\n
\u6309\u7167\u6211\u4eec\u4e0a\u8bfe\u65f6\u7684\u987a\u5e8f\u548c\u53d1\u7ed9\u5927\u5bb6\u7684\u63d0\u7eb2\uff0c\u4eca\u5929\u662f\u7b2c\u4e8c\u7bc7\uff1a<\/p>\n
\u300a\u9996\u53d1\u7cbe\u795e\u5206\u88c2\u75c7\u7cd6\u4ee3\u8c22\u5f02\u5e38\u4e0e\u7cbe\u795e\u75c5\u7406\u75c7\u72b6\u4e4b\u95f4\u7684\u5173\u7cfb\u300b<\/strong><\/p>\n \u4e00\u3001\u8fd9\u7bc7\u6587\u7ae0\u7684\u601d\u8def\u6bd4\u8f83 straightforward, \u5178\u578b\u7684case-control \u8bbe\u8ba1\uff0c\u4e00\u7ec4\u7cbe\u795e\u5206\u88c2\u75c7 (n=120) \u00a0vs \u4e00\u7ec4\u6b63\u5e38\u7ec4(n=31)\u3002<\/p>\n \u4e8c\u3001\u6307\u6807\u5305\u62ec\uff1a<\/p>\n 1\uff09\u7cd6\u548c\u8102\u4ee3\u8c22\u6307\u6807+\u80f0\u5c9b\u7d20(\u6765\u81ea\u5316\u9a8c\u5355)\uff1b<\/p>\n 2\uff09\u75c5\u4eba\u68c0\u6d4bPANSS\u3002<\/p>\n \u4e09\u3001\u7ed3\u679c\uff1a<\/p>\n 1\uff09\u6bd4\u8f83\u4e24\u7ec4\u4e4b\u95f4\u7684\u7cd6\u8102\u4ee3\u8c22\u6307\u6807\u5dee\u5f02\uff1b<\/p>\n 2\uff09\u5728\u75c5\u4eba\u7ec4\uff0c\u4ee3\u8c22\u6307\u6807\u662f\u5426\u4e0ePANSS\u6709\u67d0\u79cd\u5173\u8054\u3002<\/p>\n \u8fd9\u7bc7\u6587\u7ae0\u80cc\u540e\u6709\u4e24\u4e2a\u6709\u8da3\u7684\u5c0f\u6545\u4e8b\uff1a<\/p>\n 1\uff09\u8fd9\u7bc7\u6587\u7ae0\u7684\u601d\u8def\u662f\u5728\u4fee\u7a3f\u53e6\u4e00\u7bc7\u6587\u7ae0\u65f6 (\u7cd6\u8010\u91cf\u8bd5\u9a8c OGTT\uff0c\u51c6\u5907\u5728\u4e0b\u4e00\u671f\u53d1\u51fa) \u4ea7\u751f\u7684\uff0c\u90a3\u7bc7OGTT\u6587\u7ae0\u4e3b\u8981\u662f\u6bd4\u8f83\u670d\u7cd6\u540e2\u5c0f\u65f6\u7684\u8840\u7cd6\u6c34\u5e73\u5728\u7cbe\u795e\u5206\u88c2\u75c7\u75c5\u4eba\u4e0e\u6b63\u5e38\u4eba\u4e4b\u95f4\u7684\u5dee\u5f02\uff0c\u5f53\u65f6\u6211\u5c31\u60f3\u5230\uff1a\u90a3\u4e48\u670d\u7cd6\u524d\u7684\u57fa\u7840\u6c34\u5e73\u5982\u4f55\u5462\uff1f\u6240\u4ee5\u5c31\u6709\u4e86\u7edf\u8ba1\u5206\u6790\u548c\u672c\u6587\u7684\u4ea7\u751f\u3002<\/p>\n 2\uff09\u6587\u7ae0\u5199\u597d\u540e\uff0c\u6211\u5c31\u6295\u5f80Schizophrenia Research\uff0c\u56e0\u4e3a\u8fd9\u662f\u4e00\u4e2a\u8ba1\u5212\u5916\u7684\u6587\u7ae0\uff0c\u4e5f\u6ca1\u591a\u8003\u8651\uff0c\u5c31\u6295\u5f80\u8fd9\u4e2a\u6211\u6bd4\u8f83\u719f\u6089\u7684\u6742\u5fd7\uff0c\u6309\u6211\u7684\u7ecf\u9a8c\uff0c\u5e94\u8be5\u80fd\u6bd4\u8f83\u987a\u7545\u5730\u4fee\u56de\u548c\u63a5\u53d7\uff0c\u4f46\u672a\u66fe\u60f3\u5230\u7684\u662f\uff0c\u6587\u7ae0\u76f4\u63a5\u88ab\u62d2\u7a3f\u4e86\uff01\uff01\u96be\u4ee5\u7f6e\u4fe1\u554a\uff01\uff08\u540c\u5b66\u4eec\u770b\u770b\uff0c\u5373\u4f7f\u5bf9\u4e8e\u5f20\u8001\u5e08\uff0c\u88ab\u79d2\u62d2\u4e5f\u662f\u5bb6\u5e38\u4fbf\u996d\uff0c\u4f60\u4eec\u6536\u5230\u62d2\u7a3f\u4fe1\u65f6\uff0c\u4e0d\u8981\u7070\u5fc3\u5662\uff09\u3002\u6211\u75db\u5b9a\u601d\u75db\u3001\u53cd\u590d\u601d\u8003\uff0c\u7136\u540e\u6bc5\u7136\u51b3\u7136\u5730\u51b3\u5b9a\uff1a\u6295\u7a3f\u5230 Psychoneuroendocrinology\u3002 \u8fd9\u4e2a\u771f\u662f\u592a\u5927\u80c6\u51b3\u5b9a\u4e86\uff0c\u8981\u77e5\u9053Psychoneuroendocrinology\u7684\u5f71\u54cd\u56e0\u5b50\u8fdc\u8fdc\u5927\u4e8eSchizophrenia \u00a0Research\u5440\uff0c\u88ab\u4f4e\u5f71\u54cd\u56e0\u5b50\u6742\u5fd7\u79d2\u62d2\u4e86\uff0c\u8fd8\u7adf\u7136\u6562\u6295\u7a3f\u9ad8\u5f71\u54cd\u56e0\u5b50\u6742\u5fd7\uff1f\uff1f\u8fd9\u5c31\u662f\u4f60\u4eec\u5f20\u8001\u5e08\u7684\u827a\u9ad8\u4eba\u80c6\u5927\u4e86:-))\u3002\u5e78\u8fd0\u7684\u662f\uff0c\u8fd9\u4e2aPsychoneuroendocrinology\u4e3b\u7f16\u6bd4\u8f83\u53cb\u597d\uff0c\u5c31\u7ed9\u9001\u5ba1\u4e86\u54c8\u3002\u7136\u540e\u4e09\u4e2a\u5ba1\u7a3f\u8005\u4e5f\u6bd4\u8f83nice, \u00a0\u5c31\u63d0\u51fa\u6765\u4e00\u7cfb\u5217\u7684\u82db\u523b\u5efa\u8bae\u6765\uff0c\u8ba9\u6211\u53c8\u7ecf\u5386\u4e86\u4e00\u4efd\u75db\u82e6\u7684\u4fee\u7a3f\u8fc7\u7a0b\u3002<\/p>\n \u597d\uff0c\u8a00\u5f52\u6b63\u4f20\uff0c\u770b\u6211\u662f\u5982\u4f55\u7b54\u590d\u4e09\u4f4d\u5ba1\u7a3f\u8005\u610f\u89c1\uff0c\u8ba9\u4ed6\u4eec\u6b23\u7136\u5730\u63a5\u53d7\u4e86\u6211\u4eec\u7684\u6587\u7ae0\u3002<\/p>\n \u4e0b\u9762\u662f\u4fee\u6539\u540e\u7684Cover Letter, \u8fd9\u90e8\u5206\u662f\u91cd\u70b9\uff0c\u53ef\u4ee5\u5148\u770b\uff0c\u800c\u4e14\u9700\u8981\u53cd\u590d\u770b\uff1a<\/strong><\/p>\n Dear Editor,<\/p>\n Thank you very much for sending us the valuable comments of three reviewers on our manuscript (Ms. Ref. No.: \u00a0PNEC-D-15-00458; Title: Glucose disturbances in first-episode drug-na\u00efve schizophrenia: relationship to psychopathology)<\/em>, which have helped us to improve the quality of our paper greatly. We have thoroughly revised our manuscript according to the three reviewers\u2019 helpful comments and suggestions. The comments and the critiques of the reviewers have been addressed and itemized as follows:<\/p>\n Question 1: <\/strong>The study should report correlations (even if not statistically significant) for the PANSS negative symptom scale as well .<\/p>\n \u5ba1\u7a3f\u8005\u63d0\u51fa\u5bf9\u7cd6\u8102\u4ee3\u8c22\u6307\u6807\u4e0ePANSS\u9634\u6027\u75c7\u72b6\u7684\u5173\u8054\uff0c\u5373\u4f7f\u662f\u9634\u6027\u7ed3\u679c\uff0c\u4e5f\u8981\u7ed9\u51fa\u5177\u4f53\u7ed3\u679c\u3002<\/span><\/p>\n Answer: <\/strong><\/span>\u00a0This point is excellent. Correlations for the PANSS negative symptom scale have been added to the second paragraph of the Results section on Page 7, showing as \u201cA significant negative association between plasma glucose level and the PANSS positive symptom subscore was observed (r=-0.23, df=120, p=0.011) (Figure 1). However, neither significant association was found between glucose level and the PANSS negative symptom subscore (r=-0.09, df=120, p=0.22), nor between any other glucose and lipid parameters and the PANSS negative symptom subscore (all>0.05)\u201d.\u00a0<\/span><\/p>\n Question 2: <\/strong><\/span>In the discussion under “possible explanations”, the sentences regarding the first explanation are confusing and likely unnecessary – the results of this study are not explained by anti-psychotic usage if the subjects of this study have never been exposed.<\/p>\n \u7c7b\u4f3c\u8fd9\u6837\u7684\u95ee\u9898\uff0c\u4e0d\u9700\u8981\u4e89\u8fa9\uff0c\u76f4\u63a5\u5220\u9664\u5373\u53ef\uff0c\u56e0\u4e3a\u4e0d\u5f71\u54cd\u6587\u7ae0\u89c2\u70b9\u3002<\/span><\/p>\n Answer:<\/span> \u00a0<\/strong>This point is very excellent. Indeed, the sentences regarding the explanation for the associate between antipsychotic usage and abnormal glucose metabolism in schizophrenia are confusing since our subjects in this study were drug na\u00efve. These sentences have been deleted.