General psychological distress among Japan Self-Defense Forces personnel dispatched on United Nations peacekeeping operations and their spouses.

AIM: The importance of family care during international deployment is emphasized within military organizations, but mental health interactions between deployed personnel and their spouses have not yet been assessed. This study addressed this gap by examining couples' mental health throughout a deployment period. METHODS: The mental health of 324 spousal dyads of Japan Self-Defense Forces personnel dispatched for a half-year United Nations Disengagement Observer Force mission was examined, using longitudinal data derived from a survey at four time points: one-month pre-deployment, initial deployment, middle deployment, and immediately after homecoming. The 30-item General Health Questionnaire was used to evaluate general psychological distress, with high scores (≥7) indicating adverse mental health. RESULTS: The spouses' general psychological distress was significantly higher compared with the deployed personnel (P < 0.001). The high general psychological distress of personnel was significantly related to that of their spouses (odds ratio = 2.24; 95% confidence interval, 1.32-3.80), and vice versa (odds ratio = 2.38; 95% confidence interval 1.39-4.08). CONCLUSION: Mental health care will be beneficial for not only deployed personnel but also their spouses.

CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

BACKGROUND: A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition-related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD-childhood maltreatment-on inhibition-related brain function in individuals with PTSD versus trauma-exposed controls. METHODS: Individuals with PTSD (n = 37) and trauma-exposed controls (n = 53) were recruited from the primary care waiting rooms of an urban public hospital in Atlanta, GA. Participants completed an inhibition task during fMRI, and reported childhood and adult traumatic experiences. The groups were matched for adult and child trauma load. RESULTS: We observed an interaction between childhood maltreatment severity and PTSD status in the rACC (P < .05, corrected), such that maltreatment was negatively associated with inhibition-related rACC activation in the PTSD group, but did not influence rACC activation in the TC group. Rostral ACC activation was associated with inhibition-related task performance in the TC group but not the PTSD group, suggesting a possible contribution to stress resilience. CONCLUSIONS: Findings highlight individual differences in neural function following childhood trauma, and point to inhibition-related activation in rostral ACC as a risk factor for PTSD.

Effect of hyperbaric exposure on cognitive performance: an investigation conducting numerical Stroop tasks during a simulated 440 m sea water saturation diving.

BACKGROUND: Saturation diving (SD) is useful and safe in deep diving for long durations. Japan Maritime Self-Defense Force (JMSDF) Undersea Medical Center (UMC) maintained safely deep 45 ATA SDHowever, cognitive performance was reportedly impaired by hyperbaric exposure in over 31 atmosphere absolute (ATA) SD. This study investigated the effects of hyperbaric exposure during 45 ATA deep SD on expert divers' cognitive function using Stroop tasks, a useful method to examine cognitive function, especially in narrow spaces such as SD chambers. METHODS: Two numerical Stroop tasks were utilized to create two magnitude comparisons of a pair of single-digit numerical and physical tasks. Both numerical Stroop tasks were examined twice, at 1 and 45 ATAs, during a simulated 440 m of sea water depth for SD. Participants were 18 male expert JMSDF SD divers (age 36.58 ± 4.89 years). RESULTS: In the numerical task, reaction time (RT) was significantly delayed at 45 ATA compared with 1 ATA in the incongruent condition. In the physical task, RT at 45 ATA was significantly delayed under all the conditions (congruent, incongruent, and neutral). The correct rates (CR) in both numerical Stroop tasks significantly decreased at 45 ATA compared with 1 ATA in the incongruent condition. CONCLUSIONS: Our findings suggest that divers' cognition is impaired during 45 ATA deep SD. These results emphasize the importance of monitoring cognition in deep sea SD and highlight the need to educate and train for SD. Further examination combining Stroop tasks with other analyses such as event-related potential (ERP) is expected.

Empathy and Coping Strategies Predict Quality of Life in Japanese Healthcare Professionals.

