The cell cycle-related genes as biomarkers for schizophrenia.

BACKGROUND: Recent studies suggest that genomic abnormalities such as single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) may elevate the risk of schizophrenia. Such genomic abnormalities often occur during chromosomal DNA replication in the S phase of cell cycle. In addition, several studies showed that abnormal expressions of several cell cycle-related genes are associated with schizophrenia. Therefore, here we compared mRNA expression levels of cell cycle-related genes in peripheral blood cells between patients with schizophrenia and healthy controls. METHOD: mRNA expression levels of cell cycle-related genes in peripheral blood cells from patients with schizophrenia and healthy controls were measured with quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The discovery, replication and intervention studies with Q-RT-PCR were performed as follows: discovery (40 cases and 20 controls), replication (82 cases and 74 controls) and intervention (22 cases and 18 controls). RESULT: Nine genes were identified in the discovery and replication stages as schizophrenia-associated genes. Moreover, the combination of mRNA expression levels of CDK4, MCM7 and POLD4 was identified as a potential biomarker for schizophrenia with multivariate logistic regression analysis. The intervention stage revealed that the mRNA expression levels of these three genes were significantly decreased in the acute state of schizophrenia, and CDK4 was significantly recovered in the remission state of schizophrenia. CONCLUSION: The combination of mRNA expression levels of three cell cycle-related genes such as CDK4, MCM7 and POLD4 is expected to be a candidate for useful biomarkers for schizophrenia. Especially, the mRNA expression changes of CDK4 may be potential as both trait and state markers for schizophrenia.

IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions.

A role of IL-18 in the induction of gastric lesions by water immersion and restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed to WRS, levels of IL-18 in the serum and stomach increased rapidly with the development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the administration of IL-18 before exposure to WRS resulted in the induction of WRS-induced gastric lesions. WRS enhanced gastric histidine decarboxylase (HDC) activity with concomitant increases in gastric histamine content. In IL-18 KO mice, the WRS-induced elevation of gastric HDC activity and histamine levels was much less than that in wild-type mice, but it was augmented by prior administration of IL-18. Treatment of wild-type mice with cimetidine, a histamine H2 receptor antagonist, inhibited the formation of WRS-induced gastric lesions with no effect on the induction of gastric IL-18 by WRS. Levels of corticosterone, one of the stress indicators, were lower in IL-18 KO mice than in wild-type mice. The glucocorticoid receptor antagonist mifepristone had no effect on gastric IL-18 and histamine levels but aggravated the stress-induced gastric lesions, indicating that corticosterone was not involved in the IL-18-mediated formation of stress-induced gastric lesions. These results indicate that IL-18 is involved in the induction of gastric lesions by WRS through augmentation of HDC activity and production of histamine in the stomach.

[Alterations of symptoms with borderline personality disorder after fronto-temporal traumatic brain injury. A case study].

We report a case of borderline personality disorder in which severe self-mutilation, sense of futility and tendency to manipulate others disappeared after fronto (orbital cortex and dorso-lateral surface) temporal traumatic brain injury. The patient, a right-handed 34 year-old woman began having severe depressive moods, irritability, and performed recurrent self-mutilation by wrist cutting after her marriage at age 20. She was diagnosed as having borderline personality disorder. At the age of 30, she attempted to kill herself by leaping from a building, and sustained a frontotemporal traumatic brain injury. After 5 years of follow-up, she recovered from Wernicke's-like aphasia, but could not understand anything complex. She also showed disturbances of writing, calculating, attention, working memory, recent and remote memories, motivation, and sense of self. The results of tests of higher brain function were as follows: Wisconsin card sorting test (Keio version), C = 1, D = 2, P = 23; FAB (Frontal Assessment Battery) = 7/18; Trail making test B = impossible. Brain MRI demonstrated left frontal lobe (orbital cortex and dorso-lateral surface) contusions, severe atrophy in the left temporal cortex including the hippocampus and amygdala, and diffuse axonal injury in the left frontal white matter. Although her recurrent self-mutilation had disappeared after brain injury, a certain type of anxiety, which occasionally induced irritability, unstable moods and devaluation of others, occurred without any trigger once or twice a month. This anxiety continued two or three days and faded away within a week. Because of its frequency and duration, this anxiety can be considered to originate not from the traumatic brain injury, but from her intrinsic nature, and seems to be parallel to annihilation anxiety (Reich A, Klein M) and abandonment anxiety (DSM-IV). Because she showed this anxiety after a severe higher brain dysfunction including disturbances of language, attention, working memory, recent and remote memories, motivation, and sense of self, we considered this anxiety to be an unarticulated form of annihilation anxiety and abandonment anxiety.

