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1.
Artigo em Inglês | MEDLINE | ID: mdl-32008167

RESUMO

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

2.
Bipolar Disord ; 21(4): 330-341, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30864200

RESUMO

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.


Assuntos
Sintomas Afetivos , Transtorno Bipolar , Filho de Pais Incapacitados/psicologia , Creatina/análise , Giro do Cíngulo/metabolismo , Fosfocreatina/análise , Córtex Pré-Frontal/metabolismo , Medição de Risco , Adolescente , Adulto , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/metabolismo , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Criança , Creatina/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Espectroscopia de Prótons por Ressonância Magnética/métodos , Medição de Risco/métodos
3.
Rev. bras. psiquiatr ; 40(3): 244-248, July-Sept. 2018. tab
Artigo em Inglês | LILACS-Express | ID: biblio-959236

RESUMO

Objective: To compare social skills and related executive functions among bipolar disorder (BD) patients with a family history of mood disorders (FHMD), BD patients with no FHMD and healthy control (HCs). Methods: We evaluated 20 euthymic patients with FHMD, 17 euthymic patients without FHMD, and 31 HCs using the Social Skills Inventory (SSI) and a neuropsychological battery evaluating executive function, inhibitory control, verbal fluency and estimated intelligence. Results: Both BD groups had lower SSI scores than controls. Scores for one subfactor of the social skills questionnaire, conversational skills and social performance, were significantly lower among patients with FHMD than among patients without FHMD (p = 0.019). Both groups of BD patients exhibited significant deficits in initiation/inhibition, but only BD patients with FHMD had deficits in verbal fluency, both compared to HC. There were no associations between social skills questionnaire scores and measures of cognitive function. Conclusion: Euthymic BD patients have lower social skills and executive function performance than HC. The presence of FHMD among BD patients is specifically associated with deficits in conversational and social performance skills, in addition to deficits in verbal fluency. Both characteristics might be associated with a common genetically determined pathophysiological substrate.

4.
J Affect Disord ; 241: 192-199, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30130684

RESUMO

OBJECTIVE: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (1H-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC. METHODS: 129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan (1H-MRS) using a PRESS ACC single voxel (8cm3) sequence. RESULTS: BD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy). CONCLUSION: The results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Ciclotímico/tratamento farmacológico , Compostos de Lítio/farmacologia , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/enzimologia , Química Encefálica , Colina/análise , Transtorno Ciclotímico/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Humanos , Inositol/análise , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Psychiatry Res Neuroimaging ; 278: 13-20, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-29944976

RESUMO

The neural mechanisms underlying the therapeutic effects of lamotrigine in bipolar depression are still unexplored. This preliminary study compares the effects of a 12-week treatment with lamotrigine on brain volumes in adults with bipolar disorder (BD).12 BD type II patients (age: 49.33 ± 9.95 years, 3 males, 9 females) and 12 age and gender-matched healthy controls (HC) (HC; age: 41 ± 8.60 years, 3 males, 9 females). BD patients were initially administered 25 mg/day of lamotrigine, which was progressively escalated to 200 mg/d. BD participants underwent brain imaging prior to and following lamotrigine treatment. A 50% reduction in depressive scores indicated "remission". Bayesian general linear models controlled for age, gender and intracranial volume were used to examine changes in relevant brain region following treatment. A posterior probability > 0.90 indicated evidence that there was an effect of diagnosis or remission on brain volumes. Probability distributions of interaction effects between remission and time indicated that BD responders displayed decreased amygdala, cerebellum and nucleus accumbens volumes following lamotrigine treatment. No serious adverse side effects were reported. The antidepressant effects of lamotrigine may be linked to volumetric changes in brain regions involved in mood and emotional regulation. These findings are preliminary and replication in a larger sample is warranted.


