Prevalence of liver disease in veterans with bipolar disorder or schizophrenia

Objective

To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder.

Methods

A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis.

Results

Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27).

Conclusions

This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis.     

住院双相障碍与精神分裂症患者自知力水平的保护性因素

目的 探讨住院双相障碍与精神分裂症患者自知力水平及其保护性因素。方法 在广州市4家精神科住院部连续入组符合《国际疾病分类（第10版）》（ICD-10）双相障碍或精神分裂症诊断标准的患者465例。采用自编人口学及临床特征问卷、自知力与治疗态度问卷（ITAQ）进行调查,比较不同自知力水平患者的人口学和临床特征,采用两分类Logistic回归分析探讨自知力的保护因素。结果 年龄小（OR=0.977）、男性（OR=1.705）、曾经结婚或同居（OR=1.677）、诊断为双相障碍（OR=2.185）、最近一个月有悲观厌世（OR=2.663）、每天睡眠时间≥7小时（OR=1.620）、每周运动1~2次（OR=1.770）是住院双相障碍和精神分裂症患者自知力的保护因素。结论 住院双相障碍和精神分裂症患者自知力水平与多种人口学特征及临床特征相关。     

Influence of TPH2 variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia

The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within the tryptophan hydroxylase 2 gene (TPH2) could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants, mood stabilizers and antipsychotics, respectively. One hundred forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for six TPH2 SNPs (rs4570625, rs10748185, rs11179027, rs1386498, rs4469933, and rs17110747). Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale and Positive and Negative Syndrome Scale, for patients with MD, BD and schizophrenia, respectively were recorded. None of the SNPs under investigation were associated with MD, BD and schizophrenia. However, in patients with MD, the rs4570625-rs10748185 G-A haplotype was significantly associated with higher endpoint MADRS severity, though not with response. Our results suggest that TPH2 variants neither have a major role in MD, BD and schizophrenia nor in response to treatments.     

Metacognition in psychosis: Comparison of schizophrenia with bipolar disorder

While deficits in metacognition have been observed in schizophrenia (SZ), it is less clear whether these are specific to the disorder. Accordingly, this study compared metacognitive abilities of patients with schizophrenia and bipolar disorder (BD) and examined the degree to which neurocognition contributed to metacognitive deficits in both groups. Participants were 30 patients with SZ and 30 with BD. Metacognitive capacity was measured using the Metacognition Assessment Scale Abbreviated (MAS-A). This scale comprises four domains: self-reflectivity, understanding others? minds, decentration and mastery. Verbal memory, executive functioning and symptoms were concurrently assessed. Group comparisons revealed that SZ patients had greater deficits in metacognitive self-reflectivity, which correctly classified 85.2% of patients with SZ in a logistic regression. Self-reflectivity and understanding others? minds were related to verbal memory and executive functioning in the SZ group, but not in the BD group. Furthermore, greater positive and general psychotic symptoms were associated with poorer metacognition in SZ. Results suggest SZ involves unique deficits in the ability to self-reflect and that these deficits may be uniquely linked with neurocognition.     

Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior

Bipolar disorder (BD) is a severe psychiatric illness characterized by the occurrence of elevated mood alternating with depressive episodes, having a estimated lifetime prevalence of 0.4-1.6% using DSM-IV criteria. Disturbances of the central serotonergic system has been associated with the pathophysiology of affective disorders and suicidal behavior. Tryptophan hydroxylase 2 (TPH2) which is a rate limiting enzyme in the serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. Our sample consisted of 527 subjects (303 diagnosed with bipolar disorder and 224 healthy controls) which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the whole gene of the human TPH2. Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview^®. Single markers, genotype and haplotype association analysis did not show significant genetic association with bipolar disorder or suicidal behavior. Our findings do not support the association between diagnosis of BD or suicidal behavior and TPH2 polymorphisms.     

