Infrared spectroscopy and theoretical structure analyses of protonated fluoroalcohol clusters: the impact of fluorination on the hydrogen bond networks.

To explore the impact of fluorination on the hydrogen bond networks of protonated alkylalcohols, infrared spectroscopy and theoretical computations of protonated 2,2,2-trifluoroethanol clusters, H+(TFE)n, (n = 4-7), were performed. It has been demonstrated that the development of the hydrogen bond networks from a linear type to cyclic types occurs in this size region for the protonated alkylalcohol clusters. In contrast, infrared spectroscopy of H+(TFE)n in the OH/CH stretch region clearly indicated that the linear type structures are held in the whole size range, irrespective of temperature of the clusters. The extensive stable isomer structure search of H+(TFE)n based on our latest sampling approach supported the strong preference of the linear type hydrogen bond networks. Detailed analyses of the free OH stretching vibrational bands evidenced the intra- and intermolecular OH⋯FC interactions in the clusters. In addition, infrared spectra of protonated clusters of 2,2-difluoroethanol, 2,2-difluoropropanol, and 3,3,3-trifluoropropanol were measured for n = 4 and 5, and their spectra also indicated the effective inhibition of the cyclic hydrogen bond network formation by the fluorination.

Effects of mixing between short-chain and branched-chain alcohols in protonated clusters.

The previous analysis of the neat protonated branched-chain alcohol clusters revealed the impact of steric repulsion and dispersion of the bulky alkyl group on the hydrogen-bonded (H-bonded) structures and their temperature-dependence. To further understand the influence of the alkyl groups in H-bonded clusters, we studied the mixing of the two extremes of alcohols, methanol (MeOH) and tert-butyl alcohol (t-BuOH), with an excess proton. Infrared spectroscopy and a structural search of first principles calculations on the size-selected clusters H+(MeOH)m(t-BuOH)t (m + t = 4 and 5) were conducted. Temperature-dependence of the dominant H-bonded structures was explored by the Ar-tagging technique and quantum harmonic superposition approach. By introducing the dispersion-corrected density functional theory methods, it was shown that the effects of dispersion due to the bulky alkyl groups in the mixed clusters cannot be ignored for t≥ 2. The computational results qualitatively depicted the characteristics of the observed IR spectra, but overestimation of the temperature-dependence with dispersion correction was clearly seen due to the unbalanced correction between linear H-bonded structures and compact cyclic ones. These results demonstrate the importance of extensive investigation and benchmarks on different levels of theory, and that a properly sampled structure database is crucial to evaluate theoretical models.

Attention-deficit/hyperactivity disorder symptoms and suicidal behavior in adult psychiatric outpatients.

AIM: We aimed to examine the association between attention-deficit/hyperactivity disorder (ADHD) symptoms and suicidal behavior in psychiatric outpatients and whether this association differs among patients with different psychiatric disorders. METHODS: Cross-sectional data came from the Japan Prevalence Study of Adult ADHD at Psychiatric Outpatient Care, which included psychiatric outpatients aged 18-65 years recruited from one university hospital and three general psychiatric outpatient clinics in Kitakyushu City, Fukuoka, Japan from April 2014 to January 2015 (N = 864). The Adult ADHD Self-Report Scale (ASRS) Screener was used to collect information on ADHD symptoms. Reports of current and lifetime suicidal behavior were also obtained. A multivariable Poisson regression analysis was used to examine the association between ADHD symptoms and suicidal behavior. RESULTS: After adjusting for covariates there was a strong association between possible ADHD (ASRS ≥14) and suicidal behavior with prevalence ratios ranging from 1.17 (lifetime suicidal ideation) to 1.59 (lifetime suicide attempt) and 2.36 (current suicidal ideation). When ASRS strata were used, there was a dose-response association between increasing ADHD symptoms and suicidal ideation and suicide attempts. Analyses of individual ICD-10 psychiatric disorders showed that associations varied across disorders and that for anxiety disorder, ADHD symptoms were significantly linked to all forms of suicidal behavior. CONCLUSION: ADHD symptom severity is associated with an increased risk for suicidal behavior in general psychiatric outpatients. As ADHD symptoms are common among adult psychiatric outpatients, detecting and treating ADHD in this population may be important for preventing suicidal behavior.

