Search

Background People with bipolar disorder (BD) have high rates of smoking. However, the scientific literature examining the association between clinical outcomes in BD and tobacco smoking is still limited and there are conflicting results. The objective of the current study was to comprehensively investigate associations between BD and tobacco smoking in a large Brazilian sample. Methods This study evaluated 336 outpatients from the Brazilian Bipolar Research Network, which is a collaboration between three large academic centers in Brazil. Main findings Regarding the categorical analysis (i.e. current smokers versus non-smokers), tobacco smokers showed: 1) a higher percentage of individuals identifying as Non-Caucasians; 2) a longer duration of illness; 3) a longer duration of untreated illness; 4) more severe manic symptoms; 4) a stronger family history of mood disorder; and 6) a higher current prevalence of alcohol/substance use disorder. The dimensional analysis in smokers (i.e. number of cigarettes per day versus clinical variables) found a positive correlation between number of cigarettes per day and a) age, b) age at onset of BD, c) duration of illness, and d) current diagnosis of panic disorder. Conclusion This study found important clinical correlates of tobacco smoking in BD subjects. We observed that the variables associated with current smoker status (categorical approach) are not necessarily correlated with number of cigarettes per day (dimensional approach). Duration of illness appears to be a particularly relevant clinical variable in the association between BD and tobacco smoking. [ABSTRACT FROM AUTHOR]

Objectives: Decreased levels of brain derived neurotrophic factor (BDNF) have been found in adult patients with bipolar disorder (BD) compared with a comparison group, yet there are no data specifically examining this in geriatric patients. The objective of this study was to examine whether euthymic late-life BD patients have lower BDNF levels than healthy comparators.Design: Cross-sectional study.Setting: Clinics at the University of Pittsburgh and the Centre for Addiction and Mental Health (Toronto).Participants: Older patients with BD (age ≥50 years, N = 118) and similarly aged healthy comparators (N = 76). There were both BD type I (N = 91) and type II (N = 27) patients.Measurements: Serum BDNF levels were assessed in BD patients and healthy comparators.Results: We found lower levels of BDNF in patients with BD than in healthy comparators (9.0 ± 6.2 versus 12.3 ± 8.9 pg/µg, t(192) = -3.01, p = 0.002), which remained even after controlling for age, sex, lithium use, and site (F(1,176) = 4.32, p = 0.039). This decrease was found specifically in patients with BD type I (8.0 ± 5.5 versus 12.3 ± 8.9 pg/µg, t(165) = 3.7, Bonferroni p < 0.001), but not type II (12.0 ± 7.5 versus 12.3 ± 8.9 pg/µg, t(101) = 0.14, Bonferroni p = 1.0).Conclusions: Older patients with BD have lower serum levels of BDNF compared with similarly aged comparators. These effects appear to be specific to patients with BD type I. Future studies are needed to investigate the impact of reduced BDNF levels on cognition, mood, and other aspects of BD throughout the life course. [ABSTRACT FROM AUTHOR]

Background Facial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD. Methods We studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18 years old and a diagnosis of DSM-IV BD type I. Results Euthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks. Conclusion Our results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD. [ABSTRACT FROM AUTHOR]

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, posttraumatic 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. Objective: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. Methods: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–defined bipolar I or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. Results: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. Conclusions: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses. [Copyright &y& Elsevier]

Abstract: Introduction: Compulsive buying (CB) is currently classified as an impulse control disorder (ICD) not otherwise classified. Compulsive buying prevalence is estimated at around 5% of the general population. There is controversy about whether CB should be classified as an ICD, a subsyndromal bipolar disorder (BD), or an obsessive-compulsive disorder (OCD) akin to a hoarding syndrome. To further investigate the appropriate classification of CB, we compared patients with CB, BD, and OCD for impulsivity, affective instability, hoarding, and other OCD symptoms. Method: Eighty outpatients (24 CB, 21 BD, and 35 OCD) who were neither manic nor hypomanic were asked to fill out self-report questionnaires. Results: Compulsive buying patients scored significantly higher on all impulsivity measures and on acquisition but not on the hoarding subdimensions of clutter and “difficulty discarding.” Patients with BD scored higher on the mania dimension from the Structured Clinical Interview for Mood Spectrum scale. Patients with OCD scored higher on obsessive-compulsive symptoms and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients with CB (79%), BD (71%), and OCD (77%). Conclusion: Patients with CB came out as impulsive acquirers, resembling ICD- rather than BD- or OCD-related disorders. Manic symptoms were distinctive of patients with BD. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group. [Copyright &y& Elsevier]

