Systematic analysis of proximal midgut- and anorectal-originating contractions in larval zebrafish using event feature detection and supervised machine learning algorithms.

BACKGROUND: Zebrafish larvae are translucent, allowing in vivo analysis of gut development and physiology, including gut motility. While recent progress has been made in measuring gut motility in larvae, challenges remain which can influence results, such as how data are interpreted, opportunities for technical user error, and inconsistencies in methods. METHODS: To overcome these challenges, we noninvasively introduced Nile Red fluorescent dye to fill the intraluminal gut space in zebrafish larvae and collected serial confocal microscopic images of gut fluorescence. We automated the detection of fluorescent-contrasted contraction events against the median-subtracted signal and compared it to manually annotated gut contraction events across anatomically defined gut regions. Supervised machine learning (multiple logistic regression) was then used to discriminate between true contraction events and noise. To demonstrate, we analyzed motility in larvae under control and reserpine-treated conditions. We also used automated event detection analysis to compare unfed and fed larvae. KEY RESULTS: Automated analysis retained event features for proximal midgut-originating retrograde and anterograde contractions and anorectal-originating retrograde contractions. While manual annotation showed reserpine disrupted gut motility, machine learning only achieved equivalent contraction discrimination in controls and failed to accurately identify contractions after reserpine due to insufficient intraluminal fluorescence. Automated analysis also showed feeding had no effect on the frequency of anorectal-originating contractions. CONCLUSIONS & INFERENCES: Automated event detection analysis rapidly and accurately annotated contraction events, including the previously neglected phenomenon of anorectal contractions. However, challenges remain to discriminate contraction events based on intraluminal fluorescence under treatment conditions that disrupt functional motility.

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. These include enhancement of depolarizing spontaneous fluctuations of membrane potential (DSFs), which were analyzed quantitatively for the first time in human DRG neurons. The functional alterations were indistinguishable from SA-driving alterations reported for nociceptors in rodent chronic pain models. Irregular, low-frequency DSFs in human DRG neurons closely resemble DSFs described in rodent nociceptors while differing substantially from the high-frequency sinusoidal oscillations described in rodent LTMRs. These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons. PERSPECTIVE: Electrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.

Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity.

Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of 'silent' neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.

Paraventricular hypothalamus mediates diurnal rhythm of metabolism.

Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening rhythmicity of GABAergic input to the PVH reduces diurnal rhythmicity in metabolism and causes obesity. Finally, BMAL1 deletion blunts PVH neuron responses to external stressors, an effect mimicked by HFD feeding. Thus, BMAL1-driven PVH neuron responsiveness in dynamic activity changes involving rhythmic GABAergic neurotransmission mediates diurnal rhythmicity in metabolism and is implicated in diet-induced obesity.

Disrupted hypothalamic CRH neuron responsiveness contributes to diet-induced obesity.

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both of which showed HFD-mimicking, blunted PVH CRH neuron responsiveness. Strikingly, both models developed rapid HFD-induced obesity, associated with HFD-mimicking, reduced diurnal rhythmicity in feeding and energy expenditure. Thus, blunted responsiveness of PVH CRH neurons, but not their absolute activity levels, underlies HFD-induced obesity and may also contribute to stress-induced obesity.

Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia.

There is evidence that obesity or higher body mass index is correlated with cognitive impairment in schizophrenia. Recent studies have demonstrated that genetic risk factors, such as the NRG3, are correlated with both elevated BMI and reduced cognitive function. In present study, we aimed to determine whether possession of the NRG3 rs10748842 influences the correlation between elevated BMI and reduced cognitive ability in schizophrenia. To our knowledge, this has never been examined before. A total of 625 inpatients with schizophrenia and 400 controls were recruited. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. We used multiple analysis of covariance (MANCOVA), analyses of covariance (ANCOVA), Pearson correlations, partial correlations, and multivariate regression analysis to test the influence of NRG3 rs10748842 on the aforementioned variables. All RBANS five sub-scores and total score were lower in patients than those in controls (all p < 0.001). Patients carrying NRG3 rs10748842 TC + CC heterozygous genotype had lower attention score compared to TT homozygous genotype (adjusted F = 4.77, p = 0.029). BMI was positively associated with language score in patients (ß = 0.387, t = 2.59, p = 0.01). Interestingly, we further found positive association between BMI and language score in TT carriers (partial correlations: r = 0.13, adjusted p = 0.004; multivariate regression: ß = 0.42, t = 2.66, p = 0.008), but not in CT + CC carrier (p > 0.05). Our study demonstrated that NRG3 rs10748842 was associated with cognitive impairments, especially attention performance in schizophrenia. Moreover, NRG3 rs10748842 altered the effect of BMI on cognitive impairments as measured by the RBANS language score in chronic patients with schizophrenia.

