Relationship between severity of obsessive-compulsive symptoms and schizotypy in obsessive-compulsive disorder.

PURPOSE: Obsessive-compulsive disorder (OCD) patients exhibit a noninhibition response pattern very similar to that observed in schizotypy patients in cognitive tasks. It has been suggested that the reduced cognitive inhibition observed in both schizotypy and OCD may result in the frequent entry into awareness of unacceptable urges and intrusive thoughts. The aim of this study was to investigate the relationship between the severity of obsession or compulsion and schizotypy in OCD. PATIENTS AND METHODS: Sixty subjects (25 males and 35 females) who were OCD outpatients in the University Hospital at the Kyoto Prefectural University of Medicine during the period 2008-2010 were enrolled in the study. Assessments of these patients were made using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Schizotypal Personality Questionnaire (SPQ), the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). The Pearson correlation coefficients between Y-BOCS and SPQ scores were calculated. Furthermore, hierarchical multiple linear regression analyses were conducted to assess whether schizotypy predicted the severity of obsession and compulsion. RESULTS: By calculating the Pearson correlation coefficient, it was found that the Y-BOCS obsession score, not the Y-BOCS compulsion score, was correlated with the SPQ total score. Results of the hierarchical multiple linear regression analysis showed that SPQ total score was a significant predictor of the Y-BOCS obsession score, after accounting for control variables (ie, HAM-D and HAM-A). CONCLUSION: Results of this study showed that the Y-BOCS obsession score, not the Y-BOCS compulsion score, was correlated with the SPQ total score. This finding suggests that OCD patients with an elevated SPQ total score experience a reduction of cognitive inhibition, resulting in the frequent entry into obsession. Future longitudinal studies are recommended to clarify the effect of schizotypy on the clinical course of OCD.

[Alcohol and substance dependence].

In this paper, we have outlined the neurobiological basis of alcohol and drug dependence. The prevalence of drug dependence is a serious social problem in many countries, including Japan. This problem involves many background factors, including those pertaining to medical sciences, socio economics, and politics. First, we briefly describe the findings pertaining to psychotomimetic drugs as a model of schizophrenia. The biological pathogenesis of schizophrenic disorders is still unknown. The symptoms of methamphetamine (MAP) and phencyclidine (PCP) psychoses are very similar to those of schizophrenic disorders involving hallucination or delusion. PCP causes not only positive symptoms but also negative symptoms. Therefore, it has been considered as a more comprehensive model of schizophrenia than other drugs. Furthermore, amotivational syndrome, which is observed in patients with chronic cannabis and organic solvent dependence, is similar to the negative symptoms of schizophrenia. Understanding the neurobiological basis of drug dependence by using the molecular biological approach will provide an important clue for elucidating the mechanisms underlying schizophrenia and endogenous psychiatric disorders. Next, we discuss account for the neurobiological mechanisms underlying drug dependence. The reward system in the brain, which is common for all dependent drugs, has been explained, and the stages of addiction corresponding to the development of drug dependence have been discussed followed. In addition, we have discussed the epigenetics aspects of substance dependence, which is one of the hottest topics in psychiatric genetics. We expect that further studies of the mechanisms underlying drug dependence will aid in elucidating of the pathophysiology of various psychiatric diseases.

[Inhalant-related disorder].

Inhalant abuse and dependence are prevalent in adolescent population because inhalants are inexpensive, legal and accessible substance for youth. In Japan, the prevalence of inhalant abuse and dependence is gradually declining in these days, although inhalants can still become a "gateway drug" to other dependent substances such as cocaine and cannabinoids. Inhalant abuse causes show serious mental and somatic symptoms, and mortality in acute and chronic phases, while the abusers are ignorant about it. This paper reviews recent studies that investigate the symptoms and the treatments of inhalant abuse and dependence.

Serotonergic mediation of the antidepressant-like effect of the green leaves odor in mice.