Burnout and secondary traumatic stress (STS), also referred to as compassion fatigue, are undeniable negative consequences experienced by healthcare professionals when working with patients. As frontline healthcare professionals are essential to communities, it is crucial to understand their mental health and how they cope with negative psychological responses. This study investigated the relationships between burnout, STS, compassion satisfaction, dispositional empathy, and stress management among Japanese healthcare professionals and students taking care of patients in clinical practice. The participants were 506 Japanese healthcare professionals and students (doctors, nurses, medical students, and nursing students) affiliated with Japanese Ministry of Defense Hospitals. The data were collected from March 2020 to May 2021. We assessed burnout, STS, and compassion satisfaction using the Professional Quality of Life Scale, dispositional empathy using the Interpersonal Reactivity Index, and coping with stress using the Coping Orientation to Problems Experienced Inventory (Brief-COPE). Exploratory factor analysis of the Brief-COPE yielded three factors: active coping; support-seeking; and indirect coping. Personal distress, a self-oriented emotional empathy index, was related to higher burnout and STS scores and lower compassion satisfaction. Empathic concern, an other-oriented emotional empathy index, was associated with lower burnout and higher compassion satisfaction. Active coping strategies were associated with lower burnout and higher compassion satisfaction, whereas indirect coping strategies were associated with higher burnout and STS scores. In a comparison of empathy in professional categories, nurses presented higher personal distress than nursing students, and medical doctors showed lower fantasy tendencies than medical students. These results imply the complex relationships between empathy, coping strategies, and psychological responses among healthcare professionals. Further longitudinal study is needed to explore these complex relationships and to develop more precise and effective psycho-educational interventions to prevent burnout and STS.

Psychological and traumatic stress and the risk of developing diabetes and psychiatric disorders after a disaster-relief mission: An eight-year longitudinal study of Japan Maritime Self-Defense Force personnel dispatched for the 2011 Great East Japan Earthquake disaster-relief mission.

The Great East Japan Earthquake caused triple disasters-the earthquake itself, tsunamis, and nuclear leakage. Japan Maritime Self-Defense Force (JMSDF) personnel engaged in disaster-relief suffered various degrees of psychological stress, which is associated with psychiatric as well as physical disorders, such as diabetes. This study aimed to assess the effect of mission-related stress on the development of diabetes and psychiatric disorders in these personnel using JMSDF annual physical check-up data from 2010 to 2018 and Impact of Events Scale-Revised (IES-R) and Kessler Psychological Distress Scale (K-10) questionnaire data. Cox proportional hazard models were used to assess the hazard ratios (HRs) of developing diabetes and psychiatric disorders in the dispatched (N = 3686) vs. non-dispatched (N = 13,953) groups and high IES-R (score ≥25) vs. low IES-R score and high K-10 (score ≥25) vs. low K-10 score subgroups. We found a significantly higher HR of developing diabetes in the high IES-R score subgroup (2.02; 95% confidence interval [CI], 1.08-3.80). However, the HRs were not significant when comparing dispatched vs. non-dispatched groups and high vs. low K-10 score subgroups. Although the HR of developing psychiatric disorders was significantly lower in the dispatched group (0.64; 95% CI, 0.48-0.84), it was significantly higher in the high IES-R (7.95; 95% CI, 3.38-18.74) and high K-10 (8.76; 95% CI, 4.34-17.68) score subgroups. Thus, this study indicates the importance of paying closer attention to the risk of diabetes and psychiatric disorders in individuals with high IES-R or K-10 scores after disaster-relief activities.

Sept5 deficiency exerts pleiotropic influence on affective behaviors and cognitive functions in mice.

