Abnormal regional homogeneity of drug-naive obsessive-compulsive patients

To explore the possible abnormal resting-state activity in patients with obsessive-compulsive disorder (OCD), the regional homogeneity (ReHo) of 22 pairs of patients and well-matched healthy controls was calculated. Compared with controls, the patients showed higher ReHo in the left anterior cingulate cortex, but lower ReHo in the left inferior temporal gyrus. These findings supported the abnormal resting-state brain activity in drug-naive OCD patients. No significant correlations between ReHo value and four clinical characteristics were found, suggesting that abnormal ReHo might be trait-related in OCD. NeuroReport 21:786-790 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

阿片药物依赖的神经机制---内侧前额叶与药物的心理依赖

Mental dependence, characterized by craving and impulsive seeking behavior, is the matter of intensive study in the field of drug addiction. The mesolimbic dopamine system has been suggested to play an important role in rewarding of drugs and relapse. Although chronic drug use can induce neuroadaptations of the mesolimbic system and changes of drug reinforcement, these mechanisms cannot fully account for the craving and the compulsive drug-using behavior of addicts. Acknowledging the reinforcement effects of drugs, most previous studies have studied the impact of environmental cues and conditioned learning on addiction behavior, often using established classical or operant conditioning model. These studies, however, paid little attention to the role of cognitive control and emotion in addiction. These mental factors that are believed to have an important influence on conditioned learning. The medial prefrontal cortex (mPFC) has close anatomic and functional connections with the mesolimbic dopamine system. A number of the cognitive neurological studies demonstrate that mPFC is involved in motivation, emotional regulation, monitoring of responses and other executive functions. Thus we speculated that the function of abnormality in mPFC following chronic drug use would cause related to the abnormal behavior in addicts including impulse and emotional changes. In the present study of a series of experiments, we used functional magnetic resonance imaging to examine the hemodynamic response of the mPFC and related circuits to various cognitive and emotional stimuli in heroin addicts and to explore the underlying dopamine neuromechnism by microinjection of tool drugs into the mPFC in laboratory animals. In the first experiment, we found that heroin patients, relative to the normal controls, took a much shorter time and committed more errors in completing the more demanding of cognitive regulation in the reverse condition of the task, while the neural activity in anterior cingulate cortex (ACC) was attenuated. In the second experiment, the scores of the heroin patients in self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were significantly higher than the normal controls and they rated the negative pictures more aversive than the normal controls. Being congruent with the behavioral results, hemodynamic response to negative pictures showed significant difference between the two groups in bilateral ventral mPFC (VMPFC), amygdala, and right thalamus. The VMPFC of patients showed increased activation than normal controls, whereas activation in the amygdala of patients was weaker than that in normal subjects. Our third experiment showed that microinjection of D1 receptor agonist SKF38393 into the mPFC of rats decreased hyperactivity, which was induced by morphine injection, in contrast, D1 receptor antagonist SCH23390 increased the hyperactivity, These findings suggest: (1) The behavior and neural activity in ACC of addicts changed in chronic drug users. Their impulsive behavior might result from the abnormal neural activity in the mPFC especially the ACC. (2) Heroine patients were more depress and anxiety than normal controls. The dysfunction of the mPFC---amygdala circuit of heroine addicts might be related to the abnormal emotion response. (3) Dopamine in the mPFC has an inhibitory effect on morphine induced behavior. The hyperactivity induced by chronic morphine was reduced by dopamine increase with D1 receptor agonist, confirm the first experiment that the neuroadaption of mPFC system induced by chronic morphine administration appears to be the substrate the impulse behavior of drug users.

