Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by the bilateral development of multiple cysts in the kidneys. Pain management is a clinically important issue, especially because approximately 60% of patients with ADPKD experience chronic pain related to hemorrhage from renal cysts, which significantly reduces their daily life. The cystic fibrosis transmembrane conductance regulator, the molecule responsible for cyst formation in ADPKD, is also the cause of cystic fibrosis. Since attention deficit hyperactivity disorder (ADHD) is known to occur frequently in conjunction with cystic fibrosis, ADPKD may be associated with ADHD. However, to our knowledge, no study has investigated 1) ADHD or autism spectrum disorder (ASD) as comorbidities with ADPKD, 2) the effects of ADHD medications on chronic pain in ADPKD, or 3) cerebral blood flow corresponding to guanfacine (GF) or methylphenidate (MP) treatment for chronic pain. We report the case of a 15-year-old girl with ADPKD, who had chronic back pain associated with ADPKD and had to withdraw from high school because the pain interfered with her daily life. Although she took antihypertensive medications to prevent bleeding, they did not provide adequate blood pressure control. The patient was referred to a child psychiatrist and diagnosed with ASD; however, the pain did not improve. Subsequently, she was referred to our pain center. The diagnosis of ADHD was confirmed and treatment with ADHD medications was initiated. Monotherapy with MP, atomoxetine, and GF resulted in hypertension and hypotension as side effects; however, a combination of MP 18â mg and GF 4â mg provided pain relief and moderate blood pressure control, and the patient was able to go on to college. During the course of treatment, there was an improvement in the distribution of cerebral blood flow in the prefrontal and insular cortices. Confirmation of an ADHD diagnosis comorbid with ASD enabled the use of ADHD medications. The combination of MP and GF improved chronic back pain and high blood pressure due to ADPKD and cerebral blood flow. Screening for ADHD is important in the treatment of ADPKD.
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.
Objective: This study aimed to assess the efficacy and safety of quadripulse transcranial magnetic stimulation-50 (QPS-50) in patients with intractable epilepsy. Methods: Four patients were included in the study. QPS-50, which induces long-term depression in healthy subjects, was administered for 30â¯min on a weekly basis for 12â¯weeks. Patients' clinical symptoms and physiological parameters were evaluated before, during, and after the repeated QPS-50 period. We performed two control experiments: the effect in MEP (Motor evoked potential) size after a single QPS-50 session with a round coil in nine healthy volunteers, and a follow-up study of physiological parameters by repeated QPS-50 sessions in four other healthy participants. Results: Motor threshold (MT) decreased during the repeated QPS-50 sessions in all patients. Epileptic symptoms worsened in two patients, whereas no clinical worsening was observed in the other two patients. In contrast, MT remained unaffected for 12â¯weeks in all healthy volunteers. Conclusions: QPS-50 may not be effective as a treatment for intractable epilepsy. Significance: In intractable epilepsy patients, administering repeated QPS-50 may paradoxically render the motor cortex more excitable, probably because of abnormal inhibitory control within the epileptic cortex. The possibility of clinical aggravation should be seriously considered when treating intractable epilepsy patients with non-invasive stimulation methods.
AIMS: Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA-seq data and a correlation analysis between levels of gene expression and lipids. METHODS: RNA-Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). RESULTS: Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3-kinase (PI3K)-Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. CONCLUSIONS: This study provided results of the integrated analysis of the schizophrenia-associated transcriptome and lipidome within the PFC and revealed that lipid-correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.
Phospholipids , Prefrontal Cortex , Schizophrenia , Transcriptome , Humans , East Asian People , Ethers/metabolism , Lipid Metabolism/genetics , Phosphatidylinositol 3-Kinases/analysis , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phospholipids/analysis , Phospholipids/genetics , Phospholipids/metabolism , Prefrontal Cortex/chemistry , Prefrontal Cortex/metabolism , Schizophrenia/genetics , Schizophrenia/metabolism , Autopsy
Key Clinical Message: Persistent idiopathic facial pain (PIFP) and attention-deficit/hyperactivity disorder (ADHD) may coexist and can be improved with ADHD medications. Thus, clinicians should screen for ADHD by a multidisciplinary approach when treating PIFP and differentiate between other odontogenic disorders. Abstract: We report a case of a woman with persistent idiopathic facial pain (PIFP) and attention-deficit/hyperactivity disorder (ADHD) that markedly improved with the administration of a combination of aripiprazole (APZ) and methylphenidate (MP) treatment. Screening for ADHD and administration of APZ and/or MP may be considered in treating PIFP.
