Hypomyelinating Leukodystrophy 10 (HLD10)-Associated Mutations of PYCR2 Form Large Size Mitochondria, Inhibiting Oligodendroglial Cell Morphological Differentiation.

Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). In the CNS, myelin sheaths are derived from differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve neuronal functions. Nucleotide mutations of the pyrroline-5-carboxylate reductase 2 (PYCR2) gene are associated with HLD10, likely due to PYCR2's loss-of-function. PYCR2 is a mitochondrial residential protein and catalyzes pyrroline-5-carboxylate to an amino acid proline. Here, we describe how each of the HLD10-associated missense mutations, Arg119-to-Cys [R119C] and Arg251-to-Cys [R251C], lead to forming large size mitochondria in the FBD-102b cell line, which is used as an oligodendroglial cell differentiation model. In contrast, the wild type proteins did not participate in the formation of large size mitochondria. Expression of each of the mutated R119C and R251C proteins in cells increased the fusion abilities in mitochondria and decreased their fission abilities relatively. The respective mutant proteins, but not wild type proteins also decreased the activities of mitochondria. While cells expressing the wild type proteins exhibited differentiated phenotypes with widespread membranes and increased expression levels of differentiation marker proteins following the induction of differentiation, cells harboring each of the mutant proteins did not. Taken together, these results indicate that an HLD10-associated PYCR2 mutation leads to the formation of large mitochondria with decreased activities, inhibiting oligodendroglial cell morphological differentiation. These results may reveal some of the pathological mechanisms in oligodendroglial cells underlying HLD10 at the molecular and cellular levels.

Parents' Perspectives on Their Relationship With Their Adolescent Children With Internet Addiction: Survey Study.

BACKGROUND: Parents of adolescents with internet addiction are confronted with their children's internet problems on a daily basis. Parents may notice that adolescents with addiction may also have emotional and behavioral problems, including impulsivity and violence. Parenting styles have been found to be related to internet addiction. OBJECTIVE: The purpose of this study is to investigate parents' perspectives on their parenting style, relationship with their child, and the degree of internet addiction and emotional and behavioral problems of their child. METHODS: A web survey was conducted with 600 parents of children between the ages of 12 and 17 years, from October 14 to 18, 2021, across Japan. Respondents were recruited by an internet research company and were asked to complete an anonymous online questionnaire. The survey was divided into two groups: 300 parents who answered "yes" to the question "Do you think your child is dependent on the internet?" and 300 parents who answered "no" to that question. Questionnaires were collected until each group had 300 participants. The questionnaire included (1) the Parent-Child Internet Addiction Test (PCIAT), (2) the daily time spent using the internet, (3) the Strengths and Difficulties Questionnaire (SDQ), (4) the Parenting Style and Dimensions Questionnaire (PSDQ), and (5) the Relationship Questionnaire (RQ) measuring self-report attachment style prototypes. RESULTS: Mean scores of the PCIAT and the daily time spent using the internet for the group with probable internet addiction were significantly higher than those of the group without probable internet addiction (50%; P<.001). The total difficulties score from the SDQ for the group with probable internet addiction (mean 10.87, SD 5.9) was significantly higher than that for the group without probable internet addiction (mean 8.23, SD 5.64; P<.001). The mean score for authoritarian parenting from the PSDQ for the group with probable internet addiction (mean 2.1, SD 0.58) was significantly higher than that for the group without probable internet addiction (mean 2.1, SD 0.58; P<.001). Regarding the RQ, there were no significant differences between the two groups. CONCLUSIONS: Our findings suggest that parents who think their child is addicted to the internet may recognize emotional and behavioral problems of the child and have an authoritarian parenting style.

Schnurri 3 promotes Th2 cytokine production during the late phase of T-cell antigen stimulation.

Th1 and Th2 polarization is determined by the coordination of numerous factors including the affinity and strength of the antigen-receptor interaction, predominant cytokine environment, and costimulatory molecules present. Here, we show that Schnurri (SHN) proteins have distinct roles in Th1 and Th2 polarization. SHN2 was previously found to block the induction of GATA3 and Th2 differentiation. We found that, in contrast to SHN2, SHN3 is critical for IL-4 production and Th2 polarization. Strength of stimulation controls SHN2 and SHN3 expression patterns, where higher doses of antigen receptor stimulation promoted SHN3 expression and IL-4 production, along with repression of SHN2 expression. SHN3-deficient T cells showed a substantial defect in IL-4 production and expression of AP-1 components, particularly c-Jun and Jun B. This loss of early IL-4 production led to reduced GATA3 expression and impaired Th2 differentiation. Together, these findings uncover SHN3 as a novel, critical regulator of Th2 development.

