Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

OBJECTIVE: Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. METHODS: The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. RESULTS: The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. CONCLUSIONS: The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden.

A structural model of age, grey matter volumes, education, and personality traits.

BACKGROUND: When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education. METHODS: We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors. RESULTS: The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score. CONCLUSIONS: Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course.

Delayed atrophy in posterior cingulate cortex and apathy after stroke.

OBJECTIVE: A few studies have been performed on chronic structural changes after stroke. The primary purpose of the present study was to investigate regional cortical volume changes after the onset of stroke and to examine how the cortical volume changes affected neuropsychiatric symptoms. METHODS: Participants were 20 stroke patients and 14 control subjects. T1-MRI was performed twice, once at the subacute stage and again 6 months later, and whole brain voxel-based morphometric (VBM) analysis was used to detect significant cortical gray matter volume changes in patients. We also assessed the correlation between changes in cortical volumes and changes in neuropsychiatric symptoms during the 6 months following a stroke. RESULTS: In the present study, we found significant volume reductions in the anterior part of the posterior cingulate cortex (PCC) over the 6 months following a stroke by exploratory VBM analysis. We also found that the amount of volume change was significantly correlated with the change in apathy-scale scores during the 6 months poststroke. CONCLUSIONS: The present study suggests that delayed atrophic change is evident in the PCC 6 months after a stroke. There was greater apathetic change in the stroke patients with the larger volume reductions. The delayed atrophy of the PCC may reflect degeneration secondary to neuronal loss due to stroke. Such degeneration might have impaired control of goal-directed behavior, leading to the observed increase in apathy.

Decision-making deficit of a patient with axonal damage after traumatic brain injury.

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.

Association between depressive symptoms and metabolic syndrome in Japanese community-dwelling older people: a cross-sectional analysis from the baseline results of the Fujiwara-kyo prospective cohort study.

OBJECTIVE: Metabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community-dwelling older people is unclear. This study was performed to answer this important question. METHODS: Cross-sectional analyses were performed on 3796 community-dwelling independent older people (≥ 65 years, 1911 men and 1885 women) from the 2007-2008 baseline examination of the Fujiwara-kyo study, a prospective cohort study on successful aging. Depressive symptoms were assessed using the 15-item short form of the Geriatric Depression Scale and metabolic syndrome was defined according to the 2005 International Diabetes Federation. Covariates were social supports, negative life events, health behavior, education, cognitive function, anthropometric status, and others. Multiple logistic regression analyses were performed to determine the relationships between depressive symptoms and these variables. RESULTS: The prevalence of depressive symptoms (Geriatric Depression Scale-15 ≥ 6) and metabolic syndrome were 14.8% and 16.6%, respectively. Significant protective factors against depressive symptoms were higher education, more opportunity for drinking of alcohol, better social supports, and more walking daily. Metabolic syndrome was statistically associated with depressive symptoms (adjusted odds ratio = \ 1.32, 95% confidence interval = 1.03-1.68). Other risk factors significantly associated with depressive symptoms were sleep disturbance, visual or hearing impairment, and negative life events. CONCLUSIONS: The present study showed an association between metabolic syndrome and depressive symptoms in ambulatory Japanese older people, as in western countries.

Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia.

BACKGROUND: Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial. METHODS: Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients' neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J). RESULTS: No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test. CONCLUSIONS: It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients.

Parkinsonism with multiple cysts in the bilateral striata.

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.

Uncinate fasciculus-correlated cognition in Alzheimer's disease: a diffusion tensor imaging study by tractography.

BACKGROUND: Neuroimaging studies show increased diffusivity and decreased anisotropy in Alzheimer's disease (AD) patients by diffusion tensor imaging (DTI). Previous reports have analyzed a correlation with cognitive function and DTI parameters, but their results are inconsistent. A reason for this might be a region of interest (ROI) method, used to calculate parameters for DTI, because this method has various usages of how to place a ROI and includes summations of values for various neuronal fiber tracts, resulting in contamination of unintended fibers. To improve the instability with ROI placement, a tractography-based method might be useful. Our coworker reported decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) of uncinate fasciculus (UF) in patients with AD by tractography. To confirm whether DTI parameter values are related to severity of cognitive function in patients with AD, we measured mean diffusion anisotropy and diffusivity of coregistered voxels along the tracking lines (i.e. tract of interest) of UF. METHODS: The subjects were 30 patients with probable AD (NINCDS-ADRDA criteria). Assessment of cognitive function was carried out according to the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog). A 1.5-T clinical magnetic resonance unit was used to obtain diffusion tensor images. Diffusion tensors were computed and fiber-tract maps were created using 'dTV II' DTI software developed by Masutani et al. We measured mean FA and ADC values along the bilateral UF. RESULTS: FA values were positively correlated with MMSE score (r= 0.67) and were negatively correlated with ADAS-Jcog score (r=-0.62), while ADC values were negatively correlated with MMSE score (r=-0.58) and were positively correlated with ADAS-Jcog score (r= 0.59). CONCLUSION: FA and ADC values might reflect the severity of cognitive dysfunction. The tract-of-interest method might be a useful tool for objectively evaluating DTI parameters in AD.