Introduction: Oral dysesthesia is a disease characterized by pain and/or abnormal sensations in the oral region, without any organic abnormality. Its symptoms include pain, and it is considered to be a disorder associated with idiopathic oral-facial pain. It is also known that idiopathic oral-facial pain tends to coexist with chronic musculoskeletal pain, including low back pain, even before its onset. Such coexisting idiopathic pain conditions are also called chronic overlapping pain conditions (COPCs). In general, COPCs are often refractory to treatment. Recently, it has been reported that attention deficit hyperactivity disorder (ADHD) is associated with many COPCs, such as pain in the facial and lower back regions and so on. However, there are no reports of (1) ADHD as a comorbidity with oral dysesthesia (OD) or (2) of the therapeutic effects of ADHD medications or dopamine agonists on low back pain and OD or an (3) evaluation of cerebral blood flow over time after treatment with these medications for OD and low back pain. Case Presentation: In this study, we report the case of an 80-year-old man with OD and chronic low back pain that persisted for more than 25 years. His OD and chronic back pain were refractory to standard treatment, prevented him from continuing work, and tended to be exacerbated by conflicts in his relationship with his son. In recent years, ADHD has often been found to be comorbid with chronic pain, and ADHD medications have been reported to improve chronic pain as well. The patient was confirmed to have undiagnosed ADHD and was treated with the ADHD medication atomoxetine and dopamine agonist pramipexole, which dramatically improved his OD, chronic back pain, and cognitive function. Furthermore, along the course of treatment, there was improvement in cerebral blood flow in his prefrontal cortex, which was thought to reflect improved function in the region. Consequently, he was able to resume work and improve his family relationships. Conclusion: Therefore, in the cases of ODs and COPCs, screening for ADHD and, if ADHD is diagnosed, ADHD medications or dopamine agonists may be considered.
Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with primary chronic pain syndromes, such as fibromyalgia, migraine, and chronic low back pain. Although idiopathic orofacial pain (IOP) is classified as burning mouth syndrome or persistent idiopathic facial or dentoalveolar pain and as a primary chronic pain, the association between IOP and ADHD has not been investigated. This retrospective cohort study investigated the severity of ADHD symptoms measured using the ADHD scale and the effects of treatment using ADHD drugs and the dopamine system stabilizer aripiprazole. The participants were 25 consecutive patients with refractory IOP referred to a psychiatrist and diagnosed with coexisting ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5. The ADHD scale scores were higher in patients with intractable IOP than those in the general population. Pharmacotherapy used in this study led to clinically significant improvements in pain, anxiety/depression, and pain catastrophizing. Intractable IOP and ADHD were shown to be associated. In the future, screening and pharmacotherapy for ADHD should be considered in the treatment of intractable IOP.
Attention Deficit Disorder with Hyperactivity , Chronic Pain , Humans , Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/drug therapy , Chronic Pain/complications , Chronic Pain/diagnosis , Chronic Pain/drug therapy , Retrospective Studies , Aripiprazole/therapeutic use , Facial Pain/diagnosis , Facial Pain/drug therapy , Facial Pain/complications
John Fitzgerald Kennedy (JFK), the 35th President of the USA, had chronic low back pain deemed to be centralized pain. Reportedly, attention-deficit/hyperactivity disorder (ADHD) could associate with centralized pain. Based on his biographies, JFK could have had ADHD, a plausible cause of pain that afflicted him.
