Mood disorders among adolescents in conflict with the law and in custody.

The high prevalence of psychiatric symptoms among juvenile delinquents is a well-replicated international finding. This study aimed to find the prevalence of mood disorders and their relationship with serious criminal acts in a population of adolescents in conflict with the law and in custody. A total of 123 male inmates aged 14 to 17 years were interviewed and assessed. Mood disorders were diagnosed in 15% of the sample for current episode and 31% for lifetime, making them third most prevalent after dependence disorders and disruptive disorders. The psychopathological profile of the adolescents who had committed violent crimes corroborates other studies reporting a high prevalence of mood disorders in this population. Several factors have been found to influence the formation of juvenile delinquency, including absence of family structure, social inequality, lack of quality school education, alcohol and drug abuse/addiction and disruptive disorders. The present results confirm mood disorders as another such factor.

Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study.

BACKGROUND: Distorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients' perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period. METHOD: These are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24. RESULTS: Results showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment. CONCLUSION: Cognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions. TRIAL REGISTRATION: NCT02268487.

Hamilton depression rating scale and montgomery-asberg depression rating scale in depressed and bipolar I patients: psychometric properties in a Brazilian sample.

BACKGROUND: The Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Scale (MADRS) are used worldwide and considered standard scales for evaluating depressive symptoms. This paper aims to investigate the psychometric proprieties (reliability and validity) of these scales in a Brazilian sample, and to compare responses in bipolar and unipolar patients. METHODS: The sample comprised 91 patients with either bipolar I or major depressive disorder from a psychiatric institute at São Paulo, Brazil. Participants were recruited and treated by clinicians through the Structured Interview for DSM-IV criteria, and had previously been interviewed by a trained, blind tester. RESULTS: Both scales indicated good reliability properties; however, the MADRS reliability statistics were higher than those of the HAM-D for detecting initial symptoms of unipolar depression. Correlation between the tests was moderate. Despite demonstrating adequate validity, neither test achieved the levels of sensitivity and specificity required for identification of a cutoff score to differentiate bipolar I and unipolar patients. CONCLUSIONS: Both scales demonstrate adequate reliability and validity for assessing depressive symptoms in the Brazilian sample, and are good options to complement psychiatric diagnosis, but are not appropriate for distinguishing between the two affective disorder types.

Number of manic episodes is associated with elevated DNA oxidation in bipolar I disorder.

Bipolar disorder (BD) is a major public health problem characterized by progressive functional impairment. A number of clinical variables have been associated with progression of the disease, most notably number of affective episodes and presence of psychotic symptoms, both of which correlate with greater cognitive impairment, lower response rates for lithium, and possibly lower levels of neurotrophic factors. Oxidative damage to cytosine and guanosine (8-OHdG) has been described as a modulator of DNA methylation, but the extent of DNA oxidative damage involvement in BD remains unclear. The aim of this study was to evaluate the extent of DNA oxidative damage to 8-OHdG and 5-methylcytosine (5-HMec), as well as global methylation (5-Mec), in BD patients and healthy controls. Potential association with clinical variables was also investigated. DNA levels of 8-OHdG, 5-HMec and 5-Mec were measured in 50 BD type I patients and 50 healthy controls. DNA 8-OHdG levels were higher in BD patients compared to healthy controls and found to be positively influenced by number of previous manic episodes. BD subjects had lower levels of 5-HMec compared to controls, whereas this measure was not influenced by the clinical features of BD. Number of manic episodes was correlated with higher levels of 8-OHdG, but not of 5-Mec or 5-HMec. Lower demethylation activity (5-HMec) but no difference in global 5-Mec levels was observed in BD. This finding suggests that oxidative damage to 8-OHdG might be a potential marker of disease progression, although further prospective cross-sectional studies to confirm neuroprogression in BD are warranted.

A sib-pair analysis of impulsivity in bipolar disorder type I.