Abstract: Background: The association between suicidal behavior and quality of life (QoL) in bipolar disorder (BD) is poorly understood. Worse QoL has been associated with suicide attempts and suicidal ideation in schizophrenic patients, but this relationship has not been investigated in BD. This study tested whether a history of suicide attempts was associated with poor QoL in a well-characterized sample of patients with BD, as has been observed in other psychiatric disorders and in the general population. Methods: One hundred eight patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition BD type I (44 with previous suicide attempts, 64 without previous suicide attempts) were studied. Quality of life was assessed using the World Health Organization''s Quality of Life Instrument–Short Version. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale–17 items and the Young Mania Rating Scale. Results: Patients with BD and previous suicide attempts had significantly lower scores in all the 4 domains of the World Health Organization''s Quality of Life Instrument–Short Version scale than did patients with BD but no previous suicide attempts (physical domain P = .001; psychological domain P < .0001; social domain P = .001, and environmental domain P = .039). In the euthymic subgroup (n = 70), patients with previous suicide attempts had significantly lower scores only in the psychological and social domains (P = .020 and P = .004). Limitations: This was a cross-sectional study, and no causal associations can be assumed. Conclusions: Patients with BD and a history of previous suicide attempts seem to have a worse QoL than did patients who never attempted suicide. Poorer QoL might be a marker of poor copying skills and inadequate social support and be a risk factor for suicidal behavior in BD. Alternatively, poorer QoL and suicidal behavior might be different expressions of more severe BD. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of the study was to analyze the impact of lifetime panic disorder (PD) diagnosis in a sample of patients with bipolar disorder type I (BPI), evaluating clinical and demographic variables. Methods: Ninety-five outpatients from the Bipolar Disorder Research Program at the Institute of Psychiatry of the University of Sao Paulo Medical School were enrolled. Twenty-seven BPI patients with PD were compared to 68 BPI patients without any anxiety disorders regarding clinical and demographic variables. Results: Compared to BPI patients without any anxiety disorders, patients with BPI + PD presented significantly higher number of mood episodes (18.9 ± 13.8 vs 8.5 ± 7.8; P < .001), depressive episodes (10.8 ± 8.2 vs 4.6 ± 4.8; P = .001), and manic episodes (7.4 ± 7.3 vs 3.6 ± 3.6; P = .008). Patients with BPI + PD had more frequently a depressive episode as their first one compared to BPI patients without anxiety disorders (94.1% vs 57.5%; P = .011). Patients with BPI + PD had more comorbidity with lifetime diagnosis of drug abuse or dependence (33.3% vs 8.8%; P = .010) and eating disorders (29.6% vs 6.0%; P = .004). Conclusions: The higher number of mood episodes in general presented by patients with BPI + PD when compared with BPI patients without any anxiety disorders, along with the higher frequencies of drug misuse and eating disorders, indicates that PD comorbidity is associated with a poorer course and outcome of BPI. The higher frequency of depression as the onset mood episode and the higher number of manic episodes in the group with PD may have important treatment implications and should be further investigated. [Copyright &y& Elsevier]

To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38–3.30]), renal (5.97 [1.31–43.16]), musculoskeletal (2.09 [1.30–3.43]) and endocrine (1.90 [1.20–3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99–2.49]), genitourinary (1.72 [1.02–2.92]), musculoskeletal (2.64 [1.66–4.37]) and endocrine (1.71 [1.08–2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes of mania or hypomania and depression, expressed by changes in energy levels and behavior. However, most of relapse studies use evidence-based approaches with statistical methods. With the advance of the precision medicine this study aims to use machine learning (ML) approaches as a possible predictor in depressive relapses in BD.Method: Four accepted and well used ML algorithms (Support Vector Machines, Random Forests, Naïve Bayes, and Multilayer Perceptron) were applied to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) dataset in a cohort of 800 patients (507 patients presented depressive relapse and 293 did not), who became euthymic during the study and were followed for one year.Results: The ML algorithms presented reasonable performance in the prediction task, ranging from 61 to 80% in the F-measure. The Random Forest algorithm obtained a higher average of performance (Relapse Group 68%; No Relapse Group 74%). The three most important mood symptoms observed in the relapse visit (Random Forest) were: interest; depression mood and energy.Limitations: Social and psychological parameters such as marital status, social support system, personality traits, might be an important predictor in depressive relapses, although we did not compute this data in our study.Conclusions: Our findings indicate that applying precision medicine models by means of machine learning in BD studies could be feasible as a sensible approach to better support medical decision-making in the BD treatment and prevention of future relapses. [ABSTRACT FROM AUTHOR]