[Nicotine dependence].

Smoking is the most widespread addictive behavior in the world, and it causes physical and psychological dependence on nicotine. As for physical nicotine dependence, nicotine produces rewarding effects by interacting with nicotinic acetylcholine receptors on neurons in the brain's reward system. Psychological dependence on nicotine comes with a complex psychological procedure that is based on distorted cognition which justifies their smoking behavior. Clinicians should support smokers with willingness to quit smoking comprehensively with this knowledge, although the success rate of smoking cessation is no ideal in general.

Volume enlargement of the choroid plexus and brain ventricles in drug-naïve, first-episode major depressive disorder.

BACKGROUND: We investigated volumetric alterations in the bilateral choroid plexus (ChP) and brain ventricles of patients during their first episode of major depressive disorder (MDD) prior to antidepressant treatment. METHODS: Seventy-one first-episode drug-naïve patients with MDD and seventy-four healthy control (HC) subjects were recruited. MRI data were obtained, and bilateral ChP and brain ventricle volumes were evaluated using segmentation, based on the adaptive multiscale and expectation maximization method. One-way multivariate analysis of covariance was used to calculate volumetric differences in the bilateral ChP and brain ventricles between the groups, and partial Pearson correlation analyses were used to investigate the relationship between the volumes of the bilateral ChP and brain ventricles. RESULTS: First-episode drug-naïve patients with MDD showed enlarged volumes of the bilateral ChP, bilateral lateral ventricle (LV), and third ventricle compared with HCs. The ChP volume positively correlated with the LV and third ventricle, but not with the fourth ventricle in patients with MDD, whereas it correlated with all four brain ventricles in HCs. We did not observe significant correlations between bilateral ChP volume and brain ventricles, HAMD scores, or symptom severity. LIMITATIONS: Our study populations differed in age and sex and we did not extensively measure the amount of neuroinflammation in the brain or blood, include a functional assessment, nor evaluate other neural comorbidities or neuropsychiatric conditions. CONCLUSIONS: Our study extends the existing research to suggest that illness-related alterations in ChP volume enlargement in first-episode antidepressant-naïve patients with MDD may serve as a trait measure.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report.

BACKGROUND: Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms. CASE PRESENTATION: A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation. CONCLUSIONS: Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Triple network connectivity changes in patients with major depressive disorder versus healthy controls via structural network imaging after electroconvulsive therapy treatment.

OBJECTIVE: To investigate the effect of electroconvulsive treatment (ECT) on dynamic structural network connectivity in major depressive disorder (MDD), based on the triple-network model. METHODS: Twenty-one first-episode, drug-naïve patients with MDD and 21 age- and sex-matched healthy subjects were recruited. Bilateral electrical stimulation was performed thrice a week for a total of 4-5 weeks in the MDD group. MRI data were obtained, and triple-network structural connectivity was evaluated using source-based morphometry (SBM) analysis. A paired t-test was used to analyze structural connectivity differences between pre- and post-ECT MDD groups, one-way analysis was used to calculate three intrinsic network differences between HCs, pre- and post-ECT groups, and partial least squares structural equation modelling was used to investigate dynamic structural network connectivity (dSNC) across groups. RESULTS: Pre-ECT patients with MDD exhibited significantly lower salience network (SN) structural connectivity (p = 0.010) than the healthy control (HC) group and after ECT therapy SN structural connectivity was significantly elevated (p = 0.002) in post-ECT group compared with pre-ECT. PLS-SEM analysis conducted on inter-network connectivity in the triple-network model indicated a significant difference between SN and central executive network (CEN) in all three groups. The HC and post-ECT MDD groups showed notable direct connectivity between the SN and default mode network (DMN), while the pre-ECT MDD group showed consequential pathological connectivity between the CEN and DMN. A mediation analysis revealed a significant indirect effect of the SN on the DMN through the CEN (ß = 0.363, p = 0.008) only in the pre-ECT MDD group. CONCLUSIONS: ECT may be an effective and minimally invasive treatment for addressing structural changes in the SN and direct communication abnormalities between the three core brain networks in patients with MDD, with possible beneficial correction of indirect connections.

