Retraction: 'Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia'.

The above article from Human Psychopharmacology, first published on 25 January 2012 in Wiley OnlineLibrary (onlinelibrary.wiley.com), and in Volume 90, pp. 90-100, has been retracted by agreement between the authors, the journal Editor in Chief, David Baldwin, and John Wiley & Sons Ltd. The retraction has been agreed following an investigation by the St Marianna University Ethics Committee which determined that the paper was not as originally designed and approved. REFERENCES: Tenjin, T., Miyamoto, S., Miyake, N., Ogino, S., Kitajima, R., Ojima, K., … Yamaguchi, N. (2012). Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia. Hum. Psychopharmacol Clin Exp, 27, 90-100. https://doi.org/10.1002/hup.1276.

Neurocognitive profile of euthymic Japanese patients with bipolar disorder.

AIM: Neurocognitive impairment is one of the core symptoms of bipolar disorder (BD). The MATRICS Cognitive Consensus Battery (MCCB) is a potential consensus assessment tool to evaluate cognitive function in patients with BD. Here, we report on cognitive deficits evaluated using the MCCB Japanese version (MCCB-J) in euthymic Japanese patients with BD, and compare them with scores in previous studies. METHODS: We compared neurocognitive function in 25 patients with euthymic BD and 53 healthy controls (HC). Additionally, we searched all available databases for studies that have evaluated cognitive function in BD using the MCCB, and conducted a meta-analysis. RESULTS: Canonical discriminant analysis revealed significant differences in MCCB-J domain scores between BD and HC. Patients with BD performed significantly worse on visual learning, social cognition, speed of processing, and MCCB composite scores. Our meta-analysis revealed that patients with BD performed worse than HC, as reflected by MCCB composite scores and scores on all seven cognitive domains. However, there are differences in the cognitive deficits identified in previous studies compared with our participants, particularly social cognition. CONCLUSION: As reported in previous studies, neurocognitive deficits were observed in Japanese euthymic BD patients assessed using the MCCB-J. Further study is needed to clarify whether differences in social cognition between this study and previous studies are a result of coping mechanisms for social settings in Japanese populations.

Long-term efficacy and safety of blonanserin in patients with first-episode schizophrenia: a 1-year open-label trial.

AIMS: The purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. METHODS: Twenty-three antipsychotic-naïve patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24 mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms. RESULTS: Fourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period. CONCLUSIONS: Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings.

Measurement and Treatment Research toImprove Cognition in Schizophrenia Consensus Cognitive Battery: validation of the Japanese version.

AIM: This preliminary study was performed to test the reliability and validity of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), developed by the National Institute of Mental Health MATRICS initiative, as an assessment tool in a Japanese-language version (MCCB-J). METHODS: The subjects for the present study were 37 patients with schizophrenia. Each subject gave written informed consent to participate in the research. In order to examine the validity of the MCCB-J, the correlation between the MCCB-J and the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) was determined. RESULTS: Cronbach's alpha for the MCCB-J was 0.72. The MCCB-J composite score was significantly correlated with all subtests of the MCCB-J. There was a significant correlation between the MCCB-J and the BACS composite score. CONCLUSION: This preliminary study indicates that the MCCB-J has good psychometric properties and validity.

Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the effects of blonanserin, a novel antipsychotic, on cognitive function in first-episode schizophrenia. METHODS: Twenty-four antipsychotic-naïve patients with first-episode schizophrenia participated in the study. Blonanserin was given in an open-label design for 8 weeks. The Brief Assessment of Cognition in Schizophrenia-Japanese language version (BACS-J) was administered as the primary outcome measure at baseline and 8 weeks. Clinical evaluation included the Positive and Negative Syndrome Scale (PANSS), the Schizophrenia Quality of Life Scale-Japanese language version (SQLS-J), and the Clinical Global Impression-Severity of Illness Scale (CGI-S). To exclude the possibility of retest effects on the BACS-J, 10 age-matched patients with chronic schizophrenia treated with blonanserin were tested at baseline and after an 8-week interval. RESULTS: Twenty first-episode patients completed the study. Repeated measures analysis of covariance revealed a significant group-by-time interaction effect on the letter fluency task due to better performance in the first-episode group, but not in the control group. Main effect of time or group-by-time interaction effect on the Tower of London task was not significant; however, the first-episode group, but not the control group, showed substantial improvement with a moderate effect size. All items on the PANSS, SQLS-J, and CGI-S significantly improved after 8 weeks of treatment. CONCLUSIONS: These results suggest that blonanserin improves some types of cognitive function associated with prefrontal cortical function.