The prevalence, risk factors and clinical correlates of diabetes mellitus in Chinese patients with schizophrenia.

Diabetes is one of the most common comorbid diseases in patients with schizophrenia. The present study examined the prevalence of diabetes and its clinical correlates in a large sample of Chinese patients with schizophrenia, which has not been examined systemically. In this cross-sectional study, a total of 1189 patients (males/females = 938/251; average age: 48.51 ± 10.09 years) were recruited. Fasting blood samples were collected to diagnose diabetes. Psychiatric symptoms were measured with the Positive and Negative Syndrome Scale (PANSS). The prevalence of diabetes was 12.53% with a significant gender difference (males: 10.87% versus females: 18.73%). Compared to patients without diabetes, those with diabetes were older, had a later age of onset, had a higher BMI, had higher positive symptom scores and had higher level of metabolic indices, including triglyceride, cholesterol and HDL cholesterol. After stepwise binary logistic regression analysis, age, BMI, and triglyceride level remained significantly associated with diabetes. This study suggests that diabetes occur with high prevalence in Chinese schizophrenia patients. In addition, age, BMI, and triglyceride level possibly are useful markers predicting an increased risk for diabetes.

Identification of a neurocircuit underlying regulation of feeding by stress-related emotional responses.

Feeding is known to be profoundly affected by stress-related emotional states and eating disorders are comorbid with psychiatric symptoms and altered emotional responses. The neural basis underlying feeding regulation by stress-related emotional changes is poorly understood. Here, we identify a novel projection from the paraventricular hypothalamus (PVH) to the ventral lateral septum (LSv) that shows a scalable regulation on feeding and behavioral changes related to emotion. Weak photostimulation of glutamatergic PVH→LSv terminals elicits stress-related self-grooming and strong photostimulation causes fear-related escape jumping associated with respective weak and strong inhibition on feeding. In contrast, inhibition of glutamatergic inputs to LSv increases feeding with signs of reduced anxiety. LSv-projecting neurons are concentrated in rostral PVH. LSv and LSv-projecting PVH neurons are activated by stressors in vivo, whereas feeding bouts were associated with reduced activity of these neurons. Thus, PVH→LSv neurotransmission underlies dynamic feeding by orchestrating emotional states, providing a novel neural circuit substrate underlying comorbidity between eating abnormalities and psychiatric disorders.

Defensive Behaviors Driven by a Hypothalamic-Ventral Midbrain Circuit.

The paraventricular hypothalamus (PVH) regulates stress, feeding behaviors and other homeostatic processes, but whether PVH also drives defensive states remains unknown. Here we showed that photostimulation of PVH neurons in mice elicited escape jumping, a typical defensive behavior. We mapped PVH outputs that densely terminate in the ventral midbrain (vMB) area, and found that activation of the PVH→vMB circuit produced profound defensive behavioral changes, including escape jumping, hiding, hyperlocomotion, and learned aversion. Electrophysiological recordings showed excitatory postsynaptic input onto vMB neurons via PVH fiber activation, and in vivo studies demonstrated that glutamate transmission from PVH→vMB was required for the evoked behavioral responses. Photostimulation of PVH→vMB fibers induced cFos expression mainly in non-dopaminergic neurons. Using a dual optogenetic-chemogenetic strategy, we further revealed that escape jumping and hiding were partially contributed by the activation of midbrain glutamatergic neurons. Taken together, our work unveils a hypothalamic-vMB circuit that encodes defensive properties, which may be implicated in stress-induced defensive responses.

Association of Brain-Derived Neurotrophic Factor With Cognitive Function: An Investigation of Sex Differences in Patients With Type 2 Diabetes.

