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1.
J Affect Disord ; 266: 387-393, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056904

RESUMO

BACKGROUND: Individuals with mood disorders experience a higher rate of obesity than the general population, putting them at risk for poorer outcomes. The relationship between obesity and a core feature of the mood disorders, neurocognition, is less understood. We examined the interaction of obesity as indexed by body mass index (BMI) and working memory performance in a large sample of individuals with bipolar disorder (BD), major depressive disorder (MDD), and healthy controls (HC). METHODS: Participants with BD (n = 133), MDD (n = 78), and HC (n = 113) (age range 18-40) completed a spatial working memory (SWM) task that included three-graded increases in the number of target locations. Participants were subdivided by BMI classification into six diagnostic-BMI (BMI groups: Normal Weight, Overweight/Obese) subgroups. Performance on the task was indexed by number of errors within each difficulty level. RESULTS: The number of errors, across all groups, increased with task difficulty. There was an interaction between errors and diagnostic-BMI group. Post-hoc analyses indicated that while the Normal Weight-BD group did not differ in performance from the other groups, the Overweight/Obese-BD group performed significantly worse than HC groups. LIMITATIONS: Metabolic effects of psychotropic medications due to the naturalistic nature of the study, younger age of the MDD sample, and utilizing self-reported indicators of obesity may limit generalizability. CONCLUSIONS: Individuals with BD with increased metabolic burden exhibit increased working memory errors than non-psychiatric controls who also have increased metabolic burden. Future work could address prevention and amelioration of such difficulties to reduce associated functional morbidity.

2.
Bipolar Disord ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610074

RESUMO

OBJECTIVES: Self-monitoring is recommended for individuals with bipolar disorder, with numerous technological solutions available. This study aimed to identify basic components of these solutions that increase engagement with self-monitoring. METHODS: Participants with bipolar disorder (n = 47) monitored their symptoms with a Fitbit and a smartphone app and were randomly assigned to either review or not review recorded symptoms weekly. We tested whether individuals would better adhere to and prefer monitoring with passive monitoring with an activity tracker compared to active monitoring with a smartphone app and whether individuals would better adhere to self-monitoring if their recorded symptoms were reviewed with an interviewer. RESULTS: Monitoring with a smartphone app achieved similar adherence and preference to Fitbit (P > .85). Linear mixed effects modeling found adherence decreased significantly more over the study for the Fitbit (12% more, P < .001) even though more participants reported they would use the Fitbit over a year compared to the app (72.3% vs 46.8%). Reviewing symptoms weekly did not improve adherence, but most participants reported they would prefer to review symptoms with a clinician (74.5%) and on monthly basis (57.5%) compared to alternatives. Participants endorsed sleep as the most important symptom to monitor, forgetfulness as the largest barrier to self-monitoring, and raising self-awareness as the best reason for self-monitoring. CONCLUSIONS: We recommend a combined strategy of wearable and mobile monitoring that includes reminders, targets raising self-awareness, and tracks sleep. A clinician may want to review symptoms on a monthly basis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03358238.

3.
Mol Psychiatry ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462766

RESUMO

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. A total of 222 unmedicated adults with MDD randomized to receive sertraline (n = 110) or placebo (n = 112) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study completed demographic and clinical assessments, and pretreatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression (HSRD) over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on week-8 depression levels (Fs ≥ 9.67, ps ≤ 0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pretreatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pretreatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment.

4.
Mol Neuropsychiatry ; 5(2): 115-124, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31192224

RESUMO

Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD. CACNA1C encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is involved in -circadian phase delays. It is unknown whether variants in CACNA1C or other calcium channels contribute to the circadian phenotype in BD. We hypothesized that, by using temperature cycles, we could model circadian entrainment in fibroblasts from BD patients and controls to interrogate the circadian functions of LTCCs. Using Per2-luc, a bioluminescent reporter, we verified that cells entrain to temperature rhythms in vitro. Under constant temperature conditions, the LTCC antagonist verapamil shortened the circadian period, and the RYR antagonist dantrolene lengthened the period. However, neither drug affected temperature entrainment. Fibroblasts from BD patients and controls also entrained to temperature. In cells from BD patients, the rhythm amplitude was lower under entrained, but not constant, conditions. Temperature entrainment was otherwise similar between BD and control cells. However, the CACNA1C genotype among BD cells predicted the degree to which cells entrained. We conclude that assessment of rhythms under entrained conditions reveals additional rhythm abnormalities in BD that are not observable under constant temperature conditions.