<\/p>\n Question 3:<\/span> <\/strong>In the methods section, it would be helpful to explain why the subjects of the study are anti-psychotic na\u00efve – were the data collected at the initial evaluation for psychosis, shortly before anti-psychotics were started? \u00a0Or was there some other reason that the patients did not have medication exposure?<\/p>\n \u5f88\u591a\u8001\u5916\u6559\u6388\u5bf9\u7814\u7a76\u5bf9\u8c61\u7684\u80cc\u666f\u7ec6\u8282\u8981\u6c42\u5f88\u591a\uff0c\u6211\u4eec\u4e2d\u56fd\u4f5c\u8005\u5199\u6587\u7ae0\u65f6\uff0c\u5f80\u5f80\u5bf9\u6b64\u5199\u7684\u6bd4\u8f83\u7b80\u5355\u3002\u00a0<\/span><\/p>\n Answer: <\/strong><\/span>The data were collected from these antipsychotic na\u00efve patients at the initial evaluation for psychosis, shortly before antipsychotic were started. \u00a0That means, after their first episode, they were admitted to the psychiatric hospital as inpatient. \u00a0Then after the data had been collected, they were administered on antipsychotic medications. We have re-described these subjects in the Methods section on Page 4, under the subtitle- 2.1. Subjects<\/strong>, showing as: \u201cOne hundred and twenty FEDN inpatients were recruited at the initial evaluation for psychosis shortly before anti-psychotics were started. They were followed for about 3 months as inpatients after admission in order to establish a DSM-IV diagnosis of schizophrenia\u201d.<\/span><\/p>\n Question 4:<\/span> <\/strong>Did the investigators also measure early morning cortisol levels? \u00a0Is it possible that cortisol abnormalities also contribute to the observed negative correlation between positive symptomatology and fasting plasma glucose levels?<\/p>\n \u8fd9\u4e2a\u95ee\u9898\u5e38\u5e38\u662f\u5ba1\u7a3f\u8005\u559c\u6b22\u63d0\u51fa\u7684\uff0c\u5c31\u662f\uff1a\u4e0e\u672c\u7814\u7a76\u4e2d\u7684\u751f\u7269\u5b66\u6307\u6807\u76f8\u5173\u8054\u7684\u4e00\u4e9b\u6307\u6807\uff0c\u4f46\u672c\u6587\u4e2d\u53c8\u6ca1\u68c0\u6d4b\uff0c\u540c\u65f6\u53c8\u4e0d\u53ef\u80fd\u518d\u53bb\u8865\u5b9e\u9a8c\u6216\u68c0\u6d4b\u6307\u6807\u6765\uff0c\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\u5e94\u8be5\u5982\u4f55\u529e\uff1f\u6bd4\u8f83\u597d\u529e\uff0c\u6700\u7b80\u5355\u7684\u65b9\u6cd5\u5c31\u662f\u5728Discussion \u7684\u5012\u6570\u7b2c\u4e8c\u6bb5\uff0c\u4f5c\u4e3a\u4e00\u4e2alimitation \u5217\u51fa\u6765\u3002\u6216\u8005\u662f\u50cf\u5728\u672c\u6587\u4e2d\u8fd9\u6837\uff0c\u56e0\u4e3astress \u5bf9\u7cd6\u8102\u4ee3\u8c22\u5f71\u54cd\u6bd4\u8f83\u5927\uff0c\u5c31\u88c5\u6a21\u4f5c\u6837\u5730\u5148\u53bb\u8ba8\u8bba\u4e00\u756a\uff0c\u8fd9\u4e5f\u663e\u5f97\u5bf9\u5ba1\u7a3f\u8005\u5f88\u5c0a\u91cd\uff0c\u7136\u540e\u518d\u8bf4\uff0c\u53ef\u60dc\u6211\u4eec\u6ca1\u80fd\u53bb\u68c0\u6d4b\uff0c\u662f\u4e00\u79cdlimitation\u3002<\/span><\/p>\n Answer:<\/span> <\/strong>This point is very excellent. Indeed, the stress and cortisol abnormalities may contribute to the observed negative correlation between positive symptomatology and fasting plasma glucose levels. Unfortunately, we did not measure early morning