OBJECTIVE: Although a reduction in brain-derived neurotrophic factor (BDNF) has been implicated as a cause of cognitive impairment in type 2 diabetes mellitus (T2DM), the role of sex in moderating this effect has not been explored. METHODS: We compared the difference in serum BDNF and performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) between 96 men and 134 women with T2DM. We compared this with the difference in serum BDNF and performance in the control group (104 men, 144 women). RESULTS: Patients with T2DM performed worse on most RBANS indices (η = 0.372, all p < .05); within T2DM patients, men performed worse than women on the delayed memory score (74.1 (12.1) versus 79.9 (11.5), p = .002) and on the total score (71.4 (11.5) versus 76.5 (10.8), p = .025). Serum BDNF was lower in patients with T2DM versus controls (7.5 (2.7) ng/ml versus 11.5 (2.7) ng/ml, p < .001), and in men compared with women (6.9 (2.4) versus 7.9 (2.8), p = .024). Serum BDNF levels positively correlated with delayed memory score in patients with T2DM (ß = 0.19, p = .007). However, this association was only observed in women, not in men (pinteraction = 0.04). Among healthy controls, no sex differences were noted in either RBANS or BDNF levels (η = 0.04, Cohen's d < 0.163, all p > .05). CONCLUSIONS: Our results show sex differences in poorer cognitive performance, lower BDNF concentration, and their relationship in T2DM patients, suggesting that female sex may be a protective factor for cognitive decline in T2DM patients. However, the findings should be regarded as preliminary because of the cross-sectional design and chronicity of the diabetes.

A lateral hypothalamus to basal forebrain neurocircuit promotes feeding by suppressing responses to anxiogenic environmental cues.

Animals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known. Conversely, anti-anxiety drugs such as benzodiazepines increase appetite. Here, we show that GABAergic neurons in the diagonal band of Broca (DBBGABA) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LHGABA). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBBGABA activity while inducing indiscriminate feeding. Our study reveals that the LHGABA→DBBGABA neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.

Psychological distress in cancer patients in a large Chinese cross-sectional study.

BACKGROUND: Although psychological distress is common among patients with chronic diseases, the degree of risk for developing psychological distress is not well-established. Our aim with this study is to determine the odds ratio for psychological distress in patients with cancer as compared to either 1) patients with chronic disease patients without cancer, or 2) healthy controls in a large representative sample of Chinese population. METHODS: Using a multistage, stratified cluster sampling method, 21,101 subjects 18-79 years old were interviewed face-to-face in Jilin province, China. Their psychological status was assessed with the 12-item General Health Questionnaire (GHQ-12). A total score of ≥4 was used as the threshold for determining psychological distress. RESULTS: The prevalence of psychological distress was 14.08% across the entire sample: 10.63% in healthy controls; 14.81% in patients with chronic diseases; and 20% in patients with cancer. Multiple logistic regression analysis indicated that, as compared to the health controls, both cancer (OR = 1.609, 95%CI = 1.245-2.081) and chronic disease patients (OR = 1.330, 95%CI = 1.189-1.478) were more likely to suffer from psychological distress. Moreover, cancer patients had a higher risk of psychological distress than patients with chronic diseases (OR = 1.295, 95%CI = 1.049-1.600; p = 0.016). In addition, the cancer group (2.68 ±â€¯0.114) demonstrated a higher GHQ score than the patients with chronic diseases (2.30 ±â€¯0.017) and healthy controls (1.98 ±â€¯0.029) (both p < 0.001). CONCLUSION: Our results showed both a higher rate and greater degree of psychological distress in patients with cancer. This suggests a need for better psychological management in cancer patients to help alleviate their distress.

Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients.

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.

Gender differences in the prevalence and clinical correlates of sleep disturbance in general hospital outpatients.

This study investigated gender differences in the prevalence of sleep disturbance and related demographic and clinical characteristics, including quality of life (QOL), in Chinese outpatients. Up to 4399 adult outpatients (2896 females, 1503 males) who visited the neurological, cardiovascular, gastrointestinal, and gynaecological outpatient clinics in four general hospitals were recruited. Demographic and clinical data including QOL were collected by using self-report questionnaires. The prevalence of sleep disturbance in female outpatients (671/2896, 23.2%) was significantly higher than in male outpatients (302/1503, 20.1%) and remained significant after adjusting for significant confounders in the regression analysis. In the regression analysis, divorced/widowed and unemployed status were independently associated with a higher frequency of sleep disturbance in females, while educational level was independently associated with males only. Among these factors, depressive symptoms and older age were the most common risk factors for sleep disturbance in both genders. Sleep disturbance was not associated with the mental domains of the QOL assessments in both genders. This study suggests that sleep disturbance is more frequent in female outpatients and is associated with multiple factors in both genders. A longitudinal study is warranted to confirm the current findings.