OBJECTIVE: The aim of this study was to compare impulsivity among patients with bipolar disorder, their siblings, and healthy controls in order to examine whether impulsivity in bipolar disorder is related to genetic liability for the illness. METHODS: Using the Barratt Impulsiveness Scale, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without bipolar disorder, and 70 healthy controls. RESULTS: Impulsivity scores were higher among patients with bipolar disorder than among healthy controls. Siblings showed higher motor impulsivity scores than did healthy controls. CONCLUSIONS: Our results suggest that motor impulsivity may be a vulnerability marker for bipolar disorder. Our data may contribute to further improve preventive strategies in subjects at high risk for bipolar disorder.

Latin American consensus recommendations for the management and treatment of patients with treatment-resistant depression (TRD).

Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America. METHODS: Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management. RESULTS: The expert panel agreed that 'treatment-resistant depression' (TRD) is defined as 'failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode'. A stepwise treatment approach should be employed for the management of TRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Nonpharmacological treatments, such as electroconvulsive therapy, are also appropriate options for patients with TRD. CONCLUSION: These consensus recommendations on the operational definition of TRD and approved treatments for its management can be adapted to local contexts in the Latin American countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with TRD.

COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder.

OBJECTIVE: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients. The objective of this study was to investigate the association between COMT SNPs and acute CD during BD mood episodes. METHODS: Seventy-two symptomatic, medication-free subjects with bipolar I disorder (BD-I) and 76 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT SNPs rs4680 and rs165599. RESULTS: Patients undergoing mania and mixed episodes carrying the COMT allele G had better performance on executive function, memory, verbal fluency, and intelligence tests. Moreover, an interaction was detected between the COMT allele G and the Young Mania Rating Scale in BD CD. CONCLUSIONS: Allele G from COMT SNPs rs4680 and rs165599 may represent reliable state-dependent predictors of global CD during manic and mixed episodes in BD. Further studies in larger samples are necessary to confirm these findings.

Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression.

OBJECTIVE: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. METHODS: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. RESULTS: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. CONCLUSION: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression.

Intramuscular ketamine vs. escitalopram and aripiprazole in acute and maintenance treatment of patients with treatment-resistant depression: A randomized double-blind clinical trial.

Objective: Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, can promote rapid action in the management of individuals with treatment-resistant depression (TRD) at sub-anesthetic doses. However, few studies have investigated the long-term use of ketamine administered intravenously (IV) and intranasally (IN). We report the design and rationale of a therapeutic trial for assessing the efficacy, safety, and tolerability of repeated-dose intramuscular (IM) ketamine vs. active treatment (escitalopram and aripiprazole) in TRD patients. Methods: A comparative, parallel-group, randomized double-blind trial assessing the efficacy, safety, and tolerability of acute (4 weeks) and maintenance (24 weeks) use of IM ketamine (0.75 mg/kg) vs. active control (escitalopram 15 mg and aripiprazole 5 mg) in individuals with moderate-severe intensity TRD (no psychotic symptoms) with or without suicide risk will be conducted. Patients with TRD (18-40 years) will be randomized and blinded to receive ketamine IM or active treatment at a 1:1 ratio for 4 weeks (active treatment) and 24 weeks (maintenance treatment). Subjects will be assessed using clinical scales, monitored for vital signs (VS) after application of injectable medication, and undergo neuropsychological tests. The primary outcome will be changed on the Montgomery-Åsberg Depression Rating Scale (MADRS) during the course of the trial. The study is in running. Results: This study can potentially yield evidence on the use of IM ketamine in the treatment of depressive disorders as an ultra-rapid low-cost therapy associated with less patient discomfort and reduced use of medical resources, and can elucidate long-term effects on different outcomes, such as neuropsychological aspects. Conclusions: The trial can help promote the introduction of a novel accessible approach for the treatment of complex disease (TRD) and also allow refinement of its long-term use. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04234776, identifier: NCT04234776.

Personality traits in bipolar disorder type I: a sib-pair analysis.

