To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH).

Case–control study.

Osaka University Hospital.

Patients with possible iNPH underwent a CSF tap test.

Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients.

We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline.

A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.

Abnormalities in neurotransmission via N-methyl-d-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients.

Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, l-serine, and d-serine levels were measured before and after treatment.

There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients, there was a significant correlation between levels of glutamate in serum and BDI (ρ = 0.428, p = 0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. d-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. l-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group.

The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects.

Although alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).

We examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.

Spine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.

The results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.

The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study.

In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age–sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels.

The mean serum G72 protein values were 495.90±152.03 pg/ml in the schizophrenia group and 346.10±102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=−3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821.

We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia.

Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression.

We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78).

Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001).

This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.

Treatment-resistant depression is a challenging problem in the clinical setting. Tipepidine has been used as a non-narcotic antitussive in Japan since 1959.

We administered tipepidine to 11 patients with treatment-resistant depression. Tipepidine was given for 8 weeks as an augmentation.

Tipepidine significantly improved depression scores on the Hamilton Rating Scale for depression. Add-on treatment with tipepidine significantly improved scores on the trail making test and Rey auditory verbal learning test. However, no changes were observed in blood concentrations of stress-related hormones (adrenocorticotropic hormone, cortisol, dehydroepiandrosterone sulphate) with tipepidine augmentation.

Tipepidine might be a potential therapeutic drug for treatment-resistant depression.

Accumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.

Levels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.

Serum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.

The results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.

A recent clinical study demonstrated that sodium benzoate (SB), a prototype competitive d-amino acid oxidase inhibitor, was effective in the treatment of several symptoms, such as positive and negative symptoms, and cognitive impairment in medicated patients with schizophrenia. The objective of the study was to examine the effects of SB on behavioural abnormalities such as pre-pulse inhibition (PPI) deficits and hyperlocomotion in mice after a single administration of the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP).

The effects of SB on behavioural abnormalities (PPI deficits and hyperlocomotion) in mice after PCP administration were examined. Furthermore, effects of SB on tissue levels of amino acids were also examined.

A single oral dose of SB (100, 300, or 1000 mg/kg) attenuated PPI deficits in mice after administration of PCP (3.0 mg/kg, s.c.) in a dose-dependent manner. In contrast, L-701,324 (10 mg/kg), an antagonist at the glycine site of the NMDA receptor, did not affect the effect of SB (1000 mg/kg) on PCP-induced PPI deficits. Furthermore, a single oral dose of SB (1000 mg/kg) significantly attenuated the hyperlocomotion in mice after administration of PCP (3.0 mg/kg, s.c.). However, a single oral dose of SB (1000 mg/kg) caused no changes to d-serine levels in plasma or in the frontal cortex, hippocampus, and striatum of these animals.

This study suggests that SB induced antipsychotic effects in the PCP model of schizophrenia, although it did not increase d-serine levels in the brain.