Prevalence and Clinical Correlates of and Cognitive Function at the Time of Suicide Attempts in First-Episode and Drug-Naive Patients With Schizophrenia.

BACKGROUND: It is well established that patients with chronic schizophrenia have a substantially higher rate of attempted and completed suicide than the general population. However, the actual prevalence of suicide attempts at first-episode psychosis is relatively unknown. Previous studies showed that suicidal schizophrenia patients demonstrate higher cognitive function than nonsuicidal patients, though with inconsistent results. The aims of the study were to examine the prevalence of suicide attempts and the association of this prevalence with demographic and clinical variables and cognitive function in Chinese first-episode, drug-naive (FEDN) schizophrenia patients using a cross-sectional and case-control design. METHOD: A total of 357 FEDN inpatients meeting DSM-IV criteria for schizophrenia and 380 healthy controls were enrolled and completed a detailed in-house questionnaire. The suicide attempt data were collected from medical records and interviews with the patients and their family members. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to measure cognition in the 28 patients with and 95 patients without a history of suicide attempt and 151 healthy controls. Also, patients were rated on the Positive and Negative Syndrome Scale (PANSS). This study was conducted from June 2013 to December 2015. RESULTS: A suicide attempt rate of 12.0% was found in inpatients with first-episode schizophrenia. The attempters were more likely to smoke (34.4% vs 17.9%; χ² = 5.49, P = .019) and had lower severity of negative symptoms (F1,354 = 4.12, P = .043) as compared to FEDN patients without a suicide attempt. All 5 RBANS subscales (all P < .001) except for the Visuospatial/Constructional index (P > .05) showed significantly lower cognitive performance for FEDN patients than for healthy controls. Among the FEDN patients, the suicide attempters performed better than nonattempters on attention (F1,121 = 5.12, P = .025), with an effect size of 0.49. The following variables were independently associated with suicide attempt as shown by multivariate regression analysis: PANSS negative symptom subscale score (Wald χ²1 = 7.90 P = .005; adjusted OR = 0.807, 95% CI, 0.696-0.936) and Attention (Wald χ²1 = 4.69, P = .03; adjusted OR = 0.957, 95% CI, 0.918-0.997). CONCLUSIONS: FEDN patients with schizophrenia attempt suicide more often than the general population. The suicidal patients were more likely to smoke, had lower severity of negative symptoms, and showed better attention than nonsuicidal patients.

Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain.

Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors, but rodent models of pain-related OA have concentrated on allodynia rather than ongoing pain, and on OA generated in non-nociceptive Aß fibers rather than C-fiber nociceptors. Little is known about how ongoing pain or nociceptor OA is generated. To define neurophysiological alterations underlying nociceptor OA, we have used isolated dorsal root ganglion neurons that continue to generate OA after removal from animals displaying ongoing pain. We subclassify OA as either spontaneous activity generated solely by alterations intrinsic to the active neuron or as extrinsically driven OA. Both types of OA were implicated previously in nociceptors in vivo and after isolation following spinal cord injury, which produces chronic ongoing pain. Using novel automated algorithms to analyze irregular changes in membrane potential, we have found, in a distinctive, nonaccommodating type of probable nociceptor, induction by spinal cord injury of 3 alterations that promote OA: (1) prolonged depolarization of resting membrane potential, (2) a hyperpolarizing shift in the voltage threshold for action potential generation, and (3) an increase in the incidence of large depolarizing spontaneous fluctuations (DSFs). Can DSFs also be enhanced acutely to promote OA in neurons from uninjured animals? A low dose of serotonin failed to change resting membrane potential but lowered action potential threshold. When combined with artificial depolarization to model inflammation, serotonin also strongly potentiated DSFs and OA. These findings reveal nociceptor specializations for generating OA that may promote ongoing pain in chronic and acute conditions.