Chronic pain has recently been associated with developmental disorders [autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)]. Regarding chronic pain in adulthood, fibromyalgia, migraine, and chronic low back pain have been associated with ADHD. The ICD-11 disease classification categorizes these pain diseases as chronic primary pain, suggesting high comorbidity with developmental disorders in chronic primary pain. Atypical odontalgia (AO) is a persistent tooth pain that occurs in the absence of any of the usual dental causes, most of which are triggered by dental treatment. Conditions characterized by tooth pain with no apparent cause are also classified as chronic primary pain. Approximately half the patients with AO are diagnosed with psychiatric disorders; the most common are depression (15.4%) and anxiety disorders (10.1%). However, there are no reports on neurodevelopmental disorders comorbid with AO. In the present study, we report a case of a 46-year-old man with numerous complaints (e.g., occlusal instability, difficulty eating, difficulty speaking), who took work leave due to worsening of his symptoms after periodontal scaling ("gingival recession" and "aggressive periodontal treatment") and frequently expressed dissatisfaction and anger at the hospital, making the dental treatment difficult. After a referral to a psychiatrist specializing in chronic pain, AO and previously undiagnosed comorbidity of ASD and ADHD were confirmed. Atypical antipsychotic risperidone for ASD irritability and an ADHD medication, atomoxetine dramatically reduced anger, pain, anxiety, depression, and pain catastrophizing thoughts, leading to reduced obsession with his symptoms and less frequent complaints. After risperidone (1 mg/day) + atomoxetine (120 mg/day) were ultimately prescribed after adjustment, he was able to return to work 226 days after initiation of psychiatric treatment. Recent studies show that comorbidity of developmental disorders in patients with chronic pain is likely to be undetected. Clinicians should include screening for ASD and ADHD not only in cases of fibromyalgia, migraine, and chronic low back pain, but also in orofacial pain such as AO and other treatments for chronic primary pain. For patients diagnosed with ASD or ADHD, an effective drug therapy for ASD and ADHD should be considered.
This study was a systematic review of research using the Wechsler Intelligence Scale for Children (WISC) with Autism Spectrum Disorder (ASD) to examine cognitive characteristics of children with ASD beyond the impact of revisions based on WISC and diagnostic criteria changes. The classic "islets of ability" was found in individuals with full-scale IQs < 100. The "right-descending profiles" were observed among high IQ score individuals. High levels on the Block Design and low Coding levels were consistently found regardless of the variation in intellectual functioning or diagnosis. This review identified patterns of cognitive characteristics in ASD individuals using empirical data that researchers may have previously been aware of, based on their experiences, owing to the increased prevalence of ASD.
Autism Spectrum Disorder , Aptitude , Autism Spectrum Disorder/diagnosis , Child , Cognition , Humans , Prevalence , Wechsler Scales
AIM: Clozapine is currently the only effective drug for treatment-resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine. METHODS: First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine-binding proteins in extracts from the cerebra of 7-week-old ICR mice were isolated and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy. RESULTS: Alpha and ß tubulins were the most abundant clozapine-binding proteins. We also found that clozapine directly binds with α and ß tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells. CONCLUSION: These results suggest that α and ß tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.
Clozapine , Tubulin , Animals , Chromatography, Liquid , Clozapine/pharmacology , HeLa Cells , Humans , Mice , Mice, Inbred ICR , Microtubules/metabolism , Tandem Mass Spectrometry , Tubulin/chemistry , Tubulin/metabolism , Tubulin/pharmacology
BACKGROUND: Associations between attention-deficit/hyperactivity disorder (ADHD) and chronic pain disorders, such as fibromyalgia, have been reported. However, associations between persistent chronic nonspecific low back pain (CNLBP) and ADHD have not yet been investigated. OBJECTIVES: This study aimed to investigate the positive rates of possible ADHD, as assessed by self-reported ADHD scales, in patients with persistent CNLBP, using data from self-reported questionnaires completed by patients and their families. This study also aimed to compare the self-reported scores obtained from existing standardized data for healthy individuals, and to examine whether the ADHD scale scores of patients with persistent CNLBP are associated with pain variables. STUDY DESIGN: Cross-sectional study. SETTING: The specialized