Mood Disorder Subjects Research Articles

Factors associated with onset-age in major affective disorders.

Research findings on factors associated with onset-age (OA) with bipolar (BD) and major depressive disorders (MDD) have been inconsistent, but often indicate greater morbidity following early OA. We considered factors associated with OA in 1033 carefully evaluated, systematically followed mood disorder subjects with DSM-5 BD (n=505) or MDD (n=528), comparing rates of descriptive and clinical characteristics following early (age <18), intermediate (18-40), or later onset (≥40 years), as well as regressing selected measures versus OA. Exposure time (years ill) was matched among these subgroups. As hypothesized, many features were associated with early OA: familial psychiatric illness, including BD, greater maternal age, early sexual abuse, nondepressive first episodes, co-occurring ADHD, suicide attempts and violent suicidal behavior, abuse of alcohol or drugs, smoking, and unemployment. Other features increased consistently with later OA: %-time-depressed (in BD and MDD, women and men), as well as depressions/year and intake ratings of depression, educational levels, co-occurring medical disorders, rates of marriage and number of children. OA averaged 7.5 years earlier in BD versus MDD (30.7 vs. 38.2). Some OA-associated measures may reflect maturation. Associations with family history and suicidal risk with earlier OA were expected; increases of time-depressed in both BD and MDD with later OA were not. We conclude that associations of OA with later morbidity are complex and not unidirectional but may be clinically useful.

Physical exercise, depression, and anxiety in 2190 affective disorder subjects

BackgroundThis study evaluated associations of PE with symptomatic status in mood and anxiety disorder subjects, and considered many other associated factors so as to expand on comparable previous studies. MethodsConsenting adults at a mood disorder center were assessed for associations of PE frequency ([never, past only, ≤once/week] vs. regularly at 2–3- or >3-times/week) with standard psychometric measures of depression and anxiety symptoms, selected demographic, clinical factors, using bivariate and multivariate methods. ResultsOf 2190 subjects (58.8% women; mean age 42.6 years; 44.8% with major depressive, 40.6% bipolar, and 14.6% anxiety disorders), 22.5% currently engaged in regular PE. Such engagement was associated with lower morbidity ratings, youth, male sex, being unmarried, more education, higher socio-economic status (SES), less religious practice, less early abuse, younger age at illness onset and at intake, fewer years ill, lower BMI, fewer siblings, hyperthymic temperament, less time depressed before intake, and living at higher population density. Greater PE-frequency was associated with lower ratings of depression (but not anxiety), male sex, younger age, and lower BMI. Factors independently associated with PE in multivariate modeling ranked by significance: older age at intake ≥ lower BMI > more education > higher SES > male sex. LimitationsPE assessment did not include type, intensity or duration. Some information provided may be subject to recall bias, though it should not affect comparisons among subjects. ConclusionRegularly repeated PE again appeared to be beneficial for patients with depression or anxiety and should be included in their treatment interventions.

Overweight in mood disorders: Effects on morbidity and treatment response

ObjectiveAs it is not clear how body-mass index (BMI) may relate to diagnosis, symptom-severity, illness-course, and treatment-response among psychiatric patients, we related BMI to psychiatric diagnosis and to selected clinical and demographic factors in major affective disorder subjects. MethodsWe analyzed mean BMI levels vs. diagnosis, and evaluated selected risk factors for association with overweight and obesity among subjects with DSM-5 major affective disorders. ResultsIn 1884 subjects, BMI ranged from 23.4 kg/m2 with anxiety disorders to 27.6 with psychotic disorders, and averaged 24.1 among 1469 affective disorder subjects. Mood-disorder subjects with BMI ≥ 25 (overweight/obese) were more likely: men, older, married, with more children and siblings, less education, lower socioeconomic status, engaged less in physical exercise, smoked more, and lived in less densely populated areas. They also were more likely to have: BD than MDD, familial mood disorders, no co-occurring ADHD, higher serum triglyceride levels, more time depressed and less improvement in depression ratings with treatment. ConclusionsRisk of being overweight or obese was greatest with psychoses, least with anxiety, personality, and minor depressive disorders, and intermediate with major mood disorders. Several plausible risk factors for high BMI were identified in mood disorder subjects, including male sex and with BD > MDD. Striking were selectively greater prospective morbidity and decreased treatment-response for depression vs. mania with BMI ≥ 25.