[Effect of estrogen on nucleotide excision repair of N2a neuroblastoma cells].

Until now reduced estrogen level has been considered to affect some psychiatric symptoms, because there are sex differences in onset of Schizophrenia and Alzheimer's disease. Estrogen is associated with cognitive functions, and it has been reported to protect oxidative damage of DNA related to base excision repair (BER). Some patients with Xeroderma Pigmentosum, who have normal BER and impaired nucleotide excision repair (NER), are known to be suffering from mental retardation. Therefore we hypothesized that impaired NER was partly associated with pathology of mental disorder and investigated the effects of estrogen on NER for ultraviolet-induced DNA damage. The N2a neuroblastoma cell line was used as a representative of neuronal cells and 17p-estradiol was selected as one of the most active estrogen derivatives. There were no significant effects of 17p-estradiol on prevention of DNA damage, promotion of DNA repair, or cell survival at the concentration of 0-0.1 microM 17p-estradiol (below cytotoxicity level). These results described that estrogen might not directly affect NER except through another DNA repair system.

Microstructural Differences in the Corpus Callosum in Patients With Bipolar Disorder and Major Depressive Disorder.

OBJECTIVE: It is difficult to distinguish between bipolar disorder and major depressive disorder (MDD) in patients lacking a clear history of mania. There is an urgent need for an objective biomarker for differential diagnosis. Using diffusion tensor imaging, this study investigated the differences in the brain white matter microstructure between patients with bipolar disorder and MDD. METHODS: Participants included 16 patients with bipolar disorder and 23 patients with MDD having depressed or euthymic states based on DSM-IV-TR criteria and 23 healthy volunteers. Whole-brain voxel-based morphometric analysis was used to detect any significant differences in fractional anisotropy between patients with bipolar disorder and MDD. The study was conducted between August 2011 and July 2015. RESULTS: We found a significant decrease in fractional anisotropy values in the anterior part of the corpus callosum in patients with bipolar disorder compared with MDD (P < .001), which did not depend on the patients' affective state. This decrease was associated with increased radial diffusivity values (P < .05), which was also found in patients with bipolar disorder when compared with healthy volunteers (P < .05). We predicted bipolar disorder and MDD in all patients using the fractional anisotropy values, with a correct classification rate of 76.9%. CONCLUSIONS: The present study revealed that patients with bipolar disorder have microstructural abnormalities in the corpus callosum during depressed or euthymic states, which may deteriorate the exchange of emotional information between the cerebral hemispheres, resulting in emotional dysregulation. Our results indicate the possible use of diffusion tensor imaging as a differential diagnostic tool.

Diffusion tensor studies and voxel-based morphometry of the temporal lobe to determine the cognitive prognosis in cases of Alzheimer's disease and mild cognitive impairment: Do white matter changes precede gray matter changes?

PURPOSE: The purpose of the current study was to assess the feasibility of diffusion tensor imaging (DTI) parameters for determining the prognosis of Alzheimer's disease (AD). We also analyzed the correlation among DTI, voxel-based morphometry (VBM), and results of the mini-mental state examination (MMSE). METHODS: The subjects of this prospective study were patients with AD and mild cognitive impairment. We performed annual follow-ups with DTI, VBM, and MMSE for 2 or 3 years. On DTI, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the uncinate fascicles were measured. VBM was performed to provide a z-score for the parahippocampal gyrus. The correlations among these factors were evaluated in the same period and the next period of the follow-up study. RESULTS: For evaluation of the same period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score. Also for evaluation of the next period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score of the next period. We observed a statistically significant correlation between the ADC value of the uncinate fascicles and the z-score of the next period. CONCLUSIONS: Diffusion tensor parameters (ADC and FA) of the uncinate fascicles correlated well with cognitive function in the next year and seemed to be feasible for use as biomarkers for predicting the progression of AD. In addition, the white matter changes observed in the ADC seemed to precede changes in the gray matter volume of the parahippocampal gyrus that were represented by z-scores of VBM.

