DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

Minimal amount of tissue-based pH measurement to improve quality control in neuropsychiatric post-mortem brain studies.

AIM: Tissue pH and RNA integrity are crucial quality-control indicators of human post-mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post-mortem tissues. METHODS: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post-mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 µL/10 mg tissue) and 10 volumes (1000 µL/100 mg tissue) of nuclease-free water and subjected to pH measurements using an InLab Ultra micro pH electrode. RESULTS: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. CONCLUSION: The proposed protocol used one-tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post-mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post-mortem brain studies by diminishing confounding factors.

Effects of cognitive remediation on cognitive and social functions in individuals with schizophrenia.

Individuals with schizophrenia exhibit cognitive impairments, which are related to impairments in social functions. This study investigated the effects of cognitive remediation on cognitive, social, and daily living impairment. Participants were individuals with schizophrenia between 20 and 60 years old (N = 44). Participants were randomly assigned to two groups: a cognitive remediation intervention group and a non-intervention control group. The control group was provided with conventional drug therapy and either day care or occupational therapy. The intervention group was provided with the "neuropsychological educational approach to cognitive remediation" developed by Medalia and co-workers. We assessed cognitive functions using the brief assessment of cognition in schizophrenia (BACS), and evaluated social and daily living functions using the global assessment of functioning (GAF) scale. Significant group by time interaction effects indicated that verbal memory, working memory, attention, and executive function showed significantly greater improvement at post-intervention for the intervention group than the control group. Social and daily living function also improved in the intervention group and improvements were maintained one year after intervention. These preliminary findings indicate that the combination of cognitive remediation and psychiatric rehabilitation is effective for facilitating improvements in cognitive function and social and daily living functions in individuals with schizophrenia.

Design and synthesis of a novel series of orally active, selective somatostatin receptor 2 agonists for the treatment of type 2 diabetes.

The discovery of a novel series of ß-methyltryptophan (ß MeTrp) derivatives as selective and orally active non-peptide somatostatin receptor 2 (SSTR2) agonists for the treatment of Type 2 diabetes is described. In our previous research, Compound A, ß-MeTrp derivative with highly potent and selective SSTR2 agonistic activity IC50 (SSTR2/SSTR5)=0.3/>100 (nM), was identified asa drug candidate for treatment of Type 2 diabetes which lowers significantly plasma glucose level in Wistar fatty rats in its oral administrations. However, as serious increase in AUC and phospholipidosis (PLsis) were observed in its toxicological studies in rats, follow-up compounds were searched to avoid risk of PLsis with reference to their in vitro PLsis potentials evaluated on the basis of accumulation of phospholipids in HepG2 cells exposed to the compounds. It has been found that introduction of a carbonyl group onto the piperidine and piperazine or aniline moiety of compounds A and B reduced markedly the in vitro PLsis potentials. And further modification of the compounds and their evaluation led to a discovery of compounds 3k with lower in vitro PLsis potentials exhibiting lowering effect of hypoglycemia-induced glucagon secretion in SD rats (ED50=1.1mg/kg) and glucose excursion in meal tolerance test in Wistar fatty diabetic rats (MED=3.0mg/kg) in oral administrations. Compound 3k was selected asa new drug candidate of selective and orally active non-peptide SSTR2 agonists for treatment of Type 2 diabetes with low in vivo PLsis potential.

Reduced frontal activation during verbal fluency task in chronic hepatitis C patients with interferon-based therapy as measured by near-infrared spectroscopy.

AIM: Psychiatric side-effects are the main reason for discontinuation of interferon (IFN)-based therapy. Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. We prospectively evaluated brain activation in 20 chronic hepatitis C patients with or without IFN-based therapy by using NIRS during a verbal fluency task (VFT). METHODS: The relative concentrations of oxygenated hemoglobin were measured while patients completed a questionnaire survey at the start of treatment and at 4 and 12 weeks during treatment, using NIRS. RESULTS: The VFT performance did not change among the two groups. Patients with IFN-based therapy showed significantly lower activation during VFT in frontal channels at 12 weeks than those at the start of treatment and control (P < 0.05). Their Center for Epidemiologic Studies Depression Scale scores were significantly higher at 12 weeks than those at the start of treatment, although major depressive symptoms were not found (8.3 ± 7.9 vs. 13.2 ± 6.0, P < 0.001). CONCLUSION: The decrease in oxygenated hemoglobin concentrations of the frontal lobe detected using NIRS in this study reflects hypofunction of the frontal lobe. This functional decline that was caused by IFN-based therapy may be associated with the prodromal phase of depression.

