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Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia.

The apolipoprotein E (APOE) gene is associated with structural and functional brain changes. We have used multiscale entropy (MSE) analysis to detect changes in the complexity of resting blood oxygen level-dependent (BOLD) signals associated with aging and cognitive function. In this study, we further hypothesized that the APOE genotype may affect the complexity of spontaneous BOLD activity in younger and older adults, and such altered complexity may be associated with certain changes in functional connectivity. We conducted a resting-state functional magnetic resonance imaging experiment in a cohort of 100 younger adults (aged 20–39 years; mean 27.2 ± 4.3 years; male/female: 53/47) and 112 older adults (aged 60–79 years; mean 68.4 ± 6.5 years; male/female: 54/58), and applied voxelwise MSE analysis to assess the main effect of APOE genotype on resting-state BOLD complexity and connectivity. Although the main effect of APOE genotype on BOLD complexity was not observed in younger group, we observed that older APOE ɛ4 allele carriers had significant reductions in BOLD complexity in precuneus and posterior cingulate regions, relative to noncarriers. We also observed that reduced BOLD complexity in precuneus and posterior cingulate regions was associated with increased functional connectivity to the superior and inferior frontal gyrus in the older group. These results support the compensatory recruitment hypothesis in older APOE ɛ4 carriers, and confer the impact of the APOE genotype on the temporal dynamics of brain activity in older adults. Hum Brain Mapp 35:3238–3248, 2014. © 2013 Wiley Periodicals, Inc.

The cholinergic receptor, nicotinic, alpha 4 (CHRNA4) gene encodes the neuronal nicotinic acetylcholine receptor alpha-4 subunit. Recent research has shown that a variation in CHRNA4 (rs1044396) affects attention and negative emotionality in normal adults. To determine the link between CHRNA4 variation and cognitive function/depressed mood, this study conducted a genotype-phenotype correlation analysis between the common CHRNA4:rs1044396 variant and several baseline parameters of cognition and depressed mood in 192 elderly male subjects without major psychiatric disorders or dementia. Study findings identified a significant link between the CHRNA4:rs1044396 polymorphism and depression and loneliness in the aged. Compared to carriers of at least one T-allele, carriers of the homozygous C/C genotype described themselves as more depressed and lonely. This is the first evidence which may implicate CHRNA4 in depressed emotions in the elderly.

Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)-based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high-frequency coupling, an index of stable sleep, an increase in low-frequency coupling, an index of unstable sleep, and an increase in very-low-frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG-based cardiopulmonary coupling analysis may provide a simple, cost-efficient point-of-care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression.

The p75 neurotrophin receptor (p75NTR) is an essential component of neurotrophin system, and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to delineate the association between phenotype (MDD susceptibility and antidepressant response) and genotype (p75NTR common genetic variants) in a Chinese population. A total of 228 MDD patients and 402 unrelated controls were recruited. Subjects took selective serotonin reuptake inhibitors (SSRIs) and responders were defined as those with at least a 50% decrease in score of the Hamilton Rating Scale for Depression (HAM-D) from baseline. Five p75NTR polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single marker analysis. No significant association with MDD was discovered in single locus or haplotype analyses. With regard to the therapeutic outcome, however, one missense polymorphism (S250L) showed association in both genotype distribution (P = 0.039) and allele frequency (P = 0.012). Haplotype analysis also revealed that p75NTR TCT carriers had a more unfavorable response to therapy (P = 0.010). Our exploratory study has demonstrated the association between p75NTR and SSRI response for the first time, which may assist in individualized therapy for MDD patients in the future. © 2007 Wiley-Liss, Inc.

The anticipation phenomenon is an important aspect in several genetic disorders in which the age at onset (AAO) decreases and the severity of illness increases in successive generations. This phenomenon has been reported in several schizophrenic family studies, and expanded repeat mutations are implicated. In the present study, we investigate the anticipation phenomenon in Chinese schizophrenic families. We compare the AAO between two generations of 38 unilinear schizophrenic families. Intergenerational comparisons show that the AAO was significantly earlier in the offspring generation (mean AAO, 22.2 years) than that in the parental generation (mean AAO, 31.0 years) (P < 0.001). When only including the offspring generation who married, the AAO difference between the two generations was not significant (28.4 years vs 31.0 years, P = 0.151). Our findings suggest that a selection bias in the parental group might greatly impact the study of anticipation in schizophrenia. Other unavoidable biases associated with these analyses are discussed in the text.