OBJECTIVE: The aim of this study was to compare temperament and character traits among patients with bipolar disorder (BD), their siblings, and healthy controls (HCs) in order to examine whether personality traits are related to the genetic vulnerability to develop BD. METHODS: Using the Temperament and Character Inventory, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without BD, and 70 HCs. RESULTS: Scores on harm avoidance, novelty seeking, and self-transcendence were significantly higher among patients with BD than among HCs, whereas those on self-directedness and cooperativeness were significantly lower. Siblings showed higher scores on harm avoidance and lower scores on self-directedness than did HCs. As some of the siblings presented at least one lifetime psychiatric disorder other than BD (n = 35), we examined the subset of siblings who had no lifetime psychiatric disorder (n = 32). This group showed statistically higher harm avoidance scores than HCs. CONCLUSIONS: Our results suggest that the harm avoidance temperament trait and, to a lesser extent, the self-directedness character trait may represent vulnerability factors for BD.

Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A 1H magnetic resonance spectroscopy study.

BACKGROUND: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. OBJECTIVE: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. METHODS: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. RESULTS: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. CONCLUSION: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.

Posture and body image in individuals with major depressive disorder: a controlled study.

OBJECTIVE: In this study, we aimed to quantify posture and body image in patients with major depressive disorder during episodes and after drug treatment, comparing the results with those obtained for healthy volunteers. METHOD: Over a 10-week period, we evaluated 34 individuals with depression and 37 healthy volunteers. Posture was assessed based on digital photos of the subjects; CorelDRAW software guidelines and body landmarks were employed. Body image was evaluated using the Body Shape Questionnaire. RESULTS: During depressive episodes (in comparison with the post-treatment period), patients showed increased head flexion (p<0.001), increased thoracic kyphosis (p<0.001), a trend toward left pelvic retroversion (p=0.012) and abduction of the left scapula (p=0.046). During remission, patient posture was similar to that of the controls. At week 1 (during the episode), there were significant differences between the patients and the controls in terms of head flexion (p<0.001) and thoracic kyphosis (p<0.001); at weeks 8-10 (after treatment), such differences were seen only for shoulder position. The mean score on the Body Shape Questionnaire was 90.03 during the depressive episode, compared with 75.82 during remission (p=0.012) and 62.57 for the controls. CONCLUSION: During episodes of depression, individuals with major depressive disorder experience changes in posture and mild dissatisfaction with body image. The findings demonstrate that the negative impact of depression includes emotional and physical factors.

Reliability and validity of a Brazilian version of the Hypomania Checklist (HCL-32) compared to the Mood Disorder Questionnaire (MDQ).

OBJECTIVE: Bipolar disorders are often not recognized and undertreated. The diagnosis of current or past episodes of hypomania is of importance in order to increase diagnostic certainty. The Hypomania Checklist-32 is a self-applied questionnaire aimed at recognizing these episodes. As part of the international collaborative effort to develop multi-lingual versions of the Hypomania Checklist-32, we aimed to validate the Brazilian version and to compare its psychometric properties with those of the Mood Disorder Questionnaire. METHOD: Adult outpatients with bipolar disorder I (n=37), bipolar disorder II (n=44) and major depressive disorder (n=42) of a specialized mood disorder unit were diagnosed according to DSM-IV-TR using a modified version of the SCID. We analyzed the internal consistency and discriminative ability of the Hypomania Checklist-32 Brazilian version in relation to the Mood Disorder Questionnaire. RESULTS: The internal consistency of the Brazilian Hypomania Checklist-32, analyzed using Cronbach's alpha coefficient, was 0.86. A score of 18 or higher in the Hypomania Checklist-32 Brazilian version distinguished between bipolar disorder and major depressive disorder, with a sensitivity of 0.75 and a specificity of 0.58, compared to 0.70 and 0.58, respectively, for the Mood Disorder Questionnaire (score>7). The Hypomania Checklist-32 Brazilian version showed a dual factor structure characterized by "active/elated" and "risk-taking/irritable" items. Hence, the Hypomania Checklist-32 Brazilian version was found to have a higher sensitivity but the same specificity as the Mood Disorder Questionnaire. CONCLUSION: The Brazilian version of the Hypomania Checklist-32 has adequate psychometric properties and helps discriminating bipolar disorder from major depressive disorder (but not bipolar disorder I from bipolar disorder II) with good sensitivity and specificity indices, similar to those of the Mood Disorder Questionnaire.

