双相障碍抑郁发作及单相抑郁症患者血清T3、T4、TSH和BDNF水平的相关性分析

目的:分析双相障碍抑郁发作及单相抑郁症患者与血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、甲状腺激素(TSH)和脑源性神经营养因子(BDNF)水平的相关性。方法:选取2017年12月～2019年12月我院收治的120例抑郁症患者为研究对象,按照病情不同分为双相障碍抑郁发作组(n=50)、单相抑郁症组(n=70),同时选取同期于本院进行体检的30例健康者作为对照组,检测血清T3、T4、TSH和BDNF水平,并进行汉密尔顿抑郁(HAMD)量表评分,分析血清T3、T4、TSH和BDNF水平的相关性。结果:双相障碍抑郁发作组起病年龄低于单相抑郁症组(P0.05);治疗前双相障碍抑郁发作组和单相抑郁症组血清T3水平高于对照组,TSH、BDNF水平低于对照组(P0.05),双相障碍抑郁发作组血清T4水平高于对照组,单相抑郁症组和对照组血清T4水平比较差异无统计学意义(P0.05),双相障碍抑郁发作组血清T4水平高于单相抑郁症组,TSH、BDNF水平低于单相抑郁症组(P0.05);治疗后双相障碍抑郁发作组和单相抑郁症组血清T4水平低于对照组,双相障碍抑郁发作组血清T4水平低于单相抑郁症组(P0.05),且三组血清T3、TSH、BDNF水平比较差异无统计学意义(P0.05);治疗后双相障碍抑郁发作组认知障碍因子评分低于单相抑郁症组(P0.05);Spearman相关分析显示,血清T3、T4、TSH水平和HAMD评分与BDNF呈负相关,TSH水平与BDNF呈正相关(P0.05)。结论:抑郁症患者血清T3、T4、TSH和BDNF水平存在异常,可作为判断双相障碍抑郁发作及单相抑郁症的指标。     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

I. The 24-hour profile of prolactin in depression

The 24-hour profile of plasma PRL was studied in 10 patients with unipolar depression and 8 patients with bipolar depression and compared to 18 control profiles obtained in healthy subjects. Alterations in the basal PRL secretion as well as the characteristics of the 24-hour rhythm were found in all patients but differed strikingly according to the type of depressive illness. The basal PRL level was elevated in unipolars, mainly as a result of increased secretion during wakefulness, and lowered in bipolars because of a lack or reduction of sleep-associated elevation. The nocturnal rise of PRL was maintained in unipolars but absent in 75% of the bipolar subjects. The variability of PRL levels around the 24-hour mean appeared to be reduced in both types of affective illness. These abnormalities in the 24-hour profile of PRL could serve as a biological marker of sub-types of depression.     

The genetics of affective disorder and genetic counseling

Abstract

Affective disorders—depression and mania—occurring with no preexisting psychiatric condition, severe physical illness, or recent personal loss can be divided into unipolar (depression only) and bipolar (both manic and depressive episodes) disorders. Bipolar illness is transmitted in some families as an X‐linked dominant factor. In other families, X‐linked transmission does not occur. Hence, bipolar illness may be similar to retinitis pigmentosa. This makes some types of genetic counseling difficult to apply to bipolar families. There is no evidence that unipolar depressive illness is transmitted by an X‐linked factor. Family studies indicate that there might be more than one type of unipolar illness. Limited prediction of risk of depression and other psychiatric conditions in other family members can be based on family studies which show that alcoholism and personality disorder occur frequently in families of early onset depressives but much less frequently in families of late onset depressives (age 40 or older).     

Advanced melatonin onset relative to sleep in women with unmedicated major depressive disorder

ABSTRACT

Studies on circadian timing in depression have produced variable results, with some investigations suggesting phase advances and others phase delays. This variability may be attributable to differences in participant diagnosis, medication use, and methodology between studies. This study examined circadian timing in a sample of unmedicated women with and without unipolar major depressive disorder. Participants were aged 18–28 years, had no comorbid medical conditions, and were not taking medications. Eight women were experiencing a major depressive episode, nine had previously experienced an episode, and 31 were control participants with no history of mental illness. Following at least one week of actigraphic sleep monitoring, timing of salivary dim light melatonin onset (DLMO) was assessed in light of <1 lux. In currently depressed participants, melatonin onset occurred significantly earlier relative to sleep than in controls, with a large effect size. Earlier melatonin onset relative to sleep was also correlated with poorer mood for all participants. Our results indicate that during a unipolar major depressive episode, endogenous circadian phase is advanced relative to sleep time. This is consistent with the early-morning awakenings often seen in depression. Circadian misalignment may represent a precipitating or perpetuating factor that could be targeted for personalized treatment of major depression.     