Drinking Behavior and Mental Illness Among Evacuees in Fukushima Following the Great East Japan Earthquake: The Fukushima Health Management Survey.

BACKGROUND: Recent evidence from alcohol and trauma studies suggests that disasters are associated with increases in the consumption of alcohol. The Great East Japan Earthquake and the associated nuclear disaster have continued to affect the mental health of evacuees from Fukushima. This study aimed to extend these findings by examining the relationship between drinking behaviors and the risk of mental illness after the compound disaster. METHODS: We conducted the Mental Health and Lifestyle Survey with 56,543 evacuees. Kessler's K6 was used to assess the risk of mental illness, and logistic regression models were applied to analyze how drinking behavior patterns influence the risk of serious mental illness after adjustment for confounding variables. RESULTS: Logistic regression analysis evidenced that beginning heavy and light drinkers had the highest and a higher risk of serious mental illness, respectively. Individuals who were nondrinkers pre- and postdisaster had the lowest proportional risk of mental illness. Abstainers also had some risk to their mental health after the compound disaster. CONCLUSIONS: The results of this study highlight that beginning drinkers have a high risk of serious mental illness. Thus, mental health professionals should pay attention to the drinking behaviors of evacuees, which might predict increased risk of serious mental illness and consequently indicate a need for psychological intervention.

Psychological distress and the perception of radiation risks: the Fukushima health management survey.

OBJECTIVE: To assess relationships between the perception of radiation risks and psychological distress among evacuees from the Fukushima nuclear power plant disaster. METHODS: We analysed cross-sectional data from a survey of evacuees conducted in 2012. Psychological distress was classified as present or absent based on the K6 scale. Respondents recorded their views about the health risks of exposure to ionizing radiation, including immediate, delayed and genetic (inherited) health effects, on a four-point Likert scale. We examined associations between psychological distress and risk perception in logistic regression models. Age, gender, educational attainment, history of mental illness and the consequences of the disaster for employment and living conditions were potential confounders. FINDINGS: Out of the 180,604 people who received the questionnaire, we included 59,807 responses in our sample. There were 8717 respondents reporting psychological distress. Respondents who believed that radiation exposure was very likely to cause health effects were significantly more likely to be psychologically distressed than other respondents: odds ratio (OR) 1.64 (99.9% confidence interval, CI: 1.42-1.89) for immediate effects; OR: 1.48 (99.9% CI: 1.32-1.67) for delayed effects and OR: 2.17 (99.9% CI: 1.94-2.42) for genetic (inherited) effects. Similar results were obtained after controlling for individual characteristics and disaster-related stressors. CONCLUSION: Among evacuees of the Fukushima nuclear disaster, concern about radiation risks was associated with psychological distress.

Facial expression perception correlates with verbal working memory function in schizophrenia.

AIMS: Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. METHODS: Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. RESULTS: Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. CONCLUSIONS: These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia.

Computational psychological study of the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) for patients with chronic low back pain: verification of responsiveness.

BACKGROUND: We developed the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP, physician and patient versions) and have previously shown that the BS-POP is reliable and has construct validity, criterion validity, and reproducibility. The present study aimed to proactively verify the responsiveness of the BS-POP with regard to chronic low back pain (LBP) patients. METHODS: The study subjects included 193 chronic LBP patients (81 males, 112 females; mean age 62 years) who had suffered from persistent LBP for ≥3 months. During the first test (before the treatment), the BS-POP, the Minnesota Multiphasic Personality Inventory (MMPI), the Profile of Mood States (POMS), the 36-item Short-form Health Survey version 2 (SF-36 v2), and the Roland-Morris Disability Questionnaire (RDQ) were conducted. The BS-POP, POMS, SF-36 v2, and RDQ for the third test were conducted (4-6 weeks after treatment) on all patients who had participated in the first test to determine the responsiveness of the BS-POP. The responsiveness of the BS-POP was investigated statistically. RESULTS: The total crude BS-POP scores were significantly lower for both physician and patient versions in the third test than in the first test. Moreover, the crude RDQ scores and SF-36 v2 items, physical functioning (PF), bodily pain (BP), MH, VT, and GH, and POMS items, tension-anxiety (T-A), D, F, and confusion (C) improved significantly, confirming responsiveness to treatment. DISCUSSION: The present findings indicate that the BS-POP possesses sufficient responsiveness from a computational psychology perspective. The BS-POP constitutes a tool enabling orthopaedists to easily identify psychiatric problems in orthopaedic patients.