伴自杀未遂双相障碍患者的血清脑源性神经营养因子水平

目的 分析伴自杀未遂的双相障碍（BD）患者与不伴自杀未遂患者及健康人群间血清BDNF水平的差异,探讨BDNF在预防BD患者自杀中的作用.方法 采用DSM-IV轴Ⅰ障碍用临床定式检查（患者版）（SCID-I/P）对临床诊断为心境障碍的患者进行评佑.纳入111例BD患者（26例有自杀未遂史）及41例健康对照.使用汉密尔顿抑郁量表（HAMD-17）及杨氏躁狂量表（YMRS）评估患者症状严重程度;使用酶联免疫吸附测定法测定所有研究对象的血清BDNF水平.结果 伴自杀未遂的BD患者血清BDNF水平（13.8±7.4） ng/ml显著低于无自杀未遂患者（18.7±11.9） ng/ml及健康对照组（26.0±12.9）ng/ml（F=9.371,P＜0.01）;伴自杀未遂的BD患者抑郁发作次数显著多于不伴自杀未遂患者,在控制抑郁发作次数后,两组间血清BDNF水平差异消失（P=0.236）;伴自杀未遂的BD患者血清BDNF水平和抑郁发作次数有相关性的倾向（r=-0.388,P=0.068）,与HAMD-17得分呈负相关（r=-0.585,P＜0.01）.结论 本研究提示BDNF在BD及BD患者自杀未遂的病理生理机制中起重要作用;伴自杀未遂的BD患者血清BDNF水平可能与抑郁发作次数、抑郁严重程度相关;通过有效治疗来提高BDNF水平可能通过减少抑郁发作次数,降低抑郁严重程度来降低自杀风险.     

Pain conditions among veterans with schizophrenia or bipolar disorder

Objective

The purpose of this study was to assess the rates of chronic, noncancer pain conditions in patients with schizophrenia or bipolar disorder within the Veterans Health Administration (VHA) System.

Method

This cross-sectional study used administrative data extracted from VHA treatment records of all individuals receiving VHA services in fiscal year 2008 (N= 5,195,551). The associations between severe psychiatric disorders (schizophrenia and bipolar disorder) and chronic pain (arthritis, back pain, chronic pain, migraine, headache, psychogenic and neuropathic) were evaluated using a series of logistic regression analyses.

Results

Veterans with schizophrenia [odds ratio (OR)=1.21] and bipolar disorder (OR=2.17) were significantly more likely to have chronic pain overall relative to veterans without these psychiatric conditions. These associations were slightly lower than for the association between depression and pain in this sample (OR=2.61). The highest associations between specific psychiatric diagnosis and pain condition were found with chronic pain, headache and psychogenic pain.

Conclusions

Noncancer pain conditions occur in elevated rates among patients with schizophrenia and bipolar disorder. Future research could further examine possible barriers to adequate pain treatment among people with serious mental illness, as well as the extent to which chronic pain might impact mental health recovery.     

Childhood traumas in euthymic bipolar disorder patients in Eastern Turkey and its relations with suicide risk and aggression

Abstract

Purpose: The aim of this study was to determine the relationship between childhood trauma and aggression-suicidal behavior in patients with bipolar disorder.

Material and Methods: A total of 112 outpatients diagnosed with bipolar disorder in remission in the province of Siirt on the east coast of Turkey were included in this study carried out between January and June 2018. Personal Information Form, Childhood Trauma Questionnaire (CTQ), Buss–Perry Aggression Scale (BPAS) and Suicide Probability Scale (SPS) were used for data acquisition.

Results: It was determined that patients with bipolar disorder have 89.3% of physical neglect, 74.1% of emotional neglect, 75.9% of physical abuse, 79.5% of emotional abuse and 40.2% of sexual abuse. The mean score of CTQ was 66.8?±?19.2, the total score of BPAS was 94.6?±?28.8 and the total score of SPS was 85.3?±?17.9. A statistically significant and positive correlation was determined between CTQ, BPAS and SPS (p?<?0.05).

There was a weak and positive relationship between BPAS, CTQ (r?=?0.325**; p?<?0.05) and subscales of CTQ which are emotional abuse (r?=?0.350**; p?<?0.05), physical abuse (r?=?0.354**; p?<?0.01), physical neglect (r?=?0.313**; p?<?0.01) and emotional neglect (r?=?0.316**; p?<?0.01). A statistically significant difference was observed between the regular use of drugs, violence against others and total score of CTQ, BPAS and SPS (p?<?0.05).