Deletion or duplication of the human chromosome 22q11.2 is associated with many behavioral traits and neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. However, why phenotypes vary widely among individuals with identical deletions or duplications of 22q11.2 and which specific 22q11.2 genes contribute to these phenotypes are still poorly understood. Previous studies have identified a approximately 200 kb 22q11.2 region that contributes to behavioral phenotypes in mice. We tested the role of Septin 5 (Sept5), a gene encoded in the approximately 200 kb region, in affective behaviors, cognitive capacities and motor activity. To evaluate the impact of genetic backgrounds on behavioral phenotypes of Sept5 deficiency, we used mice on two genetic backgrounds. Our data show that Sept5 deficiency decreased affiliative active social interaction, but this phenotypic expression was influenced by genetic backgrounds. In contrast, Sept5 deficiency decreased anxiety-related behavior, increased prepulse inhibition and delayed acquisition of rewarded goal approach, independent of genetic background. These data suggest that Sept5 deficiency exerts pleiotropic effects on a select set of affective behaviors and cognitive processes and that genetic backgrounds could provide an epistatic influence on phenotypic expression.

Psychological and physical condition of Japan maritime self-defense force personnel who performed disaster-relief missions after the 2011 great east Japan earthquake.

The Great East Japan Earthquake, which occurred on March 11, 2011, was the most powerful earthquake ever recorded in Japan. In the present study, we examine personnel from the Japan Maritime Self-Defense Force who performed disaster relief in the earthquake's aftermath, focusing on the associated psychological and physical impacts. Overall, 8733 personnel were examined. In both July-August 2011 (M1) and July 2012 (M2), these personnel answered the Impact of Events Scale-Revised, the Kessler Psychological Distress Scale, and the Disaster Relief Questionnaire. We also analyzed the sample's physical examination records for the periods before and after the earthquake, using as controls a sample of peers who were not dispatched to the disaster area (N = 32,270). The psychological examinations showed that, in M1, holding the rank of private/sergeant (odds ratio [OR] = 2.13), performing body-recovery duties (OR = 1.94), and having disaster-affected family members (OR = 2.13) were significant risk factors for high post-traumatic stress response (PTSR). In M2, performing body-recovery duties (OR = 1.45) and having disaster-affected family members (OR = 2.60) were significant risk factors for high PTSR. Also, being woman (OR = 2.18) and having disaster-affected family members (OR = 1.68) were significant risk factors for high general psychological distress. For the physical examinations, the mean alanine transaminase in the dispatched group (31.73 ± 25.21) was significantly higher than that in the non-dispatched group (29.56 ± 21.03). These findings suggest that personnel involved in disaster relief experience psychological impacts in the subacute stage, but that these impacts attenuate one year after the event.

Algorithm-guided treatment versus treatment as usual for major depression.

AIMS: The remission rates for patients with major depressive disorder (MDD) during algorithm-guided treatment (AGT), which consisted of four treatment strategy steps were prospectively compared with treatment as usual (TAU). METHODS: The remission rates of patients with mild or moderate MDD during AGT (n = 83) were compared with TAU (n = 127). RESULTS: The remission rate in the AGT group (60.2%) was approximately 10% greater than that in the TAU group (49.7%). The median number of days to achieve remission in the AGT group (93 days) was half as long as that in the TAU group (191 days). The hazard ratio of remission was 1.5 (95% confidence interval: = 1.2-1.8). A higher rate of lithium augmentation in the AGT group (20.5%) compared to the TAU (4.7%) may have led to the greater remission rate. Most participants who did not achieve remission either during the initial or second treatment steps dropped out from AGT. CONCLUSIONS: AGT may be superior to TAU for patients with mild or moderate MDD, based on the remission rates achieved. The later treatment steps in the AGT, however, were rarely utilized because participants who did not receive any benefit dropped out early.

Mental health in Japanese members of the United Nations peacekeeping contingent in the Golan Heights: effects of deployment and the Middle East situation.