Test-retest reproducibility of extrastriatal binding with 123I-FP-CIT SPECT in healthy male subjects.

123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) is used to assess striatal dopamine transporter (DAT) expression, but it can also quantify extrastriatal serotonin transporter (SERT) expressions. While FP-CIT uptake in extrastriatal regions has been quantified, no information exists on the reproducibility of the 123I-FP-CIT specific uptake ratio (SUR) in extrastriatal regions. We investigated test-retest reproducibility of 123I-FP-CIT binding in the striatum, the midbrain, and cortical regions in eight healthy male subjects. All subjects underwent two 123I-FP-CIT SPECT scans, and SUR was calculated using the cerebellum as the reference. We found good test-retest reproducibility of 123I-FP-CIT SUR in the midbrain, and in the lateral frontal/temporal cortex and combined cortical regions. The overall variability and intraclass correlation of SUR were, respectively, 4.9-7.8% and 0.90-0.96 in striatal regions, 8.6% and 0.79 in the midbrain, and 3.6-9.1% and 0.84-0.95 in the lateral frontal/temporal cortex and combined cortical regions. Our results provide evidence that 123I-FP-CIT SPECT is a valid technique for analyzing striatal DAT, as well as extrastriatal SERT in areas such as the SERT-enriched midbrain. In addition, our data suggest that 123I-FP-CIT could be used for analyzing SERT in regions with relatively low SERT expression (e.g., temporal or frontal cortices).

Increased binding of 5-HT1A receptors in a dissociative amnesic patient after the recovery process.

Dissociative amnesia is characterized by an inability to retrieve information already saved in memories. 5-HT has some role in neural regulatory control and may be related to the recovery from dissociative amnesia. To examine the role of 5-HT1A receptors in the recovery from dissociative amnesia, we performed two positron emission tomography (PET) scans on a 30-year-old patient of dissociative amnesia using [(11)C]WAY-100635, the first at amnesic state, and the second at the time he had recovered. Exploratory voxel-based analysis (VBA) was performed using SPM software. 5-HT1A BPND images were compared between the patient at amnesic and recovery states and healthy subjects (14 males, mean age 29.8 ± 6.45) with Jack-knife analysis. 5-HT1A receptor bindings of the patient at the recovery state were significantly higher than those of healthy subjects in the right superior and middle frontal cortex, left inferior frontal and orbitofrontal cortex and bilateral inferior temporal cortex. The increase in BPND values of recovery state was beyond 10% of those of amnesia state in these regions except in the right superior frontal cortex. We considered that neural regulatory control by the increase of 5-HT1A receptors in cortical regions played a role in the recovery from dissociative amnesia.

Microstructural changes of the nucleus accumbens due to increase of estradiol level during menstrual cycle contribute to recurrent manic episodes--a single case study.

We examined a rapid-cycling bipolar disorder patient who demonstrated manic episode regularly at around day 7 of the menstrual cycle. We hypothesize that gonadal hormones may induce a state-dependent change in cerebral microstructure and function. Following this hypothesis, the serum levels of estradiol and progesterone were analyzed and diffusion tensor imaging data were examined between the manic and euthymic states of the patient. Estradiol levels increased in the late follicular phase at manic state when compared to the luteal or early follicular phase at euthymic state. DTI results showed that the patient had increased fractional anisotropy values at manic state in the bilateral nucleus accumbens (NAc) and its connected areas, which is a major projection field of the mesolimbic dopamine (DA) system, perhaps reflecting microstructural changes due to neuronal activation related to manic episodes. According to these results, we consider that the mesolimbic DA system of this patient has hypersensitivity to estradiol, and elevation of the estradiol level increases the activity of the dopaminergic system, which in turn may contribute to recurrent manic episodes. Our findings provide a clue for understanding how fluctuations in gonadal hormone may amplify or ameliorate the symptomatology of psychiatric disorders related to the menstrual cycle.

Gray and white matter changes in subjective cognitive impairment, amnestic mild cognitive impairment and Alzheimer's disease: a voxel-based analysis study.