Assuntos
Antidepressivos/farmacologia , Transtorno Bipolar/patologia , Encéfalo/patologia , Lamotrigina/farmacologia , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Teorema de Bayes , Transtorno Bipolar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Cerebelo/patologia , Emoções/fisiologia , Feminino , Humanos , Modelos Lineares , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/patologia , Tamanho do Órgão/efeitos dos fármacos , Resultado do Tratamento
6.
Neuropsychopharmacology ; 43(11): 2256-2263, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29946107

RESUMO

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Córtex Cerebral/diagnóstico por imagem , Carbonato de Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adolescente , Antidepressivos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Criança , Feminino , Humanos , Carbonato de Lítio/farmacologia , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Valor Preditivo dos Testes , Fumarato de Quetiapina/farmacologia , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-29789269

RESUMO

BACKGROUND: Bipolar disorder is a chronic and recurrent illness characterized by depressive and manic episodes. Proton magnetic resonance spectroscopy (1H-MRS) studies have demonstrated glutamate (Glu) system abnormalities in BD, but it is unclear how Glu varies among mood states and how medications modulate it. The objective of this study was to investigate the influence of mood stabilizers on anterior cingulate cortex Glu levels using 1H-MRS during euthymia. METHODS: One hundred twenty-eight bipolar I disorder (BDI) euthymic subjects and 80 healthy control subjects underwent 3T brain 1H-MRS imaging examination including acquisition of an anterior cingulate cortex single voxel (8 cm3) 1H-MRS, based on a point resolved spectroscopy (PRESS) sequence with an echo time of 80 ms and a repetition time of 1500 ms (BIPUSP MRS study). The Glu system was described by measuring Glu and the sum of Glu and glutamine (Glx) using creatine (Cre) as a reference. RESULTS: Euthymic BDI subjects presented with higher ratios of Glu/Cre and Glx/Cre compared to healthy control subjects. Glu/Cre ratios were lower among patients using anticonvulsants, while Glx/Cre did not differ between the two groups. Lithium, antipsychotics, and antidepressants did not influence Glu/Cre or Glx/Cre. CONCLUSIONS: We reported Glu/Cre and Glx abnormalities in the largest sample of euthymic BDI patients studied by 1H-MRS to date. Our data indicate that both Glu/Cre and Glx/Cre are elevated in BDI during euthymia regardless of medication effects, reinforcing the hypothesis of glutamatergic abnormalities in BD. Furthermore, we found an effect of anticonvulsants on Glu/Cre during euthymia, which might indicate a mechanism of mood stabilization in BD.


Assuntos
Afeto/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Ácido Glutâmico/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Adolescente , Adulto , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacologia , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Antimaníacos/metabolismo , Antimaníacos/farmacologia , Antipsicóticos/metabolismo , Transtorno Bipolar/diagnóstico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtorno Ciclotímico/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adulto Jovem
8.
Braz J Psychiatry ; 40(3): 244-248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29590265

RESUMO

OBJECTIVE: To compare social skills and related executive functions among bipolar disorder (BD) patients with a family history of mood disorders (FHMD), BD patients with no FHMD and healthy control (HCs). METHODS: We evaluated 20 euthymic patients with FHMD, 17 euthymic patients without FHMD, and 31 HCs using the Social Skills Inventory (SSI) and a neuropsychological battery evaluating executive function, inhibitory control, verbal fluency and estimated intelligence. RESULTS: Both BD groups had lower SSI scores than controls. Scores for one subfactor of the social skills questionnaire, conversational skills and social performance, were significantly lower among patients with FHMD than among patients without FHMD (p = 0.019). Both groups of BD patients exhibited significant deficits in initiation/inhibition, but only BD patients with FHMD had deficits in verbal fluency, both compared to HC. There were no associations between social skills questionnaire scores and measures of cognitive function. CONCLUSION: Euthymic BD patients have lower social skills and executive function performance than HC. The presence of FHMD among BD patients is specifically associated with deficits in conversational and social performance skills, in addition to deficits in verbal fluency. Both characteristics might be associated with a common genetically determined pathophysiological substrate.


Assuntos
Transtorno Bipolar/psicologia , Transtornos Cognitivos/psicologia , Cognição , Função Executiva , Transtornos do Humor/psicologia , Habilidades Sociais , Adolescente , Adulto , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtornos Cognitivos/genética , Feminino , Humanos , Inteligência , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Indução de Remissão , Comportamento Verbal/fisiologia , Adulto Jovem
9.
Bipolar Disord ; 19(7): 524-543, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28944987

RESUMO

OBJECTIVES: Over the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings. METHODS: An international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps. RESULTS: Substantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic/mixed episodes, whereas fewer data address bipolar depression and maintenance/continuation treatment. Adjunctive psychosocial treatment provides a forum for psychoeducation and targets primarily depressive symptoms. Numerous neurocognitive and neuroimaging studies, and increasing peripheral biomarker studies, largely converge with prior findings from adults with BD. CONCLUSIONS: As data have accumulated and controversy has dissipated, the field has moved past existential questions about PBD toward defining and pursuing pressing clinical and scientific priorities that remain. The overall body of evidence supports the position that perceptions about marked international (US vs elsewhere) and developmental (pediatric vs adult) differences have been overstated, although additional research on these topics is warranted. Traction toward improved outcomes will be supported by continued emphasis on pathophysiology and novel therapeutics.