Natural disaster and mental health in Asia.

The purpose of the present article was to review the literature on disaster mental health in relation to natural disasters such as earthquakes, volcanic eruptions, typhoons and cyclones throughout Asia. Articles reviewed show that disaster psychiatry in Asia is beginning to emerge from and leave behind the stigma attached to mental health. The emergence of the acceptance of disaster mental health throughout Asia can be attributed in part to the acceptance of the notion of post-traumatic stress disorder (PTSD). This has allowed greater involvement of mental health professionals in providing ongoing support to survivors of natural disasters as well as providing greater opportunities for further research. Also, articles reviewed in the present paper commonly suggested the need for using standardized diagnostic tools for PTSD to appropriately interpret the discrepancy of results among studies. The importance of post-disaster support services and cultural differences is highlighted.

Features of obsessive-compulsive disorder in patients primarily diagnosed with schizophrenia.

We investigated the prevalence of obsessive-compulsive disorder (OCD) among patients who were primarily diagnosed with schizophrenia. We investigated the differences in the neuropsychiatric features and motor symptoms between patients with schizophrenia who did or did not have OCD. Seventy-one subjects with the DSM-IV diagnosis of schizophrenia were evaluated by the Structured Clinical Interview for DSM-IV Axis I Disorders, the Yale-Brown Obsessive-compulsive Scale and the Positive and Negative Syndrome Scale. To assess their motor symptoms, the Abnormal Involuntary Movements Scale, the Barnes rating scale for drug-induced akathisia and the Simpson and Angus extrapyramidal symptoms (EPS) rating scale were used. The 13 subjects with OCD (18.3%) had significantly more severe motor symptoms than the non-OCD subjects. Patients with schizophrenia who exhibit moderate to severe motor symptoms as side-effects of neuroleptics, should be examined for OCD comorbidity. Patients who are found to have OCD comorbidity must be treated with carefully chosen medications, including serotonin re-uptake inhibitors.

[A case of intra-axial multiple cavernous angiomas, presented with dementia and cerebellar signs].

We reported a case of intra-axial multiple cavernous angiomas, presented with dementia and cerebellar signs. The patient, a right-handed 73-year-old woman, showed gait disturbances, tremor increased while writing and hypoactivity at the age of 71. Treatment with 1-dopa was not effective. At the age of 73, she was diagnosed as having intra-axial multiple cavernous angiomas on the gradient echo MRI study, which demonstrated large numbers of small low density areas (small dots) in the cerebellar cortex and moderate numbers of those in the cerebral cortices. Those small dots were not detected in the basal ganglia, the brain stem, and increased the thalamus. She clinically showed cerebellar signs, such as dysmetria, adiadochokinesia, and tremor worsening in the course of writings, in additions to the constructural apraxia, disturbances of writing, and severe perseverations. Those symptoms slightly fluctuated. However, she did not show any character changes. The results of Wisconsin card sorting test and Trial making test A were different from those usually seen in dementia with multiple infarctions in the cerebral white matters and basal ganglia. Although her cerebellar signs are considered to be due to numerous small dots in the cerebellar cortex, her parietal symptoms could not be understood by slight parietal changes such as hypoperfusions of SPECT, cerebral small dots, and infarctions in the white matters. We speculated that, by interactions between the cerebellar dysfunctions and slight parietal dysfunctions, she developed the parietal symptoms described above, which differed from dementia or Parkinsonism due to multiple cerebral infarctions, and which were characterized by slight fluctuations and alleviations with habituation.

Plasma interleukin-18 levels in patients with psychiatric disorders.

There are an increasing number of reports on an association between the alteration of circulating cytokine levels and pathophysiology of psychiatric disorders. Plasma concentrations of interleukin (IL)-18 were measured in 13 nonmedicated patients with psychiatric disorders. There was a significant elevation of IL-18 levels in patients with major depression (n = 8) and panic disorder (n = 5), compared with normal controls. The mean IL-18 value of our psychiatric patients was comparable with that of various somatic disorders reported. We suggest that the elevation of plasma IL-18 levels reflects the increased production and release of IL-18 in the central nervous system under stressful settings. We propose that the measurement of IL-18 plasma levels may provide a useful index for the involvement of immune system in psychiatric disorders.