Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.

Sequential provocation of Ekbom's syndrome and acute mania following AstraZeneca COVID-19 vaccination.

ChAdOx1 nCoV-19 vaccine (so called AZ vaccine), is widely used to prevent the SARS-CoV-2 pandemic and shows powerful effectiveness to deter community transmission. There are common immunogenicity-related side effects such as fever, myalgia, lethargy, and headache; however, rare report on the neuropsychiatric problems (Ramasamy et al., 2021). In Taiwan, more than 15,200,000 doses of AZ vaccine were injected by the end of 2022. Here we presented a unique case with separated episode of Ekbom's syndrome, also called delusion of parasitosis, and mania following successive AZ vaccination in three-month interval.

The Effects of Poria cocos on Rho Signaling-Induced Regulation of Mobility and F-Actin Aggregation in MK-801-Treated B35 and C6 Cells.

Methods: B35 neuronal cells and C6 glial cells were incubated with MK-801 for 7 days followed by MK-801, MK801 in combination with water extracts of P. cocos (PRP for P. cocos cum Radix Pini or WP for White Poria) treatment for an additional 7 days. Analysis of cell mobility, F-actin aggregation, and Rho signaling modulation was performed to clarify the roles of PRP or WP in MK-801-treated B35 and C6 cells. Results: MK-801 decreases B35 cell mobility, whereas the inhibited cell migration ability and F-actin aggregation in MK-801-treated B35 or C6 cells could be reversed by PRP or WP. The CDC42 expression in B35 or C6 cells would be reduced by MK-801 and restored by treating with PRP or WP. The RhoA expression was increased by MK-801 in both B35 and C6 cells but was differentially regulated by PRP or WP. In B35 cells, downregulation of PFN1, N-WASP, PAK1, and ARP2/3 induced by MK-801 can be reversely modulated by PRP or WP. PRP or WP reduced the increase in the p-MLC2 expression in B35 cells treated with MK-801. The reduction in ROCK1, PFN1, p-MLC2, and ARP2/3 expression in C6 cells induced by MK-801 was restored by PRP or WP. Reduced N-WASP and PAK1 expression was differentially regulated by PRP or WP in MK-801-treated C6 cells.

Neurobehavioral Differences of Valproate and Risperidone on MK-801 Inducing Acute Hyperlocomotion in Mice.

OBJECTIVE: The glutamate system plays a major role in the development of neuropsychiatric disorders such as addiction, epilepsy, dementia, and psychosis. MK-801 (dizocilpine), an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, could increase locomotor activity and stereotyped neurobehaviors mimicking schizophrenic-like features in the mouse model. The study would explore the neuropharmacological differences of risperidone and valproic acid on the MK-801-induced neurobehavioral changes. METHODS: The subjects were male C57BL/6J mice obtained from the National Laboratory Animal Center. Drug effects were assessed using the open field with a video-tracking system and gaiting tests. After habitation, risperidone (0, 0.1 mg/kg) or valproic acid (0, 200 mg/kg) was injected and ran locomotion for 30 mins. Sequentially, mice were followed by intraperitoneal injection (i.p.) with MK-801 (0, 0.2 mg/kg) and ran locomotion for 60 mins. Gaiting behaviors such as step angles, stride lengths, and stance widths were measured following the study drugs. RESULTS: The results showed that risperidone and valproic acid alone could not alter the locomotor activities. Following the MK-801 injection, the travelled distance and speed in the entire open field dramatically increased. The dose 0.1 mg/kg of risperidone could totally inhibit the MK-801-induced hyperlocomotion compared with that of the saline-injected group (p < 0.001). The valproic acid (200 mg/kg) partially suppressed the hyperlocomotion which is induced by MK801. CONCLUSION: The more dominant effect of risperidone to rescue MK-801 induced hyperlocomotion compared with that of valproic acid. The partial suppression of valproic acid may imply the psychopharmacological evidence as adjuvant effect to treat psychotic patients through tuning glutamatergic neurotransmission.

Ketamine Inhalation Alters Behavior and Lower Urinary Tract Function in Mice.

We aimed to evaluate behavioral and lower urinary tract changes in mice using a novel ketamine inhalation model mimicking human ketamine abusers and compare the results to those obtained using a ketamine intraperitoneal injection model. C57BL/6N mice were placed in a transparent acrylic observation cage connected to an ultrasonic nebulizer producing ketamine (KI) or saline (SI) fog. The mice were given KI or SI fog twice a week for three months. In another experiment arm, the mice were given intraperitoneal ketamine injections (KP) or saline injections (SP) twice a week for three months. The presence of urine ketamine (>100 ng/mL) was determined using a quick test kit. Locomotor activity was recorded by video using the open field test. Lower urinary tract function was assessed using urine spots, cystometry and histology. KI and KP mice crossed the center more frequently and traveled farther than SI and SP mice. Only KI mice, however, demonstrated popcorn-like jumping, and frequent center crossing. Detrusor overactivity, reduced cystometric bladder capacity, and denuded mucosa were observed in both KI and KP mice. Ketamine inhalation induces behavioral and lower urinary tract changes in mice that are comparable to intraperitoneal ketamine injections.

Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele.

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2-ALDH2*1/*1 (n = 23), ADH1B*2/*2-ALDH2*1/*2 (n = 27), and ADH1B*1/*1-ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.

Memantine Rescues Neurosyphilis-Related Schizophrenic-like Features and Cognitive Deficit.

OBJECTIVES: Neurosyphilis, an infectious neuroinflammatory disorder, could cause diverse neuropsychiatric symptoms mimicking disorders of schizophrenia and dementia; hence, it is known as the "chameleon of psychiatry." Here, we present a subject with neurosyphilis with schizophrenic features and share the treatment outcome. METHODS: A 42-year-old single man had schizophrenic-like features and cognitive dysfunction for 1 year. Neurosyphilis was confirmed by a cerebral spinal fluid study. The brain image revealed multiple punctuated white matter gliosis in the bilateral frontal lobes and old lacunar infarctions in the bilateral basal hippocampus. The neuropsychiatric functions were declined until adjunctive memantine therapy. RESULTS: With the add-on therapy of memantine 10 mg daily, the psychotic and dementic symptoms markedly improved, and the patient recovered to the premorbid state in the 2-year follow-up course. CONCLUSIONS: Memantine has an adjunctive effect on neurosyphilis-related neuropsychiatric disorder via modulation of the glutamatergic neurotransmission and microglia-induced neuroinflammation.

Diversities of behavioral traits and neuropsychological function in different substance addiction.

OBJECTIVE: There are various temperaments and personality characters that modulate the development of substance addiction. The pharmacological properties of substances would alter the homeostasis of brain function and influence the neuropsychological performance through different neurotransmissions which then facilitate diverse emotional and behavioral responses. Our goal is to assess the interaction between personality characteristics, neuropsychological performances and Stroop interference in alcoholics, heroin and amphetamine dependent persons. METHODS: Subjects with alcohol (N=95), heroin (N=82) and amphetamine (N=57) dependence were recruited. Diagnostic interview and questionnaires evaluating the psychiatric symptoms were done, followed by neuropsychological assessments of Stroop and Wisconsin card sorting tests (WCST). Differences between the study groups were analyzed by one-way ANOVA with Scheffe's test. RESULTS: The individuals with alcohol dependence had significantly higher scores of neurotic, dysphoric and impulsive traits (P<0.001) than heroin and amphetamine dependent groups. In Stroop tests, the alcohol dependent subjects also showed delayed response on incongruent naming interferences compared to both of heroin and amphetamine groups (P<0.001). Perseverative errors and responses of WCST were significantly higher in heroin than in alcoholic dependent persons (P<0.01). CONCLUSIONS: Individuals with different substance dependence have distinct behavioral traits for developing addicted behaviors and had variant deficits of neuropsychological function.

Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.

Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia.

N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.

Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression.

ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings.

OBJECTIVE: It has been well documented that variant alleles of both ADH1B*2 of alcohol dehydrogenase (ADH) and ALDH2*2 of aldehyde dehydrogenase (ALDH) protect against the development of alcoholism in East Asians. However, it remains unclear whether ADH1B*2 contributes significantly toward the accumulation of systemic blood acetaldehyde and whether it plays a critical role in the alcohol flushing reaction. PARTICIPANTS AND METHODS: Sixty-one adult Han Chinese men were recruited and divided into six combinatorial genotypic groups: ALDH2*1/*1-ADH1B*1/*1 (12), ALDH2*1/*1-ADH1B*1/*2 (11), ALDH2*1/*1-ADH1B*2/*2 (11); ALDH2*1/*2-ADH1B*1/*1 (9), ALDH2*1/*2-ADH1B*1/*2 (9), and ALDH2*1/*2-ADH1B*2/*2 (9). After ingesting 0.3 g/kg of alcohol, blood ethanol, acetaldehyde, and acetate concentrations, as well as the facial skin blood flow (FSBF) and pulse rate were measured for 130 min. RESULTS: The ALDH2*1/*2 heterozygotes carrying three ADH1B allelotypes showed significantly higher peak levels and areas under the concentration curve (AUCs) of the blood acetaldehyde as well as significantly greater increases in the peak pulse rate and peak FSBF compared with the ALDH2*1/*1 homozygotes. However, no significant differences in peak levels and AUCs of blood ethanol, acetaldehyde or acetate, or the peak cardiovascular responses, were found between the ADH1B allelotypes carrying ALDH2*1/*1 or between those with ALDH2*1/*2. Partial correlation analyses showed that peak blood acetaldehyde, rather than the blood ethanol or acetate, was correlated significantly with the peak responses of pulse rate and FSBF. CONCLUSION: Findings indicate that ALDH2*2, rather than ADH1B2*2, is a causal variant allele for the accumulation of blood acetaldehyde and the resultant facial flushing during low alcohol consumption.

