched healthy controls were included for analysis. The resting brain activity was recorded by 64-channel electroencephalography. EEG microstate parameters and intracerebral current sources of each EEG microstate were compared between the two groups. Generalized linear regression model was used to explore the correlation between significant microstates with drug history and cognitive functions. RESULTS: MUD patients showed lower mean durations of the microstate classes A and B, and a higher global explained variance of the microstate class C. Besides, MUD patients presented with different current density power in microstates A, B, and C relative to the HC. The generalized linear model showed that MA use frequency is negatively correlated with the MMD of class A. Further, the generalized linear model showed that MA use frequency, scores of Two-back task, and the error rate of MA word are correlated with the MMD and GEV of class B, respectively. CONCLUSIONS: Intracranial current source densities of resting EEG microstates are disrupted in MUD patients, hence causing temporal changes in microstate topographies, which are correlated with attention bias and history of drug use.

Smaller Feedback-Related Negativity (FRN) Reflects the Risky Decision-Making Deficits of Methamphetamine Dependent Individuals.

Methamphetamine (MA) chronic users show risky decision-making deficits. However, the neural mechanisms underlying these deficits remain unclear. A case-control study was conducted to understand how MA users and healthy controls differ in electrophysiological responses associated with series decision-making. Electroencephalography of 31 MA users and 27 healthy controls was recorded when they performed the Balloon Analogue Risk Task involving risky decision-making with uncertain gain or loss. Feedback-related negativity (FRN) was measured and their association with their risky decision-making and impulsivity were examined. Compared to healthy controls, MA users showed smaller peak FRN amplitudes in fronto-central electrodes (F (1, 56) =4.559, p=0.037), and the attenuated peak FRN amplitudes correlated with more risk-taking behavior (r=0.48, p=0.012). Besides, MA users exhibited later FRN (F (1, 56) = 7.561, p=0.008) and earlier P300 (F (1, 56) = 3.582, p = 0.041) compared to healthy controls in fronto-central electrodes, which were correlated with higher score of impulsivity. These findings provided further evidence that MA users showed insensitivity to negative feedback in risky decision-making. FRN might be a promising biomarker of dependence.

Effectiveness of music therapy on improving treatment motivation and emotion in female patients with methamphetamine use disorder: A randomized controlled trial.

OBJECTIVES: The purpose of the study was to investigate whether Group Music Therapy (GMT) could enhance the treatment motivation and change the negative emotion among female patients with methamphetamine use disorder in a randomized clinical trial. Methods: Participants (N = 60) were randomized to the group of GMT combined with treatment as usual (TAU) or the group with TAU only. Questionnaire of Motivation for Abstaining from Drugs was used to measure the motivation for abstaining from drugs of the female patients. And Self-Rating Depression Scale and Self-Rating Anxiety Scale were used to measure negative emotion of participants. The measurements were conducted at T0 (baseline), T1 (post 13 sessions of intervention) and T2 (3-month follow-up after T1) by the independent trained researcher. Results: The postintervention and 3-month follow-up results according to the intention-to-treat principle indicated that GMT + TAU intervention showed significantly positive group-by-time effect on the scores of the subscale-tending to rehabilitation-internal motivation (p = 0.01) and avoiding abuse-external motivation (p = 0.04). In 3-month follow-up, total scores of the questionnaire of motivation for abstaining from drugs (p = 0.02), scores of avoiding abuse-internal motivation subscale (p = 0.05), and scores of confidence of abstaining from drugs subscale (p = 0.01) in GMT + TAU were also presented with significantly positive group x time effect. The changes of total score of Questionnaire of Motivation for Abstaining from Drugs (from baseline to 3-month follow-up) was significantly positive association with the changes of scores of SAS in GMT + TAU group (r = -0.55, p = 0.00). Conclusions: The present study suggests that GMT could be used as an effective treatment strategy to enhance treatment motivation of female patients with methamphetamine use disorder.

History of Alcohol and Opioid Use Impacts on the Long-Term Recovery Trajectories of Methamphetamine-Dependent Patients.

Methamphetamine (MA) has become one of the most widely used illicit substances in China and the rest of the world as well. Relapse, incarceration or death was observed after compulsory rehabilitation. However, the knowledge of recovery patterns among MA-dependent patients, early or late occurrence of these negative consequences, is limited. The aims were to explore the long-term recovery patterns and associated factors among MA-dependent patients in Shanghai, China. MA-dependent patients discharged from Shanghai compulsory rehabilitation facilities in 2009-2012 were recruited in a baseline survey. The baseline data of 232 patients were then linked with their long-term follow-up data from official records. Group-based trajectory modeling was applied to identify distinctive trajectories of the occurrence of negative consequences (incarceration, or readmission to compulsory rehabilitation, or death). Patients with monthly status data were found recovering with three distinctive trajectories: rare, late, and early occurrence groups. Multinomial logistic regression showed that having alcohol use history was associated with an increased likelihood of being in the late occurrence group relative to the rare occurrence group. Having opioid use history was associated with an increased likelihood of being in the early occurrence group relative to the rare occurrence group. In addition, being female was associated with decreased likelihood of being in the late occurrence group relative to the rare occurrence group.