Neuroimaging-aided differential diagnosis of the depressive state.

A serious problem in psychiatric practice is the lack of specific, objective biomarker-based assessments to guide diagnosis and treatment. The use of such biomarkers could assist clinicians in establishing differential diagnosis, which may improve specific individualised treatment. This multi-site study sought to develop a clinically suitable neuroimaging-guided diagnostic support system for differential diagnosis at the single-subject level among multiple psychiatric disorders with depressive symptoms using near-infrared spectroscopy, which is a compact and portable neuroimaging method. We conducted a multi-site, case-control replication study using two cohorts, which included seven hospitals in Japan. The study included 673 patients (women/men: 315/358) with psychiatric disorders (major depressive disorder, bipolar disorder, or schizophrenia) who manifested depressive symptoms, and 1007 healthy volunteers (530/477). We measured the accuracy of the single-subject classification in differential diagnosis among major psychiatric disorders, based on spatiotemporal characteristics of fronto-temporal cortical haemodynamic response patterns induced by a brief (<3 min) verbal fluency task. Data from the initial site were used to determine an optimal threshold, based on receiver-operator characteristics analysis, and to generate the simplest and most significant algorithm, which was validated using data from the remaining six sites. The frontal haemodynamic patterns detected by the near-infrared spectroscopy method accurately distinguished between patients with major depressive disorder (74.6%) and those with the two other disorders (85.5%; bipolar disorder or schizophrenia) that presented with depressive symptoms. These results suggest that neuroimaging-guided differential diagnosis of major psychiatric disorders developed using the near-infrared spectroscopy method can be a promising biomarker that should aid in personalised care in real clinical settings. Potential confounding effects of clinical (e.g., age, sex) and systemic (e.g., autonomic nervous system indices) variables on brain signals will need to be clarified to improve classification accuracy.

Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

OBJECTIVE: Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. METHODS: Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. RESULTS: There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. CONCLUSIONS: There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia.

Plasma levels of leptin in reproductive-aged women with mild depressive and anxious states.

AIMS: Recent studies suggest that leptin may have an effect on emotion and mood. Low levels of leptin in depression and anxiety have been reported in many animal models; however in humans, it has yet to be elucidated as to whether plasma leptin levels are low in similar states. Therefore, in this study we investigated how plasma leptin level and salivary stress markers of reproductive-aged women, who constitute the majority of patients with mild depression and anxiety in our clinic, are different from those of healthy women. METHODS: We compared the results of the Medical Outcome Study 36-Item Short-Form Health Survey, the Self-rating Questionnaire for Depression, the State-Trait Anxiety Inventory, plasma leptin levels, and salivary stress markers in 29 depressive and anxious reproductive-aged female patients with those in 26 age- and body-mass-index-matched healthy female volunteers. RESULTS: The Short-Form 36, Self-rating Questionnaire for Depression and State-Trait Anxiety Inventory scores in the patients were worse and their leptin levels were lower than those in the healthy volunteers. There were no significant differences in salivary stress markers, such as chromogranin A and cortisol, between the patients and healthy volunteers. CONCLUSION: This study suggests that leptin might play a pathophysiological role in reproductive-aged female patients for mild depression and anxiety.

Mental disorders that exacerbated due to the Fukushima disaster, a complex radioactive contamination disaster.