Analysis of treatment-resistant schizophrenia and 384 markers from candidate genes.

The treatment of patients with schizophrenia who fail to respond to antipsychotics is a major challenge and the proportion of treatment-resistant patients is estimated to be 20 to 40%. There are few genetic association studies that have compared resistant versus non-resistant schizophrenic patients; however, many genetic association studies focusing on antipsychotic response have been published. This contribution investigates the genetics of treatment-resistant schizophrenia, testing 384 candidate gene loci related to the neurobiology of the disease. First, we identified a subgroup of treatment-resistant patients in a sample of 240 schizophrenia patients using the American Psychiatric Association criteria and then we genotyped all patients using a custom Illumina Bead Chip comprising of 384 single nucleotide polymorphisms. We screened all markers for nominal significance and for statistical significance after multiple-testing correction. The most significant single nucleotide polymorphism was the rs2152324 marker in the NALCN gene (P=0.004); however, after the FDR correction, the P-value was not significant. Our analysis of 384 markers across candidate genes did not indicate any robust association with treatment-resistant schizophrenia. However, this phenotype can be assessed retrospectively in cross-sectional studies and these preliminary results point out the importance of choosing alternative phenotypes in psychiatric pharmacogenetics.

[Antidepressants: clinical guidance of treatment for people with depression and physical health problems].

Current management in primary care of depression with comorbid physical illness is considered suboptimal. Detection and management of depression is somewhat complex. In particular, primary care clinicians need guidance to address the social needs of depressed patients. This review for clinical physicians provides guidance how to treat those patients with depression in particular at primary care settings. The viewpoints of clinical use of newer antidepressants including SSRIs and SNRIs are described. Given that depression would affect the outcome of physical illness, managing depressed people with comorbid physical illness is very important and understanding relevant drug treatment for depression is essential for primary care physicians.

Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia.

OBJECTIVE: The D-amino acid oxidase activator (DAOA, or G72) is involved in the oxidation of D-serine, an endogenous modulator of N-methyl-D-aspartate receptors and thus represents an important candidate in psychotic disorders. Several studies reported the DAOA/G72 gene to be associated with schizophrenia (SZ) and bipolar disorder (BD); however, the associated polymorphisms varied between SZ and BD. This study attempts to replicate the DAOA/G72 findings in BD and to conduct subgroup analyses based on the presence or absence of psychotic symptoms. METHODS: Five polymorphisms of the DAOA/G72 gene (rs1341402, rs1935062, rs2391191, rs947267, and rs778294) were analysed for association with BD in a family-based study design (303 core families including 916 individuals). We also conducted a meta-analysis of DAOA/G72 polymorphisms in BD and SZ. RESULTS: Marker rs1935062 was significantly associated with BD diagnosis in our sample (Z-score for C-allele= -2.33, p=0.02, uncorrected for genome-wide multiple comparisons). When we examined the subset of BD patients with psychotic symptoms (157 families), no significant results were obtained. Our meta-analysis yielded negative findings for DAOA/G72 markers in BD and positive findings for marker rs2391191 in SZ in East Asians. However, significant heterogeneity across studies limits interpretation. CONCLUSIONS: Our results provide evidence that suggests a possible role of the DAOA/G72 gene in BD and SZ. Marker rs1935062 may be specifically associated with BD, while marker rs2391191 may be associated with SZ but not with BD. Together with previous studies, these findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders.

Lack of association between the leptin receptor gene (LEPR) Gln223Arg polymorphism and late-onset Alzheimer disease.