Bipolar II disorder has the highest prevalence of seasonal affective disorder in early-onset mood disorders: Results from a prospective observational cohort study.

Many mood disorder patients experience seasonal changes in varying degrees. Studies on seasonality have shown that bipolar disorder has a higher prevalence rate in such patients; however, there is limited research on seasonality in early-onset mood disorder patients. This study estimated the prevalence of seasonality in early-onset mood disorder patients, and examined the association between seasonality and mood disorders. Early-onset mood disorder patients (n = 378; 138 major depressive disorder; 101 bipolar I disorder; 139 bipolar II disorder) of the Mood Disorder Cohort Research Consortium and healthy control subjects (n = 235) were assessed for seasonality with Seasonality Pattern Assessment Questionnaire (SPAQ). A higher global seasonality score, an overall seasonal impairment score, and the prevalence of seasonal affective disorder (SAD) and subsyndromal SAD showed that mood disorder subjects had higher seasonality than the healthy subjects. The former subject group had a significantly higher mean overall seasonal impairment score than the healthy subjects (p < .001); in particular, bipolar II disorder subjects had the highest prevalence of SAD, and the diagnosis of bipolar II disorder had significantly higher odds ratios for SAD when compared to major depression and bipolar I disorder (p < .05). Early-onset mood disorders, especially bipolar II disorder, were associated with high seasonality. A thorough assessment of seasonality in early-onset mood disorders may be warranted for more personalized treatment and proactive prevention of mood episodes.

Similarities of Aspects of Biological Rhythms between Major Depression and Bipolar II Disorder Compared to Bipolar I Disorder: A Finding from the Early-Onset Mood Disorder Cohort.

ObjectiveThe biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects. MethodsA total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation. ResultsThe mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I <BD II, p<0.001) and between BD I and MDD (BD I<MDD, p< 0.001) but no difference was observed between BD II and MDD. ConclusionBD II and MDD are similar to each other but different from BD I in biological rhythm patterns in early-onset mood disorder cases. Biological rhythm disturbances are similar for early-onset major depression and BD II.

EEG Microstates Temporal Dynamics Differentiate Individuals with Mood and Anxiety Disorders From Healthy Subjects.

Electroencephalography (EEG) measures the brain’s electrophysiological spatio-temporal activities with high temporal resolution. Multichannel and broadband analysis of EEG signals is referred to as EEG microstates (EEG-ms) and can characterize such dynamic neuronal activity. EEG-ms have gained much attention due to the increasing evidence of their association with mental activities and large-scale brain networks identified by functional magnetic resonance imaging (fMRI). Spatially independent EEG-ms are quasi-stationary topographies (e.g., stable, lasting a few dozen milliseconds) typically classified into four canonical classes (microstates A through D). They can be identified by clustering EEG signals around EEG global field power (GFP) maxima points. We examined the EEG-ms properties and the dynamics of cohorts of mood and anxiety (MA) disorders subjects (n = 61) and healthy controls (HCs; n = 52). In both groups, we found four distinct classes of EEG-ms (A through D), which did not differ among cohorts. This suggests a lack of significant structural cortical abnormalities among cohorts, which would otherwise affect the EEG-ms topographies. However, both cohorts’ brain network dynamics significantly varied, as reflected in EEG-ms properties. Compared to HC, the MA cohort features a lower transition probability between EEG-ms B and D and higher transition probability from A to D and from B to C, with a trend towards significance in the average duration of microstate C. Furthermore, we harnessed a recently introduced theoretical approach to analyze the temporal dependencies in EEG-ms. The results revealed that the transition matrices of MA group exhibit higher symmetrical and stationarity properties as compared to HC ones. In addition, we found an elevation in the temporal dependencies among microstates, especially in microstate B for the MA group. The determined alteration in EEG-ms temporal dependencies among the cohorts suggests that brain abnormalities in mood and anxiety disorders reflect aberrant neural dynamics and a temporal dwelling among ceratin brain states (i.e., mood and anxiety disorders subjects have a less dynamicity in switching between different brain states).