AIM: The Fukushima disaster was caused by an earthquake that occurred on 11 March 2011. Following the serious damage caused by the earthquake and the subsequent tsunami, radioactive contamination occurred because of the meltdown accident at the Fukushima nuclear power plant. We investigated what mental disorders were likely to become exacerbated under these conditions. METHODS: We surveyed psychiatric outpatients at Fukushima Medical University Hospital for 1 month (31 days) from the day of the earthquake (March­April 2011). RESULTS: The survey revealed that bipolar I disorder was most likely to become exacerbated under the conditions and that the exacerbation exhibited was more likely to involve manic switches than depression. CONCLUSION: On the basis of the results of our study, particular care must be taken to follow up bipolar I disorder patients after a natural disaster. Our results also suggested the possible origin of bipolar I disorder.

New instrument for measuring multiple domains of social cognition: construct validity of the Social Cognition Screening Questionnaire (Japanese version).

AIM: The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ) (Japanese version). METHODS: We first tested whether the subscale scores and the total score of the SCSQ could discriminate patients with schizophrenia from normal controls. Next, we tested the internal consistency. Finally, we investigated the relation between the subscale scores and other measures of social cognition and social functioning that were presumed to correspond to the subscale's scores, including the Hinting Task, the Ambiguous Intentions Hostility Questionnaire (AIHQ), the Beck Cognitive Insight Scale and the Social Functioning Scale. RESULTS: The subscale scores and the total score appeared to show more robust between-group differences than other measures of social cognition, such as the AIHQ and the Hinting Task. The total score distinguished the patients from normal controls with an area under the receiver-operator curve of 0.84, which indicated a high level of discrimination. The Cronbach's alpha for the four subscales was 0.72, which was considered acceptable. In terms of criterion-related validity, theory of mind, metacognition and hostility bias subscale scores showed significant correlations with the Hinting Task, Beck Cognitive Insight Scale and AIHQ, respectively. Moreover, the theory of mind subscale score showed a significant correlation with four domain scores of the Social Functioning Scale. The present results indicated good construct validity and internal consistency of the SCSQ. CONCLUSIONS: Although this is an interim report with a small sample size, the SCSQ holds promise as an efficient measure for social cognition.

[A new structure for mental health and welfare in the Soso area to promote the recovery of people in Fukushima from the 3.11 earthquake and nuclear power plant accident].

Immediately after the 3.11 Earthquake and Fukushima Dai-Ichi Nuclear Power Plant Accident, 5 hospitals with psychiatric beds within a 30-km radius of the nuclear power plant were ordered to move their inpatients to other hospitals outside the 30-km zone. As a result, more than 800 inpatients in total were transferred to other hospitals within or outside Fukushima Prefecture, and the 5 hospitals were closed. In addition, 3 psychiatric clinics within the 30-km radius stopped operating temporarily. In March of 2011, several volunteer members of the Department of Neuropsychiatry and the Mental Health Division, Family Nursing Department, Fukushima Medical University, organized the Mental Health Care Team of Fukushima Medical University to support the disaster victims. The team opened a temporary psychiatric outpatient clinic in Soma City General Hospital through the courtesy of its staff to provide services for people needing and seeking assistance for mental health. The team continued to provide psychiatric services in this temporary clinic until the end of 2011. A new psychiatric clinic, 'Mental Clinic Nagomi', was inaugurated by the team in January 2012 with the kind support of many volunteers from throughout Japan. At the same time, the NPO 'New Psychiatric Care, Health and Welfare System in Soso (Kokoro-no-Care Nagomi)' was also inaugurated mainly by the team members. Mental Clinic Nagomi and Kokoro-no-Care Nagomi closely collaborate with each other to provide new community-based and out-reach mental health services in the Soso area. Kokoro-no-Care Nagomi (abbreviated as KCN) has accepted the role of the Soso Branch of Fukushima Kokoro-no-Care Center entrusted by the Fukushima Center. KCN has also been designated as a facility performing the Out-Reach Project responding to the complex disaster in Fukushima planned by the Japanese Government. KCN has been engaged in work to support and ensure the mental health of disaster victims, persons with psychiatric problems, and community residents living in temporary or their own houses located in the Soso area. We wish to express our sincere thanks to the Japanese Society of Psychiatry and Neurology (JSPN) for awarding us the 2013 JSPN Award for Special Contributions to Psychiatric Practice. We think that this award represents JSPN's wish to encourage the people and psychiatric professionals of the Tohoku District. Encouraged by the award, we have resolved to continue our efforts to facilitate the recovery of the mental health of victims and residents of Fukushima. We wish to express our sincere and deep gratitude to Fukushima Prefecture, the Japan Society, Japanese Medical Society of America, JAMSNET Tokyo, CWAJ (College Women's Association of Japan), The Englewood NJ Rotary Club, The NJ Rotary District 7490, Médecins du Monde (MDM), Shin-Nihon Seiyaku Company Ltd., and all the individuals who have kindly supported us.