This study evaluates the mental health of Japan Self-Defense Force (JSDF) members of the peacekeeping contingent in the Golan Heights before and since the Second Gulf War between 1998 and 2003. Before the war, the General Health Questionnaire 30 (GHQ30) scores during and after duty tended to be lower than those before duty; all scores were lower than those of adult Japanese men in general. After the war, GHQ30 scores did not significantly change between before, during, and after duty. Manifest Anxiety Scale (MAS) scores were not significantly different between groups. Stressors identified included problems with foreign language and familial matters at home. Post war stressors included work content and relationships with collaborating foreign army units. These findings suggest that the mental health of contingent members remained stable, with some variation in mental health conditions influenced by the situation in the Middle East. This study suggests that the stable mental condition of JSDF personnel during their deployment in the absence of combat, and that this could be enhanced by education about mental health issues and by providing counseling support to their families.

Stress vulnerabilities in an animal model of post-traumatic stress disorder.

We have studied the effects of inescapable electric foot shocks (ISs) on rats by using a subsequent avoidance/escape task performed in a shuttle box as an animal model of post-traumatic stress disorder (PTSD). In this study, the behavioral differences and the effects of chronic stress exposure prior to IS were examined among male rats of the Wistar, Fischer 344, and Lewis strains. In concordance with our previous report on the Wistar rats, we observed the characteristic features of PTSD in all three rat strains tested, that is, the hyperactive and hypoactive bidirectional behavioral changes that are associated with hypervigilant and hyperarousal behavior, and the numbing and avoidant behavior, respectively. The induction of hypoactive behaviors after IS was most exaggerated in the Fischer and Lewis strains. Although the count of hyperactive behaviors was maximal in the Fischer strain both at basal levels without IS and after IS, the increase in the rate of hyperactive behaviors by IS was the most prominent in the Lewis strain. In addition, preloaded chronic variable stress (CVS) enhanced the degree of hyperactive behavioral changes in the Wistar strain. Thus, we consider that the present study further validates the use of shuttle box paradigm as an animal model of PTSD by demonstrating the vulnerability due to genetic background and environmental preloaded stress.

A cross species study of heterogeneity in fear extinction learning in relation to FKBP5 variation and expression: Implications for the acute treatment of posttraumatic stress disorder.

Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM). Study 2 (Mice) tests if increasing doses of dexamethasone administered prior to extinction alters Fkbp5 mRNA production in the amygdala after extinction and recall and prevents the development of abnormal extinction phenotypes. In humans, abnormal extinction was associated with the TT homozygous genotype of FKBP5 SNPs RS9470080 and RS1360780, and hyperarousal symptoms. In mice, dexamethasone 300 µg/kg was associated with increased amygdala Fkbp5 mRNA following extinction and robust extinction learning while lower doses were not associated with amygdala Fkbp5 mRNA or differences in extinction learning. Further, mice that extinguished on dexamethasone 300 µg/kg maintained low levels of freezing behavior during recall training while mRNA levels were no longer elevated. Together, findings indicate that FKBP5 confers risk for fear extinction deficits. However, this risk may be ameliorated by increasing fkbp5 mRNA expression in the amygdala during memory consolidation making this mechanism a plausible point of acute intervention to prevent the development of PTSD.

[An animal model of posttraumatic stress disorder in rats using a shuttle box].

We administered inescapable footshocks (IS) to male Wistar rats in a shuttle box, and after 2 weeks, an avoidance/escape task was performed in the same box. The rats exposed to IS 2 weeks beforehand exhibited PTSD-like bi-directional changes similar to symptoms of "avoidance/ numbing" and "hyperarousal". That is, in the relatively calm period just before the avoidance/escape task, spontaneous locomotor activities decreased. On the other hand, in the stressful situation after starting the task, not only responses to external stimuli but also locomotor activities increased. Thus, the paradigm we have used until now could serve as a useful PTSD model because of its "face validity". To demonstrate the greater validity, we administered paroxetine (PRX), which is effective for PTSD, to rats to examine its chronic effect on our model. We also substituted F344 rats, which are vulnerable to various stressors, for the Wistar rats to investigate the difference between the strains. Two weeks of PRX treatment significantly reduced hyperarousal-like behavior, and its ameliorating effect on avoidance/numbing-like behavior was also significant. F344 showed more significant 'bi-directional changes' than Wistar rats. These findings demonstrate that our paradigm is sufficiently valid for an animal model of PTSD, especially in "predictive validity" and "construct validity."