The principal hypothesis for pathogenesis of Alzheimer disease (AD) is the amyloid cascade hypothesis, which emphasizes an imbalance between production and clearance of beta-amyloid (Abeta) in the brain. Insulin has important effects on the regulation of the Abeta level in the brain, modulating both Abeta production and clearance. An optimal brain insulin level promotes Abeta clearance, which may play protective roles against AD. A functional human leptin receptor gene (LEPR) polymorphism, a glutamine to an arginine substitution at codon 223 (Gln223Arg), has been associated with insulin resistance capacity and an altered leptin-binding activity. The LEPR Gln223Arg polymorphism may thus play an important role in the pathogenesis of AD. In this study, we examined the association between the LEPR Gln223Arg polymorphism and late-onset Alzheimer disease (LOAD) in a Japanese population. Our sample includes 49 patients with LOAD and 134 normal controls. Our preliminary data showed no significant association between the LEPR Gln223Arg polymorphism and LOAD (genotype distribution: chi=0.11, df=2, P=0.945; allele frequency: chi=0.058, df=1, P=0.81, odds ratio=1.08, 95% confidence interval=0.59 to 2.03). Our results suggest that the LEPR polymorphism may not play a major role in the development of LOAD.

[Mental health issues in workplace: perspective of a psychiatrist as an occupational physician].

Working in close cooperation with the clinician in charge, the human resource department, and line managers, the occupational physician plays a key role in employees' healthy adaptation to the workplace. In the workplace, it is not sufficient for an employee's depressive symptoms to disappear; it is also necessary that the employee be able to function according to job demands. It is becoming increasing difficult to distinguish between depression and related disorders that manifest depressive symptoms, such as adjustment disorder and personality issues. Using a complex case of dysthymia in the workplace, the author examines the management of such cases, as well as ways of collaborating closely with the clinician in charge.

Brain structural network alterations related to serum cortisol levels in drug-naïve, first-episode major depressive disorder patients: a source-based morphometric study.

Higher cortisol levels due to a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p < .01; insula-temporal network, p < .01). Serum cortisol levels showed a statistically significant negative correlation with the loading coefficients of the prefrontal network (r = - 0.354, p = 0.02). In conclusion, increased serum cortisol levels were associated with reductions in the prefrontal network in the early stage of MDD, and SBM may be a useful approach for analyzing structural MRI data.

No association between a functional polymorphism in the promoter region of the neuropeptide Y gene (-485C>T) and schizophrenia.

It has been suggested that hypoactivity of neuropeptide Y (NPY) may be involved in the pathophysiology of schizophrenia. A post-mortem study revealed a decreased level of NPY in the brain of patients with schizophrenia. An increased level of NPY after antipsychotic treatment was also reported in animal brain and cerebrospinal fluid of patients. Previously Itokawa et al. reported a positive association between the functional -485C>T polymorphism in the NPY gene and schizophrenia in a Japanese population. The aim of this study is to replicate their positive findings in an independent Japanese case-control sample. Our sample includes 260 patients with schizophrenia (DSM-IV) and 196 control subjects. No significant differences in distribution of genotype or allele frequencies between patients and controls were observed. Our results suggest that the NPY -485C>T polymorphism may not confer susceptibility to schizophrenia, at least in our sample. Further studies in larger samples are warranted.

Association analysis between the C-1291G polymorphism in the promoter region of the adrenergic alpha2A receptor gene and polydipsia in schizophrenia.

Several lines of studies have shown the existence of an important inhibitory mechanism for the control of water intake involving adrenergic alpha2A receptors (ADRA2A). A human study using patients with schizophrenia demonstrated an exacerbation of polydipsia by the administration of clonidine, an ADRA2A-agonist, and a relief of polydipsia by mianserin, an ADRA2A-antagonist, suggesting the involvement of the central adrenergic system in the drinking behavior of patients with schizophrenia. Based on these findings we examined a possible association between the C-1291G polymorphism in the promoter region of the ADRA2A gene and polydipsia in schizophrenia using a Japanese case-control sample. Our sample includes 348 patients with schizophrenia (DSM-IV) (84 with polydipsia and 264 without polydipsia). No significant association between the ADRA2A C-1291G polymorphism and polydipsia was found. Our result suggests that the ADRA2A C-1291G polymorphism may not confer susceptibility to polydipsia in schizophrenia in our sample. Further studies with larger samples are warranted.

Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects.

Abnormal activities of critical antioxidant enzymes and other indices of lipid peroxidation in plasma and red blood cells were detected in patients with schizophrenia. Other results have shown that oxidative stress may be modulated by clozapine. Based on that and some studies already found different clinical relations between reactive oxygen species and negative and positive symptoms, we evaluated association between clinical response and the polymorphism in the human glutathione peroxidase (GPX1) (Pro200Leu, rs1050450) and manganese SOD (MNSOD) (Ala16Val, rs4880) gene in 216 clozapine-treated patients with schizophrenia. No association was found with these two functional polymorphisms and clozapine response and symptom change after 6 months. No correlations were found between positive/negative symptoms score and both polymorphisms. Our results present that GPX1 (Pro200Leu) and MNSOD (Ala16Val) polymorphisms seem do not play a central role in the clozapine response, although studies in larger and independent samples are necessary to confirm our findings.

Hemifield Crossings during Multiple Object Tracking Affect Task Performance and Steady-State Visual Evoked Potentials.

The ability to track multiple objects is important for daily life activities such as driving, but it is subject to some restrictions. One limitation concerns the hemifields in which objects move. A previous study showed that when subjects were restricted to the use of one hemifield, both the maximum number of tracked objects and the tracking accuracy were lower than when they were permitted to use both hemifields. However, daily life involves many tracked objects moving between hemifields. In this study, we investigated the effects of such hemifield crossings on behavioral performance (Behavioral experiment) and on the amplitudes and phase synchronization of steady-state visual evoked potentials (SSVEPs) (SSVEP experiment) by comparing the Within condition, in which tracked objects moved within their respective hemifields, and the Crossover condition, in which tracked objects moved between hemifields. In the Behavioral experiment, tracking performance was worse under the Crossover condition than under the Within condition. In the SSVEP experiment, SSVEP amplitudes for target and distractor frequencies differed under the Within condition but did not differ under the Crossover condition. However, phase synchronization between the left and right hemifields exhibited the opposite trend. This study provides evidence that attention to objects moving between hemifields is suppressed relative to attention to objects moving within hemifields and that Crossover tracking diminishes attentional modulation at an early sensory processing level while modulating interhemispheric functional connectivity.

Genetic association between the dopamine D3 gene polymorphism (Ser9Gly) and schizophrenia in Japanese populations: evidence from a case-control study and meta-analysis.

Dysregulation in the dopaminergic system has been implicated in the pathophysiology of schizophrenia (SCZ). Dopamine D3 receptors (DRD3) concentrated in limbic regions of the brain (important for cognitive, emotional and endocrine function) may be particularly relevant to SCZ. A recent meta-analysis with mixed ethnicities reported a marginal significant association between the Ser9Gly homozygosity in the first exon of the DRD3 gene and SCZ. To further evaluate the controversial association between this polymorphism and SCZ, a case-control study and meta-analysis was conducted using the homogeneous Japanese population. In our Japanese case-control sample (246 cases/198 controls), we found an association between the DRD3 Ser9Gly polymorphism and SCZ (genotype: chi(2) = 9.76, d.f. = 2, p = 0.008; Ser allele versus Gly allele: chi(2) = 7.96, d.f. = 1, p = 0.0048; OR = 0.65; 95% CI = 0.48-0.88). However in a meta-analysis of nine Japanese case-control studies comprising 2056 subjects the association between DRD3 Ser9Gly polymorphism and SCZ did not persisted. The Mantel-Haenszel pooled OR for SCZ among carriers of the DRD3 Ser9Gly homozygosity (Ser/Ser homozygotes and Gly/Gly homozygotes) of the nine Japanese studies was 1.16 (95% CI 0.97-1.39), pointing to a non-significant effect of the DRD3 Ser9Gly homozygosity as a risk factor for SCZ. Overall, our results suggest that the DRD3 Ser9Gly polymorphism may not confer susceptibility to SCZ in the Japanese population. Given that the Ser9Gly variant may play a putative role in DRD3 function, further studies on the DRD3 with linked variants are warranted.