5.
Biol Psychiatry ; 85(10): 872-880, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30718038

RESUMO

BACKGROUND: Baseline rostral anterior cingulate cortex (rACC) activity is a well-replicated nonspecific predictor of depression improvement. The rACC is a key hub of the default mode network, which prior studies indicate is hyperactive in major depressive disorder. Because default mode network downregulation is reliant on input from the salience network and frontoparietal network, an important question is whether rACC connectivity with these systems contributes to depression improvement. METHODS: Our study evaluated this hypothesis in outpatients (N = 238; 151 female) enrolled in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) 8-week randomized clinical trial of sertraline versus placebo for major depressive disorder. Depression severity was measured using the Hamilton Rating Scale for Depression, and electroencephalography was recorded at baseline and week 1. Exact low-resolution electromagnetic tomography was used to compute activity from the rACC, and key regions within the default mode network (posterior cingulate cortex), frontoparietal network (left dorsolateral prefrontal cortex), and salience network (right anterior insula [rAI]). Connectivity in the theta band (4.5-7 Hz) and beta band (12.5-21 Hz) was computed using lagged phase synchronization. RESULTS: Stronger baseline theta-band rACC-rAI (salience network hub) connectivity predicted greater depression improvement across 8 weeks of treatment for both treatment arms (B = -0.57, 95% confidence interval = -1.07, -0.08, p = .03). Early increases in theta-band rACC-rAI connectivity predicted greater likelihood of achieving remission at week 8 (odds ratio = 2.90, p = .03). CONCLUSIONS: Among patients undergoing treatment, theta-band rACC-rAI connectivity is a prognostic, albeit treatment-nonspecific, indicator of depression improvement, and early connectivity changes may predict clinically meaningful outcomes.

7.
J Affect Disord ; 245: 1070-1078, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699849

RESUMO

BACKGROUND: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia. METHODS: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia. RESULTS: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia. LIMITATIONS: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data. CONCLUSIONS: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.


Assuntos
Anedonia/fisiologia , Transtornos de Ansiedade/psicologia , Cognição/fisiologia , Transtorno Depressivo Maior/psicologia , Neuroticismo/fisiologia , Adulto , Antidepressivos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Recompensa , Resultado do Tratamento
8.
Pharmacotherapy ; 39(2): 161-170, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30620405

RESUMO

STUDY OBJECTIVE: Previous studies identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment that may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be beneficial in obesity and glucose regulation, but little is known mechanistically about their ability to modify gut microbiota in AAP-treated individuals. This investigation was undertaken to delineate mechanistically the effects of AAP treatment and resistant starch supplementation on gut microbiota in a psychiatric population. DESIGN: Cross-sectional cohort study. SETTING: The study was performed in an outpatient setting. PATIENTS: A total of 37 adults with a diagnosis of bipolar disorder or schizophrenia who were treated with an AAP (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone [21 patients]) or lithium and/or lamotrigine (16 patients) for at least 6 months. INTERVENTION: Patients in the AAP group received raw unmodified potato starch (resistant starch) daily for 14 days. MEASUREMENTS AND MAIN RESULTS: Of the 37 patients, the mean ± SD age was 52.2 ± 12.5 years, and 57% were male. The primary outcome was gut microbiome DNA composition. Microbiome DNA obtained from stool samples from all patients was subject to 16S ribosomal RNA (rRNA) gene sequencing before and during resistant starch supplementation. Inter- and intragroup microbial diversity measures were performed by permutational multivariate analysis of variance and the Inverse Simpson Diversity Index, respectively. Differentially abundant organisms were detected by using linear discriminant analysis effect size. Although no significant difference in overall microbiota composition was detected at baseline between AAP users and nonusers, non-AAP users showed increased fractional representation of Alistipes. AAP-treated women exhibited decreased diversity compared with non-AAP-treated women. Although the microbiome of AAP-treated patients varied with resistant starch administration, an increased abundance of the Actinobacteria phylum was observed. CONCLUSION: These data suggest that AAP treatment is associated with measurable differences in gut microbiota, particularly in female AAP-treated patients in whom reduced species richness was observed. Additionally, variable microbiome responses to resistant starch supplementation were seen, with a significant increase in starch degraders.

10.
Psychol Med ; 49(7): 1118-1127, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29962359

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits. METHODS: Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics. RESULTS: Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58). CONCLUSIONS: A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.