Clinical correlates associated with cognitive dysfunction in people with schizophrenia.

AIMS: The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia. METHODS: The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = -0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = -0.51, P < 0.01), verbal fluency score (r = -0.39, P < 0.01), and composite score (r = -0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = -0.45, P < 0.01), and composite score (r = -0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores. CONCLUSIONS: These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction.

[Schizophrenia Cognition Rating Scale Japanese version (SCoRS-J) as a co-primary measure assessing cognitive function in schizophrenia].

The assessment of cognitive function is important for patients with schizophrenia because cognitive impairment is a core feature of the disease, and is a major determinant of functional outcome. To implement a practical assessment tool, we previously developed the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia that objectively measures cognitive domains relevant to outcome. Meanwhile, the U.S. Food and Drug Administration took the position that a drug to improve coghition should show changes on an additional measure (a co-primary), in addition to an accepted consensus cognitive performance measure that is considered functionally meaningful. Thus, four potential co-primary measures, two measures of functional capacity and two interview-based measures of cognition, were evaluated for psychometric properties and validity. The Schizophrenia Cognition Rating Scale (SCoRS) is one of the interview-based measures of cognition. It consists of 20 questions to measure attention, memory, reasoning and problem solving, working memory, language production, and motor skills, which are related to day-to-day functioning. University of California at San Diego Performance-Based Skills Assessment (UPSA) is one of the measures of functional capacity. For its clinical application, we developed the Japanese-language version of the SCoRS (SCoRS-J) and UPSA (UPSA-J) through back-translation into English.

Determinants of work outcome in neuroleptic-resistant schizophrenia and schizoaffective disorder: cognitive impairment and clozapine treatment.

There is considerable evidence that cognitive impairment is a better predictor of work and social function in schizophrenia than are positive and negative symptoms. Atypical antipsychotic drugs have been shown to improve cognitive function in schizophrenia patients, but it is unclear whether this improves patients' ability to gain employment. Data from a prospective longitudinal study was used to test the hypotheses that (1) clozapine treatment would improve employment outcome in treatment-resistant schizophrenia or schizoaffective disorder patients, and (2) specific cognitive functioning at baseline and after treatment would predict work status at baseline and change in work status. Employment status and cognitive assessment data were collected in 59 treatment-resistant schizophrenia or schizoaffective disorder patients. Forty-seven of 59 (79.7%) patients were unemployed at baseline. Over a 12-month period, 23 (48.9%) additional patients were able to gain paid or volunteer jobs, or attend school. As predicted, neurocognitive performance was a better predictor of employment status and ability to gain of employment than clinical symptoms. Improvement in verbal working memory was found to be a better predictor of employment outcome than other cognitive functions. Treatment that enhances cognitive function, especially verbal working memory, may lead to better employment outcomes in treatment-resistant schizophrenia or schizoaffective disorder patients.

Predictors of life skills in people with schizophrenia.

Objective : The purpose of the present study is to examine clinical factors related to life skills in people with schizophrenia. Method : The participants were 51 stabilized outpatients with schizophrenia. Their mean age was 38.91 (SD = 10.73) years. Life skills were assessed using the Life skills profile (LSP). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Results : Cognitive function was not correlated with the LSP scores at all. Among clinical symptoms, scores of the PANSS positive and negative syndrome scales, the CDSS, and the DIEPSS had negative correlations with the LSP total score and the subscales. Stepwise regression analyses showed that the CDSS and PANSS negative syndrome scale scores were independent predictors of the LSP total score and two of the subscales. Conclusions : These results indicate that cognitive function is not associated with life skills but clinical symptoms such as depressive and negative symptoms have considerable impacts on life skills in people with schizophrenia. J. Med. Invest. 67 : 75-82, February, 2020.