Conclusion: It is suggested that patients diagnosed with bipolar disorder should be evaluated with regards to childhood trauma history by taking into consideration sociodemographic characteristics and psychiatric support in order to prevent their aggression and suicide attempts.     

Differences in metacognitive beliefs among patients with bipolar disorder with or without previous suicide attempts

Abstract

Purpose: The aim of this study is to compare differences in metacognitive beliefs between patients with bipolar disorder type I (BPDI) with previous suicide attempts (BPDI+), those without suicide attempts (BPDI?), and a control group. It also discusses the relationship between metacognitive beliefs and suicidal behavioral parameters.

Materials and methods: The study included 72 BPDI+ and 73 BPDI? euthymic patients and 86 healthy age- and gender-matched individuals. All participants completed a sociodemographic data form, the Beck Depression Inventory, Metacognition Questionnaire-30 (MCQ-30), Suicide Behaviors Questionnaire, and Structured Clinical Interview for DSM-IV Axis I. In addition, the Young Mania Rating Scale was used for the patient groups.

Results: Both the BPDI+ and BPDI? patients had higher MCQ-30 scores than the control group (p?<?.01). Scores for the ‘need to control thoughts’ subscale were higher in the BPDI+ group than in the BPDI? group and were also higher in both the BPDI+ and BPDI? groups compared to the control group (p?<?.01). In addition, the ‘cognitive self-consciousness’ sub-scores of the BPDI? group were higher than those of the BPDI+ and the control group.

Conclusion: The scores of ‘cognitive self-consciousness’ and ‘need to control thoughts’ vary across BPDI+ and BPDI? patients. It seems important to consider metacognitive beliefs regarding ‘need to control thoughts’ and ‘cognitive self-consciousness’ in terms of suicide prevention.     

Improvements in metabolic abnormalities among overweight schizophrenia and bipolar disorder patients

PurposeAs weight-gain and metabolic abnormalities during treatment with psychotropic drugs are of great concern, we evaluated effects of psycho-education and medical monitoring on metabolic changes among severely mentally ill patients.Materials and methodsDuring repeated, systematic psycho-education about general health among 66 consecutive patients diagnosed with DSM-IV-TR schizophrenia (n = 33) or type-I bipolar disorder (n = 33), we evaluated (at intake 1, 2, 3, and 6 months) clinical psychiatric status, treatments and doses, recorded physiological parameters, and assessed attitudes about medication.ResultsAt intake, patients with schizophrenia vs bipolar disorder were receiving 3–7 times more psychotropic medication, with 14% higher initial body-mass index (BMI: 29.1 vs 25.6 kg/m2), 12 times more obesity, and significantly higher serum lipid concentrations. During 6-months follow-up, among bipolar disorder patients, polytherapy and serum lipid concentrations declined more than among schizophrenia patients (e.g., total cholesterol + triglycerides, by 3.21 vs 1.75%/month). BMI remained stable. Declining lipid levels were associated with older age, bipolar disorder, being unemployed, higher antipsychotic doses, and lower initial BPRS scores (all P ≤ 0.001).ConclusionsPsychotropic treatments were more complex, and metabolic measures more abnormal among bipolar disorder than schizophrenia patients. Intensive psycho-education, clinical monitoring, and encouragement of weight-control for six months were associated with improvements in metabolic measures (but not to BMI), and more realistic attitudes about medication.     

Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics

There is accumulating evidence for an increased prevalence of metabolic syndrome (MetS) in bipolar patients, which is comparable to the prevalence of MetS in patients with schizophrenia. Hyperhomocysteinaemia has emerged as an independent and graded risk factor for the development of cardiovascular disease (CVD), which is, at the same time, the primary clinical outcome of MetS. The aim of this study was to ascertain if the presence of MetS was associated with hyperhomocysteinaemia in patients with bipolar disorder (N = 36) and schizophrenia (N = 46) treated with second-generation antipsychotics (SGA). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria and the cut-off point for hyperhomocysteinaemia was set up at 15 μmol l^-1. Results of the study indicated that the presence of the MetS is statistically significantly associated with the elevated serum homocysteine in all participants. As hyperhomocysteinaemia has emerged as an independent risk factor for psychiatric disorder and CVD, it could be useful to include fasting homocysteine serum determination in the diagnostic panels of psychiatric patients to obtain a better assessment of their metabolic risk profile.     

Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia.

BACKGROUND: Growing evidence indicates that the entorhinal cortex (ECx) might be affected in schizophrenia (SZ) and bipolar disorder (BD). To test whether distinct interneuronal subpopulations might be altered, numbers of parvalbumin-immunoreactive (PVB-IR) neurons were measured in the ECx of BD and SZ subjects. These neurons play a pivotal role within ECx intrinsic circuits. METHODS: Numbers, numerical density, and soma size of PVB-IR neurons were measured in the ECx of normal control (n = 16), BD (n = 10), and SZ (n = 10) subjects. The volume of the ECx was measured in Nissl-stained sections. RESULTS: In BD, decreases of total numbers (p = .02) and numerical densities (p = .01) of PVB-IR neurons were detected in the ECx. Within distinct subregions, reductions were detected in the superficial layers of the lateral (p = .02), intermediate (p = .04), and caudal (p = .01) ECx. In SZ, total numbers and numerical densities were not altered. A reduction of soma size was present in the intermediate ECx (p = .01). Volume was unaffected in either disorder. CONCLUSIONS: In BD, a decrease of PVB-IR neurons may alter intrinsic inhibitory networks within the superficial layers of the ECx. The likely consequence is a disruption of integration and transfer of information from the cerebral cortex to the hippocampus.     

Risk of suicide attempt and suicide death in patients treated for bipolar disorder

OBJECTIVES: To evaluate demographic and clinical predictors of suicide attempt and suicide death in a population-based sample of people treated for bipolar disorder (BD). METHODS: Computerized records were used to identify 32,360 individuals treated for BD at two large prepaid health plans. Suicide attempts were identified using computerized records of outpatient visit diagnoses and hospital discharge diagnoses. Suicide deaths were identified using state death certificate data. RESULTS: Overall event rates were 1.06 per 1,000 person-years for suicide death, 5.6 per 1,000 person-years for suicide attempt leading to hospitalization, and 13.9 per 1,000 person-years for suicide attempt not leading to hospitalization. Men had a significantly lower rate of suicide attempt [hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.56-0.83] but a higher rate of suicide death (HR 2.70, 95% CI 1.69-4.31). Suicide attempts were significantly more frequent among younger patients, but suicide deaths did not vary significantly by age. Substance use comorbidity was significantly related to risk of suicide attempt (HR 2.53, 95% CI 2.07-3.09) but not to risk of suicide death (HR 1.02, 95% CI 0.54-1.93). Comorbid anxiety disorder was associated with significantly higher risk of both suicide attempt (HR 1.40, 95% CI 1.14-1.72) and suicide death (HR 1.81, 95% CI 1.09-2.99). CONCLUSIONS: Among people treated for BD, risk of suicide death is significantly related to male sex and comorbid anxiety disorder. The predictors of suicide death differ markedly from predictors of suicide attempt.     

Insights into myelin dysfunction in schizophrenia and bipolar disorder

Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.     

Specific executive/attentional deficits in patients with schizophrenia or bipolar disorder who have a positive family history of psychosis

Neurocognitive impairments are well documented in patients with schizophrenia and their healthy first-degree biological relatives. Less is known about neuropsychological performance in bipolar disorders, but some studies indicate that, compared to schizophrenia, bipolar disorder displays a similar profile pattern with less severe deficits. The genetic and environmental contributions to the development of neurocognitive deficits are also unclear. This study explored the effect of a family history (FH) of psychotic disorders in first-degree relatives on a variety of cognitive domains (abstraction and flexibility, verbal fluency, verbal memory, motor activity and visual-motor processing/attention) in 30 patients with schizophrenia, and 24 type I bipolar patients. After adjusting the results for age, gender, education level and pre-morbid intelligence, patients with schizophrenia or bipolar disorder with positive FH (n=18) performed significantly worse than patients with negative FH (n=36) on the visual-motor processing/attention domain. These findings were independent of the specific diagnosis. Moreover, when logistic regression analysis was performed, poor Digit Symbol performance was the only predictor of belonging to the positive FH group. Our results are compatible with the existence of some common genetic factors between the illnesses, as well as the involvement of identical, or at least similar, disordered brain systems in both disorders. These findings are discussed within the context of the continuum model of psychosis.     