cortisol levels in this study, which has been added to the last paragraph of the Discussion section on Page 13 as one of limitations. At the same time, we have discussed more about the role of stress and cortisol in the observation negative correlation between positive symptomatology and fasting plasma glucose levels. \u00a0Please read the last paragraph of the Discussion section on Page 11 and 12, showing as follows: A further consideration is the contribution of stress to the observed negative correlation between positive symptomatology and fasting plasma glucose levels, since a number of findings have demonstrated that stress may affect both the clinical symptoms of schizophrenia and the glucose metabolism (Lopuszanska et al 2014). Under the influence of stressors, there is increased activity of the hypothalamic-pituitaryadrenal (HPA) axis, resulting in hypercortisolemia, connected with the development of abnormal glucose metabolism and metabolic syndrome (Lopuszanska et al 2014). Stress-induced release of cortisol direct the processes of metabolism glycogenolysis in the liver and muscles, and gluconeogenesis in the liver and kidneys (Corcoran et al 2003). \u00a0Also, previous studies showed that the high level of cortisol leads to hyperinsulinaemia, insulin resistance abdominal obesity and other components of the metabolic syndrome (Toalson et al 2004; Manoudi et al., 2012), and is a risk factor for type 2 diabetes (Brown et al., 2004). Moreover, in the case of patients with schizophrenia, hypercortisolism leads to increased accumulation of visceral fat, and impaired glucose tolerance (Toalson et al 2004). On the other hand, cortisol was found to be positively correlated with positive symptoms (Walder et al 2000), as well as with negative symptoms in schizophrenia (Zhang et al 2005). It should be pointed out that the experience of acute psychosis in schizophrenia patients was stressful itself. The physiological effects of this stress appear to be different in patients vs controls. It is possible, therefore, that stress may play a role in the negative correlation between positive symptoms and fasting plasma glucose levels in our present study. Unfortunately, we did not measure the early morning cortisol levels and 24-hour urinary cortisol. Further studies will need to evaluate the role of stress in our finding, for example, through the measurement of hormone level related to the hypothalamic-pituitary-adrenal axis. The data on plasma cortisol levels and its correlation to glucose levels and symptom scores would verify this viewpoint on the role of stress in psychosis.<\/span><\/p>\n Question 1<\/span>: <\/strong>The interpretation of the findings exaggerates the importance of statistical differences. For example, there is no meaning in the difference between HOMA-IR’s of 1.21 and 0.81, because the cut off for insulin resistance is at least 5.