[Examination of factors for promoting cooperation using documents between occupational health physicians and psychiatrists].

OBJECTIVES: There is little specific information concerning the method and the efficacy of sharing information between occupational health physicians and psychiatrists regarding the employment status and medical history of their patients with mental illnesses. To promote cooperation between occupational health physicians and psychiatrists, we examined the points necessary to be included on medical information request forms exchanged between them. METHODS: We conducted focused group discussion (FGD) to identify the points that need to be described on the request form and the concerns in cooperation between occupational health physicians and psychiatrists. We conducted FGDs twice, with two different groups of nine psychiatrists participating in each round. We extracted and organized FGD results and determined the necessary request form points. Next, we assumed two different cases of workers with mental illnesses and created three request form templates with differing item descriptions and lengths. We also conducted a questionnaire survey among clinical psychiatrists to determine their impression of the templates. We performed logistic regression analysis on the obtained results. RESULTS: On the basis of the FGD results we extracted the situation in the workplace, clarification of points to be confirmed, representation of the occupational health physician's position, and handling of information provided by the doctor as points required for the request form. On the basis of these results and the opinions of occupational health specialists, we created a new request form using these points. Additionally, the results from the questionnaire survey about the prescribed items revealed the proportion of favorable answers regarding sufficient information written on the request form and a feeling of security for information provision increased (p < 0.01). Conversely, the proportion of favorable responses for readability decreased. CONCLUSIONS: Psychiatrists are concerned about the possibility that their patient may be at a disadvantageous situation by providing their personal medical information and believe the clinical information required by the occupational health physicians is unclear. This suggests that there are factors impeding the cooperation between the occupational health physicians and psychiatrists. When an occupational health physician writes a request form, cooperation with psychiatrists may be promoted by enriching the request form contents and by including the representation of the occupational health physician's position and the intended purpose of the provided information by paying attention to the volume of sentences.

The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia.

The underlying pathophysiology of primary polydipsia in schizophrenia (SCZ) is poorly understood. Our previous study, however, suggested that this condition may have a genetic component [Shinkai et al 2003 Am J Med Genet 119B 7-12]. Orexins, also called hypocretins, play an important role in feeding and drinking behavior. Administration of orexin in rats has been shown to induce increased water intake with a longer-lasting effect than angiotensin II, which is also known as a potent dipsogen. Meerabux et al. [2005 Biol Psychiatry 58 401-407] reported an association between the 408Val allele of the orexin 1 receptor (HCRTR1) gene and polydipsia-hyponatremia in a sample of Japanese patients with SCZ. In the present study, we attempted to replicate the findings of Meerabux et al. in an independent Japanese case-control sample. Our sample included 312 patients with SCZ (DSM-IV) (65 with polydipsia and 247 without polydipsia). We also observed an association between the HCRTR1 Ile408Val polymorphism and polydipsia (genotype distribution: chi2 = 9.85, df = 2, P = 0.007). Meerabux et al. (2005) previously demonstrated an association between the 408Val allele of the HCRTR1 gene and polydipsia. In contrast with Meerabux et al. study, we found that the 408Ile allele was associated with polydipsia in our sample (chi2 = 8.00, df = 1, P = 0.0047; OR = 0.53; 95%CI = 0.34-0.83). How either allele contributes to the development of polydipsia in SCZ is unclear at this stage. It is possible that Ile408Val polymorphism is a non-functional marker that lies in linkage disequilibrium with an as-yet undetected functional variant. In any case, our results support the hypothesis that the HCRTR1 Ile408Val polymorphism may confer susceptibility to polydipsia in SCZ. Further studies examining the association between the orexin system and polydipsia in SCZ are warranted.