Anxious and suicidal behaviors among relatives are associated with suicide attempts and hospitalizations in mood disorder subjects

Anxious and suicidal behaviors among relatives are associated with suicide attempts and hospitalizations in mood disorder subjects

The Association Between Childhood Abuse and Neglect and Clinical Severity in Mood Disorders

The Association Between Childhood Abuse and Neglect and Clinical Severity in Mood Disorders

Anxious and Suicidal Behaviors Among Relatives Are Associated with Suicide Attempts and Hospitalizations in Mood Disorder Subjects

Anxious and Suicidal Behaviors Among Relatives Are Associated with Suicide Attempts and Hospitalizations in Mood Disorder Subjects

Comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar disorder in a specialized mood disorders outpatient clinic

BackgroundComorbidity between ADHD and Bipolar Disorder (BD) is associated with greater severity of BD. The current study aims at investigating, in a specialized mood disorders clinic, the percentage of comorbid ADHD–BD subjects and assessing the impact of ADHD on the severity of BD. MethodsOut of 539 mood disorders subjects, the medical records of 138 BD subjects were scrutinized in terms of their clinical and demographic characteristics, and their scores at the Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist were logged. Those positively scoring at the ASRS-v1.1 underwent clinical assessment by a senior psychiatrist specialized in ADHD. Comorbid ADHD–BD subjects were then compared with BD sufferers without ADHD. ResultsSixty-three (45.65%) of the participants were screened positive at the ASRS-v1.1. 49 were clinically assessed for the presence of ADHD. Only 27 (55%) received a diagnosis of ADHD. Comorbid ADHD–BD subjects were found to be younger at the onset of BD, showed higher numbers of depressive episodes, more anxiety and substance use disorders, more borderline personality traits and greater cyclothymic temperament. Comorbid BD–ADHD subjects reported more childhood emotional abuse. LimitationsSome subjects were unreachable and thus not clinically assessed for ADHD. ConclusionsMore than 20% of BD subjects were suffering from ADHD. The comorbidity of the two disorders was associated with worse outcomes, possibly resulting from stressful early-life events. More than 40% of the subjects who scored positively at the ASRS-v1.1 did not suffer from ADHD, which suggests that this scale should be used with caution in BD subjects.

The Neuroepigenetics of Suicide

The Neuroepigenetics of Suicide

Polygenic Risk and White Matter Integrity in Individuals at High Risk of Mood Disorder

Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterized by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured with diffusion tensor magnetic resonance imaging, that are also heritable. However, it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities might help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction. In the current study, we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n = 70) and comparison subjects (n = 62). Polygenic risk scores were calculated separately for BD and MDD on the basis of genome-wide association study data from the Psychiatric GWAS Consortia. We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster, with a peak in the right-sided superior longitudinal fasciculus. These findings suggest that the polygenic approach to examining brain imaging data might be a useful means of identifying traits linked to the genetic risk of mood disorders.

Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide

Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

Phenomenology of psychotic mood disorders: Lifetime and major depressive episode features

The nosological and clinical implications of psychotic features in the course of mood disorders have been widely debated. Currently, no specification exists for defining a subgroup of lifetime Psychotic Mood Disorder (PMD) patients. A total of 2178 patients were examined, including subjects with Bipolar Disorder (BP) type I (n=519) and II (n=207) and Major Depressive Disorder (n=1452). Patients were divided between PMD (n=645) and non-psychotic Mood Disorders (MD) (n=1533) by the lifetime presence of at least one mood episode with psychotic features. Subjects having a depressive episode at the time of assessment were also examined: HAM-D and YMRS scores were compared between MD and PMD subjects, both with and without current psychotic features. A diagnosis of BP-I, a higher familial load for BP, a higher number of mood episodes lifetime, and a higher prevalence of OCD and somatic comorbidities were all associated to PMD. A diagnosis of BP (OR=4.48) was the only significant predictor for psychosis. PMD with non-psychotic depression were apparently less severe than MD patients and had a lower rate of "non-responders" to AD treatment. Sub-threshold manic symptoms and suicidal risk were also more pronounced among PMD. The lack of information about number and polarity of previous psychotic mood episodes may be the major limitations of our study. BP diagnosis is the most significant predictor for psychosis in mood disorders. Non-psychotic mood episodes in PMD patients may be characterized by a distinctive symptom profile and, possibly, a different response to treatment.

Comprehensive analysis of the genes responsible for neuroacanthocytosis in mood disorder and schizophrenia

Neuroacanthocytosis syndromes are mainly comprised of two diseases: chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). There is a high incidence of psychiatric disorders such as mood disorder and schizophrenia among neuroacanthocytosis patients. We hypothesized that neuroacanthocytosis-related-genes might be associated with susceptibility to these psychiatric disorders. We performed a comprehensive mutation screen of VPS13A and XK, the gene responsible for ChAc and MLS, respectively, in 85 mood disorder subjects and XK in 86 schizophrenia subjects and compared the variants to 100 or more control alleles. We also performed copy number variation (CNV) analysis in 72 mood disorder subjects and 86 schizophrenia subjects. We identified three non-synonymous, two synonymous and six intron variants in mood disorder subjects and a novel GAT triplet repeat polymorphism in VPS13A. By CNV analysis, we identified a heterozygous exon 60–61 deletion in VPS13A in one mood disorder subject. We identified one non-synonymous and one intron variant in mood disorder and schizophrenia subjects, respectively, in XK. The presence of a pathogenic mutation or a potentially functional variant in mood disorder or schizophrenia subjects suggests that neuroacanthocytosis-related-genes might be involved in the pathogenesis of these psychiatric disorders.

Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients

Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

Case–control association study of TGOLN2 in attempted suicide

Family, twin, and adoption studies provide convincing evidence for a genetic contribution to suicidal behavior. The heritability for suicidal behavior depends in part on the transmission of psychiatric disorders, such as mood disorders and substance use disorders, but is also partly independent of them. Three linkage studies using the attempted suicide phenotype in pedigrees with bipolar disorder, major depression, or alcoholism have provided consistent evidence that 2p11-12 harbors a susceptibility gene for attempted suicide. A microarray expression study using postmortem brain samples has implicated a gene from the 2p11-12 candidate region, the trans-Golgi network protein 2 (TGOLN2) gene, as being consistently up-regulated in suicide cases as compared to controls. Here, we present a TGOLN2 case-control association study using nine single nucleotide polymorphisms (SNPs). These nine SNPs, which include seven tag SNPs and two coding SNPs, have been genotyped in 517 mood disorder subjects with a history of attempted suicide and 515 normal controls. Allelic and genotypic analyses of the case-control sample did not provide evidence for association with the attempted suicide phenotype. Eight of the nine SNPs provided supportive evidence for association (P-values ranging from 0.008 to 0.03) when we compared the attempted suicide cases with a history of alcoholism to the attempted suicide cases without a history of alcoholism. However, this association finding was not replicated in an independent sample. Taken together, these analyses do not provide support for the hypothesis that common genetic variation in TGOLN2 contributes significantly to the risk for attempted suicide in subjects with major mood disorders.