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1β, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1β (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1β and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1β (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations. • Relationship between brain inflammation and symptomatology in BD is still unknown. • We sought for neuroinflammation and neuropsychiatric symptoms across brain regions. • Neuropsychiatric symptoms associate with neuroinflammation in brain-specific manners. • Neuroinflammatory changes occurring in BD may underlie clinical symptoms. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log 2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life. • Knowledge of molecular changes in older BD is limited. • Hippocampus is involved in BD pathophysiology and neuroprogression. • Gene expression changes were examined in older BD using feature selection analysis. • Twenty-five genes differentiated BD and control groups. • Identified targets enable us to better understand gene expression changes in older BD. [ABSTRACT FROM AUTHOR]

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 ± 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease (p = 0.039, p = 0.003, and p = 0.003 respectively); LLD, and DS were associated with brain infarcts (p = 0.012, p = 0.018, respectively) and Lewy body disease (p = 0.043, p = 0.002, respectively). DS was associated with beta-amyloid plaque burden (p = 0.027) and cerebral amyloid angiopathy (p = 0.035) in cognitively normal individuals (Clinical Dementia Rating scale = 0). Vascular brain pathology was the strongest correlate of clinical depictions of depression in the absence of dementia, corroborating the vascular hypothesis of depression. Lewy body pathology underlay DS. An older adult with DS or LLD should be monitored for possible cognitive decline or neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 (coronavirus disease 2019)-related pandemic represents a global source of societal and health burden. Yet, the impact of the pandemic on people with severe mental illness, including bipolar disorder (BD), remains unclear, warranting scoping review on the matter.Methods: The MEDLINE and EMBASE databases were systematically searched from inception up to April 24, 2021, adopting broad inclusion criteria to assess a variety of clinical and public health themes related to people with a primary diagnosis of BD during the COVID-19 pandemics. The present work complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) registered in the Open Science Framework (OSF) repository (https://osf.io/7evpx/).Results: Fourteen papers informed the present scoping review. Four major themes were identified: (i) impact of COVID-19-related stressors on BD; (ii) impact of COVID-19 on mental health service utilization among people with BD; (iii) impact of BD on the risk of acquiring SARS-CoV-2 infection; (iv) engagement in preventative behaviors among people with BD. Additional themes warranting further research were nonetheless detected.Limitations: Further original studies are needed.Conclusion: The present study confirmed the high-vulnerability hypothesis concerning people with BD versus the general population, reinforcing the need for further research related to the COVID-19 pandemic. Additional information is warranted to compare the impact of the pandemic period among BD people against pre-pandemic records, the general population, and other severe mental illnesses, namely people with schizophrenia or major depressive disorder, to inform the public health and the delivery of patient-tailored interventions. [ABSTRACT FROM AUTHOR]

Mental disorders are highly prevalent and important causes of medical burden worldwide. Co-occurrence of neurological and psychiatric symptoms are observed among mental disorders, representing a challenge for their differential diagnosis. Psychiatrists and neurologists have faced challenges in diagnosing old adults presenting behavioral changes. This is the case for early frontotemporal dementia (FTD) and bipolar disorder. In its initial stages, FTD is characterized by behavioral or language disturbances in the absence of cognitive symptoms. Consequently, patients with the behavioral subtype of FTD (bv-FTD) can be initially misdiagnosed as having a psychiatric disorder, typically major depression disorder (MDD) or bipolar disorder (BD). Bipolar disorder is associated with a higher risk of dementia in older adults and with cognitive impairment, with a subset of patients presents a neuroprogressive pattern during the disease course. No mendelian mutations were identified in BD, whereas three major genetic causes of FTD have been identified. Clinical similarities between BD and bv-FTD raise the question whether common molecular pathways might explain shared clinical symptoms. Here, we reviewed existing data on clinical and molecular similarities between BD and FTD to propose biological pathways that can be further investigated as common or specific markers of BD and FTD. • Differential diagnosis of psychiatric and neurological disorders remains a challenge. • Clinical similarities between bv-FTD and BD can lead to misdiagnosis. • Specific inflammatory and neuroprotective changes may underlie both bv-FTD and BD. • Further molecular studies can provide translational insights with therapeutic implications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Major depression (MDD) is a chronic psychiatric condition in which patients often show increasing cognitive impairment with recurring episodes. Neurodegeneration may play an important component in the pathogenesis of MDD associated with cognitive complaints. In agreement with this, patients with MDD show decreased brain volumes in areas implicated in emotional regulation and cognition, neuronal and glial cell death as well as activation of various pathways that can contribute to cell death. Therefore, the aim of this review is to provide an integrative overview of potential contributing factors to neurodegeneration in MDD. Studies have reported increased neuronal and glial cell death in the frontal cortex, amygdala, and hippocampus of patients with MDD. This may be due to decreased neurogenesis from lower levels of brain-derived neurotrophic factor (BDNF), excitotoxicity from increased glutamate signaling, and lower levels of gamma-aminobutyric acid (GABA) signaling. In addition, mitochondrial dysfunction and oxidative stress are found in similar brain areas where evidence of excitotoxicity has been reported. Also, levels of antioxidant enzymes were reported to be increased in patients with MDD. Inflammation may also be a contributing factor, as levels of inflammatory cytokines were reported to be increased in the prefrontal cortex of patients with MDD. While preliminary, studies have also reported neuropathological alterations in patients with MDD. Together, these studies suggest that lower BDNF levels, mitochondrial dysfunction, oxidative stress, inflammation and excitotoxicity may be contributing to neuronal and glial cell death in MDD, leading to decreased brain volume and cognitive dysfunction with multiple recurrent episodes. This highlights the need to identify specific pathways involved in neurodegeneration in MDD, which may elucidate targets that can be treated to ameliorate the effects of disease progression in this disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