[Present status and prospects about an animal model of post-traumatic stress disorder in rats using a shuttle box].

Wistar rats exposed to inescapable foot shocks (IS) for 2 wk exhibited PTSD-like bi-directional changes similar to avoidance/numbing and hyperarousal symptoms when placed in a shuttle box. Paroxetine administration after IS reduced the hyperarousal-like behavior, and its therapeutic effect on avoidance/numbing-like behavior was also significant. Further, F344 rats, which were more vulnerable to various kinds of stressors, showed more significant 'bi-directional changes' than Wistar rats. Thus, the paradigm we have developed could serve as a useful PTSD model because of its face, predictive, and construct validity. Moreover, the intensity of IS dose-dependently induced PTSD-like behaviors and hypo-activity in a shuttle box, similar to the 'avoidance/numbing' that reappeared in a square open field. These findings further support the construct validity of this paradigm. Both electro-convulsive shock treatment before and after IS ameliorated the PTSD-like behaviors in this model, so electro-convulsive therapy may be an effective method for prevention and medical treatment of PTSD in the future. On the other hand, pretreatment with fluvoxamine before IS did not have a significant effect, and its improving effect after IS was only observed for 'hyperarousal' behavior. Lastly, we recently developed a useful criterion, which is represented as a 'bi-directional index', for separating real PTSD rats from those exposed to IS.

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

Effect of paroxetine on a model of posttraumatic stress disorder in rats.

To better understand neurochemical and psychopharmacological aspects of post-traumatic stress disorder (PTSD), it is necessary to establish an animal model of PTSD in which behavioral changes persist after the initial traumatization. We administered inescapable electric foot-shock (IS) to male Wistar rats in a shuttle-box with the gate closed. With or without paroxetine (PRX; belonging to selective serotonin reuptake inhibitors) treatment for 2 weeks after IS, we performed an avoidance/escape task session in the shuttle-box using signal lights as non-specific anxiogenic stimulants. Locomotor activity decreased before the task session and avoidance behavior increased during the session. Two weeks of PRX administration reduced hypervigilant behavior during the task session. We considered these behavioral changes as representative of numbing/avoidance and hypervigilance, referred to as bi-directional changes in PTSD.

The effect of paroxetine on Taijinkyofusho: a report of three cases.

Taijinkyofusho is a culture-related syndrome conceptualized in Japan. While previous studies suggest its psychopathological similarities to social phobia and obsessive-compulsive disorder, introspection regarding shame and low self-esteem is particularly linked to Japanese culture. We present three cases of Taijinkyofusho: Cases 1 and 2 show neurotic features while Case 3 shows delusional thoughts. Paroxetine was used for treatment but was productive in only the first two cases. Phobic and obsessive thought patterns were altered in Cases 1 and 2, suggesting that the significant core symptoms were responding to the treatment. In the future, large-scale pharmacological studies will be necessary to investigate treatment outcomes Taijinkyofusho. Such studies would contribute to providing information for effective treatment as well as for examining relationships between Taijinkyofusho and related disorders.

The effectiveness of lithium augmentation of milnacipran: preliminary data using the modified Japanese Psychopharmacology Algorithm.

Medication algorithms based on the best evidence available together with expert consensus are considered to promote logical consistent clinical decision making in the choice of antidepressant drugs. We report our preliminary results using the modified algorithm established by the Japanese Psychopharmacology Algorithm Project (JPAP). Subjects were 24 patients with major depressive disorders who presented to the outpatient clinic of the Department of Psychiatry at the National Defense Medical College prior to any treatment for the current episode. Ultimately, 15 patients recovered with treatment according to our protocol, including 7 who recovered upon treatment with first-line drugs; the most effective of these was paroxetine, followed by fluvoxamine and then milnacipran. Six patients recovered with second-line treatments. Among these, a combination of milnacipran and lithium was most effective, with recovery of 4 of 4 patients. We have formed a strong impression that augmentation therapy, especially with milnacipran plus lithium, is likely to be effective if the first-line antidepressant is ineffective. Investigation of more cases will be needed to confirm or refine details of the algorithm and, more generally, to determine the best approach to antidepressant medication.

