Shin-ichi Okada

Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population

Recently a relationship between serotonin transporter transcriptional control region (5-HTTLPR) polymorphism and anxiety related personality traits in Caucasians was reported. We performed PCR of DNAs from the blood for determining the 5-HTTLPR genotypes of 191 Japanese subjects, which were medical staff and students, and obtained Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI) in 144 subjects. The association was analyzed by one-way ANOVA. The present study demonstrated that allelic frequency of 5-HTTLPR (s allele frequency was 0.785) in our subjects was considerably different from that in Caucasians. No significant differences were found in the anxiety-related personality traits among genotypes, while cooperativeness in TCI showed a significant difference among genotypes. The property of 5-HTTLPR may not be reflected directory on the personality inventories.

Possible role of d-serine in the pathophysiology of Alzheimer's disease

Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site on the N-methyl-D-aspartate (NMDA) receptor that has been implicated in the pathophysiology of Alzheimers disease (AD). The purpose of the study was to determine whether serum levels of D- and L-serine in patients with AD are altered as compared with normal controls. Serum levels of D- and L-serine in patients of AD and age- and gender-matched normal controls were determined using a high-performance liquid chromatography (HPLC). Serum levels of D-serine in the patients with AD were slightly (z=-1.77, p=0.078) lower than those of normal controls. In contrast, serum levels of L-serine in the patients were slightly (z=-1.73, p=0.083) higher than those of controls. In addition, the percentage (%) of D-serine in the total (L+D) serine in the patients was significantly (z=-2.36, p=0.018) lower than that of controls. The present study suggests that the reduced activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine may play a role in the pathophysiology of AD.

Decreased Regional Cerebral Metabolic Rate for Glucose in Systemic Lupus erythematosus Patients with Psychiatric Symptoms

To determine brain functional abnormality in systemic lupus erythematosus (SLE) patients with psychiatric symptoms, we evaluated 12 active SLE patients with or without psychiatric symptoms by means of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (PET), magnetic resonance imaging and neuropsychological testing. Patients with psychiatric symptoms showed significantly poorer performance in tests which subserved attentional function. The PET study revealed that the psychiatric patients had significantly decreased regional cerebral metabolic rates for glucose in the prefrontal, inferior parietal and anterior cingulate regions. Prefrontal, inferior parietal and anterior cingulate dysfunction may be related to attentional deficits that are involved in various psychiatric symptoms in SLE. PET is an invaluable tool to reveal such brain functional abnormality seen in SLE patients with psychiatric symptoms.

Increased levels of serum basic fibroblast growth factor in schizophrenia

Basic fibroblast growth factor (bFGF) is a multifunctional growth factor that has been implicated in a variety of neurodevelopmental processes. The aim of the present study was to examine whether bFGF contributes to the pathophysiology of schizophrenia. Serum bFGF levels in 40 patients with schizophrenia (15 drug-naive and 25 medicated patients) and in 40 age- and sex-matched healthy normal controls were measured. Serum bFGF levels were significantly higher in the medicated patients than in the normal controls. Analysis of partial correlation coefficients showed that the increased bFGF levels might not be attributable to antipsychotic medication. Although there was no significant overall difference in bFGF levels between drug-naive patients and normal controls, the bFGF levels in these patients significantly correlated with the severity of negative symptoms. Furthermore, we found a significant negative correlation between serum bFGF levels and the age of onset in the entire patient group. Our finding of elevated bFGF levels in the serum of patients with schizophrenia, especially in earlier age-of-onset cases considered to have more neurodevelopmental insults, suggests that bFGF abnormalities may be involved in the pathophysiology of schizophrenia.

Effects of MRI abnormalities on WAIS-R performance in solvent abusers.

Objective ‐ To clarify how chronic solvent abuse affects cognitive function using magnetic resonance imaging as an index of brain damage. Material and methods ‐ A total of 25 chronic solvent abusers underwent magnetic resonance imaging with quantitative neurometry and Wechsler Adult Intelligence Scales revised. Results ‐ The abusers with white matter change (n=10) showed significantly (P < 0.05) lower performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01). Conclusions ‐ These data indicate that solvent abuse causes the decline in the test performance reflecting cognitive and fine motor dysfunction and that white matter changes and pontine atrophy may have some roles in this decline.

Regional cerebral blood flow abnormalities in chronic solvent abusers.

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers. Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N‐isopropyl‐p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P < 0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition–apathy scale on SANS (left; P < 0.05, right; P < 0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.

Familial frontotemporal dementia with a P301L tau mutation in Japan

We have reported the family line with frontotemporal dementia (FTD) in Japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Picks disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1s oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1s second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1s oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5s PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in Japan.

Predictors of 1-Year Outcome for Patients With Panic Disorder

The course of panic disorder (PD) is often prolonged, but factors that affect the social outcome have not yet been made clear. The aim of this study was to find predictors of outcome for patients with PD. The subjects were 65 outpatients (28 men and 37 women) with PD (DSM-III-R) who were treated at our hospital for more than 1 year. The factors affecting 1-year outcome were evaluated by multiple regression analysis. We found that the following were predictors of poor social outcome in PD: (1) severe agoraphobia at the first psychiatric examination and (2) long duration of illness before the first psychiatric consultation. Furthermore, the complication of hypochondriacal symptoms predicted a poor outcome for PD. Early attention to agoraphobia and hypochondriasis is essential for the treatment of PD, and early introduction to psychiatric treatment is recommended.

Activation of non‐primary motor areas during a complex finger movement task revealed by functional magnetic resonance imaging

We examined the brain activation induced by a complex finger movement task using functional magnetic resonance imaging (fMRI) with echo planar imaging (EPI). Imaging planes were set up for the observation of non‐primary motor areas. Among five normal males examined, four subjects naive to the task showed activations in contralateral primary and supplementary motor areas and the ipsilateral superior anterior part of the cerebellar hemisphere. Also, the bilateral premotor areas and the contralateral ventrolateral nucleus of thalamus were occasionally activated. No changes were observed in the putamen and globus pallidus. The subject accustomed to the task showed activation in the narrow areas of the contralateral primary motor and supplementary motor and premotor areas but not in the cerebellum. These results suggest that fMRI has nearly the same degree of detectability to that of positron emission tomography (PET) in regard to motor functions.

Depressive disorders as psychiatric complications after obesity surgery

Three case reports of morbidly obese patients (two women and a man) who underwent vertical banded gastroplasty and who subsequently fell into depression, are presented here. The psychiatric diagnosis according to DSM‐III‐R (Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised), the eating pattern before obesity surgery, the past history of mental disorder, social adaptation before surgery, psychological gain from their obese state, and the presence of unrealistic expectations of obesity surgery were investigated. Case 1 was diagnosed postoperatively as having a major depressive episode without a personality disorder. Case 2 was diagnosed postoperatively as having a major depressive episode. Case 3 had a depressive disorder not otherwise specified. Cases 2 and 3 had a social phobia with comorbidity of personality disorders. Binge eating disorder was confirmed in all patients before obesity surgery. There were differences between case 1 and cases 2 and 3 based on the presence of personality disorder and the time of onset of depression. When some psychiatric characteristics are confirmed in obese patients, obesity surgery should be undertaken more prudently because the patients may manifest depression postoperatively. The pre‐operative psychiatric assessment is essential for a decision on indication of obesity surgery.