Drug-related Virtual Reality Cue Reactivity is Associated with Gamma Activity in Reward and Executive Control Circuit in Methamphetamine Use Disorders.

BACKGROUND: Accumulated studies in substance use disorders indicated that the mesocorticolimbic reward circuit and executive control circuit played interactive roles in the cue-reactivity and gamma oscillatory in the cortex, as well as autonomic nervous activity was associated with it. AIM OF THE STUDY: This study aimed to explore the mechanism of processing drug-related cues. METHODS: Sixty methamphetamine users were recruited and exposed to the drug-related virtual reality (VR) environments. Self-reported craving was assessed and skin conductance level (SCL) and heart rate variability were used to measure the autonomic nervous reactivity. With source estimation, gamma current density was used to measure the activity of medial prefrontal cortex/orbitofrontal cortex (MPFC/OFC) and dorsolateral prefrontal cortex (DLPFC) which are responsible for the mesocorticolimbic reward circuit and the executive control circuit. RESULTS: The VR drug-related cue induced an increased craving and SCL compared with the neutral condition. Gamma activity in MPFC/OFC and right DLPFC were decreased after cue exposure and predicted the SCL changes. However, no association was found between self-reported craving and electrophysiological response. CONCLUSIONS: Cue-reactivity in cortex and ANS, as well as their association, were observed in this study. Cue-induced electrophysiological responses were related to gamma activity in the mesocorticolimbic reward circuit and the executive control circuit.

A Research of Methamphetamine Induced Psychosis in 1,430 Individuals With Methamphetamine Use Disorder: Clinical Features and Possible Risk Factors.

Background and Aims: Methamphetamine (MA) abuse is commonly associated with the development of psychotic symptoms. The predictors and related risk factors of MA induced psychosis (MIP) are poorly understood. We investigated the occurrence of MIP, and analyzed the clinical features and possible risk factors among individuals with MA use disorder Method: One thousand four hundred and thirty participants with MA use disorder were recruited from compulsory rehabilitation centers in Shanghai. A structured questionnaire including demographic characteristics, drug use history, visual analog scales, Beck Depression Inventory-13 (BDI-13), and Hamilton anxiety scale-14 (HAMA-14) were used to collect clinical related information. Fifty-six participants had accomplished the test of CogState Battery. Results: Among the 1430 individuals with MA use disorder, 37.1% were diagnosed as MIP according DSM-IV. There were significant differences in age, marital status, age of drug use onset, MA use years, Average MA use dose, interval of MA use, maximum dose, concurrent use of alcohol, and other drugs, VAS score, MA dependence, BDI-13 scores, HAMA-14 scores, verbal learning memory, and visual learning memory between the MIP group and the none MIP group (P < 0.05). The age of drug use onset (OR = 0.978, p = 0.011), average drug use dose (OR = 1.800, p = 0.015), craving score (OR = 1.069, p = 0.031), MA dependence (OR = 2.214, p < 0.001), and HAMA scores (OR = 1.028, p < 0.001) were associated to MIP. Conclusion: Individuals with MIP had more severe drug use problems, emotional symptoms and cognitive impairment. Earlier onset of drug use, higher quantity of drug use, higher craving, middle or severe drug use disorder and more anxiety symptoms may be related risk factors of MIP.

A Newly Designed Mobile-Based Computerized Cognitive Addiction Therapy App for the Improvement of Cognition Impairments and Risk Decision Making in Methamphetamine Use Disorder: Randomized Controlled Trial.

BACKGROUND: Cognitive rehabilitation therapy has been found to improve cognitive deficits and impulse control problems in methamphetamine use disorder (MUD). However, there is limited research regarding this therapy's feasibility when using mobile-based health technologies in supporting recovery from MUD in China. OBJECTIVE: The main aim of this study was to test whether 4 weeks of a newly designed computerized cognitive addiction therapy (CCAT) app can improve cognitive impairments, eliminate drug-related attention bias, and attenuate risk decision-making behaviors in participants with MUD. METHODS: Forty MUD participants were assigned randomly to either the CCAT group (n=20), who received 4 weeks of CCAT plus regular detoxification treatment as usual, or the control group (n=20), who only received the regular detoxification treatment as usual, in drug rehabilitation centers in Shanghai. The CCAT was designed by combine methamphetamine use-related picture stimuli with cognitive training with the aim of improving cognitive function and eliminating drug-related attention bias. The CogState Battery, Delay Discounting Task (DDT), Iowa Gambling Task (IGT), and Balloon Analog Risk Task (BART) were administered face-to-face to all participants before and after CCAT interventions. RESULTS: Forty male patients were recruited. The mean age was 32.70 (SD 5.27) years in the CCAT group and mean 35.05 (SD 8.02) years in the control group. Compared to the control group, CCAT improved working memory in the CCAT group (P=.01). Group×time interactions were observed among DDT, IGT, and BART tasks, with rates of discounting delayed rewards, IGT, and BART scores (P<.001) being reduced among those who received CCAT, whereas no changes were found in the control group. CONCLUSIONS: The newly designed CCAT can help to improve cognitive impairment and impulsive control in MUD. Further study is needed to understand the underlying brain mechanisms of the cognitive therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03318081; https://clinicaltrials.gov/ct2/show/NCT03318081 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT03318081).