A personality-based latent class typology of outpatients with major depressive disorder: association with symptomatology, prescription pattern and social function.

BACKGROUND: While major depressive disorder (MDD) is considered to be a heterogeneous disorder, the nature of the heterogeneity remains unclear. Studies have attempted to classify patients with MDD using latent variable techniques, yet the empirical approaches to symptom-based subtyping of MDD have not provided conclusive evidence. Here we aimed to identify homogeneous classes of MDD based on personality traits, using a latent profile analysis. METHODS: We studied 238 outpatients with DSM-IV MDD recruited from our specialized depression outpatient clinic and assessed their dimensional personality traits with the Temperament and Character Inventory. Latent profile analysis was conducted with 7 dimensions of the Temperament and Character Inventory as indicators. Relationships of the identified classes with symptomatology, prescription pattern, and social function were then examined. RESULTS: The latent profile analysis indicated that a 3-class solution best fit the data. Of the sample, 46.2% was classified into a "neurotic" group characterized by high harm avoidance and low self-directedness; 30.3% into an "adaptive" group characterized by high self-directedness and cooperativeness; and 23.5% into a "socially-detached" group characterized by low reward dependence and cooperativeness and high self-transcendence. The 2 maladaptive groups, namely neurotic and socially-detached groups, demonstrated unique patterns of symptom expression, different classes of psychotropic medication use, and lower social functioning. LIMITATIONS: Generalizability of the findings was limited since our patients were recruited from the specialized depression outpatient clinic. CONCLUSIONS: Our personality-based latent profile analysis identified clinically meaningful 3 MDD groups that were markedly different in their personality profiles associated with distinct symptomatology and functioning.

24-h activity rhythm and sleep in depressed outpatients.

Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression.

Autistic-like traits in adult patients with mood disorders and schizophrenia.

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.

Personality in remitted major depressive disorder with single and recurrent episodes assessed with the Temperament and Character Inventory.

AIM: Previous studies consistently reported increased harm avoidance (HA) assessed with the Temperament and Character Inventory (TCI) in patients with major depressive disorder (MDD). However, such findings may have been related with depression severity and number of depressive episodes. The aims of the present study were twofold: to examine TCI personality profile in remitted MDD (DSM-IV) patients and to compare TCI personality between MDD patients with single episode (SGL-MDD) and those with recurrent episodes (REC-MDD) in order to elucidate personality profile associated with recurrence. METHODS: TCI was administered to 86 outpatients with remitted SGL-MDD (12 male and 17 female patients; mean age 43.2 ± 12.1 years) and REC-MDD (26 male and 31 female patients; 40.3 ± 11.6 years), and 529 healthy controls (225 men and 304 women; 43.4 ± 15.5 years), matched for age, sex and education years. Logistic regression analyses were performed in which single/recurrent episodes of depression were the dependent variable and age, sex, age of onset, family history of psychiatric disease and TCI scores were entered as possible predictors. RESULTS: The remitted MDD patients had significantly higher scores on HA (P < 0.001) and lower scores on self-directedness (P < 0.001), compared with the controls. HA (P = 0.03), its subscore, fatigability (P = 0.03), and family history of psychiatric disease were found to be positive predictors for recurrence. CONCLUSION: There are differences in personality profile between remitted MDD patients and controls, and between remitted REC-MDD and SGL-MDD patients, suggesting that they are trait markers. HA and fatigability might be useful to assess risk for recurrence of depression.

White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study.

AIM: The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. METHODS: Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. RESULTS: There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. CONCLUSION: Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD.

The common functional FKBP5 variant rs1360780 is associated with altered cognitive function in aged individuals.

The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 (FKBP5) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD). In the present study, we examined whether this SNP is associated with cognitive function in a non-clinical population. The full versions of the Wechsler Memory Scale-Revised and Wechsler Adult Intelligence Scale-Revised were administered to 742 and 627 Japanese individuals, respectively, followed by genotyping of rs1360780 by the TaqMan 5'-exonuclease allelic discrimination assay. For both cognitive tests, we found significantly poorer attention/concentration (working memory) in aged (>50 years old) individuals carrying the T allele compared with their counterparts. This finding accords with an altered HPA axis and vulnerability to stress-related psychiatric disorders.

Relationship between lifetime suicide attempts and schizotypal traits in patients with schizophrenia.

Patients with schizophrenia are at increased risk for suicide. Various risk factors for suicide have been reported in schizophrenia; however, few studies have examined the association between personality traits and suicidal behavior. We administered the Schizotypal Personality Questionnaire (SPQ) to 87 Japanese patients with schizophrenia (49 males; mean age 38.1 ± 10.6 years) with and without a history of suicide attempts (SA and nSA groups, respectively), and 322 controls (158 males; mean age 40.8 ± 13.9 years). As expected, an analysis of covariance (ANCOVA) controlling for age and sex showed that all SPQ indices (total SPQ score and all three factors, i.e., cognitive-perceptual, interpersonal, and disorganized) were significantly higher in patients with schizophrenia (SA+nSA groups), than controls (p<0.001 for all comparisons). Furthermore, there were significant differences in the total score and the interpersonal and disorganized factors between the SA and nSA groups (nSA

Characteristic distributions of regional cerebral blood flow changes in major depressive disorder patients: a pseudo-continuous arterial spin labeling (pCASL) study.