Efficacy, Safety, and Tolerability of Theta-Burst Stimulation in Mixed Depression: Design, Rationale, and Objectives of a Randomized, Double-Blinded, Sham-Controlled Trial.

INTRODUCTION: Mixed-specifier mood disorders are probably a different subgroup in terms of response to treatment, socio-demographic parameters, course, and family history. Here we describe the rationale and design of a clinical trial aimed to test the efficacy, safety, and tolerability of a non-pharmacological treatment known as theta-burst stimulation (TBS) for treating the mixed depressive episodes of both bipolar (I or II), and unipolar depression. METHODS: The study is designed as a randomized, sham-controlled, double-blinded clinical trial evaluating TBS for the treatment of moderate or severe major depressive episodes with mixed features of patients receiving at least one first or second-line pharmacological treatment for depressive episodes without adequate response. Ninety adult (18 to 65 years old) patients will be enrolled and submitted to 6-week (comprising 5 consecutive days a week sessions for the first 3 weeks and then 2 days a week for a further 3 week) of inhibitory followed by excitatory TBS in dorsolateral prefrontal cortex. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in Montgomery-Åsberg Depression Scale (MADRS) score over time and across groups. Cognitive parameters will also be assessed with neuropsychological tests. RESULTS: The clinical results will provide evidence about TBS as an adjunctive treatment for mixed depression treatment and neuropsychological parameters will contribute toward an improved understanding the effects of TBS in cognition. CONCLUSION: Our results could introduce a novel therapeutic technique for mixed depressive episodes of both bipolar and unipolar disorders. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT04123301; date of registration: 10/10/2019; URL: https://clinicaltrials.gov/ct2/show/NCT04123301?term=NCT04123301&rank=1.

The prevalence of psychopathology in offspring of bipolar women from a Brazilian tertiary center.

OBJECTIVE: No previous study has assessed the occurrence of psychopathology in offspring of bipolar women from South America. The objective of this study was to assess the prevalence of psychopathology in offspring of bipolar mothers from Brazil compared with two control groups. METHOD: Children and adolescents aged 6 to 18 years of bipolar disorders mothers (n = 43), mothers with other mild to moderate mental disorders (n = 53) and mothers without any psychiatric disorder (n = 53) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia present and lifetime version, the Child Behavior Checklist and the Youth Self-Report. Raters were blind to the mothers' diagnoses, who were interviewed by means of the Structured Clinical Interview. RESULTS: Bipolar offspring had twice the chance of having one or more lifetime Axis I diagnoses [prevalence ratio = 2.11 (95% CI: 1.30-3.42) and p = 0.003] and 2.8 higher risk of having a lifetime anxiety disorder [prevalence ratio = 2.83 (95% CI: 1.39-5.78) e p = 0.004] than the offspring of mothers with no mental disorder. In addition, significantly higher scores on Child Behavior Checklist thought problems and Youth Self-Report social problems, as well as anxiety/depression and internalizing problems were observed. CONCLUSION: Our results confirm previous findings suggesting higher psychiatric problems in offspring of bipolar mothers and extend them to the Brazilian society.

A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study.