White matter (WM) abnormalities have been reported in bipolar disorder (BD) patients, as well as in their non-BD relatives, both children and adults. Although it is considered an emerging vulnerability marker for BD, there are no studies investigating WM alterations in pediatric unmedicated patients and young healthy offspring. In this study, we evaluated the presence of WM alterations in 18 pediatric, non medicated BD patients, as well as in 18 healthy offspring of BD type I parents and 20 healthy controls. 3T DT-MRI data were acquired and scans were processed with tract-based spatial statistics to provide measures of fractional anisotropy and diffusivity. We found no significant differences in WM microstructure between BD patients, healthy offspring and healthy controls. Previous studies that reported WM alterations investigated older subjects, either on medication (BD patients) or with psychiatric diagnoses other than BD (unaffected offspring). Our findings highlight the importance of the understanding of disease ontogeny and brain development dynamics in the search for early vulnerability markers for psychiatric disorders. [ABSTRACT FROM AUTHOR]

Abstract: Up to 50% of bipolar disorder (BD) patients present a lifetime diagnosis of alcohol use disorders (AUD). BD patients with comorbid AUD, even when in remission from the AUD, have a poorer outcome and functional impairment than patients with BD alone. The neurobiological abnormalities that potentially characterize this severe subgroup of BD patients are unknown. Our goal was to investigate gray matter (GM) volume abnormalities in BD I patients with comorbid AUD. Twenty-one BD-AUD patients, 21 BD-nonAUD BD patients, and 25 healthy controls (HC), matched by age, gender, and handedness were studied. The BD-AUD patients were in remission from AUD on average for 6.8 years. 3D SPGR MRIs (TR=25ms, TE=5ms, slice thickness=1.5mm) were acquired from all subjects using a 1.5T GE Signa Imaging System. We used an optimized voxel-based morphometry protocol to compare GM volumes among the groups. BD-AUD patients presented smaller GM volumes in the left medial frontal and the right anterior cingulate gyri compared to BD-nonAUD patients. BDnon-AUD patients did not present GM volume differences compared to HC. These findings provide evidence for an effect of comorbid AUD on regional brain structure of BD I patients and warrant further research on neurobiological aspects of this prevalent and severe comorbidity. [Copyright &y& Elsevier]

Abstract: The neurobiology of Bipolar Disorder (BD) is not completely understood, although abnormalities in neuroplasticity and control of apoptosis have been considered as central events in its pathophysiology. The molecules of the Wnt family comprise a class of proteins that control essential developmental processes such as embryonic patterning, cell growth, migration, and differentiation with their actions largely exerted by modulating gene transcription. The Wnt signaling pathway has interface with some mediators with a well documented action in neuroplasticity and regulation of cell surviving. In addition, mood stabilizers such as lithium and valproate may have their neuroprotective properties in part mediated by the Wnt pathway. This article is an overview of how the Wnt signaling cascade might be involved in the pathogenesis of BD and also in details of intracellular events related to this pathway. Further studies of Wnt signaling may lead to a better comprehension of the neuroprotective actions of mood stabilizers and contribute to improving the therapeutics of BD. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to examine N-acetyl-aspartate (NAA), glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in the frontal cortical areas in children and adolescents with bipolar disorder (BP). The participants of the study involving pediatric patients with BP were examined. Results revealed that low NAA and PCr+Cr levels of the participants with BP may indicate neurodevelopmental disorders.