Assuntos
Transtorno Bipolar/psicologia , Depressão/psicologia , Adolescente , Comitês Consultivos , Antimaníacos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/terapia , Criança , Consenso , Depressão/terapia , Diagnóstico Diferencial , Humanos , Humor Irritável , Reabilitação Psiquiátrica , Sociedades Médicas
10.
J Affect Disord ; 209: 246-253, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27936454

RESUMO

BACKGROUND: Studying youth at high risk of developing bipolar disorder may clarify neurobiological factors associated with vulnerability to this illness. We present here a baseline characterization of brain structure in youth at-risk for bipolar disorder. METHODS: Magnetic resonance images were obtained from 115 child and adolescent offspring of bipolar disorder type I subjects and 57 healthy child and adolescent offspring of healthy parents (healthy control offspring). Offspring of parents with bipolar disorder were divided into healthy bipolar offspring (n=47) or symptomatic bipolar offspring (n=68), according to presence or absence of childhood-onset psychopathology. All bipolar offspring were free of major mood and psychotic disorders. Gray (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. RESULTS: No differences in GM volumes were found across groups. Healthy bipolar offspring presented with decreased WM volumes in areas of the right frontal, temporal and parietal lobes, and in the left temporal and parietal lobes compared to healthy control offspring. Symptomatic bipolar offspring did not present with any differences in WM volumes compared to either healthy bipolar offspring or healthy control offspring. LIMITATIONS: Cross-sectional design and heterogeneous sample of symptomatic bipolar offspring. CONCLUSIONS: WM volume decreases in areas of the frontal, occipital, and parietal lobes are present in bipolar offspring prior to the development of any psychiatric symptoms, and may be a correlate of familial risk to bipolar disorder. In this large cohort, we have not found evidence for regional GM volume abnormalities as an endophenotype for bipolar disorder.


Assuntos
Transtorno Bipolar , Encéfalo/diagnóstico por imagem , Filho de Pais Incapacitados , Pais , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Criança , Estudos Transversais , Endofenótipos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/fisiologia
11.
Rev. bras. psiquiatr ; 38(3): 197-200, July-Sept. 2016. tab, graf
Artigo em Inglês | LILACS-Express | ID: lil-792748

RESUMO

Objective: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. Methods: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. Results: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. Conclusion: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

12.
Braz J Psychiatry ; 38(3): 197-200, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26870912

RESUMO

OBJECTIVE: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. METHODS: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. RESULTS: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. CONCLUSION: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.


Assuntos
Transtorno Bipolar/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Família , Adulto , Análise de Variância , Biomarcadores/sangue , Transtorno Bipolar/genética , Estudos de Casos e Controles , Endofenótipos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Valores de Referência , Fatores de Risco , Adulto Jovem
13.
J Affect Disord ; 192: 28-33, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26706829

RESUMO

OBJECTIVES: To investigate the association between history of suicide attempts (SA) and family functioning in bipolar disorder (BD) patients. METHODS: Thirty-one BD type I patients with lifetime history of SA, 31 BD type I with no lifetime history of SA, participating in the Outpatient Clinic of the Bipolar Disorder Program at the Institute of Psychiatry of the University of São Paulo Medical School were recruited for this study. We used the Family Assessment Device (FAD) to evaluate family functioning. We compared these two groups on demographic and clinical variables to identify which variables were associated with family functioning impairment. Fifty-one relatives of the same patients were also asked to complete a FAD. RESULTS: BD patients with SA presented more psychiatric hospitalizations, higher frequency of psychotic symptoms, and higher scores on depressive, manic, and suicidal ideation than BD patients without SA. BD patients with SA presented significantly higher scores in several subscales of the FAD, including Problem Solving (p=0.042), Communication (p=0.009), Roles (p=0.006), and General Functioning (p=0.025), when compared with BD patients without SA. Relatives of BD patients with SA presented significantly higher scores in Communication, Roles, Affective Responsiveness, and General Functioning than relatives of BD patients without SA. LIMITATIONS: Cross-sectional study and long time elapsed since last SA. CONCLUSION: History of SA in BD is associated with worse family functioning in several domains of FAD, including Problem Solving, Communication, Roles, and General Functioning. As suicide attempts are routinely assessed in clinical practice, these findings may help to identify patients with poorer family functioning and may suggest a role for environmental risk factors in suicidal behavior among BD patients.