[Mental health in evacuees from the 3.11 complex disaster in Japan].

Two years after the "3.11" complex disaster--the Great East Japan Earthquake, the resulting tsunami, and the Fukushima nuclear power plant accident--that occurred on March 11, 2011, approximately 150,000 people were still living as evacuees, with approximately 50,000 evacuees living outside Fukushima Prefecture. In a survey conducted by the Asahi Shimbun newspaper in February 2012, the top three sources of anxiety among evacuees were radiation contamination (mentioned by 56% of respondents), income (48%), and school attendance of children (21%). In June 2012, results from the Mental Health Survey, which was conducted as part of the Fukushima Health Management Survey, indicated that 14.8% of adult evacuees had K6 scores equal to or greater than the standard cut-off of 13, a much higher proportion than the 3% found in previous studies. In the same survey, 21.5% of child evacuees had SDQ scores equal to or greater than the standard cut-off of 16, whereas previous studies suggest a typical ratio of around 9.5%. It is natural for people to experience anxiety when facing radiation exposure, even at low levels. Here the important thing is to be "accurately" afraid: people should pay attention to scientific facts, and avoid danger appropriately, but not be unduly frightened. However, some people remain anxious even when objective radiation levels are low enough to not result in harm. A number of parents with young children decided to relocate outside of Fukushima Prefecture. In consideration of the desires of these parents to have areas where their children could play without being concerned about radiation, some municipalities constructed spacious indoor play facilities where parents have increased opportunities to communicate with each other, which actually leads to effective risk communication. Compared to the trajectory of mental health recovery after the 1995 Hanshin-Awaji Earthquake, recovery after the present disaster is delayed, particularly in Fukushima. In Fukushima, many disturbing events, such as the issue of water contaminated by radiation, have distressed evacuees, resulting in their delayed recovery in terms of mental health.

Case report: Atomoxetine improves chronic pain with comorbid post-traumatic stress disorder and attention deficit hyperactivity disorder.

Background: It is known that patients reporting chronic pain often experience trauma or post-traumatic stress disorder (PTSD) and tend to be more difficult to treat. Attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder, is frequently associated with chronic pain. Furthermore, patients diagnosed with ADHD are more likely to encounter trauma and develop PTSD because of their inattentive and impulsive tendencies. There are reports stating that atomoxetine (ATX), a selective noradrenaline reuptake inhibitor for ADHD, is effective in patients diagnosed with PTSD and ADHD. However, there have been no reports on cases of comorbid PTSD and ADHD with chronic pain, and ATX's potential in improving chronic pain coexisting PTSD. Furthermore, no reports have evaluated patient cerebral blood flow in conjunction with the course of treatment with ATX for chronic pain. Case report: In this study, we reported a case where ATX improved chronic pain with PTSD and improved cerebral blood flow. The patient was a 56-year-old woman exhibiting chronic pain with PTSD, resulting from 6 years of severe domestic violence from her common-law husband. She had no history of ADHD diagnosis, but through aggressive screening, comorbid ADHD was diagnosed. When treated with ATX, there were significant improvements in her pain, quality of life, anxiety, depression, catastrophic thoughts, and cerebral blood flow. As a result, she could resume work after 11 years. Conclusion: The study showed that chronic pain with PTSD may be comorbid with ADHD. Moreover, we found that ATX can improve chronic pain with PTSD and cerebral blood flow. Aggressive screening of ADHD is important because once the diagnosis of comorbidity is confirmed, an ideal ADHD treatment can be selected. Therefore, based on the results of this study, ATX may be a candidate for treatment for cases of chronic pain with PTSD and ADHD.