Objectives: The correlation between anxiety and interstitial cystitis has, as best we know, not yet been reported on. The present study investigated the psychological profile, including anxiety and depression, of patients suffering from interstitial cystitis (IC). Methods: A total of 47 IC patients, all of whom met National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) criteria, plus a group of 31 age-matched, asymptomatic women received a structured interview on depression (Hamilton Rating Scale for Depression) and also on anxiety symptoms (Hamilton Rating Scale for Anxiety). IC patients also completed questionnaires relating to IC symptom severity, including urgency and frequency (visual analog scale) and O'Leary Sant index. Results: A total of 85% of our IC patients featured significant affective symptoms. The average depression scores were 16.6. Fifteen patients (31.9%) featured mild depressive symptoms, five (10.6%) had mild to moderate and 20 (42.6%) had moderate to severe depression symptoms. The mean anxiety score was 21.0, with 21 (44.7%), nine (19.1%) and 17 (36.2%) patients revealing mild, mild to moderate, and moderate to severe anxiety symptoms, respectively. Further, IC patients reported a significantly greater extent of depression and anxiety than was the case for controls. Pain scale and O'Leary Sant index were significantly correlated to anxiety and depression score. Conclusions: Most of our IC patients feature significant depression and anxiety. The extent of affective symptoms would appear to correlate well with IC symptom severity.

Variation in the number of tandem repeats of a 48 base pair (bp) unit was found in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the 48bp unit was shown to influence the binding of clozapine, which suggests that different alleles may function differently in vivo and affect the pathogenesis of schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis. There was no significant difference in genotypic or allelic distributions among the four groups. Significant differences in the frequencies of two- and seven-repeats alleles between the Chinese and Caucasians controls were noted. The present study did not support that a particular allele or genotype of the 48bp-repeat of DRD4 was associated with schizophrenia.

Apolipoprotein E (apoE) is the major brain apolipoprotein, and is related to the functional integrity of the central nervous system. It has been reported that the apoE genetic polymorphism is associated with several components of childhood and adolescent temperament. To study the effect of the presence of the apoE e4 allele on adult personality factors, tridimensional personality questionnaire (TPQ) scores were compared for e4 and non-e4 carriers in a sample population consisting of 135 young females. No significant differences were demonstrated comparing the scores for the two groups. Our findings suggest that the investigated apoE polymorphism does not play a major role in personality trait factors, as assessed by TPQ. © 2004 Wiley-Liss, Inc.

A significant increase of 267C allele of the 5-HT6 receptor gene has been reported in patients with Alzheimer's disease (AD). Because a deficit in serotonergic neurotransmission is involved in major depression, we tried to find out whether 267C allele is associated with depressive disorders in AD. A psychiatrist interviewed all AD patients and their caregivers for evidence of depression using a Chinese version of the Standard Clinical Interview for DSM-III-R. The difference in the 5-HT6 genotype or allele distributions between the AD patients with depressive disorders (n = 25) and those without (n = 120) was not significant.

Human personality traits are partially determined by genes. It has been suggested that the reward-dependence dimension assessed by the Tridimensional Personality Questionnaire (TPQ) is related to the central noradrenergic system. Our population-based association study tested the hypothesis that genetic variants of the adrenoceptor are associated with this personality trait. The α 1a - and the α 2a -adrenoceptor genotypes were determined for 198 healthy Han Chinese who had completed the TPQ. We found no significant differences for TPQ personality-factor scores, including reward dependence and its subscales, for subjects showing different adrenoceptor genotypes. Our negative findings suggest that polymorphisms of the α 1a adrenoceptor and of the promoter region of the α 2a -adrenoceptor have no major effect on the reward-dependence personality trait as assessed by TPQ.

Increased butyrylcholinesterase (BChE) activity has been reported to be associated with the formation of amyloid plaques and neurofibrillary tangles and may consequently be involved in the pathogenesis of Alzheimer disease (AD). Because the catalytic activity of BChE-K variant is reduced by one-third compared with non-variant, we speculated that BChE-K variant has a protective effect on AD. However, Lehmann et al. [1997] reported a synergistic effect between the genes for BChE-K variant and apolipoprotein E (ApoE) epsilon 4, which increases the risk for late onset AD. In the present study, we tested 89 Chinese AD patients and 101 Chinese controls and found no evidence of association between BCHE-K and AD of either early or late onset (age > 65 years). No evidence of a synergistic effect was found between the BCHE-K variant and APOE epsilon 4 in this study. Our data suggest that BChE-K variant has no modifying effect on the pathogenesis of AD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:167-169, 2000.

Nitric oxide synthase (NOS) has been implicated in the pathogenesis of Alzheimer disease (AD). To examine the role of the neuronal NOS (nNOS) gene in AD, patients (n = 139) and control subjects (n = 101) were genotyped for the nNOS dinucleotide polymorphism. No association was demonstrated for AD and this particular nNOS polymorphism.

The serotonergic system is implicated in the etiology of mood disorders. Among those most recently discovered serotonin receptors, the relative abundance of serotonin type 6 receptor (5-HT6) in the limbic area and the high affinity of some antidepressants to 5-HT6 receptors suggest that this receptor might be involved in the pathogenesis of mood disorders. In a population-based association study, we tested the hypothesis that the allelic variant (C267T) of the human 5-HT6 gene confers susceptibility to mood disorders. We genotyped the 5-HT6 receptor in 139 patients with mood disorders and 147 controls. The results demonstrated that there were no significant differences in genotype or allele frequencies between controls and all patients, or between controls and patients with bipolar disorders or major depression, separately. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:601–602, 1999. © 1999 Wiley-Liss, Inc.