Determinants of work outcome in schizophrenia and schizoaffective disorder: role of cognitive function.

Cognitive impairment has been reported to be more important than clinical symptomatology as a determinant of work and social function in schizophrenia. In a retrospective analysis of a group of 152 patients with chronic schizophrenia or schizoaffective disorder, performance on a battery of neuropsychological tests was contrasted in employed (32, 21.1%) versus unemployed subgroups. As predicted, neurocognitive performance was more important than clinical symptoms in predicting employment status. Among neurocognitive functions, verbal working memory (as reflected by the Consonant Trigram Test) was the strongest predictor of employment status.

Subjective and objective quality of life, levels of life skills, and their clinical determinants in outpatients with schizophrenia.

The purpose of the present study is to investigate the relationships among subjective and objective quality of life (QOL), and levels of life skills, and their clinical determinants in outpatients with schizophrenia by using schizophrenia disease-specific QOL measures. Data collected from 64 outpatients were analyzed. Subjective QOL was measured with the Schizophrenia Quality of Life Scale (SQLS) and objective QOL with the Quality of Life Scale (QLS). Patients' family members completed the Life Skills Profile (LSP). Clinical symptoms were also assessed with several scales including the Brief Psychiatric Rating Scale (BPRS) and the Calgary Depression Scale for Schizophrenia (CDSS). Only the motivation/energy scale, but not the other scales of the SQLS, correlated with the QLS. The LSP rated by the family showed significant correlations with both the SQLS and the QLS. The CDSS score predicted each scale of the SQLS, and the BPRS negative symptoms score predicted the QLS. The LSP was predicted by the BPRS negative symptoms score and the CDSS score independently. These results indicate that the patient's QOL could be predicted by the life skills measured by a family member and suggest that active treatment for depressive and negative symptoms might be recommended to improve the patient's QOL and life skills.

Predictors of subjective and objective quality of life in outpatients with schizophrenia.

AIM: In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease-specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL. METHODS: Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively. RESULTS: Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL. CONCLUSION: Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL.

Neurocognitive Impairments Are More Severe in the Binge-Eating/Purging Anorexia Nervosa Subtype Than in the Restricting Subtype.

Objective: To evaluate cognitive function impairment in patients with anorexia nervosa (AN) of either the restricting (ANR) or binge-eating/purging (ANBP) subtype. Method: We administered the Japanese version of the MATRICS Consensus Cognitive Battery to 22 patients with ANR, 18 patients with ANBP, and 69 healthy control subjects. Our participants were selected from among the patients at the Kobe University Hospital and community residents. Results: Compared to the healthy controls, the ANR group had significantly lower visual learning and social cognition scores, and the ANBP group had significantly lower processing speed, attention/vigilance, visual learning, reasoning/problem-solving, and social cognition scores. Compared to the ANR group, the ANBP group had significantly lower attention/vigilance scores. Discussion: The AN subtypes differed in cognitive function impairments. Participants with ANBP, which is associated with higher mortality rates than ANR, exhibited greater impairment severities, especially in the attention/vigilance domain, confirming the presence of impairments in continuous concentration. This may relate to the impulsivity, an ANBP characteristic reported in the personality research. Future studies can further clarify the cognitive impairments of each subtype by addressing the subtype cognitive functions and personality characteristics.

Relationship between social and cognitive functions in people with schizophrenia.