Taiwan consensus of pharmacological treatment for bipolar disorder.

Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) - the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP). The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts' experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.

A comparison of complex sleep behaviors with two short-acting Z-hypnosedative drugs in nonpsychotic patients.

OBJECTIVE: Complex sleep behaviors (CSBs) are classified as "parasomnias" in the International Classifcation of Sleep Disorders, Second Edition (ICSD-2). To realize the potential danger after taking two short-acting Z-hypnosedative drugs, we estimated the incidence of CSBs in nonpsychotic patients in Taiwan. METHODS: Subjects (N = 1,220) using zolpidem or zopiclone were enrolled from the psychiatric outpatient clinics of a medical center in Taiwan over a 16-month period in 2006-2007. Subjects with zolpidem (N = 1,132) and subjects with zopiclone (N = 88) were analyzed. All subjects completed a questionnaire that included demographic data and complex sleep behaviors after taking hypnotics. RESULTS: Among zolpidem and zopiclone users, 3.28% of patients reported incidents of somnambulism or amnesic sleep-related behavior problems. The incidence of CSBs with zolpidem and zopiclone were 3.27%, and 3.41%, respectively, which was signifcantly lower than other studies in Taiwan. CONCLUSION: These results serve as a reminder for clinicians to make inquiries regarding any unusual performance of parasomnic activities when prescribing zolpidem or zopiclone.

Lifestyle modification and behavior therapy effectively reduce body weight and increase serum level of brain-derived neurotrophic factor in obese non-diabetic patients with schizophrenia.

The goal of the study was to elucidate the relationship between serum circulating brain-derived neurotrophic factor (BDNF) and body weight reduction via lifestyle modification and behavior therapy in obese non-diabetic patients with chronic schizophrenia. Thirty-three obese non-diabetic subjects with schizophrenia treated with stable antipsychotic medication in a day-care unit for at least 3 months were recruited. Thirty age-, body weight-matched subjects without psychiatric disorders were enrolled as controls. All participants underwent a 10-week weight reduction program, including lifestyle modification, psychosocial treatment, behavior therapy and exercise in the day-care unit. Blood biochemistry, serum BDNF, adipokine (adiponectin), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha and interleukin-6) and oral glucose tolerance test were evaluated before and after the program. Serum BDNF concentrations were significantly lower among patients with schizophrenia compared to control subjects. Serum BDNF levels were significantly increased following the weight reduction program. Elevations in serum BDNF levels were positively correlated with body weight and body mass index reduction. Altogether, our results demonstrate that a non-pharmacological weight reduction program effectively reduces body weight with significant elevation of serum BDNF levels in obese non-diabetic patients with schizophrenia.

The role of ALDH2 and ADH1B polymorphism in alcohol consumption and stroke in Han Chinese.

The genes encoding the enzymes for metabolising alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) - exhibit genetic polymorphism and ethnic variations. Although the ALDH2*2 variant allele has been widely accepted as protecting against the development of alcoholism in Asians, the association of the ADH1B*2 variant allele with drinking behaviour remains inconclusive. The goal of this study was to determine whether the polymorphic ADH1B and ALDH2 genes are associated with stroke in male Han Chinese with high alcohol consumption. Sixty-five stroke patients with a history of heavy drinking (HDS) and 83 stroke patients without such a history (NHDS) were recruited for analysis of the ADH1B and ALDH2 genotypes from the stroke registry in the Tri-Service General Hospital, Taipei, Taiwan, between January 2000 and December 2001. The allelotypes of ADH1B and ALDH2 were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The HDS patients (3 per cent) showed a significantly lower ALDH2*2 allele frequency than NHDS patients (27 per cent) (p < 0.001). After controlling for age, patients with HDS were associated with a significantly higher occurrence of cigarette smoking (p < 0.01) and liver dysfunction (p < 0.01). Multiple logistic regression analyses revealed that the ALDH2*2 variant allele was an independent variable exhibiting strong protection (odds ratio 0.072; 95 per cent confidence interval 0.02-0.26) against HDS after adjustment for hypertension, diabetes mellitus, smoking status and liver dysfunction. By contrast, allelic variations in ADH1B exerted no significant effect on HDS. The present study indicated that, unlike ALDH2*2, ADH1B*2 appears not to be a significant negative risk factor for high alcohol consumption in male Han Chinese with stroke.