<\/p>\n \u8fd9\u4e2a\u5ba1\u7a3f\u8005\u7684\u8fd9\u4e2a\u610f\u89c1\u6709\u4e9b\u8fc7\u5206\u4e86\uff0c\u5b9e\u9645\u4e0a\u80f0\u5c9b\u7d20\u62b5\u6297\u7684cutoff \u70b9\u6ca1\u6709\u660e\u786e\u5b9a\u4e49\u3002\u4f46\u5343\u4e07\u8bb0\u4f4f\u4e00\u70b9\uff0c\u4e0d\u5fc5\u8981\u4e0e\u5ba1\u7a3f\u8005\u8fdb\u884c\u4e89\u8fa9\uff0c\u987a\u7740\u4ed6\/\u5979\u7684\u5efa\u8bae\u7b54\u590d\u5c31\u53ef\u4ee5\u4e86\u3002<\/span><\/p>\n Answer: \u00a0<\/strong><\/span>This point is excellent. Indeed, there is no meaning in the difference between HOMA-IR’s of 1.21 and 0.81, because the cut off for insulin resistance is at least 5. This interpretation of the findings exaggerates the importance of statistical differences, which has been added to the first paragraph of the Discussion section on Page 7 and 8, showing as \u201cOur findings of higher levels of fasting plasma glucose and insulin, and potential insulin resistance in FEDN patient with schizophrenia is in accordance with a previous study (Ryan et al. 2003). However, it is worth noting that although there was significant difference in HOMA-IR with 1.21 for patients and 0.81 for healthy controls, there is no special meaning at this point, because the cut off for insulin resistance is at least 5. \u00a0Moreover, it is unfortunate that the control cohort is much smaller than the patient cohort, which may lead to bias in the statistical analysis due to the imbalance in the sample size of two groups in our current study\u201d.<\/span><\/p>\n Question 2:<\/span> <\/strong>Other interpretations are not supported by the data. For example, the authors hypothesize that the patients had a greater amount of intra-abdominal fat than weight-matched control. These interpretation is not supported by the identical levels of triglycerides in the 2 groups.<\/p>\n \u770b\u6765\u8fd9\u4f4d\u5ba1\u7a3f\u8005\u4e0d\u5f88\u53cb\u597d\uff0c\u63d0\u51fa\u4e86\u8fc7\u5206\u7684\u95ee\u9898\uff0c\u4f46\u6b63\u5982\u6211\u5728\u4e0a\u9762\u6240\u8bf4\uff0c\u4e0d\u8981\u540c\u4ed6\/\u5979\u4e89\u8fa9\uff0c\u987a\u7740\u4ed6\/\u5979\u7b54\u590d\u5c31\u53ef\u4ee5\u4e86\uff0c\u5982\u679c\u5b9e\u5728\u662f\u4e0d\u597d\u7b54\u590d\uff0c\u5c31\u653e\u5230limitation \u91cc\u3002<\/span><\/p>\n Answer:<\/span> <\/strong>This point is excellent, which has been added to the Discussion section on Page 9 and 10, showing as \u201cThere are several possible explanations for the glucose metabolism abnormalities in schizophrenia. Firstly, \u2026.. However, it is worthy of mentioning that the patients may have a greater amount of intra-abdominal fat than weight-matched control is only our speculation. Our finding of the identical levels of triglycerides in the 2 groups does not support this speculation. Further study investigating the abdominal body fat determined by magnetic resonance imaging and its relation to abnormal glucose metabolism in schizophrenia will be needed\u201d.<\/span><\/p>\n Question 3:<\/span> <\/strong>The patient group was studied during an acute episode of psychotic illness. Acute illness is associated with hypercortisolemia, which may have explained the increase in fasting glucose and corresponding (appropriate) increase in insulin levels. Unfortunately, the AM cortisol levels and 24-hour urinary cortisol were not measured. In the absence of such measurements, the study is not valid.