The green odor (GO) that emanates from green leaves has been observed to have many physiological actions in mammals and may be associated with a healing effect in humans. This study examined the effect of GO (we used a mixture of cis-3-hexenol and trans-2-hexenal) on behavior in the forced swim test (FST) of depression in mice. Exposure of GO showed the antidepressant-like effect in the FST, i.e., a significant decrease in immobility time and increase in swimming time, but no change in climbing time. The behavioral responses of GO-exposed animals to FST were similar to those observed for animals given citalopram, which is a selective serotonin reuptake inhibitor. In contrast, desipramine, which is a selective noradrenaline reuptake inhibitor, decreased immobility time and increased climbing time without affecting swimming time. To examine the involvement of the serotonergic system in mediating the antidepressant-like action of GO, we performed further FST examinations in which GO-exposed mice were treated with p-chlorophenylalanine (PCPA). Prior PCPA administration induced depletion of central 5-HT in the brain and completely diminished the GO effect on the behavioral responses seen during the FST. No changes in locomotor activity after GO inhalation were observed. These results indicate that acute exposure to GO has an antidepressant-like effect that may involve the serotonergic system.

Effects of rat medial prefrontal cortex lesions on olfactory serial reversal and delayed alternation tasks.

When reward reinforcement in a two-choice discrimination task is regularly changed from one stimulus to another immediately after one learning acquisition session, the learning efficiency of a rat increases as if the rat has come to recognize this regularity of reversal. To investigate how the rat medial prefrontal cortex (mPFC) is involved in such improvement, we examined the performance of mPFC-lesioned rats in a serial reversal task of olfactory discrimination. The performance of other mPFC-lesioned rats in a delayed alternation task was also analyzed using the same apparatus to evaluate the contribution of the mPFC to working memory. The mPFC-lesioned rats demonstrated selective difficulty in the second reversal session in the serial reversal task and also showed performance impairment in the delayed alternation task. These results suggest that the rat mPFC mediating working memory is involved in early progress in learning efficiency during experiences of multiple reversals, which may be relevant to cognitive operations in reversal learning beyond a one-time reversal of stimulus response associations.

[Addictive behavior disorders].

"Addiction" used to remind anyone of the use or abuse of chemical substances. In recent years, however, researchers and clinicians have begun to classify other excessive behaviors including gambling, eating shopping and self-injury into the addictive behavior. Above all, pathological gambling and bulimia nervosa patients often make trouble for psychiatrists and psychologists, not only for their family. On the other hand, the neural substrata underlying substance dependence have been revealed. Especially, it is implicated that the mesolimbic neuron plays a crucial role on the reward system. The recent studies suggest that reduced activation of the reward system might be related to the addictive behaviors such as pathological gambling, binge eating and sexual behavior. Further biological researches about the addictive behavior would help our deeper understanding of its disorders. As to the pharmacotherapy, many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating the addictive behaviors.

Relationship between limbic and cortical 5-HT neurotransmission and acquisition and reversal learning in a go/no-go task in rats.

RATIONALE: Specific brain structures have been suggested to be involved in impulsive responding assessed by a variety of operant tasks. Central serotonin (5-HT) function has also been widely implicated in impulsivity; however, little research has addressed the regional aspect of 5-HT roles in different impulsive indices of task performance. OBJECTIVE: We analyzed the relationships between acquisition and reversal learning in a go/no-go task as different behavioral measures of impulsivity and focal concentrations of 5-HT and its metabolites in the brain. MATERIALS AND METHODS: Rats administered with parachloroamphetamine (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no-go visual discrimination task. Neurochemical analysis was performed to determine 5-HT concentrations in micropunched brain tissues. RESULTS: PCA administration induced regionally 5-HT depletion in the brain and impaired learning performance in both tests. For both tests, significant negative correlations between learning performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast, significant negative correlations between learning performance and 5-HT and 5-HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively in the reversal learning phase. CONCLUSIONS: The present data indicate that 5-HT neurotransmission to the mPFC and Amyg is involved in inhibitory control over responses to discriminated stimuli associated with the go/no-go paradigm common to both tests. In contrast, 5-HT neurotransmission to the OFC is especially involved in additional processes associated with reversal learning.