11.
Suicide Life Threat Behav ; 49(5): 1360-1378, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30450613

RESUMO

OBJECTIVE: To evaluate the effects of mood and anxiety symptoms in relation to personality dimensions and clinical features such as trauma and substance use on suicidal behaviors in a longitudinal sample of individuals with bipolar illness (BP) and healthy controls (HC). METHODS: Mood, personality, and clinical features were assessed in 151 individuals with BP I and 119 HC. Clinical data were collected at baseline and at 2-year follow-up. Personality traits were measured using the NEO PI-R. RESULTS: In bivariate analyses, personality measures were significantly different between BP and HC, and between BP based on suicide attempt history. However, in regression analyses, baseline measures of depression, mania, anxiety, trauma, education, and age of BP onset correlated with personality domains, while a history of suicide attempts did not. Logistic regressions showed that prospective depression or mania, and a pattern of mixed mood features and chronicity of illness, along with two Neuroticism facet scores (N4-Self-Consciousness and N6-Vulnerability) were predictive of suicide ideation (SI) in the 2-year follow-up period. CONCLUSIONS: While dimensions of personality, trauma, and substance use clearly correlated with suicidal behaviors in BP, in multivariate models emerging mood symptoms were the most robust predictors of suicidality. These results reinforce the importance and attributable role of mood and anxiety symptoms in evaluating suicidal risk.

12.
Neuropsychopharmacology ; 44(3): 620-628, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30487653

RESUMO

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Ritmo Circadiano , Fibroblastos , Compostos de Lítio/farmacologia , Adulto , Animais , Transtorno Bipolar/genética , Células Cultivadas , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Técnicas de Genotipagem , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Medições Luminescentes , Camundongos , Células NIH 3T3 , Proteínas Circadianas Period , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos
13.
J Biomech ; 82: 266-270, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30455058

RESUMO

The aim of this study was to investigate balance control during gait and sit-to-walk in individuals with bipolar disorder and healthy controls by examining the inclination angles between the whole-body center-of-mass (COM) and ankle in the sagittal plane. Twenty-one individuals with bipolar disorder in the euthymic (i.e., asymptomatic; n = 11) and depressed (n = 10) phases and 7 healthy controls (ages between 18 and 45) performed gait and sit-to-walk at self-selected comfortable speed. Mood phases for individuals with bipolar disorder were measured using the Patient Health Questionnaire and Altman Self-Rating Mania Scale. We collected motion data using a 16-camera motion capture technology. We found smaller COM-ankle inclination angles at seat-off during sit-to-walk for the bipolar-depressed group compared to the bipolar-euthymic and healthy groups, indicating poorly controlled balance for the bipolar-depressed group in sit-to-walk. However, we found larger COM-ankle inclination angles at beginning of single stance phase of gait for the bipolar-euthymic group compared to the healthy group, indicating well controlled balance for the bipolar-euthymic group in gait. Our results suggest an association between the depressed phase and balance impairment during daily movements in relatively young adults (ages ≤ 45 years). Our results also suggest that the depressed phase may be as detrimental to balance control as the effect of age-related neuromuscular weakness.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Equilíbrio Postural , Adolescente , Adulto , Tornozelo/fisiopatologia , Estudos de Casos e Controles , Feminino , Marcha/fisiologia , Humanos , Masculino , Adulto Jovem
14.
J Affect Disord ; 246: 126-131, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30580198

RESUMO

BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Escalas de Graduação Psiquiátrica , Adulto , Ansiolíticos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Comorbidade , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fumarato de Quetiapina/uso terapêutico , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Eur Neuropsychopharmacol ; 29(1): 156-170, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503783

RESUMO

Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder (BD) that focuses on an important aspect of disease course, the functional outcome. FIERS identified a significantly associated locus on chromosome 15 (hg38: chr15:48965004 - 49464789 bp) with consistent effect strength between two independent studies (GAIN/TGen: European Americans, BOMA: Germans; n = 1592 BD patients in total). Protective and risk haplotypes were found on the most strongly associated SNPs. They contain a CTCF binding site (rs586758); CTCF sites are known to regulate sets of genes within a chromatin domain. The rs586758 - rs2086256 - rs1904317 haplotype is located in the promoter flanking region of the COPS2 gene, close to microRNA4716, and the EID1, SHC4, DTWD1 genes as plausible biological candidates. While implication with BD is novel, COPS2, EID1, and SHC4 are known to be relevant for neuronal differentiation and function and DTWD1 for psychopharmacological side effects. The test strategy FIERS that enabled this discovery is equally applicable for tag SNPs and sequence data.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Predisposição Genética para Doença/genética , Adolescente , Adulto , Idoso , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Escalas de Graduação Psiquiátrica , Adulto Jovem
16.
Bipolar Disord ; 20(8): 697-707, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30294823

