Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD)

Object We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. METHODS: Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. RESULTS: Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. Conclusion Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.     

Plato's Hypothetical Inquiry in the Meno

This paper argues that the hypothesis proposed in the Meno is the proposition ‘virtue is good’ alone, and that its epistemic nature is essentially insecure. It has been an object of huge scholarly debate which other hypothesis Socrates posited with regard to the relationship between virtue and knowledge. This debate is, however, misleading in the sense of making us believe that the hypothesis that virtue is good is regarded as a truism in the light of the process of positing a higher hypothesis described in the Phaedo and the Republic. I argue that the hypothesis in question is presented as a result of the earlier discussion of Meno's third definition of virtue (77b2–79a2), which implies the consequence that morally correct actions are beneficial whether or not accompanied by conventional goods such as wealth and honour. The underlying role of presenting it as a hypothesis is therefore to postpone demonstrating the truth of a controversial thesis which needs a substantial justification. In conclusion, I suggest that Plato's real intention in introducing the method of hypothesis in the dialogue is not to answer the original question but to lead Meno to seek for knowledge.     

THE EFFECTS OF KNOWN-ITEM INTERSPERSAL ON ACQUISITION AND RETENTION OF SPELLING AND SIGHTREADING WORDS1

The use of well-documented procedures such as shaping, differential reinforcement, and fading may not be the most practical for teaching certain academic behaviors. An alternative procedure of interspersing trials on previously trained items with trials on unknown items has been suggested, but its effects on acquisition and retention have not been systematically examined. This study investigated the effects of interspersing known items during training on new tasks. Six mentally retarded adolescents were given pretests on spelling and sightreading words, which were divided into pools of learned and unlearned items. Training and baseline conditions were implemented concurrently, using a multi-element design. During interspersal training sessions, 10 known words from the pretest were alternately presented with each of 10 test words that were incorrect on the pretest. The ratio of previously mastered words to test words was gradually reduced. During baseline sessions, 10 different test words were presented without alternation of previously known words. During this condition, a procedure involving high-density social reinforcement contingent on task-related behaviors, but not necessarily correct responses, was later introduced, followed by a return to the original noninterspersal baseline. During all conditions, test words were deleted and replaced after meeting a mastery criterion of three consecutive correct trials. Retention tests were administered over learned test words for all conditions, at specified intervals. Results showed that both acquisition and retention of spelling and sightreading words were facilitated by the interspersal procedure. All subjects acquired more words during the interspersal condition than either the high-density or baseline conditions. The effectiveness of the procedure may possibly be attributed to better maintenance of attending behavior to unknown items as a function of the inclusion of known items, which directly increase the amount of reinforcement for correct responses during the early stages of skill acquisition.     

Paroxysmal compulsion to handle keys in a computer operator due to meningioma in the left supplementary motor area

We describe the case of a computer operator who experienced paroxysmal attacks several times in which she felt a compulsion to handle keys with her right hand or actually her right hand moved involuntarily in a key-handling rhythm. Cranial CT and MRI revealed a mass lesion in the left medial aspect of the frontal lobe (supplementary motor area). After the removal of this tumor (meningioma), there were no more paroxysmal attacks. We suggest that voluntary movements controlled by the supplementary motor area were deranged by seizures provoked by the tumor. This case is attractive in relation to obsessive-compulsive disorder.     

EXPERIMENTAL ANALYSIS AND EXTINCTION OF SELF-INJURIOUS ESCAPE BEHAVIOR

Three studies are presented in which environmental correlates of self-injurious behavior were systematically examined and later used as the basis for treatment. In Study 1, 7 developmentally disabled subjects were exposed to a series of conditions designed to identify factors that maintain self-injurious behavior: attention contingent on self-injurious behavior (positive reinforcement), escape from or avoidance of demands contingent on self-injurious behavior (negative reinforcement), alone (automatic reinforcement), and play (control). Results of a multielement design showed that each subject's self-injurious behavior occurred more frequently in the demand condition, suggesting that the behavior served an avoidance or escape function. Six of the 7 subjects participated in Study 2. During educational sessions, “escape extinction” was applied as treatment for their self-injurious behavior in a multiple baseline across subjects design. Results showed noticeable reduction or elimination of self-injurious behavior for each subject and an increase in compliance with instructions in all subjects for whom compliance data were taken. The 7th subject, whose self-injurious behavior during Study 1 occurred in response to medical demands (i.e., physical examinations), participated in Study 3. Treatment was comprised of extinction, as in Study 2, plus reinforcement for tolerance of the examination procedure, and was evaluated in a multiple baseline across settings design. Results showed that the treatment was successful in eliminating self-injurious behavior and that its effects transferred across eight new therapists and three physicians. General implications for the design, interpretation, and uses of assessment studies are discussed.     

Reinforcing efficacy of food on performance during pre- and postmeal sessions

Assessments were conducted to identify preferred foods for 9 adults with severe to profound mental retardation. Subsequently, the reinforcing effects of each participant's most highly preferred food were evaluated during sessions conducted before and after lunch. Results showed that 4 participants' response rates were higher during premeal sessions than during postmeal sessions. By contrast, pre- and postmeal response rates were indistinguishable for the other 5 participants. These results indicate that the reinforcing efficacy of food may (but does not necessarily) diminish following meals and suggest that the influence of meal schedules should be examined on an individual basis when food is used as reinforcement during training sessions.     

ASSESSING AND PROGRAMMING GENERALIZED BEHAVIORAL REDUCTION ACROSS MULTIPLE STIMULUS PARAMETERS

Generalization across three stimulus parameters was examined for 5 individuals whose self-injurious behavior was maintained by escape from task demands. Prior to treatment, three stimulus parameters (therapist, setting, and demands) were systematically varied across baseline sessions. These variables were held constant during treatment, which consisted of escape extinction. When treatment was completed, three novel stimulus parameters were probed. If the rate of self-injury was high during this probe, treatment was reimplemented with one new stimulus parameter (the other two were the same as in the original treatment condition). Following this second treatment, another probe with three novel stimuli was conducted. If the rate of self-injury was again high, treatment was implemented again while a second stimulus parameter was changed. This sequence continued until generalization was observed across the three parameters. Results showed idiosyncratic differences in generalization. The behavior of 2 subjects showed complete generalization during the first novel probe. A 3rd subject's behavior showed generalization following treatment across two stimulus parameters (setting and therapist). The behavior of the 2 remaining subjects showed a complete lack of generalization across the three parameters; both subjects required training for novelty by randomly varying the stimulus parameters for a substantial number of sessions.     

MOMENTUM AND EXTINCTION EFFECTS ON SELF-INJURIOUS ESCAPE BEHAVIOR AND NONCOMPLIANCE

Previous research on applications of behavioral momentum has indicated that a high-probability (high-p) instructional sequence, in which a series of instructions for which there is a high probability of compliance is presented immediately before an instruction for which there is a low probability of compliance, is an effective method for increasing compliance. It is not dear, however, whether the procedure is effective when individuals actively attempt to escape from the instructional situation. In this study, we examined the effects of the high-p sequence, when implemented first alone and then later with an extinction component, as treatment for the self-injurious escape behavior of 2 individuals. Results showed that when the instructional sequence was implemented without extinction, rates of self-injury increased and percentage of compliance decreased. In addition, the percentage of trials occasioning escape behavior increased for both high- and low-probability instructions. When an extinction component was added to the high-p sequence, rates of self-injury and the percentage of trials containing self-injury decreased, and compliance increased. These findings suggest that extinction may be an important component of treatment when escape behavior such as self-injury accompanies noncompliance in instructional contexts and competes with compliant behavior.