BACKGROUND: Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial. OBJECTIVE: The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals. METHODS: LICAVAL was a randomized, unicenter, open-label, parallel-group trial that was conducted from January 2009 to December 2012 in a tertiary hospital in São Paulo, Brazil. Participants were between 18 and 35 years old and were followed up for 2 years. Our primary outcome was the number of participants achieving/maintaining response and remission during the acute and maintenance phases of BD treatment, respectively. Other outcomes assessed were symptom severity and adverse events throughout the study. In the analysis of the primary outcome, we compared groups by using a two-way repeated measures analysis of variance and estimated effect sizes by using Cohen's d. RESULTS: Of our 64 participants, 36 were allocated to Li/VPA and 28 to Li/CBZ. Our sample was composed predominantly of females (66.6%) and the average age was 27.8 years. A total of 27 (45.0%) participants had depression, 17 (28.3%) had mania/hypomania, and 16 (26.7%) had a mixed state. We found no between-group differences in CGI-BP (Clinical Global Impression Scale modified for use in bipolar disorder) scores (P = 0.326) or in any other outcome. Side effects differed significantly between groups only in the first week of treatment (P = 0.021), and there were more side effects in the Li/VPA group. Also, the Li/VPA group gained weight (+2.1 kg) whereas the Li/CBZ group presented slight weight loss (-0.2 kg). CONCLUSION: Our study suggests that Li/VPA and Li/CBZ have similar efficacy and tolerability in BD but that Li/CBZ might have metabolic advantages in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00976794 . Registered on September 9, 2009.

Molecular genetic case-control women investigation from the first Brazilian high-risk study on functional psychosis.

OBJECTIVE: Data from epidemiological studies have demonstrated that genetics is an important risk factor for psychosis. The present study is part of a larger project, pioneer in Brazil, which has been conducted by other researchers who intend to follow a high-risk population (children) for the development of schizophrenia and bipolar disorder. In this first phase of the project, the objective was to investigate the distribution of four candidate genetic polymorphisms for functional psychosis (Ser9Gly DRD3, 5HTTLPR, the VNTR 3'-UTR SLC6A3 and Val66Met BDNF) in a case-control sample. METHOD: A total of 105 women (58 with schizophrenia and 47 with bipolar disorder) and 62 gender-matched controls were investigated. RESULTS: Allele and genotype distributions of all identified functional polymorphisms did not differ statistically between cases and controls. CONCLUSIONS: These results suggest that the investigated polymorphisms were not related to susceptibility to functional psychoses in our Brazilian sample. These findings need to be validated in larger and independent studies.

What is the nonverbal communication of depression? Assessing expressive differences between depressive patients and healthy volunteers during clinical interviews.

BACKGROUND: It is unclear if individuals with Major Depressive Disorder (MDD) present different nonverbal behavior (NVB) compared with healthy individuals, and also if depression treatments affect NVB. In this study, we compared the NVB of MDD subjects and healthy controls. We also verified how MDD subjects' NVB is affected by depression severity and acute treatments. METHODS: We evaluated 100 MDD outpatients and 83 controls. We used a 21-category ethogram to assess the frequency of positive and negative NVB at baseline. MDD subjects were also assessed after eight weeks of treatment (pharmacotherapy or neuromodulation). We used the Wilcoxon signed-rank test to compare the NVB of MDD subjects and controls; beta regression models to verify associations between MDD severity and NVB; the Shapiro-Wilk test to verify changes in NVB after treatment; and logistic regression models to verify NVB associated with treatment response according to the Hamilton depression rating scale. RESULTS: Compared with controls, MDD subjects presented higher levels of six negative NVB (shrug, head and lips down, adaptive hand gestures, frown and cry) and lower levels of two positive NVB (eye contact and smile). MDD subjects' NVB was not associated with depression severity, and did not significantly change after depression treatment. Treatment responders showed more interpersonal proximity at baseline than non-responders. LIMITATIONS: Our ethogram had no measure of behavior duration, and we had a short follow-up period. CONCLUSIONS: MDD subjects have more negative and less positive social NVB than controls. Their nonverbal behavior remained stable after clinical response to acute depression treatments.

Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A 1H-MRS study.

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.

Anterior Cingulate Cortex Glutamatergic Metabolites and Mood Stabilizers in Euthymic Bipolar I Disorder Patients: A Proton Magnetic Resonance Spectroscopy Study.

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.