Abstract: Alcoholism is highly prevalent among bipolar disorder (BD) patients, and its presence is associated with a worse outcome and refractoriness to treatment of the mood disorder. The neurobiological underpinnings that characterize this comorbidity are unknown. We sought to investigate the neurochemical profile of the dorsolateral prefrontal cortex (DLPFC) of BD patients with comorbid alcoholism. A short-TE, single-voxel 1H spectroscopy acquisition at 1.5T from the left DLFPC of 22 alcoholic BD patients, 26 non-alcoholic BD patients and 54 healthy comparison subjects (HC) were obtained. Absolute levels of N-acetyl aspartate, phosphocreatine plus creatine, choline-containing compounds, myo-inositol, glutamate plus glutamine (Glu+Gln) and glutamate were obtained using the water signal as an internal reference. Analysis of co-variance was used to compare metabolite levels among the three groups. In the primary comparison, non-alcoholic BD patients had higher glutamate concentrations compared to alcoholic BD patients. In secondary comparisons integrating interactions between gender and alcoholism, non-alcoholic BD patients presented significantly higher glutamate plus glutamine (Glu+Gln) than alcoholic BD patients and HC. These results appeared to be driven by differences in male subjects. Alcoholic BD patients with additional drug use disorders presented significantly lower myo-inositol than BD patients with alcoholism alone. The co-occurrence of BD and alcoholism may be characterized by neurochemical abnormalities related to the glutamatergic system and to the inositol second messenger system and/or in glial pathology. These abnormalities may be the neurochemical correlate of an increased risk to develop alcoholism in BD, or of a persistently worse clinical and functional status in BD patients in remission from alcoholism, supporting the clinical recommendation that efforts should be made to prevent or early diagnose and treat alcoholism in BD patients. [Copyright &y& Elsevier]

Abstract: Objective: To study the executive functioning in euthymic bipolar patients in comparison to healthy controls and to examine the relationship between neuropsychological deficits and clinical variables. Methods: Twenty-five euthymic bipolar patients and 31 controls underwent a battery of executive tasks including mental flexibility, inhibitory control and verbal fluency tests. Results: There were no significant differences between bipolar patients and controls in relation to mental flexibility and inhibitory control. However, patients performed worse than controls on verbal fluency tests. Poor performances on the Stroop Test and the Hayling and Brixton Tests — part A were associated to lifetime occurrence of psychotic symptoms, prior number of episodes, and previous hospitalizations. Conclusions: In our study, only verbal fluency tests differentiated bipolar euthymic patients from healthy controls. Patients who showed deficits in information processing speed and inhibitory control had more episodes and hospitalizations and lifetime occurrence of psychotic symptoms. [Copyright &y& Elsevier]

Abstract: In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age±S.D.=13.0±2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age±S.D.=13.9±2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89±0.16cm3 versus 1.99±0.18cm3, respectively; F =5.0, d.f.=1/39, p =0.03; effect size: =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F =2.8, d.f.=2/38, p =0.07; effect size: =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction. [Copyright &y& Elsevier]

Abstract: The dorsolateral prefrontal cortex (DLPFC) plays an essential role in mood regulation and integration of cognitive functions that are abnormal in major depressive disorder (MDD). Few neuroimaging studies have evaluated the still maturing DLPFC in depressed children and adolescents. We conducted single voxel proton magnetic resonance spectroscopy (1H MRS) of the left DLPFC in 14 depressed children and adolescents (13.3±2.3 years old, 10 males) and 22 matched healthy controls (13.6±2.8 years old, 13 males). Depressed subjects had significantly lower levels of glycerophosphocholine plus phosphocholine (GPC+PC; or choline-containing compounds) and higher myo-inositol levels in the left DLPFC compared to healthy controls. In the depressed subjects, we found significant inverse correlations between glutamate levels and both duration of illness and number of episodes. In healthy controls there was a significant direct correlation between age and glutamine levels, which was not present in the patient group. Lower GPC+PC levels in pediatric MDD may reflect lower cell membrane content per volume in the DLPFC. Increased myo-inositol levels in MDD may represent a disturbed secondary messenger system. GPC+PC and myo-inositol abnormalities further demonstrate the involvement of DLPFC in pediatric MDD. [Copyright &y& Elsevier]

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. To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. 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. 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. 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. • In BD, higher total CTQ score was found to be associated with lower ACC levels of Glu. • Greater severity of sexual abuse was associated with increased ACC PCr level in BD. • Greater severity of sexual abuse was associated with decreased ACC Cr level in BD. [ABSTRACT FROM AUTHOR]