<\/p>\n \u8fd9\u4e2a\u610f\u89c1\u540c\u7b2c\u4e00\u4f4d\u5ba1\u7a3f\u8005\u7684\u610f\u89c1\u7c7b\u4f3c\uff0c\u90fd\u8c08\u5230stress \u5bf9\u7cd6\u8102\u4ee3\u8c22\u5f71\u54cd\u7684\u95ee\u9898\u3002\u8fd9\u79cd\u60c5\u51b5\u4e0b\uff0c\u628a\u7b54\u590d\u7b2c\u4e00\u4f4d\u5ba1\u7a3f\u8005\u7684\u610f\u89c1\u642c\u8fc7\u6765\u5373\u53ef\uff0c\u4f46\u540c\u65f6\u53c8\u4e13\u95e8\u5217\u5165\u4e00\u6761 limitation\u3002<\/span><\/p>\n Answer:<\/span> <\/strong>These points are very excellent. Indeed, the patient group was studied during an acute episode of psychotic illness. Acute illness is associated with hypercortisolemia, which may have explained the increase in fasting glucose and corresponding (appropriate) increase in insulin levels. Unfortunately, we did not measure early morning cortisol levels and 24-hour urinary cortisol in this study, which has been added to the last paragraph of the Discussion section on Page 11 and 12 as one of limitations. Combining our answers to the Question 4 of the Reviewer 1, we have discussed in details about the role of stress and cortisol in the observation findings, showing as follows: A further consideration is the contribution of stress to the observed negative correlation between positive symptomatology and fasting plasma glucose levels, since a number of findings have demonstrated that stress may affect both the clinical symptoms of schizophrenia and the glucose metabolism (Lopuszanska et al 2014). Under the influence of stressors, there is increased activity of the hypothalamic-pituitaryadrenal (HPA) axis, resulting in hypercortisolemia, connected with the development of abnormal glucose metabolism and metabolic syndrome (Lopuszanska et al 2014). Stress-induced release of cortisol direct the processes of metabolism glycogenolysis in the liver and muscles, and gluconeogenesis in the liver and kidneys (Corcoran et al 2003). \u00a0Also, previous studies showed that the high level of cortisol leads to hyperinsulinaemia, insulin resistance abdominal obesity and other components of the metabolic syndrome (Toalson et al 2004; Manoudi et al., 2012), and is a risk factor for type 2 diabetes (Brown et al., 2004). Moreover, in the case of patients with schizophrenia, hypercortisolism leads to increased accumulation of visceral fat, and impaired glucose tolerance (Toalson et al 2004). On the other hand, cortisol was found to be positively correlated with positive symptoms (Walder et al 2000), as well as with negative symptoms in schizophrenia (Zhang et al 2005). It should be pointed out that the experience of acute psychosis in schizophrenia patients was stressful itself. The physiological effects of this stress appear to be different in patients vs controls. It is possible, therefore, that stress may play a role in the negative correlation between positive symptoms and fasting plasma glucose levels in our present study. Unfortunately, we did not measure the early morning cortisol levels and 24-hour urinary cortisol. Further studies will need to evaluate the role of stress in our finding, for example, through the measurement of hormone level related to the hypothalamic-pituitary-adrenal axis. The data on plasma cortisol levels and its correlation to glucose levels and symptom scores would verify this viewpoint on the role of stress in psychosis.