Potentiating effect of fluphenazine decanoate and risperidone on development of neuroleptic malignant syndrome.

We present the case of a woman with paranoid schizophrenia who was receiving oral risperidone. She developed neuroleptic malignant syndrome (NMS) following the addition of depot fluphenazine for the treatment of refractory delusions. NMS subsided and psychotic features were controlled after both antipsychotics were discontinued and the patient was treated instead with olanzapine.

A novel role for PSD-95 in mediating ethanol intoxication, drinking and place preference.

The synaptic signaling mechanisms mediating the behavioral effects of ethanol (EtOH) remain poorly understood. Post-synaptic density 95 (PSD-95, SAP-90, Dlg4) is a key orchestrator of N-methyl-D-aspartate receptors (NMDAR) and glutamatergic synapses, which are known to be major sites of EtOH's behavioral actions. However, the potential contribution of PSD-95 to EtOH-related behaviors has not been established. Here, we evaluated knockout (KO) mice lacking PSD-95 for multiple measures of sensitivity to the acute intoxicating effects of EtOH (ataxia, hypothermia, sedation/hypnosis), EtOH drinking under conditions of free access and following deprivation, acquisition and long-term retention of EtOH conditioned place preference (CPP) (and lithium chloride-induced conditioned taste aversion), and intoxication-potentiating responses to NMDAR antagonism. PSD-95 KO exhibited increased sensitivity to the sedative/hypnotic, but not ataxic or hypothermic, effects of acute EtOH relative to wild-type controls (WT). PSD-95 KO consumed less EtOH than WT, particularly at higher EtOH concentrations, although increases in KO drinking could be induced by concentration-fading and deprivation. PSD-95 KO showed normal EtOH CPP 1 day after conditioning, but showed significant aversion 2 weeks later. Lithium chloride-induced taste aversion was impaired in PSD-95 KO at both time points. Finally, the EtOH-potentiating effects of the NMDAR antagonist MK-801 were intact in PSD-95 KO at the dose tested. These data reveal a major, novel role for PSD-95 in mediating EtOH behaviors, and add to growing evidence that PSD-95 is a key mediator of the effects of multiple abused drugs.

Brain-derived neurotrophic factor, adiponectin, and proinflammatory markers in various subtypes of depression in young men.

OBJECTIVES: We aimed to investigate levels of brain-derived neurotrophic factor (BDNF), adiponectin, and proinflammatory cytokines in various subtypes of depression in a cohort of young men. METHODS: Sixty-two men 18-30 years of age were recruited for the study. Forty-two were newly diagnosed with depression according to DSM-IV criteria and were divided into three subtypes: reactive depression (N = 13), major depression (N = 18), and bipolar depression (N = 10). Controls included 21 young men without significant clinical morbidity. Serum levels of BDNF, adiponectin, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured. RESULTS: Serum BDNF was significantly lower and TNF-alpha significantly higher than controls for all subtypes of depression. No statistically significant differences between subtypes were found for BDNF, adiponectin, hsCRP, TNF-alpha, or IL-6. Although established diagnosis of depression and level of TNF-alpha were found to independently affect BDNF level in depressed subjects, they executed inverse effects. No associations were found between BDNF and adiponectin, hsCRP, TNF-alpha, or IL-6 in any depressed subject, showing that decreased BDNF in depression is influenced by multiple factors and complex mechanisms, including environmental and genetic concerns. No influence of age on BDNF level was found in any depressive subtype. CONCLUSIONS: Our results lend support to the cytokine and neurotrophic hypotheses of depression by demonstrating significantly lower levels of BDNF in all subtypes of depression. The mechanism underlying this phenomenon is uncertain and assumed to be multifactorial. Development of novel antidepressant treatments will require a multidisciplinary approach.

Maintenance therapy of celecoxib for major depression with mimicking neuropsychological dysfunction.

Growing evidence suggests that proinflammatory responses will be a crucial issue for developing neuropsychiatric disorders. Recent clinical trials demonstrated that adjunctive therapy of cyclo-oxygenase (COX)-2 inhibitor was effective for major depression. Here, we present the case of an elderly depressed woman with acute cognitive deficit who was refractory to multiple antidepressants but only responsive to celecoxib, a COX-2 inhibitor, in acute treatment and sustaining remission for a 5-year treatment course. Our finding suggests that a therapeutic effect of celecoxib exists for major depressive disorder comorbid with neurocognitive dysfunction.