[An animal model of posttraumatic stress disorder and its validity: effect of paroxetine on a PTSD model in rats].

To better understand neuroscientific aspects of posttraumatic stress disorder (PTSD), it is necessary to establish an animal model of PTSD in which behavioral changes persist after initial traumatization. We administered inescapable footshock (IS) to male Wistar rats in a shuttle-box (inescapable stress session), and after 2 weeks we performed an avoidance/escape task session in the shuttle-box using signal lights as anxiogenic external stimuli. Rats exposed to IS beforehand exhibited PTSD-like bi-directional behavioral changes, that is, "avoidance/numbing" (e.g. decreased activity, reactivity, and interest in surroundings) and "hyperarousal" (e.g. irritability and exaggerated responsiveness to external stimuli). Concretely speaking, in a relatively calm situation, spontaneous locomotion decreased during a 5-min adaptation period just before the avoidance/escape task session. On the other hand, in a stressful situation after starting the task session, not only avoidance responses to external stimuli (signal lights) but also gate-crossings during inter-trial interval increased. Accordingly, the paradigm used here could serve as a useful model of PTSD. We administered paroxetine (PRX) to rats just after IS for 2 weeks to examine its chronic effect on our animal model. Two weeks of PRX treatment significantly reduced hyperarousal-like behaviors, but no effect on avoidance/numbing-like ones was manifested.

A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice.

Human chromosome 22q11.2 has been implicated in various behavioral abnormalities, including schizophrenia and other neuropsychiatric/behavioral disorders. However, the specific genes within 22q11.2 that contribute to these disorders are still poorly understood. Here, we show that an approximately 200-kb segment of human 22q11.2 causes specific behavioral abnormalities in mice. Mice that overexpress an approximately 200-kb region of human 22q11.2, containing CDCrel, GP1Bbeta, TBX1, and WDR14, exhibited spontaneous sensitization of hyperactivity and a lack of habituation. These effects were ameliorated by antipsychotic drugs. The transgenic mice were also impaired in nesting behavior. Although Tbx1 has been shown to be responsible for many physical defects associated with 22q11.2 haploinsufficiency, Tbx1 heterozygous mice did not display these behavioral abnormalities. Our results show that the approximately 200-kb region of 22q11.2 contains a gene(s) responsible for behavioral abnormalities and suggest that distinct genetic components within 22q11.2 mediate physical and behavioral abnormalities.

Medication algorithm for mood disorders: Present status and future direction in Japan.

Medication algorithms have been used extensively in treating psychiatric patients, while geographic variations among these reflect the local history of the practice of psychiatry in each region. Here we review algorithms used for mood disorders in Japan in terms of their utility, problems, and possible future development. The first Japanese algorithm for mood disorders was completed in 1997 by the Japanese Psychopharmacology Algorithm Project (JPAP). Development of the JPAP algorithm was evidence-based, giving major but not exclusive weight to clinical trial outcomes. Unlike others, the JPAP algorithm suggests possible addition of a benzodiazepine to first-line antidepressant treatment for major depression. When the first-choice antidepressant fails, the algorithm recommends monotherapy with another antidepressant over "add-on" therapy. Clinical problems with the JPAP algorithm include lack of guidance concerning how to change from one drug to another. Psychiatry in Japan provides less formal structure for post-graduate education and undertakes less communication with the general public than in many countries. This makes use of an algorithm important for improving quality of practice, provided that clinicians remain aware of the advantages, limitations, and problems of algorithms.