pain clinic at our university hospital. METHODS: This cross-sectional study included 60 consecutive patients with persistent CNLBP who were diagnosed with a possible somatic symptom disorder and were referred to a psychiatrist in our pain clinic. The Conners' Adult ADHD Rating Scales (CAARS) self-report (CAARS-S) and observer-rated (CAARS-O) questionnaires were utilized. We investigated the CAARS scores, and the association between the CAARS subscale scores and pain variables (pain duration and pain Numeric Rating Scale) in patients with persistent CNLBP. RESULTS: Of the 60 patients, 19 (31.7%) were positive on both CAARS-S and CAARS-O questionnaires (T-score > 65). The ADHD indices, which comprised subscales of the CAARS estimating the necessity of treatment for ADHD, were significantly higher in both male and female patients with persistent CNLBP than in the Japanese standardized sample (P < 0.005). CAARS-S hyperactivity/restlessness, CAARS-O hyperactivity/restlessness, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition hyperactive-impulsive symptom subscale scores also correlated with the pain intensity (P < 0.05). LIMITATIONS: In this study, ADHD tendency was evaluated using only a self-reported questionnaire. Hence in the future, accurate and precise assessments of ADHD symptoms using structured clinical interviews conducted by ADHD experts are warranted. Additionally, the study only included patients with persistent CNLBP. Therefore in the future, it will be valuable to investigate ADHD scale scores (e.g., CAARS) among patients with CNLBP and nonspecific low back pain with larger sample sizes. CONCLUSIONS: Our findings revealed that the subscale scores on an ADHD scale were considerably high in patients with persistent CNLBP. As a previous study of our clinical experience indicates that persistent CNLBP can be substantially relieved by administering ADHD medications, ADHD screening is warranted in the treatment of persistent CNLBP.
Attention Deficit Disorder with Hyperactivity , Low Back Pain , Adult , Attention Deficit Disorder with Hyperactivity/diagnosis , Cross-Sectional Studies , Female , Humans , Low Back Pain/diagnosis , Male , Psychiatric Status Rating Scales , Self Report , Surveys and Questionnaires
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.
Autoantigens/genetics , Epilepsies, Myoclonic/pathology , Microsatellite Repeats , Nerve Tissue Proteins/genetics , RNA-Binding Proteins/genetics , Adult , Age of Onset , Case-Control Studies , Child , Epilepsies, Myoclonic/genetics , Female , Humans , Male , Middle Aged
Background: Suicide is a major concern after the 2011 earthquake and nuclear accident in Fukushima. Aims: This study delineates characteristics of the disaster-related suicides in Fukushima. Method: Data provided by the Fukushima Prefectural Police and data published by the Fukushima or Japanese Government were analyzed. Numbers of disaster-related suicides and evacuees were compared among the three prefectures affected. Age, sex, occupation, and means for disaster-related suicides in Fukushima were compared with overall suicides in Fukushima or Japan. History of medical treatment, changes in job and family structure after the disaster, and signs of contemplation were examined within the disaster-related suicides of Fukushima. Results: While other prefectures have experienced a drop in disaster-related suicides, Fukushima has not. Age-standardized disaster-related suicide rates were remarkably higher in men than in women. Moreover, disaster-related suicide rates in Fukushima were higher in women in their 50s and 80s as compared with overall suicide rates in Fukushima or Japan. Limitations: No detailed comparisons were made between disaster-related and non-disaster-related suicides. Conclusion: Disaster-related suicide rates were higher in men than in women. Also, it was found that the disaster-related suicide rates of elderly women were higher compared with overall suicide rates in Japan and Fukushima. In addition, many who died by suicide showed signs of contemplation before the attempt and had started psychiatric treatment. Improvement of suicide risk assessment skills for mental health professionals and gatekeeper training among residents will be essential to prevent disaster-related suicides.
Disasters , Earthquakes , Fukushima Nuclear Accident , Suicide , Aged , Female , Humans , Japan/epidemiology , Male
This is based on a survey of two-year-old but not three-year-old cohorts. Therefore, we cannot state anything about the incidence of autism spectrum disorder (ASD) in over three-years-old children. We submit corrections in the following errata, because the original sentences might mislead the readers without evidence from three-year-old children. Also, we would like to exclude the phrase of "low-dose radiation" from the sections of Key word, Abstract, and Conclusion, because this study did not cover its influence.Author Shuntaro ItagakiAugust 05, 2019.