Knockdown of Golgi Stress-Responsive Caspase-2 Ameliorates HLD17-Associated AIMP2 Mutant-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation.

Hypomyelinating leukodystrophy 17 is an autosomal recessive disease affecting myelin-forming oligodendroglial cells in the central nervous system. The gene responsible for HLD17 encodes aminoacyl-tRNA synthase complex-interacting multifunctional protein 2, whose product proteins form a scaffold that supports aminoacyl-tRNA synthetases throughout the cell body. Here we show that the HLD17-associated nonsense mutation (Tyr35-to-Ter [Y35X]) of AIMP2 localizes AIMP2 proteins as aggregates into the Golgi bodies in mouse oligodendroglial FBD-102b cells. Wild type AIMP2 proteins, in contrast, are distributed throughout the cell body. Expression of the Y35X mutant proteins, but not the wild type proteins, in cells upregulates Golgi stress signaling involving caspase-2 activation. Cells expressing the wild type proteins exhibit differentiated phenotypes with web-like structures bearing many processes following the induction of differentiation, whereas cells expressing the Y35X mutant proteins fail to differentiate. Furthermore, CASP2 knockdown but not control knockdown reverses the phenotypes of cells expressing the mutant proteins. These results suggest that HLD17-associated AIMP2 mutant proteins are localized in the Golgi bodies where their proteins stimulate Golgi stress-responsive CASP2 to inhibit differentiation; this effect is ameliorated by knockdown of CASP2. These findings may reveal some of the molecular and cellular pathological mechanisms underlying HLD17 and possible approaches to ameliorating the disease's effects.

Phospholipase D and phosphatidylinositol-4-phosphate 5-kinase 1 are involved in the regulation of oligodendrocyte morphological differentiation.

Oligodendroglial cells (oligodendrocytes) differentiate to form the myelin that wraps neuronal axons in the central nervous system (CNS). This myelin sheath supports the propagation of saltatory conduction and protects axons from physical stresses. When oligodendrocytes do not normally differentiate to myelinate axons, their key functions as oligodendrocytes in the CNS are severely impaired. The molecular mechanics that control differentiation still remain to be clarified. Arf6 belongs to the small GTPase family and is known to be a positive regulator of oligodendrocyte differentiation. Here, we show that the phospholipase D (PLD) and phosphatidylinositol-4-phosphate 5-kinase 1 (PIP5K1) molecules, the major effectors of Arf6, are involved in the regulation of oligodendrocyte differentiation. Knockdown of PLD1 or PIP5K type 1γ (PIP5K1C) by their respective specific siRNAs in mouse oligodendroglial FBD-102b cells inhibited morphological differentiation into structures bearing myelin-like processes; this finding is consistent with the concurrent changes in expression of differentiation and myelin marker proteins. Treatment with VU0155069 or UNC3230, specific inhibitors of PLD and PIP5K1, respectively, blunted morphological differentiation and decreased expression of myelin and differentiation marker proteins. Similar results have been obtained in studies using primary oligodendrocytes. These results suggest that the major Arf6 effector molecules PLD and PIP5K1 are among the molecules involved in the regulation of morphological differentiation in oligodendrocytes prior to myelination.

Human CD36hi monocytes induce Foxp3+ CD25+ T cells with regulatory functions from CD4 and CD8 subsets.

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3+ regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3+ T-cell differentiation, the specific antigen-presenting cells required and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14+ monocytes expressing the scavenger molecule, CD36, can generate CD4+ and CD8+ T cells that coexpress Foxp3 and T-bet from both umbilical cord blood. These Foxp3+ T-bet+ T cells potently suppress T-cell proliferation and ameliorate xenogeneic graft-versus-host disease. CD14+  CD36+ monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3+ T cells from both cord blood and adult peripheral naïve T cells. The induction of Foxp3+ T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36hi monocytes may contribute to the peripheral development of Foxp3+ T-bet+ T cells with regulatory functions in both neonates and adults.

Spectral response properties of higher visual neurons in Drosophila melanogaster.

The fruit fly Drosophila melanogaster can process chromatic information for true color vision and spectral preference. Spectral information is initially detected by a few distinct photoreceptor channels with different spectral sensitivities and is processed through the visual circuit. The neuroanatomical bases of the circuit are emerging. However, only little information is available in chromatic response properties of higher visual neurons from this important model organism. We used in vivo whole-cell patch-clamp recordings in response to monochromatic light stimuli ranging from 300 to 650 nm with 25-nm steps. We characterized the chromatic response of 33 higher visual neurons, including their general response type and their wavelength tuning. Color-opponent-type responses that had been typically observed in primates and bees were not identified. Instead, the majority of neurons showed excitatory responses to broadband wavelengths. The UV (300-375 nm) and middle wavelength (425-575 nm) ranges could be separated at the population level owing to neurons that preferentially responded to a specific wavelength range. Our results provide a first mapping of chromatic information processing in higher visual neurons of D. melanogaster that is a suitable model for exploring how color-opponent neural mechanisms are implemented in the visual circuits.

Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study.

OBJECTIVE: Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment. RESULTS: Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320).

Data on the effects of Charcot-Marie-Tooth disease type 2N-associated AARS missense mutation (Arg329-to-His) on the cell biological properties.

Charcot-Marie-Tooth (CMT) diseases are genetic neuropathies in the peripheral nervous system (PNS). Type 1 CMT diseases are neuropathies in Schwann cells, PNS myelinating glial cells, whereas type 2 CMT diseases are axonal neuropathies. In addition, there are other types of categories in CMT diseases. CMT diseases are associated with approximately 100 responsible genes. Taiwanese mutation (Asn71-to-Tyr) of alanyl-tRNA synthetase (AARS) in type 2N CMT disease has been reported to have several pathological effects on properties of AARS proteins themselves [1]. Also, some mutations in other responsible genes affect cell biological properties of their gene products [2,3]. Herein we provide the data regarding the effects of another type 2N CMT disease-associated AARS mutation (Arg329-to-His) in French family on the cellular properties.

Treatment Preferences for Internet-Based Cognitive Behavioral Therapy for Insomnia in Japan: Online Survey.

BACKGROUND: The internet has the potential to increase individuals' access to cognitive behavioral therapy (CBT) for insomnia at low cost. However, treatment preferences regarding internet-based computerized CBT for insomnia have not been fully examined. OBJECTIVE: The aim was to conduct an anonymous online survey to evaluate treatment preferences for insomnia among patients with insomnia and individuals without insomnia. METHODS: We developed an online survey to recruit a total of 600 participants living in the Kanto district in Japan. There were three subgroups: 200 medicated individuals with insomnia, 200 unmedicated individuals with insomnia, and 200 individuals without insomnia. The survey asked questions about the severity of the respondent's insomnia (using the Athens Insomnia Scale), the frequency of sleep medication use and the level of satisfaction with sleep medication use, the respondent's knowledge of CBT, his or her preference for CBT for insomnia before drug therapy, preference for CBT versus drug therapy, and preference for internet-based CBT versus face-to-face CBT. RESULTS: Of the 600 respondents, 47.7% (286/600) indicated that they received CBT before drug therapy, and 57.2% (343/600) preferred CBT for insomnia to drug therapy. In addition, 47.0% (282/600) preferred internet-based CBT for insomnia to face-to-face CBT. Although the respondents with insomnia who were taking an insomnia medication had a relatively lower preference for internet-based CBT (40.5%, 81/200), the respondents with insomnia who were not taking an insomnia medication had a relatively higher preference for internet-based CBT (55.5%, 111/200). CONCLUSIONS: The results of our online survey suggest that approximately half of the people queried preferred CBT for insomnia to drug therapy, and half of the respondents preferred internet-based CBT for insomnia to face-to-face CBT.

Internet-Based Cognitive Behavioral Therapy With Real-Time Therapist Support via Videoconference for Patients With Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Pilot Single-Arm Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. OBJECTIVES: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. METHODS: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. RESULTS: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). CONCLUSIONS: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

OBJECTIVE: Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group. RESULTS: Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).

Exploratory study of imagery rescripting without focusing on early traumatic memories for major depressive disorder.

BACKGROUND: Mental imagery has a more powerful impact on our emotions than thinking in words about the same material. Treating intrusive images with imagery rescripting (IR) has been reported for various disorders, including post-traumatic stress disorder, social anxiety disorder, and bipolar disorder. There has been less research about IR as a major depressive disorder (MDD). AIMS: We examined whether IR without focusing on early traumatic memories is effective in MDD. METHODS: We enrolled 19 participants with MDD, who received 15 weekly sessions of full CBT, including two sessions for IR of intrusive images and, separately, for memory rescripting. Before and after the IR intervention, participants were asked to rate the intrusive images they experienced against, an intrusion index that included difficulty (interference with daily life), uncontrollability, distress caused by the negative image, and vividness. We recorded the contents of each participant's negative and positive imagery to classify these. RESULTS: The intrusion index scores decreased after the IR sessions. Negative images experienced by the participants while in a depressive mood were categorized into three different types: blame, social exclusion, and loneliness. The rescripted positive images were categorized into good relations and worthy self (competent self). CONCLUSIONS: These results suggest that IR of intrusive images without focusing on early traumatic memories may usefully be incorporated into routine CBT sessions for MDD.