<\/span><\/p>\n Question 1: <\/strong><\/span>This manuscript is clear and well written, and is an interesting and potentially important study of glucose metabolism in first onset patients. To have recruited 120 first onset drug na\u00efve patients is no small achievement and the size of the cohort should be emphasized more in both the abstract and introduction. \u00a0This presents a major improvement over previous comparable studies. I would like to see the inclusion of some more details on the patient cohort, including duration of illness, the proportion of different subtypes of schizophrenia, PANSS and HAM-D scores (though HAM-D may be excluded, see below). The time period of sample collection should also be included, for both patients and controls. If the patient and control samples were collected during very different time periods this could be a limitation of the study. It is unfortunate that the control cohort is so much smaller than the patient cohort. However this should not affect the statistical analysis presented as t test\/ANOVA is not affected by unequal sample size.<\/p>\n \u6b63\u5982\u6211\u5728\u4e0a\u9762\u8bf4\u7684\uff0c\u5f88\u591a\u8001\u5916\u6559\u6388\u7279\u522b\u6ce8\u610f\u7814\u7a76\u5bf9\u8c61\u7684\u7ec6\u8282\uff0c\u8fd9\u4e2a\u5ba1\u7a3f\u8005\u5c31\u7814\u7a76\u5bf9\u8c61\u7684\u7ec6\u8282\u95ee\u9898\u4e5f\u63d0\u51fa\u5f88\u591a\u5efa\u8bae\uff0c\u6bd4\u5982\uff1a\u75c5\u7a0b\uff0c\u75c5\u4eba\u4e9a\u578b\uff0cPANSS\u603b\u5206\u53ca\u5176\u4e9a\u91cf\u8868\u7684\u5206\u6570\uff0c\u4ee5\u53ca\u5bf9\u7167\u7ec4(n=31)\u4e0e\u75c5\u4eba\u7ec4\uff08n=120\uff09\u4e0d\u5e73\u8861\u7b49\u3002<\/span><\/p>\n Answer: <\/strong><\/span>Thanks for positive comments. These points are very excellent (\u8fd9\u4e2a\u5ba1\u7a3f\u8005\u662f\u53cb\u519b\u54c8\uff0c\u610f\u89c1\u6bd4\u8f83positive\uff0c\u6240\u4ee5\u8d76\u7d27\u8868\u626c\u4e00\u4e0b\uff0c\u5b9e\u9645\u4e0a\u8fd9\u4e5f\u662f\u7ed9\u4e3b\u7f16\u770b\u7684\uff0c\u8ba9\u4ed6\u89c9\u5f97\u6211\u4eec\u7684\u7814\u7a76\u6bd4\u8f83\u597d).\u00a0<\/span><\/p>\n 1) Indeed, to have recruited 120 first onset drug na\u00efve patients is very hard, with a lot of efforts. The size of the cohort has been emphasized more in both the abstract and introduction, showing as \u201cFasting glucose and lipid profiles, as well as homeostasis model of assessment-insulin resistance (HOMA-IR) index were determined in 120 never-medicated first-episode and 31 healthy control subjects matched for gender and age\u201d<\/span> (in Abstract). “In this study, we recruited a larger sample of FEDN patients (n=120)”<\/span> (in Introduction).<\/p>\n 2) Some more details on the patient cohort, including duration of illness, the proportion of different subtypes of schizophrenia, and PANSS (HAM-D has been excluded based on the suggestion of the reviewer, shown below) have been added to the Methods section on Page 4 and 5, under the subtitle- 2.1. Subjects<\/strong><\/em>, showing: “Their clinical subtypes were: paranoid, 64 (53.3%), undifferentiated, 44 (36.7%); disorganized 10 (8.3%); others 2 (1.7%). The patients had a mean age of 28.9\u00b19.7 years (range: 16-49 year), and a mean duration of illness of 23.6\u00b119.8 months”.