PURPOSE: The purpose of the present study was to examine clinical factors related to social function in people with schizophrenia. PATIENTS AND METHODS: The participants were 55 stabilized outpatients with schizophrenia. Their mean age was 39.36 (SD =10.65) years. Social function was assessed using the Quality of Life Scale (QLS). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: Neither the MCCB cognitive domain score nor composite score was correlated with the QLS scores. However, of the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively correlated with the QLS scores. Among clinical variables, especially the PANSS negative syndrome scale score had a strong negative correlation with the QLS scores. Stepwise regression analyses showed that the PANSS negative syndrome scale score was an independent predictor of the QLS scores, and although the BACS-SC score predicted the QLS common objects and activities subscale score, the association was not so strong compared to the PANSS negative syndrome scale score. CONCLUSION: These results indicate that speed of processing evaluated by BACS-SC could predict some aspect of social function but negative symptoms have a much stronger impact on global social function in people with schizophrenia.

Differences in waveforms of cerebral evoked potentials among healthy subjects, schizophrenics, manic-depressives and epileptics.

The differences in the waveform of Cerebral EP (Evoked Potential)s; SEP, VEP and AEP, among healthy subjects, schizophrenics, manic-depressives and epileptics were investigated. In 585 subjects of both sexes comprising these diagnostic groups, 6 channels of EPs, each 2 channels for each sensory modality, were recorded simultaneously/parallelly from each subject, without assigning a mental task. Then, waveforms of the g-m (group mean) EPs of each diagnostic group were superimposed for inspection. Peak latencies and inter-peak amplitudes of individual EPs were statistically tested among (ANCOVA) and between (Scheffe's multiple comparison test) these diagnostic groups for each channel (modality), and for each sex. The waveforms of g-m EPs of each diagnostic group differed from each other. The differences of latencies and inter-peak amplitudes among these diagnostic groups attained to the significant level (P<0.05), with more significant differences between healthy subjects and each of these pathological diagnostic groups than between each of these pathological diagnostic groups, for each sex. Thus the differences in the waveform of EPs among these diagnostic groups were confirmed even taking the effect of medication on EPs into consideration. These results might suggest the existence of a waveform for individual EPs specific to each of these diagnostic groups, for each sex.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.

Subjective and objective measures of quality of life have different predictors for people with schizophrenia.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia.

OBJECTIVE: The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. RESULTS: After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. CONCLUSION: Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.

Effects of quetiapine on gonadal axis hormones in male patients with schizophrenia: a preliminary, open study.

PURPOSE: The authors investigated the effects of a novel antipsychotic agent, quetiapine administration on hypothalamo-pituitary-gonadal (HPG) axis hormones in patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were nine male inpatients. We tried to switch the patients from typical antipsychotics to quetiapine. The patients took a mean dose of 636.1 mg quetiapine daily for a mean period of 104.7 days. RESULTS: (i) Although the total Brief Psychiatric Rating Scale score did not show significant changes, no patients needed anticholinergic medications after the switch. (ii) Before the switch, only the prolactin concentration showed a significant difference between the patients and normal subjects. After the switch, neither prolactin nor HPG axis hormone concentrations showed significant differences between the groups. CONCLUSIONS: Our preliminary results indicated that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenia patients with normal levels of HPG axis hormones.

The hypothalamic-pituitary-adrenal axis in chronic schizophrenic patients long-term treated with neuroleptics.

PURPOSE: The authors investigated the hypothalamic-pituitary-adrenal (HPA) axis of regularly medicated schizophrenic patients. METHODS: The subjects were 53 patients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) criteria for schizophrenia. Each patients gave informed consent for the research. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Based on the dosages of neuroleptics (NLPs), the subjects were classified into two groups: those with lower dosages (LD) and those with higher dosages (HD). FINDINGS: (a) The medicated schizophrenic patients had significantly higher plasma corticotropin (ACTH) levels than the normals. (b) There was no significant difference in plasma cortisol levels between the schizophrenic patients and normals. (c) There was a significant difference in plasma ACTH levels between the HD and normal groups, but not between the LD and normal groups. (d) There was no significant difference in administration periods of NLPs, positive (POS) or negative symptoms (NES) between the HD and LD groups. (e) There was a positive correlation between the plasma ACTH and plasma cortisol levels in patients. CONCLUSIONS: Our results showed that, in chronic schizophrenic patients long-term treated with NLPs, ACTH secretion was elevated.