Reduced number of peripheral natural killer cells in schizophrenia but not in bipolar disorder

Overwhelming evidence indicates that subthreshold inflammatory state might be implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD). It has been reported that both groups of patients might be characterized by abnormal lymphocyte counts. However, little is known about alterations in lymphocyte proportions that may differentiate SCZ and BPD patients. Therefore, in this study we investigated blood cell proportions quantified by means of microarray expression deconvolution using publicly available data from SCZ and BPD patients. We found significantly lower counts of natural killer (NK) cells in drug-naïve and medicated SCZ patients compared to healthy controls across all datasets. In one dataset from SCZ patients, there were no significant differences in the number of NK cells between acutely relapsed and remitted SCZ patients. No significant difference in the number of NK cells between BPD patients and healthy controls was observed in all datasets. Our results indicate that SCZ patients, but not BPD patients, might be characterized by reduced counts of NK cells. Future studies looking at lymphocyte counts in SCZ should combine the analysis of data obtained using computational deconvolution and flow cytometry techniques.     

A comparison of neuropsychological dysfunction in first-episode psychosis patients with unipolar depression, bipolar disorder, and schizophrenia

The severity and profile of cognitive dysfunction in first episode schizophrenia and psychotic affective disorders were compared before and after antipsychotic treatment. Parallel recruitment of consecutively admitted study-eligible first-episode psychotic patients (30 schizophrenia, 22 bipolar with psychosis, and 21 psychotic depression) reduced confounds of acute and chronic disease/medication effects as well as differential treatment and course. Patient groups completed a neuropsychological battery and were demographically similar to healthy controls (n = 41) studied in parallel. Prior to treatment, schizophrenia patients displayed significant deficits in all cognitive domains. The two psychotic affective groups were also impaired overall, generally performing intermediate between the schizophrenia and healthy comparison groups. No profile differences in neuropsychological deficits were observed across patient groups. Following 6 weeks of treatment, no patient group improved more than practice effects seen in healthy individuals, and level of performance improvement was similar for affective psychosis and schizophrenia groups. Although less severe in psychotic affective disorders, similar profiles of generalized neuropsychological deficits were observed across patient groups. Recovery of cognitive function after clinical stabilization was similar in mood disorders and schizophrenia. To the extent that these findings are generalizable, neuropsychological deficits in psychotic affective disorders, like schizophrenia, may be trait-like deficits with persistent functional implications.     

伴非典型特征的抑郁症患者自杀未遂的危险因素分析

目的探讨伴非典型特征抑郁症患者自杀未遂的社会人口学及临床特征方面危险因素。方法来自全国13个中心的1172例抑郁症患者,纳入其中179例伴非典型特征患者,依据简明国际神经精神访谈(the Mini International Neuropsychiatric Interview,MINI)5.0中文版自杀模块的访谈结果,分为自杀未遂组和无自杀未遂组,通过多因素logistic回归分析伴非典型特征的抑郁症患者在性别、年龄等社会人口学资料及伴焦虑症状、伴精神病性症状等临床特征方面可能与自杀未遂相关的危险因素。结果伴非典型特征抑郁症患者自杀未遂的发生率为23.5%(42/179)。与无自杀未遂组患者相比,自杀未遂组患者更多伴有自杀观念、产后起病,更常使用抗抑郁剂以外的其他药物治疗(如抗精神病药、情感稳定剂及苯二氮类药)(均P0.05)。多因素logistic回归分析显示,既往住院次数(OR=1.730,95%CI:1.093~2.740)和自杀观念(OR=3.899,95%CI:1.506~10.092)与伴非典型特征的抑郁症患者发生自杀未遂相关(均P0.05)。结论既往住院次数多及伴有自杀观念是伴非典型特征抑郁症患者自杀未遂的主要危险因素。