BACKGROUND: Most previous studies that examined regional cerebral blood flow (rCBF) abnormalities in major depressive disorder (MDD) required the injection of radioisotopes into subjects. Here by using magnetic resonance imaging (MRI) with the pseudo-continuous arterial spin labeling (pCASL) method which does not require radioisotopes, we examined rCBF in patients with MDD in comparison with that in patients with schizophrenia and healthy subjects, taking the regional cerebral gray matter volume into account. METHODS: Subjects were 27 patients with MDD, 42 with schizophrenia and 43 healthy volunteers who underwent 3-T MRI with pCASL. Obtained pCASL imaging data were subject to the voxel-by-voxel statistical analysis. RESULTS: There were significant reductions of rCBF in the right inferior prefrontal cortex and anterior cingulate cortices (ACCs) in the MDD patients compared with the healthy controls. When compared with the schizophrenic patients, the MDD patients showed lower rCBF in the subgenual ACC and higher rCBF in left occipital region. LIMITATION: The abnormalities of rCBF in MDD were known to reverse during symptom remission. Further study with follow-up period would bring the perception about the treatment response. CONCLUSION: The rCBF reduction in the subgenual region may be a specific functional abnormality to MDD patients, which may provide a biological marker for MDD. The MRI with pCASL method is a promising tool to detect rCBF abnormalities controlling for gray matter volume in psychiatric disorders.

Cognitive effects of the ANK3 risk variants in patients with bipolar disorder and healthy individuals.

BACKGROUND: Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals. METHODS: In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains. RESULTS: Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals. LIMITATIONS: The sample size of patients with bipolar disorder was small, and most of the patients were on psychotropic medication. CONCLUSIONS: These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder.

Psychological coping in depressed outpatients: association with cortisol response to the combined dexamethasone/CRH test.

BACKGROUND: Depression is associated with dysfunctional coping styles and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. Studies have shown that maladaptive coping strategies relate to abnormal HPA axis function; however, such a relationship has been under-studied in patients with depression. We aimed to examine whether dysfunctional coping styles in depression would be associated with abnormal cortisol reactivity. METHODS: Seventy-four outpatients with major depressive disorder and 133 age- and sex-matched healthy individuals were recruited. Coping was assessed by the Ways of Coping Checklist. Psychological distress was assessed by the Hopkins Symptom Checklist. Cortisol reactivity was measured by the combined dexamethasone/corticotropin-releasing hormone test. RESULTS: Compared to healthy individuals, depressed patients demonstrated significantly less use of problem-solving, positive reappraisal and social support coping styles and more use of self-blame and wishful thinking styles. Such a pattern of coping styles was significantly associated with patients' greater distress. Partial correlation analysis in patients, controlling for age and sex, revealed a significant correlation between more use of escape-avoidance coping and lower levels of reactive cortisol measures. A stepwise multiple regression analysis predicting cortisol reactivity from age, sex, distress, symptom severity and coping styles revealed that escape-avoidance coping was a significant predictor. LIMITATIONS: The neuroendocrine challenge test was administered only once, based on a simple test protocol. CONCLUSIONS: More use of escape-avoidance coping in depressed patients was associated with less cortisol reactivity. Our findings shed light on the heterogeneity of depression in terms of low and high levels of avoidance associated with exaggerated and blunted HPA axis reactivity, respectively.

Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults.

BACKGROUND: Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population. METHODS: Subjects were 599 healthy adults (166 males and 433 females; mean age 43.8 ± 15.5 years). The Wechsler Memory Scale-Revised (WMS-R) was administered to all participants to assess memory performance. Genotyping was performed for 6 selected tagging SNPs of PAH (rs1722387, rs3817446, rs1718301, rs2037639, rs10860936 and rs11111419). RESULTS: Analyses of covariance controlling for sex and education years, indicated a significant association between a SNP (rs2037639) and age-corrected verbal memory index of WMS-R (nominal p = 0.0013) which remained significant after correction for multiple testing ( p = 0.0013 < 0.0017 = 0.05/30tests). Individuals with the GG genotype showed a significantly lower mean verbal memory score, compared with those individuals carrying the AA/AG genotype (106.0 ± 16.0 vs. 111.7 ± 13.4; p = 0.00099). A haplotype block containing two markers of rs2037639 and rs10860936 was associated with verbal memory index (permutation global p = 0.0091). CONCLUSIONS: Our findings suggest that common genetic variations in PAH are associated with verbal memory in healthy adults. Unknown functional polymorphisms in PAH or those in other genes nearby might affect memory performance.