Blood groups and affective disorders

Frequencies of ABO, Rh, MNSs, P, Kell, Lewis and Duffy blood groups were studied in a total of 219 patients with affective disorders. The patients were classified into four groups: (1) bipolar (manic-depressive) psychosis; (2) unipolar recurrent depressive psychosis; (3) nonpsychotic 'reactive' depression, and (4) 'unclassifiable'. The following statistically significant results were found: an increased frequency of the blood group factor B among psychotic (bipolar and unipolar) patients compared to nonpsychotic patients, a decreased frequency of the SS phenotype in the unclassifiable group and an increased frequency of the K(+) phenotype among the nonpsychotic patients. Previous results concerning differences between bipolar and unipolar patients with respect to the A and O blood types were not confirmed in this investigation.     

Daily rest-activity patterns in the bipolar phenotype: A controlled actigraphy study

This study assessed daily rest-activity patterns in euthymic, medication-naïve bipolar phenotype individuals. The Mood Disorder Questionnaire was used to identify 19 bipolar phenotype individuals and 21 controls. Participants wore an Actiwatch-L for 2 weeks to assess their sleep behaviour and circadian rest-activity rhythmicity. Bipolar phenotype individuals had increased movement during sleep, as assessed by the fragmentation index, greater activity levels during their least active 5?h (2 am–7 am), and lower circadian relative amplitude compared to controls. Higher activity levels during sleep affecting circadian amplitude in young adults with the bipolar phenotype may be associated with vulnerability for developing mood disorder.     

Circadian phase variation in bipolar I disorder

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n=75), unscreened controls (n=349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n=81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.     

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders,bipolar disorder and major depressive disorder: a systematic review and meta‐analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = ?3.6, p = 0.0003, r² = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.     

A critical analysis of data presented in eight studies favouring X-linkage of bipolar illness with special emphasis on formal genetic aspects

High lod scores were obtained in several X-linkage studies of bipolar illness under the assumption that a subgroup of manic depression follows an X-linked dominant mode of inheritance. We have previously shown that the segregation patterns do not substantiate this assumption. We now statistically address the lack of evidence for X-linked inheritance by sex-dependently analyzing segregation ratios and clinical data presented in eight positive X-linkage studies. Accordingly, affected males have significantly fewer offspring, a lower mean age and a higher bipolar to unipolar ratio than affected females. There are two possible explanations for these findings: either the X-linked subgroup of bipolar illness has unique features that have not been accounted for clinically, or (more probably) the pedigree structures could also (and might be more likely to) result from ascertaining kindreds following autosomal or multifactorial inheritance only, with exclusion of kindreds encompassing male to male transmission.     

Circadian Phase Variation in Bipolar I Disorder

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness–eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n=75), unscreened controls (n=349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n=81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi‐modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the ‘evening’ range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.     

Differences in hypothyroidism between lithium-free and -treated patients with bipolar disorders

The majority of the previous studies of thyroid abnormalities in bipolar patients was conducted in populations containing various proportions of lithium-treated subjects. In the present study, we sought to determine whether there exist differences in hypothyroid profile between lithium-free and -treated bipolar patients. Bipolar patients never treated with lithium and carbamazepine (n=78) and those currently in lithium therapy (n=53) were included in this study. Serum concentrations of total thyroxine (T(4)), total triiodothyronine (T(3)), and thyroid-stimulating hormone (TSH) were compared between lithium-free and -treated patients. The rate of hypothyroidism in lithium-free patients was significantly lower than those treated with lithium (6.3%-10.8% vs. 28.0%-32.1%). Significant changes in the three thyroid indices indicative of hypothyroidism were consistently associated with longer illness duration in lithium-free manic patients, but with greater severity of mania and more mood episodes in their lithium-treated counterparts. In lithium-free depressed patients, more episodes were associated with lower T(4) levels; whereas in their lithium-treated counterparts, longer illness duration was associated with higher TSH levels and females with lower T(3) levels. These results suggest that bipolar patients with and without lithium exposure differ in prevalence and association of hypothyroidism and may have different response to thyroid hormone therapy.     

Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia,Unipolar Depression or Bipolar Disorder

The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9–22.3 % for schizophrenia, 13.9–26.0 % for unipolar depression, 10.8–27.6 % for bipolar disorder, 12.2–28.5 % for bipolar depression, and 11.4–24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = ? 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = ? 0.21, p < 0.001), unipolar depression (r = ? 0.23, p < 0.001), bipolar depression (r = ? 0.25, p = 0.002) and bipolar disorder (r = ? 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.     