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer's disease. The subjects in this study were 39 Alzheimer's disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer's disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer's disease.

Microstructural abnormalities in white matter and their effect on depressive symptoms after stroke.

The aim of the study was to investigate the existence of microstructural abnormalities in the white matter of the brain in stroke patients, as well as the relationship between these microstructural abnormalities and changes in depressive symptoms over 6 months. Participants were 29 acute ischemic stroke patients and 37 healthy control subjects. Depressive symptoms were assessed in all subjects using the Hamilton Rating Scale for Depression and the Zung Self-rating Depression Scale. Whole brain voxel-based analysis was used to compare diffusion tensor imaging measures of Fractional Anisotropy (FA) between the groups. Six-month follow-up examinations were conducted. Patients showed significantly lower white matter FA values in the left and right anterior limbs of the internal capsule, and 6 months after the stroke they showed significantly increased FA values in these regions. We found a significant negative correlation between the increased ratio of the FA values and the change in depression scale scores at 6-month follow-up. Regional white matter damage may reflect abnormalities in neuroanatomical pathways related to the pathophysiology of depression.

Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study.

Alzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

Asymmetry, sex differences and age-related changes in the white matter in the healthy elderly: a tract-based study.

BACKGROUND: Hemispherical asymmetry, sex differences and age-related changes have been reported for the human brain. Meanwhile it was still unclear the presence of the asymmetry or sex differences in the human brain occurred whether as a normal development or as consequences of any pathological changes. The aim of this study was to investigate hemispherical asymmetry, sex differences and age-related changes by using a tract-based analysis in the nerve bundles. METHODS: 40 healthy elderly subjects underwent magnetic resonance diffusion tensor imaging, and we calculated fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the major white matter bundles. RESULTS: We identified hemispherical asymmetry in the ADC values for the cingulate fasciculus in the total subject set and in males, and a sex difference in the FA values for the right uncinate fasciculus. For age-related changes, we demonstrated a significant increase in ADC values with advancing age in the right cingulum, left temporal white matter, and a significant decrease in FA values in the right superior longitudinal fasciculus. CONCLUSION: In this study, we found hemispherical asymmetry, sex differences and age-related changes in particular regions of the white matter in the healthy elderly. Our results suggest considering these differences can be important in imaging studies.

White matter changes in dementia with Lewy bodies and Alzheimer's disease: a tractography-based study.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are different types of dementia. However, their clinical symptoms partially overlap and differential diagnosis is occasionally difficult. There is need for additional diagnostic criteria to reliably differentiate between these two conditions. Meanwhile, several imaging studies have showed inconsistent results between DLB and AD. The aim of this study was to use a tractography-based analysis to elucidate white matter alterations in subjects with DLB compared to those with AD and to controls. An understanding of the white matter connectivity differences between AD, DLB and controls will be helpful for differential diagnosis and an understanding of the pathophysiology. Twenty-six subjects with DLB, 26 with AD and 26 controls underwent magnetic resonance diffusion tensor imaging and neuropsychological assessment. Diffusion tensors were computed and fiber-tract maps were created using "dTV II" software. We measured mean fractional anisotropy (FA) values along the uncinate fasciculus (UNC), the inferior occipitofrontal fasciculus (IOFF) and the inferior longitudinal fasciculus (ILF). Both subjects with DLB and AD had lower FA values for the bilateral UNC than controls. Subjects with DLB exhibited significantly lower FA values on both sides of the IOFF and the left side of the ILF than those of controls. Although there were no significant differences between subjects with DLB and AD for any measurements, those with DLB exhibited lower FA values especially in visual-related white matter. These different changes in white matter tracts among groups could be helpful for differential diagnosis and an understanding of the pathophysiology.

Type d syndrome of inappropriate antidiuretic hormone secretion in a schizophrenia patient with polydipsia.

A 55-year-old man with schizophrenia developed water intoxication due to primary polydipsia. His manner of antidiuretic hormone secretion was investigated by water loading and infusion of hypertonic saline to clarify the form of the syndrome of inappropriate antidiuretic hormone secretion. The plasma antidiuretic hormone level, which may be involved in the occurrence of water intoxication, was consistently low in this patient, and linked to type D syndrome of inappropriate antidiuretic hormone secretion, designated "hypovasopressinemic antidiuresis". Although this type is not common, it should be considered as a pathophysiology for water intoxication in schizophrenia patients.