\u00a0<\/span><\/p>\n Also, the PANSS has been added to the Methods section on Page 5, under the subtitle-2.2. Clinical Measures<\/strong><\/em>, showing: “Mean scores on the PANSS were: positive subscore, 25.5\u00b16.6; negative subscale, 19.3\u00b17.8; general psychopathology subscale, 41.0\u00b111.8 and total PANSS score, 85.8\u00b119.9”.\u00a0<\/span><\/p>\n 3) The time period of sample collection has been included for both patients and controls in the Methods section on Page 5, under the subtitle- 2.3. Laboratory tests<\/strong><\/em>, showing:“Serum and plasma samples were collected following an overnight fast and at the same day when the clinical assessments were carried out in each subject. The patient and control samples were collected during the same time period”.<\/span><\/p>\n 4) Indeed, the control cohort is so much smaller than the patient cohort. We have added this point as one of the limitations of the study to the first paragraph of the Discussion section on Page 7 and 8, showing: “However, it is worth noting that \u2026\u2026. Moreover, it is unfortunate that the control cohort is much smaller than the patient cohort, which may lead to bias in the statistical analysis due to the imbalance in the sample size of two groups in our current study”.<\/span><\/p>\n Question 2:<\/strong><\/span> The statistical analysis is adequate, however it seems a little pointless to perform Bonferonni corrections if no discussion is made of the results. Bonferonni may be an overly stringent correction where the repeated measurements are biologically connected e.g. members of the same pathway (as is the case in this study). A better alternative would be Benjamini-Hochberg, a less stringent way of controlling the false discovery rate. Both corrected and uncorrected values should be included in the data table. The PANSS analysis is interesting and the authors correctly state that this has not been previously attempted, presumably due to the small numbers in other studies. No results are presented for HAMD and I am not sure what this adds to an analysis of schizophrenia patients, except as a negative control. The purpose of this analysis should be clarified in the text, or omitted.<\/p>\n \u8fd9\u4f4d\u5ba1\u7a3f\u8005\u5c31\u7edf\u8ba1\u65b9\u6cd5\u63d0\u51fa\u95ee\u9898\uff0c\u8fd9\u4e5f\u662f\u6bd4\u8f83\u5e38\u89c1\u60c5\u51b5\uff0c\u5c31\u662f\uff1a\u5e38\u5e38\u5ba1\u7a3f\u8005\u5bf9\u7edf\u8ba1\u65b9\u6cd5\u63d0\u51fa\u65b0\u5efa\u8bae\u548c\u4fee\u6539\u610f\u89c1\u3002\u8fd9\u4f4d\u5ba1\u7a3f\u8005\u8ba4\u4e3aBonferonni\u6821\u6b63\u8fc7\u4e8e\u4e25\u683c\uff0c\u5efa\u8bae\u91c7\u7528Benjamini-Hochberg\u65b9\u6cd5, \u5f53\u65f6\u6211\u4e5f\u4e0d\u61c2\u8fd9\u4e2aBenjamini-Hochberg\u6821\u6b63\uff0c\u5c31\u91cd\u65b0\u4e0a\u7f51\u67e5\u8d44\u6599\uff0c\u540c\u65f6\u5b66\u4e60\u4e86\u8fd9\u4e2a\u65b0\u7684\u65b9\u6cd5\u3002\u8bf4\u660e\uff1a\u6211\u7684\u5f88\u591a\u7edf\u8ba1\u65b9\u6cd5\u5c31\u662f\u901a\u8fc7\u8fd9\u79cd\u65b9\u5f0f\u5b66\u4e60\u548c\u638c\u63e1\u7684\u3002<\/span><\/p>\n![\"\"](\"http:\/\/www.ithenticate.com.cn\/news\/wp-content\/uploads\/2017\/02\/2017022808440487-1-1.jpg\")
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