Regional cerebral blood flow changes in a patient with delusional parasitosis before and after successful treatment with risperidone: a case report.

The pathophysiology and appropriate pharmacological interventions for delusional parasitosis (DP) remain unknown. Here, we present a case of DP following brain infarction of the right temporoparietal region. Pharmacotherapy with risperidone resulted in a dramatic therapeutic response over a short period. In a sequential N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked increase of rCBF in the large areas including the bilateral frontal and left temporoparietal regions, the right parietal operculum and the bilateral basal ganglia, in contrast to pre-treatment SPECT images showing a global decrease of rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for treatment of DP and that both dopaminergic and serotonergic dysfunction may play a role in DP. Our sequential SPECT findings suggest that psychiatric improvement of DP is associated with increased rCBF.

Cloning of a D-serine-regulated transcript dsr-2 from rat cerebral neocortex.

D-serine is now considered to be an endogenous co-agonist of the NMDA receptor in mammalian brain. To obtain insight into the molecular mechanisms underlying D-serine metabolism and function, we explored transcripts that are responsive to D-serine in the neocortex of the 8-day-old infant rat by a differential cloning technique, RNA arbitrarily primed PCR. We isolated a novel D-serine inducible transcript, D-serine-responsive transcript-2 (dsr-2), that was exclusively expressed in the brain. Sequence analysis of the corresponding cDNAs to the transcript revealed that the dsr-2 mRNA consists of 7199 nucleotides with an open reading frame encoding 111 amino acids. The dsr-2 gene was located on the reverse strand within an intron of the neurexin-3alpha gene, mapped to rat chromosome 6q24-31. The regional distribution of the basal expression of dsr-2 and its ontogenic changes in the brain closely correlated with those of free D-serine and of NMDA receptor R2B subunit mRNA, but were somewhat different from those of the neurexin-3alpha transcript. These findings suggest that dsr-2 may be involved in D-serine metabolism and/or function, and in the interactions between D-serine, NMDA receptor and neurexin-3alpha, in mammalian brain.

[Case report of pentazocine dependence from a standpoint of the cognitive therapy].

Drug dependence is a social problem of over the world and resistant to medical intervention by psychiatrist as well as general clinicians. In Japan, methamphetamine dependence is one of the most critical social problems, but opioid dependence is relatively rare. Pentazocine was called the non-addictive opioid at the time of development and release and there are few reports of its dependence. We experienced a medical worker with pentazocine dependence. He started to use pentazocine to reduce serious migraine and felled into dependence by changing the purpose to relaxation of stammering fear and strain towards other people. He was successfully treated by cognitive therapy.

Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study.

Three cases of general paresis were successfully treated with high-dose penicillin. In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly. Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year. Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT). Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment. 3D-SSP could not reveal remarkable CBF pattern changes through the courses. The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment. These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity. As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.

Chronic high-dose nitrazepam dependence 123I-IMP SPECT and EEG studies.

A patient who took 50-100 mg nitrazepam per day for 25 years is presented. (123)I-IMP SPECT (autoradiography method) and EEG were performed sequentially on the subject during and after the withdrawal syndrome. Severe hypoperfusion of the whole brain on SPECT and diffuse slow activity on EEG were demonstrated during the withdrawal syndrome and subsequently remarkably improved. However, the hypofrontal pattern on both early and delayed images in SPECT was unchanged. The changes observed on SPECT and EEG reflect the pathophysiology of dependence and withdrawal. Additionally, the hypofrontal pattern remained unchanged suggesting that organic brain damage can develop as a result of chronic high-dose benzodiazepine abuse.