Data on the effect of knockout of cytohesin-1 in myelination-related protein kinase signaling.

Cytohesin-1 is the guanine-nucleotide exchange factor of Arf6, a small GTPase of Arf family, and participates in cellular morphological changes. Knockout mice of cytohesin-1 exhibit decreased myelination of neuronal axons in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2012) [1]". Herein we provide the data regarding decreased phosphorylation levels of protein kinases involved in two major myelination-related kinase cascades in cytohesin-1 knockout mice.

Olfactory coding from the periphery to higher brain centers in the Drosophila brain.

BACKGROUND: Odor information is processed through multiple receptor-glomerular channels in the first order olfactory center, the antennal lobe (AL), then reformatted into higher brain centers and eventually perceived by the fly. To reveal the logic of olfaction, it is fundamental to map odor representations from the glomerular channels into higher brain centers. RESULTS: We characterize odor response profiles of AL projection neurons (PNs) originating from 31 glomeruli using whole cell patch-clamp recordings in Drosophila melanogaster. We reveal that odor representation from olfactory sensory neurons to PNs is generally conserved, while transformation of odor tuning curves is glomerulus-dependent. Reconstructions of PNs reveal that attractive and aversive odors are represented in different clusters of glomeruli in the AL. These separate representations are preserved into higher brain centers, where attractive and aversive odors are segregated into two regions in the lateral horn and partly separated in the mushroom body calyx. CONCLUSIONS: Our study reveals spatial representation of odor valence coding from the AL to higher brain centers. These results provide a global picture of the olfactory circuit design underlying innate odor-guided behavior.

Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties.

Hypomyelinating leukodystrophy (HLD) is genetic demyelinating or dysmyelinating disease and is associated with at least 13 responsible genes. The mutations seem likely cause the functional deficiency of their gene products. HLD4- and HLD5-associated HSPD1 and FAM126A mutations affect biochemical properties of the gene products (Miyamoto et al. (2015,2014) [[1], [2]]). Herein we provide the data regarding the effects of HLD6-associated tubulin beta 4A (TUBB4A) mutations on the properties.

Data supporting the role of Fyn in embryonic sciatic nerve fasciculation.

Fyn is the cytoplasmic tyrosine kinase that has critical roles in many aspects of biological functions. In the central [1] and peripheral nervous systems [2], [3], Fyn plays the key role in initiating myelination by myelin-forming glial cells (Schwann cells and oligodendrocytes). Herein we provide the data regarding the role of Fyn in fasciculation and branching of embryonic peripheral nerves.

Morphology and physiology of antennal lobe projection neurons in the hawkmoth Agrius convolvuli.

The neuronal pathways involved in the processing of sex pheromone information were investigated in the hawkmoth Agrius convolvuli (Lepidoptera: Sphingidae), which uses (E,E)-11,13-hexadecadienal (E11,E13-16:Ald) as the single sex pheromone component. We first clarified the anatomical organization of the antennal lobe of A. convolvuli. Subsequently, central neurons in the antennal lobe that responded to E11,E13-16:Ald were identified. The dendritic processes of these neurons were confined within a specific glomerulus (cumulus) in the antennal lobe. The axons of these neurons projected to the inferior lateral protocerebrum and mushroom body calyx. Although the anatomical organization and morphology of individual neurons in A. convolvuli were similar to other species in the superfamily Bombycoidea, the use of cumulus as the single pathway for sex pheromone information processing was characteristic to this species.

A feasibility study of the clinical effectiveness and cost-effectiveness of individual cognitive behavioral therapy for panic disorder in a Japanese clinical setting: an uncontrolled pilot study.

BACKGROUND: In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD) is not well established. Therefore, a feasibility study of the clinical effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting is urgently required. This was a pilot uncontrolled trial and the intervention consisted of a 16-week CBT program. The primary outcome was Panic Disorder Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ-5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end of the study. Fifteen subjects completed outcome measures at all assessment points. RESULTS: At post-CBT, the mean reduction in PDSS scores from baseline was -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88-2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By calculating areas under the curve for EQ-5D index changes, we estimated that patients gained a minimum of 0.102 QALYs per 1 year due to the CBT. CONCLUSIONS: This study demonstrated that individual CBT for PD may be useful in Japanese clinical settings but further randomized control trials are needed. TRIAL REGISTRATION: UMIN-CTR UMIN000022693 (retrospectively registered).