Affective temperaments and residual symptoms in patients with mood and anxiety disorders

Objective. Temperament conventionally refers to stable behavioural and emotional reactions that appear early in life and are influenced in part by genetic constitution. Few studies compared temperamental traits in anxiety and mood disorders even though some authors suggested a clinical and neurobiological continuum between them. The aim of the study was to compare temperamental traits and psychopathological dimensions in subjects with DSM-IV diagnoses of mood and anxiety disorders. Methods. A total of 101 clinically stabilized consecutive outpatients (45 subjects with anxiety disorders and 56 with mood disorders diagnoses) were evaluated. The brief version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego (briefTEMPS-M) and Symptom Checklist-90 (SCL-90) were used to assess temperamental traits and psychopathological dimensions, respectively. Results. No significant differences between anxiety disorders and mood disorders subjects for TEMPS-M or SCL-90 mean scores were observed. Different TEMPS-M scores differentially affect residual clinical symptoms. Conclusions. Our data represent an indirect indicator of possible common diathesis between the two different disorders. The temperament “paradigm” could explain part of the residual symptomatology. The evaluation of affective temperaments seems to add considerable clinical information to psychopathological and diagnostic descriptions.

Bipolar disorder and neurophysiologic mechanisms.

Recent studies have suggested that some variants of bipolar disorder (BD) may be due to hyperconnectivity between orbitofrontal (OFC) and temporal pole (TP) structures in the dominant hemisphere. Some initial MRI studies noticed that there were corpus callosum abnormalities within specific regional areas and it was hypothesized that developmentally this could result in functional or effective connectivity changes within the orbitofrontal-basal ganglia-thalamocortical circuits. Recent diffusion tensor imaging (DTI) white matter fiber tractography studies may well be superior to region of interest (ROI) DTI in understanding BD. A "ventral semantic stream" has been discovered connecting the TP and OFC through the uncinate and inferior longitudinal fasciculi and the elusive TP is known to be involved in theory of mind and complex narrative understanding tasks. The OFC is involved in abstract valuation in goal and sub-goal structures and the TP may be critical in binding semantic memory with person-emotion linkages associated with narrative. BD patients have relative attenuation of performance on visuoconstructional praxis consistent with an atypical localization of cognitive functions. Multiple lines of evidence suggest that some BD alleles are being selected for which could explain the enhanced creativity in higher-ability probands. Associations between ROI's that are not normally connected could explain the higher incidence of artistic aptitude, writing ability, and scientific achievements among some mood disorder subjects.

No Association of COMT Val158Met Polymorphism with Suicidal Behavior or CSF Monoamine Metabolites in Mood Disorders

The Met allele of the Catechol-O-Methyltransferase (COMT) gene functional polymorphism (COMT-V158M) is associated with lower enzymatic activity than the Val allele and is reported to be associated with aggression, depression, and suicidal behavior. Since depression and impulsive-aggressive behavior may mediate risk for suicidal behavior, we assessed the association of this polymorphism with suicidal behavior. Clinical (impulsive aggression) and biological (CSF monoamine metabolites) endophenotypes were tested as potential mediators of the effect of genotype on suicide risk. Subjects with mood disorders (N = 486) and healthy volunteers (N = 119), all European Caucasian, were genotyped for COMT-V158M and assessed for DSM IV diagnoses, lifetime suicidal behavior, lifetime impulsivity, hostility, and aggression. CSF monoamine metabolites were assayed in a sub-sample of mood disorder patients (N = 111). We found no association between genotype and mood disorder diagnosis or with reported history of suicide attempt in mood disorder subjects. There was no association between genotype and lethality or method of suicide attempt, or with aggressive/impulsive traits. Further, there was no difference in monoamine metabolites by genotype. The COMT-V158M polymorphism was not associated with suicidal behavior in a Caucasian sample of mood disorder subjects, or with possible clinical or biological endophenotypes.