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To elucidate an involvement of amyloid dysmetabolism in the pathophysiology of depression, we investigated associations of plasma amyloid-β (Aβ) levels with Alzheimer's disease-related changes in neuroimaging and cognitive dysfunction in patients with late-life depression. Higher plasma Aβ40, but not Aβ42 nor Aβ40/Aβ42 ratio, was associated with higher degree of parahippocampal atrophy and lower verbal fluency performance. Indeed, high plasma Aβ40 predicted poor cognitive prognosis of depressed patients with mild cognitive impairment. As an anti-depressive treatment, electroconvulsive therapy (ECT) resulted in a marginally significant reduction of plasma Aβ40 compared to pharmacotherapy alone, suggesting protective effects of ECT against amyloid dysmetabolism. [ABSTRACT FROM AUTHOR]

Aims The purpose of this study was to evaluate the clinical impact of addition of [11C]Pittsburgh compound-B positron emission tomography (11 C- PiB PET) on routine clinical diagnosis of Alzheimer's disease ( AD) dementia and mild cognitive impairment ( MCI), and to assess diagnostic agreement between clinical criteria and research criteria of the National Institute on Aging-Alzheimer's Association. Methods The diagnosis in 85 patients was made according to clinical criteria. Imaging examinations, including both magnetic resonance imaging and single-photon emission computed tomography/computed tomography to identify neuronal injury ( NI), and 11 C- PiB PET to identify amyloid were performed, and all subjects were re-categorized according to the research criteria. Results Among 40 patients with probable AD dementia ( ProAD), 37 were NI-positive, 29 were 11 C- PiB-positive, and 27 who were both NI- and 11 C- PiB-positive were categorized as having ' ProAD dementia with a high level of evidence of the AD pathophysiological process'. Among 20 patients with possible AD dementia ( PosAD), 17 were NI-positive, and six who were both NI- and 11 C- PiB-positive were categorized as having ' PosAD with evidence of the AD pathophysiological process'. Among 25 patients with MCI, 18 were NI-positive, 13 were 11 C- PiB-positive, and 10 who were both NI- and 11 C- PiB-positive were categorized as having ' MCI due to AD-high likelihood'. Conclusions Diagnostic concordance between clinical criteria and research criteria may not be high in this study. 11 C- PiB PET may be of value in making the diagnosis of dementia and MCI in cases with high diagnostic uncertainty. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed. [ABSTRACT FROM AUTHOR]

Objective. To revise the psychopharmacology algorithms for the treatment of mood disorders published in 1999 in Japan. Methods. The algorithms were established based on clinical psychopharmacological evidence, the results of a questionnaire survey sent to 200 Japanese psychiatrists, and the consensus of all the research members. Results. Six categorized algorithms have been developed, i.e. mild or moderate major depression, severe non-psychotic major depression, psychotic depression, mania, bipolar depression, and rapid cycling mood disorder. Conclusion. The revised algorithms will be helpful for the treatment of mood disorders in Japan. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride. Methods: Nine patients with depression were treated with 10 daily sessions of rTMS (10 Hz, 5 s train, 20 trains at 100% motor threshold per session) over the left dorsolateral prefrontal cortex (DLPFC). Each patient underwent two [11C]raclopride PET scans and neuropsychological tests — before rTMS and 1 day after rTMS. Results: In five patients, the Hamilton Rating Scale for Depression (HRSD) significantly decreased. Patients showed significant improvement in verbal memory following rTMS. There were no changes in [11C]raclopride binding in the caudate nucleus and putamen after rTMS treatment. Limitations: Our sample size was limited, and our study was an open trial lacking sham-treated controls. Conclusion: This study suggests that rTMS may be effective for the treatment of depression and also may improve verbal memory function. We observed no changes in [11C]raclopride binding, suggesting that there was no measurable increase in the release of dopamine at the second PET scan. Several animal studies and healthy human studies have indicated that dopamine can be released soon after acute rTMS. Our results suggest that release of striatal dopamine induced by rTMS may be only transient, or that dopamine release may be attenuated following chronic rTMS. [Copyright &y& Elsevier]

The answers to a questionnaire on the practical prescription in mood disorders from 298 Japanese psychiatrists was obtained. As the first-line treatment, a majority of respondents chose newer tricyclic agents (TCA) or non-TCA for moderate depression and older TCA for severe depression both with and without psychotic features. Combination therapy with antidepressants and anxiolytics was fairly popular in moderate depression, while antidepressant/neuroleptic combination was more common in severe psychotic depression. Sulpiride was the most favored drug for dysthymia. Although lithium was the most popular for bipolar mania, respondents were divided on the treatment of bipolar depression. [ABSTRACT FROM AUTHOR]

The algorithms for the treatment of bipolar disorder are presented. Lithium is the first choice when treating acute mania. Other options are antipsychotics or mood stabilizers such as carbamazepine and valproate. Mood stabilizers (often in combinations) are drugs of choice for maintenance treatment. For the treatment of acute depression under lithium maintenance, increase doses of lithium or addition of antidepressants may be necessary. [ABSTRACT FROM AUTHOR]

Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 μM) (P = 0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD. [ABSTRACT FROM AUTHOR]

Background: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically, NHD exhibits profound loss of myelin and accumulation of axonal spheroids, accompanied by intense gliosis accentuated in the white matter of the frontal and temporal lobes. At present, the molecular mechanism responsible for development of leukoencephalopathy in NHD brains remains totally unknown.Methods: By immunohistochemistry, we studied the expression of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, in 5 NHD and 12 control brains.Results: In all NHD brains, Nogo-A-positive, CNPase-positive oligodendrocytes surviving in the non-demyelinated white matter intensely expressed LC3. They also expressed ubiquitin, ubiquilin-1, and histone deacetylase 6 (HDAC6) but did not express Beclin 1 or sequestosome 1 (p62). Substantial numbers of axonal spheroids were also labeled with LC3 in NHD brains. In contrast, none of oligodendrocytes expressed LC3 in control brains. Furthermore, surviving oligodendrocytes located at the demyelinated lesion edge of multiple sclerosis (MS) did not express LC3, whereas infiltrating Iba1-positive macrophages and microglia intensely expressed LC3 in MS lesions.Conclusions: These results propose a novel hypothesis that aberrant regulation of autophagy might induce oligodendrogliopathy causative of leukoencephalopathy in NHD brains. [ABSTRACT FROM AUTHOR]