Assuntos
Transtorno Bipolar/psicologia , Relações Familiares/psicologia , Tentativa de Suicídio/psicologia , Adulto , Estudos Transversais , Transtorno Depressivo/psicologia , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/psicologia , Fatores de Risco , Ideação Suicida
14.
Psychiatry Res ; 234(2): 188-93, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26459073

RESUMO

Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Família , Substância Cinzenta/patologia , Adulto , Encéfalo/patologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Endofenótipos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
15.
J Psychiatr Res ; 64: 1-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25862378

RESUMO

BACKGROUND: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.


Assuntos
Idade de Início , Transtorno Bipolar/epidemiologia , Clima , Estações do Ano , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade
16.
J Affect Disord ; 167: 104-11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24953482

RESUMO

BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS: Recall bias for onset and family history data. CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.


Assuntos
Idade de Início , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/etiologia , Clima , Estações do Ano , Luz Solar/efeitos adversos , Adolescente , Adulto , Transtorno Bipolar/genética , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Feminino , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Estudos Retrospectivos
17.
J Affect Disord ; 161: 104-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24751316

RESUMO

OBJECTIVES: To compare clinical characteristics of bipolar disorder (BD) in patients with and without a family history of mood disorders (FHMD) in a large sample from the Brazilian Research Network of Bipolar Disorders. METHODS: Four-hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research Network of Bipolar Disorders were included. Participants were divided between those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on demographic and clinical variables and performed a logistic regression to identify which variables were most strongly associated with positive family history of mood disorders. RESULTS: BD patients with FHMD presented with significantly higher lifetime prevalence of any anxiety disorder, obsessive-compulsive disorder, social phobia, substance abuse, and were more likely to present history of suicide attempts, family history of suicide attempts and suicide, and more psychiatric hospitalizations than BD patients without FHMD. Logistic regression showed that the variables most strongly associated with a positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and family history of suicide. LIMITATIONS: Cross-sectional study and verification of FHMD by indirect information. CONCLUSION: BD patients with FHMD differ from BD patients without FHMD in rates of comorbid anxiety disorder and substance abuse, number of hospitalizations and suicide attempts. As FHMD is routinely assessed in clinical practice, these findings may help to identify patients at risk for particular manifestations of BD and may point to a common, genetically determined neurobiological substrate that increases the risk of conditions such as comorbidities and suicidality in BD patients.


Assuntos
Transtornos de Ansiedade/psicologia , Transtorno Bipolar/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/genética , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Brasil , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Suicídio , Tentativa de Suicídio/psicologia
18.
Compr Psychiatry ; 55(5): 1116-21, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24746528

RESUMO

OBJECTIVES: To investigate prevalence rates and clinical correlates of alcohol use disorders (AUD) among bipolar disorder (BD) patients in a large sample from the Brazilian Bipolar Research Network. METHODS: Four hundred and eighty-three DSM-IV BD patients, divided according to the presence or absence of a lifetime AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical characteristics of these two groups were compared. Logistic regression was performed to identify which characteristics were most strongly associated with a lifetime AUD diagnosis. RESULTS: Nearly 23% presented a lifetime AUD diagnosis. BD-AUD patients were more likely to be male, to present rapid cycling, post-traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD), family history of SUD, any substance misuse during the first mood episode, history of psychosis, suicide attempts, and younger age at onset of illness than BD-nonAUD patients. Logistic regression showed that the variables most strongly associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance misuse during the first mood episode, PTSD, male gender, suicide attempt, family history of SUD, and younger age at onset of BD. CONCLUSIONS: BD-AUD patients begin their mood disorder earlier and present more suicidal behaviors than BD-nonAUD patients. Personal and family history of SUD may be good predictors of comorbid AUD among BD patients. These variables are easily assessed in the clinical setting and may help to identify a particularly severe subgroup of BD patients.


Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtorno Bipolar/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
19.
Aust N Z J Psychiatry ; 47(12): 1124-35, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23864160

RESUMO

OBJECTIVE: Cortical and subcortical gray matter abnormalities have been reported in individuals at high genetic risk for bipolar disorder, but the findings are inconsistent. The aim of this study was to review the available literature to identify common findings that could represent brain structural vulnerability factors for bipolar disorder and to discuss challenges for the advancement of the field. METHOD: A systematic search was conducted using the PubMed database to identify all original articles investigating cortical or subcortical gray matter abnormalities in first-degree relatives of bipolar disorder patients. RESULTS: Very few findings were replicated, with the exception of larger insular cortex volumes in adult first-degree relatives and larger right inferior frontal gyrus in offspring of probands with bipolar disorder, both when compared with healthy controls. Isolated findings included decreased gray matter density in the left thalamus, decreased gray matter volumes in the left hippocampus and parahippocampal gyrus, and thicker right hippocampus in unaffected first-degree relatives. Genetic liability for bipolar disorder was associated with gray matter volumes in regions of the anterior cingulate cortex, ventral striatum, medial frontal gyrus, right precentral gyrus, right insular cortex, and medial orbital gyrus. Some studies found no evidence for gray matter abnormalities in first-degree relatives of bipolar disorder patients. CONCLUSIONS: Possible reasons for the discrepancies of findings across studies include small samples sizes, small effect size of susceptibility genes, the phenotypic heterogeneity of bipolar disorder, and the possible confounding effect of other Axis I psychopathologies among the relatives of patients. Future multisite, prospective, large studies with more homogeneous samples would be a key strategy to advance the field. The ultimate benefit would be an understanding of how to use brain imaging tools to identify individuals at increased risk for bipolar disorder and develop preventive strategies for that population.


Assuntos
Transtorno Bipolar/patologia , Encéfalo/patologia , Fibras Nervosas Amielínicas/patologia , Adulto , Transtorno Bipolar/etiologia , Transtorno Bipolar/genética , Predisposição Genética para Doença , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Neuroimagem , Fatores de Risco
20.
J Affect Disord ; 150(2): 629-33, 2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-23764385

RESUMO

In order to assess the association between therapeutic response to lithium treatment and fronto-limbic brain structures' volumes in bipolar I patients (BPI) 24 BPI and 11 healthy comparisons underwent MRI scans at baseline and 4 weeks later. The BPIs received lithium during the 4 week period with a goal of achieving therapeutic blood levels of >0.5 mEq/L (mean level 0.67 mEq/L). Mood symptoms were rated with the Hamilton Depression and the Young Mania Rating Scales at baseline and after 4 weeks, and response was defined as >50% decrease on either scale. Hippocampus, amygdala, prefrontal (PFC), dorsolateral prefrontal (DLPFC), and anterior cingulate cortex (ACC) volumes were obtained by Freesurfer image analysis suite. According to baseline symptoms and treatment response, patients were assigned to three groups: euthymics (n=6), responders (n=12) and non-responders (n=6). Taken over both time periods, non-responders had smaller right amygdala than healthy comparisons and euthymic BPI (p=0.035 and p=0.003, respectively). When baseline and after treatment volumes were compared, there was a significant enlargement in left PFC and left DLPFC in BPI who responded to treatment (p=0.002 and p=0.006, respectively). Left hippocampus and right ACC volumes decreased in non-responders (p=0.02 and p=0.0001, respectively). According to the findings decreased left hippocampus and right ACC volumes may be markers of non-response to lithium amongst BPI. Smaller right amygdala may reflect symptomatic remission and be a marker of treatment non-response. Increases in left PFC and left DLPFC as a result of lithium treatment may relate to lithium's neurotrophic effects.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Giro do Cíngulo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Compostos de Lítio/uso terapêutico , Adulto , Afeto , Feminino , Giro do Cíngulo/fisiopatologia , Hipocampo/fisiopatologia , Humanos , Compostos de Lítio/farmacologia , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Resultado do Tratamento , Adulto Jovem
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