去甲肾上腺素参与吗啡神经适应性改变的中枢机制

That relapse still exists even after prolonged withdrawal is a difficult issue in the medical cure of drug addiction. Neuro-adaptation induced by prolonged exposure to addictive drugs is the neural mechanisms of both compulsive drug seeking and relapse.Neuro-adaptation caused by addictive drugs increases the individuals’ response to drugs and on the other hand, it reduces the response to natural reward in withdrawn individuals.There must be common neural mechanisms between the co-existing phenomena, and there must also be unique neural mechanisms in the drugs.To reveal the neuro-adaptation arising in the process from random, controllable drug-use to uncontrollable compulsive drug seeking is of great significance both theoretically and practically.Based on the above hypothesis, in order to reveal the function of alpha adrenergic receptor in compulsive drug-seeking motivation during the process of drug addiction, using sensitization of morphine-induced psychomotor activity as behavioral model, through the method of behavioral pharmacology, the neural mechanisms of alpha adrenergic receptor’s involvement in the process of addiction has been studied.The adjustment function caused by alpha receptors in medial prefrontal cortex and nucleus accumbens to morphine-induced psychomotor activity has been compared in the period of first use of drugs and in repetitive-use period. Furthermore, the effect on novelty seeking caused by alpha-receptors in relevant brain areas has also been compared. Major results are as follow: 1 After prolonged morphine exposure, rats’ response to morphine-induced psychomotor activity is strengthened and response to novel object induced reward weakened. 2 Injection of prazosin in medial prefrontal cortex will block morphine-induced psychomotor activity of naïve rats, however, it will not block that of morphine-withdrawn rats, but it will block the novelty seeking behavior of morphine-withdrawn rats. 3 Injection of clonidine in medial prefrontal cortex will block morphine-induced psychomotor effect of both naïve rats and morphine-withdrawn rats, and will block the novelty seeking behavior of morphine-withdrawn rats. 4 Injection of prazosin in nucleus accumbens will not affect the morphine-induced psychomotor effect of either naïve rats or morphine-withdrawn rats, nor will it affect the novelty seeking behavior of morphine-withdrawn rats. 5 Injection of clonidine in nucleus accumbens will block morphine-induced psychomotor effect of naïve rats, however, it will not block that of morphine-withdrawn rats, nor will it affect the novelty seeking behavior of morphine-withdrawn rats. These results show: 1 The weakening of the function of alpha1 receptors in medial prefrontal cortex and alpha2 receptors in nucleus accumbens caused by repetitive exposure to morphine is probably the cause of compulsive drug-seeking activity. 2 Blocking alpha1 receptors in medial prefrontal cortex accelerates the loss of interest in natural reward after morphine withdrawal. 3 Blocking alpha2 receptors in medial prefrontal cortex not only restrains drug-seeking motivation, but also blocks the individual’s seeking motivation for novelty stimulus, which suggests that, while selecting medicine for curing addiction, it should be considered to reduce the influence on natural reward as much as possible and to avoid major side-effect.

慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制

In recent years, the deficit of inhibition has become an important reason for explaining addiction. Response inhibition resembles the compulsive drug seeking behavior and it is the basement of addiction inhibition deficits. However, there were no enough evidence for the relationship between addiction and response inhibition deficits and the results of the neuro mechanisms studies remains unclear. Few studies has focused on the exploring the heroin users. Among those paradigms for study response inhibition deficits, stop signal is a very suitable model for the representation of compulsive drug seeking, but only a few researches has worked on this paradigm. In this study, we selected about 100 heroin abusers and had behaviour and neuro imaging scannings for investigating the response inhibition deficits. The behaviour researches found: first, the chronic heroin users had longer reaction time than control group and this reaction time were not affected by stop signals in heroin users. Second, heroin users had less waiting time than control group and they were more impulsive but less flexibility. Their erro monitoring and flexibale adjustment ability decreased. Third, the SSRT of heroin users was significantly longer than control group. These results suggested that the inhibition of heroin users were impaired. Further investigation showed that the SSRT of heroin users had positive correlation of four factor scores of ASI and the macro correlation coefficient was factor three of drug use. This correlation suggested that drug use was the main reason of inhibition deficits. fMRI results mainly focused on the ANOVA analysis for group difference. First, there was no intensity difference in M1 and SMA brain areas between the two groups. Second, heroin users had less activation in right dorsalateral prefrontal cortex, right inferior prefrontal cortex and anterior cingulated cortex, while in bilateral striatum and amygdala, heroin users had more activation than control group. The right prefrontal cortex was indentified as the main inhibition brain area. The anterior cingulated cortex has relationship with erro monitoring and amygdale was an important brain area for impulsivity and emotion control. The network of these brain areas was envovled in impulsivity and inhibition and it was suggested the mainly damaged network for heroin users’ disinhibition. We also investigated the gray matter changes of heroin users and found that chonic heroin use made their gray matter density decreased in prefrontal cortex (including bilateral dorsalateral prefrontal cortex, obital frontal cortex, inferior prefrontal cortex) and anterior cingulated cortex. The gray matter density in these brain regions had negative correlation with drug use duration. In conclusion, we indentified the disinhibition of heroin users and its neuro mechanism. Their compulsivity brain areas had more activation than control group and their inhibition brain areas had less activation than normal control. On the other side, the biological mechanism of this activation changes was the gray matter density decrease in these brain areas.