RESUMO

OBJECTIVES: Delays in the diagnosis and detection of bipolar disorder can lead to adverse consequences, including improper treatment and increased suicide risk. The Mood Spectrum Self-Report Measure (MOODS-SR) was designed to capture the full spectrum of lifetime mood symptomology with factor scores for depression and mania symptom constellations. The utility of the MOODS-SR as a tool to investigate homogeneous subgroups was examined, with particular focus on a possible bipolar risk subgroup. Moreover, potential patterns of differences in MOODS-SR subtypes were probed using cognitive vulnerabilities, neuropsychological functioning, and ventral striatum connectivity. METHODS: K-mean cluster analysis based on factor scores of MOODS-SR was used to determine homogeneous subgroupings within a healthy and remitted depressed young adult sample (N = 86). Between-group comparisons (based on cluster subgroupings) were conducted on measures of cognitive vulnerabilities, neuropsychological functioning, and ventral striatum rs-fMRI connectivity. RESULTS: Three groups of participants were identified: one with minimal symptomology, one with moderate primarily depressive symptomology, and one with more severe manic and depressive symptomology. Differences in impulsivity, neuroticism, conscientiousness, facial perception accuracy, and rs-fMRI connectivity exist between moderate and severe groups. CONCLUSIONS: Within a sample of people with and without depression histories, a severe subgroup was identified with potentially increased risk of developing bipolar disorder through use of the MOODS-SR. This small subgroup had higher levels of lifetime depression and mania symptoms. Additionally, differences in traits, affective processing, and connectivity exist between those with a more prototypic unipolar subgrouping and those with potential risk for developing bipolar disorder.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Adulto , Afeto , Transtorno Bipolar/psicologia , Análise por Conglomerados , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Comportamento Impulsivo , Masculino , Fenótipo , Psicometria/métodos , Autorrelato , Adulto Jovem
17.
J Affect Disord ; 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30241956

RESUMO

BACKGROUND: Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. METHODS: We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. RESULTS: On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 = 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p = 0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only, F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating. LIMITATIONS: Bipolar CHOICE was not designed to study anthropometric outcomes. CONCLUSIONS: Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

18.
Psychiatry Res ; 269: 93-101, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30145308

RESUMO

Abnormal motor behaviors influenced by high or low energy states are key signs and symptoms for mania/hypomania or depression, respectively. Clinical evaluation is currently based on qualitative, subjective self-reports. We aimed to objectively quantify activity and energy variables during gait and sit-to-walk in bipolar disorder. Gait and sit-to-walk were analyzed in 31 individuals with bipolar disorder (five hypomanic, 14 euthymic and 12 depressed) and 14 healthy controls using a motion capture system and two force platforms. The 9-item Patient Health Questionnaire and Altman Self Rating Mania Scale were administered to evaluate mood symptoms. During gait and sit-to-walk, the hypomanic group had 20-30% greater movement speed and produced 10-60% greater peak force, and 40-140% greater peak power in the knee or ankle compared to the euthymic, depressed and healthy groups. Biomechanical measures of activity and energy correlated with clinically defined hypomania. Our findings suggest that movement speed and force production could serve as objective activity and energy markers for hypomanic symptoms in individuals with bipolar disorder, but this study was based on a relatively small sample size, and the laboratory-based assessments are not directly transferable to a clinical setting.


Assuntos
Transtorno Bipolar/fisiopatologia , Metabolismo Energético/fisiologia , Marcha/fisiologia , Locomoção/fisiologia , Postura Sentada , Caminhada/fisiologia , Adulto , Fenômenos Biomecânicos/fisiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Caminhada/psicologia
19.
J Clin Psychiatry ; 79(3)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29873955

RESUMO

OBJECTIVE: Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. METHODS: Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. RESULTS: Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). CONCLUSIONS: These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Adulto , Transtornos Psicóticos Afetivos/induzido quimicamente , Fatores Etários , Transtorno Bipolar/induzido quimicamente , Doença Crônica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
20.
Front Psychiatry ; 9: 244, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29937738

RESUMO

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

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