Unipolar and bipolar electrogram characteristics of recurrent cases of idiopathic ventricular arrhythmias undergoing repeat catheter ablation

IntroductionActivation mapping guided catheter ablation (CA) of ventricular arrhythmias (VAs) is limited in some cases when it is only relied on bipolar electrogram (EGM). We hypothesized that activation mapping with use of combined bipolar and unipolar EGM facilitates to identify the focal origin of VAs and results in reduction of recurrence rate of CA of VAs.MethodsWe analyzed the data of patients undergoing repeat ablations for idiopathic out-flow tract VAs. The EGM of the 1 st and 2 nd ablations were compared for earliest local activation time (LAT), presence of discrete potentials, and polarity reversal, unipolar potential morphology (QS or non-QS), potential amplitude and activation slope.ResultsThirty-seven patients were included. The Local activation time was significantly earlier in the 2nd ablation as compared to the 1st procedure (36.90 msec vs 31.85 msec, P < 0.01). The incidence of discrete potentials and polarity reversal were similar in both procedures (51% vs 57%, P = 0.8 and 62% in both the occasions, respectively). The unipolar voltage was similar in both occasions (6.94 mV vs 7.22 mV in repeat ablations, P = 0.7). The recurrence rate (5.7%) was significantly lower with routine use of combined unipolar and bipolar EGMs, as compared to the use of bipolar EGM alone (16.7%)ConclusionsUse of both bipolar and unipolar electrograms helps in better delineation of the sites of earliest activation for effective ablation of VAs. Use of unipolar electrograms in addition to bipolar electrograms is associated with lower long term recurrence rate.     

Clinical correlates of chronotypes in young persons with mental disorders

While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness–eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness–eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne–Östberg Morningness–Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of “eveningness”) in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of “moderate evening” types, with a similar trend for the psychosis group. The proportion of “extreme evening” types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger “eveningness” preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis.     

Effects of Age,Sex, Index Admission,and Predominant Polarity on the Seasonality of Acute Admissions For Bipolar Disorder: A Population-Based Study

Bipolar disorder seasonality has been documented previously, though information on the effect of demographic and clinical variables on seasonal patterns is scant. This study examined effects of age, sex, index admission, and predominant polarity on bipolar disorder seasonality in a nationwide population. An inpatient cohort admitted to hospital exclusively for mental illness was derived from the Taiwan National Health Insurance Research Database for 2002–2007. The authors identified 9619 inpatients with bipolar disorder, who had generated 15 078 acute admission records. An empirical mode decomposition method was used to identify seasonal oscillations in bipolar admission data, and regression and cross-correlation analyses were used to quantify the degree and timing of bipolar admission seasonality. Results for seasonality timing found that manic or mixed episodes peak in spring or summer, and depressive episodes peak in winter. Analysis for degree of seasonality revealed that (1) the polarity of patients' index admission predicted the seasonality of relapse admissions; (2) seasonality was significant in female admissions for depressive episodes and in male admissions for manic episodes; (3) young adults displayed a higher degree of seasonality for acute admissions than middle-aged adults; and (4) patients with predominantly depressive admissions displayed a higher degree of seasonality than patients with predominantly manic admissions. Demographic and clinical variables were found to affect the seasonality of acute admissions for bipolar disorders. These findings highlight the need for research on identification and management of seasonal features in bipolar patients. (Author correspondence: ccyang@physionet.org)     

Dissociated response of thyrotropin and prolactin to dopamine receptor blockade with domperidone in hypothyroid subjects.

To investigate the hypothesis of an altered hypothalamic dopaminergic activity in primary hypothyroidism, eight patients with hypothyroidism and seven normal subjects, all female, were studied. All of them were submitted to two tests: TRH stimulation and after the administration of dopamine receptor-blocking drug, Domperidone. The hypothyroid patients with basal TSH values less than or equal to 60 mU/L (4 cases--group 1) had lower PRL levels than the remaining 4 subjects with TSH greater than 60 mU/L (group 2) (p less than 0.001), despite all patients presenting the PRL levels within the normal range. A significant increase occurred for both TSH and PRL after the administration of TRH and Domperidone in normal as well as in the hypothyroid subjects, except for TSH in group 1 after the administration of Domperidone. The area under the curve for PRL response to THR was not different between the normal subjects and both hypothyroid groups, while that under the curve for TSH was greater in the hypothyroidism as a whole than in the normal subjects (p = 0.006) and between the hypothyroid groups, being greater in group 2 than in 1 (p less than 0.009). In relation to Domperidone, the area under the curve for TSH was significantly higher in group 2 when compared to the normal controls (p less than 0.001), while for PRL it was not different between hypothyroid groups in relation to normal controls and when groups I and II were compared. These results suggest that the hypothalamic dopamine activity is not altered in primary hypothyroidism and favor the small relevance of dopamine on the control of TSH secretion.     

Associations of Serum Cytokine Receptor Levels with Melancholia,Staging of Illness,Depressive and Manic Phases,and Severity of Depression in Bipolar Disorder

To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80 kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski’s stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.     

Gender Differences in Neuropsychological Performance across Psychotic Disorders – a Multi-Centre Population Based Case-Control Study

Background

Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.

Methods

Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.

Results

There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.

Conclusions

Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.