海洛因成瘾者决策障碍及其行为机制的研究----短视行为及冲动、强迫和药物在决策中的作用

Addiction can be investigated from the perspective of decision making. Addicts usually make incorrect decisions when facing drug-related cues or they are driven to drugs, resulting in repeated drug seeking and taking. The present study adopted temporal discounting as behavioral task and on the basis of the fact that heroin addicts discounted more steeply than health participants (addicts preferred to choose immediate but smaller reward, regarded as myopia) which was consistent with previous research, three questions was raised and being concentrated on in this study. The first question was whether the character of myopia would be revealed in a somewhat complicated task? We designed a card game in which the participants were tested whether they would play the trump card in order to win a trick but not the whole game. Addicts played the trump card significantly earlier than controls did, indicating they focused on immediate single trick but not the game. Moreover, the performance in the card game and temporal discounting correlated significantly, suggesting addicts would display myopic decision not only in simply task like temporal discounting but also in task more complicated and similar to daily-life decision. Secondly, the present study adopted various kinds of temporal discounting tasks. In previous research, temporal discounting gain task was usually adopted. In the present study, we also adopted temporal discounting loss task. In either gain or loss task, there are two delayed amounts. Results showed in each decision condition addicts made poorer performance compared with control but in larger amount condition, addicts actually improved their decision performance. Meanwhile, addicts did not show loss aversion due to their close discount rates in gain and loss task while for controls, the discount rates were much lower in loss task than those in gain task. Thus we demonstrated that addicts were insensitive to negative outcomes by the method of temporal discounting. Finally, we investigated three mechanisms which exerted impacts on decision making. We adopted Go/NoGo task to test impulsivity and found addicts commits more errors (higher impulsivity) than controls did. We also designed a behavioral task which could be used to test drug-related compulsive behavior on human participants. Results showed addicts produced stereotyped key-pressing behavior when presented with drug-related cues. Furthermore, it was found participants with higher impulsivity displayed poorer performance in decision making but addicts with higher compulsivity only made poorer performance in smaller amount decision and the correlation between compulsivity and decision making was relative weak. In order to investigate the role of susceptibility and effect of drugs, we adopted years of abusing heroin as the indictor and discovered addicts with longer history of heroin abusing made poorer performance in smaller amount condition than addicts with shorter history. Also, the earlier the addicts began to use drug, the worse they would do in the smaller amount decision. The results here indicated drug itself could exert impact on decision making in certain condition. The present study revealed three characters of heroin addicts from the aspect of decision making: (1) focusing upon current benefit due to they preferred to choose immediate gain and delayed loss; (2) showed no loss aversion compared with healthy participants (3) inability to inhibit inappropriate response particularly when facing drug-related cue. These characters contribute to the facts that addicts seek and take drugs repeatedly while ignoring the negative consequences caused by abusing drugs.

中学生强迫症状及其心理、环境危险因素和整合模型研究

Obsessive-Compulsive Symptoms, which are one of common factors effected on mental health of secondary school students, have been rarely studied at home and abroad. In accordance with the problems existed in these literature up till now, the thesis had mainly studied the measured tool, contents and structure, developmental features, psychosocial risk factors and integrated model of obsessive-compulsive symptoms from them by means of investigation with quetionnaires. The entire research was divided into three phases. 3185 students(age 14.68±1.75 years) were firstly measured with the 20-item Leyton Obsessional Inventory-Child Version(LOI-CV) at four secondary schools including six grades in Beijing city, which was applied to revise LOI-CV, and to study the structure and contents, developmental features and screen of obsessive-compulsive symptoms. Then, 216 subjects with obsessive-compulsive symptoms, paired with controls in the light of school, grade and gender, were investigated with 10 self-rating scales on obsessive-compulsive symptoms, anxiety, depression, personality, coping and attributional style, negative life events, parent's rearing style, family environment and life adaptation in school, and with an inventory on social demography. The results were used to explore psychosocial risk factors and integrated model of obsessive-compulsive symptoms. The third survey was only carried out, about two months after the second, among 264 subjects with obsessive-compulsive symptoms through MMOCI and Negative Life Event Scale for Adolescents, in order to probe into the integrated model. The research had mainly found: (1) LOI-CV can be used as a screen tool for obsessive-compulsive symptoms in urban adolescents in China; (2) Total screening-out ratio of obsessive-compulsive symptoms was 13.6% (male:15.0%, female:12.2%). The most common manifestations of obsessive-compulsive symptoms were hating dirt and contamination, doing things in exact manner, angry if someone messes desk, bad conscience but no one else, worry about cleanliness, repeated thoughts or words; the least were favorite or special number, spending extra time on homework, special number or words to avoid, talking or moving to avoid bad luck, fussy about hands. The checking and repetition, cleanliness and tidiness, general obsessions were more common forms than numbers-luck; (3) No differences were existed in serious degree of obsessive-compulsive symptoms, but the screening-out ratio in male was higher than it in female; (4) No differences were detected in the serious degree of obsessive-compulsive symptoms except the scores of cleanliness and tidiness among grades, but the screening-out ratio of the grades justly entering secondary school or going to graduate were higher than other ones; (5) The main psychosocial risk factors for obsessive-compulsive symptoms included anxiety, mother's over-protecting and over-interfering, fantasy, flexibility, self-actualization, peers relationship, sense of responsibility, negative life events, mother's occupation, help-seeking, and (6) The integrated model on psychosocial risk factors suggested that the possible developed and sustained mechanism of obsessive-compulsive symptoms was that personality, coping and attributional styles constructed the developmental diathesis foundation of obsessive-compulsive symptoms; negative life events were promoting factors of them. There was a dynamic interaction between personality and environmental factors. Negative emotion played a core role in the developmental process of them. The continued existence of obsessive-compulsive symptoms was related to pre-existed obsessive-compulsive symptoms and negative life events experienced by an individual. Therefore, this research not only let us get a deeper understanding of obsessive-compulsive symptoms and more entirely find out psychosocial risk factors, firstly applied diathesis-stress theory to comprehend the psychological mechanism of obsessive-compulsive symptoms and, moreover, elaborate and expand it, but also has more important practice significance of treatment, prevent and education for obsessive-compulsive symptoms in secondary school students.