Tumor necrosis factor-alpha -1031T/C polymorphism is associated with cognitive deficits in chronic schizophrenia patients versus healthy controls.

Recent compelling research has demonstrated a pathophysiologic role for proinflammatory cytokines of microglial origin in decreasing neurocognitive function. Psychiatric diseases are already known to have reduced cognitive function and are also associated with increased inflammation. To elaborate on these data, our study aims to investigate how a particular polymorphism of the tumor necrosis factor gene, TNF-α -1031T/C, affects neurocognitive performance in patients with schizophrenia. We recruited 905 patients with schizophrenia and 571 healthy control subjects. We employed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test for neurocognitive function and the positive and negative syndrome scale to evaluate schizophrenia severity. The -1031T/C polymorphism was genotyped in both healthy controls and schizophrenic patients. Our results demonstrate that patients with the C allele (either T/C or C/C) possessed increased immediate memory index, visuospatial/constructional index, and RBANS total scores as compared to patients without it (p < .05). In healthy controls, there was no significant difference across genotypes (p > .05). Our findings demonstrate that the TNF-α -1031T/C polymorphism may not play a role in the susceptibility of schizophrenia itself, but may be involved in the cognitive deficits of schizophrenia. This suggests an important role for cytokine signaling in mediating the severity of cognitive dysfunction in schizophrenia.

A neural basis for antagonistic control of feeding and compulsive behaviors.

Abnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown. Excessive self-grooming in rodents is associated with compulsivity. Here, we show that optogenetically manipulating the activity of lateral hypothalamus (LH) projections targeting the paraventricular hypothalamus (PVH) differentially promotes either feeding or repetitive self-grooming. Whereas selective activation of GABAergic LH→PVH inputs induces feeding, activation of glutamatergic inputs promotes self-grooming. Strikingly, targeted stimulation of GABAergic LH→PVH leads to rapid and reversible transitions to feeding from induced intense self-grooming, while activating glutamatergic LH→PVH or PVH neurons causes rapid and reversible transitions to self-grooming from voracious feeding induced by fasting. Further, specific inhibition of either LH→PVH GABAergic action or PVH neurons reduces self-grooming induced by stress. Thus, we have uncovered a parallel LH→PVH projection circuit for antagonistic control of feeding and self-grooming through dynamic modulation of PVH neuron activity, revealing a common neural pathway that underlies feeding and compulsive behaviors.

Prevalence, risk factors and clinical characteristics of osteoporosis in Chinese inpatients with schizophrenia.

Patients with schizophrenia have a high prevalence of developing osteoporosis and osteoporosis-related fractures. We examined the prevalence of osteoporosis and its clinical correlates in Chinese patients with schizophrenia, which is not well-studied. A total of 199 inpatients (males/females=132/67; average age: 54.5±11.1years) and 107 healthy controls (males/females=22/85; average age: 41.7±11.9years) were recruited. Bone mineral density (BMD) was measured by ultrasonography of the calcaneus. The prevalence of osteoporosis and low BMD (osteoporosis and osteopenia) was 23.1% and 65.3% for the patient group, versus 7.5% and 39.3% for the control group (both p<0.001). Further, the average BMD T-score in patients was significantly lower than in controls (p<0.05). There was gender difference in the prevalence of low BMD conditions for the patients (males: 56.1% versus females: 76.1%; p<0.01) as well as the BMD T-score (p<0.001). Several risk factors correlated with the osteoporosis classification in the patient group: older age (58.9±11.2years vs. 53.3±11.0years), lower weight (63.7±12.2kg vs. 70.4±15.2kg) and body mass index (BMI) (22.8±4.1kg/m2 vs. 24.2±4.7kg/m2; all p<0.01) than those without osteoporosis. Stepwise multiple logistic regression analysis indicated that age, weight and BMI remained significantly associated with osteoporosis. In addition, correlation analysis showed significant correlations between BMD T-score and the following parameters: gender, age and drug type (clozapine versus non-clozapine) (Bonferroni corrected p's<0.05). Our results suggest a higher prevalence of osteoporosis and osteopenia in Chinese schizophrenic inpatients, with both the expected risk factors of gender and age, as well as drug type.