Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Comparison of the neurocognitive profile of the children of parents with bipolar disorder and controls: A transnational cross-sectional study.

INTRODUCTION: Studies that have compared the cognitive alterations of the children of parents with bipolar disorder (CPBD) versus the children of control parents (CCP), present heterogeneous results due to the studies' methodological differences, the age of the population studied, and the lack of standardisation of the measures used for the different neurocognitive domains. The objective was to compare the neurocognitive profile of CPBD versus CCP to observe if there are differences that could be proposed as possible endophenotypes of BD. RESULTS: A total of 107 individuals (51 CPBD, and 56 CCP) with ages between 6 and 16 (mean, 12.2±2.80) years of age were evaluated. Seventy-four point five percent of the CPBD group had some disorder compared to 67.9% of the CCP group. Tests such as letter-F phonemic verbal fluency, letter-S phonemic verbal fluency, overall F-A-S phonemic verbal fluency, story recall and retrieval, and Wisconsin perseverative errors showed a difference with a small effect size, but with a high degree of uncertainty. CONCLUSIONS: The CPBD did not have differences in their neurocognitive profile in comparison with CCP. Both groups have a high prevalence of psychopathology, which is a factor that could explain the lack of differences in neurocognitive performance.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study.

OBJECTIVE: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). METHODS: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. RESULTS: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. CONCLUSIONS: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Predicting diagnostic conversion from major depressive disorder to bipolar disorder: an EHR based study from Colombia.

Bipolar Disorder (BD) is a severe and chronic disorder characterized by recurrent episodes of depression, mania, and/or hypomania. Most BD patients initially present with depressive symptoms, resulting in a delayed diagnosis of BD and poor clinical outcomes. This study leverages electronic health record (EHR) data from the Clínica San Juan de Dios Manizales in Colombia to identify features predictive of the transition from Major Depressive Disorder (MDD) to BD. Analyzing EHR data from 13,607 patients diagnosed with MDD over 15 years, we identified 1,610 cases of conversion to BD. Using a multivariate Cox regression model, we identified severity of the initial MDD episode, the presence of psychosis and hospitalization at first episode, family history of mood or psychotic disorders, female gender to be predictive of the conversion to BD. Additionally, we observed associations with medication classes (prescriptions of mood stabilizers, antipsychotics, and antidepressants) and clinical features (delusions, suicide attempt, suicidal ideation, use of marijuana and alcohol use/abuse) derived from natural language processing (NLP) of clinical notes. Together, these risk factors predicted BD conversion within five years of the initial MDD diagnosis, with a recall of 72% and a precision of 38%. Our study confirms many previously identified risk factors identified through registry-based studies (such as female gender and psychotic depression at the index MDD episode), and identifies novel ones (specifically, suicidal ideation and suicide attempt extracted from clinical notes). These results simultaneously demonstrate the validity of using EHR data for predicting BD conversion as well as underscore its potential for the identification of novel risk factors and improving early diagnosis.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study

Objective: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). Methods: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. Results: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. Conclusions: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Objetivo: Nuestro objetivo es determinar la prevalencia de trastornos mentales en hermanos de casos con TDAH y cómo los factores de adversidad psicosocial se relacionan con esta psicopatología en un país de ingresos bajos-medios (Colombia). Métodos: Se evaluó a sujetos con TDAH diagnosticado según los criterios del DSM-5, uno de sus padres y uno de sus hermanos (edades, 8-19 anos). Mediante la escala de calificación del TDAH y un conjunto de otros instrumentos se evaluó la presencia de trastornos mentales y adversidad psicosocial. Resultados: Se evaluó a 74 tríos formados por el caso índice con TDAH, un hermano y uno de los padres. Se halló que un 24,3% de los hermanos participantes también cumplían los criterios de TDAH y otro 24,3%, otros trastornos psiquiátricos. El riesgo de que estos hermanos tuvieran TDAH aumentó aún más cuando uno de los padres informó antecedentes de TDAH. También, que el 28,3% de las familias se enfrentaron a altos niveles de adversidad psicosocial según sus puntuaciones en el Índice de Adversidad de Rutter. Conclusiones: Los hermanos de sujetos con TDAH mostraron un significativo riesgo de TDAH y otros trastornos mentales. Ese riesgo aumenta si uno de los padres reporta antecedentes de TDAH y también cuando se presentan 2 o más factores de adversidad psicosocial. Este estudio respalda la importancia de la detección temprana con el fin de disminuir el riesgo para otros hermanos.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Ancestry component as a major predictor of lithium response in the treatment of bipolar disorder.

BACKGROUND: Bipolar Disorder (BD) represents the seventh major cause of disability life-years-adjusted. Lithium remains as a first-line treatment, but clinical improvement occurs only in 30 % of treated patients. Studies suggest that genetics plays a major role in shaping the individual response of BD patients to lithium. METHODS: We used machine-learning techniques (Advance Recursive Partitioned Analysis, ARPA) to build a personalized prediction framework of BD lithium response using biological, clinical, and demographical data. Using the Alda scale, we classified 172 BD I-II patients as responders or non-responders to lithium treatment. ARPA methods were used to build individual prediction frameworks and to define variable importance. Two predictive models were evaluated: 1) demographic and clinical data, and 2) demographic, clinical and ancestry data. Model performance was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: The predictive model including ancestry yield the best performance (sensibility = 84.6 %, specificity = 93.8 % and AUC = 89.2 %) compared to the model without ancestry (sensibility = 50 %, Specificity = 94.5 %, and AUC = 72.2 %). This ancestry component best predicted lithium individual response. Clinical variables such as disease duration, the number of depressive episodes, the total number of affective episodes, and the number of manic episodes were also important predictors. CONCLUSION: Ancestry component is a major predictor and significantly improves the definition of individual Lithium response in BD patients. We provide classification trees with potential bench application in the clinical setting. While this prediction framework might be applied in specific populations, the used methodology might be of general use in precision and translational medicine.

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Neuropsychological aspects of bipolar disorder.

Bipolar disorder (BD) is a chronic condition with serious consequences on the health and functionality of patients who suffer from it, with a high heritability and segregation, and aprevalence of between 1% and 2%. Neuropsychological deficits have been implicated as a very important issue related to BD prognosis, so a review was conducted of these deficits, the related factors and their functional consequences. It has been determined that the presence of neuropsychological deficits can vary in patients with BD according to their mood state, with a great influence of depressive symptoms on the cognitive variability of patients with respect to the general population and differences with respect to patients in the manic phase. In euthymic patients, the most affected cognitive domains are those of memory, attention, and executive function, associated with a more severe disease, sociodemographic vulnerability factors, and stable over time. A relationship has been found between poor cognitive performance, especially executive dysfunction, and objective functional deficit. Furthermore, cognitive differences have been outlined between BD and other serious mental illnesses that are described in this review.

Aspectos neuropsicológicos del trastorno afectivo bipolar / Neuropsychological Aspects of Bipolar Disorder

RESUMEN El trastorno afectivo bipolar (TAB) es una entidad crónica con graves efectos para la salud y la funcionalidad de los pacientes que la sufren, con una alta carga de heredabilidad y segregabilidad y una prevalencia que oscila entre el 1 y el 2%. Las alteraciones neuropsicológicas son características importantes relacionadas con su pronóstico, por lo cual se hizo una revisión narrativa sobre estas alteraciones, los factores asociados y sus consecuencias funcionales. Se ha determinado que la presencia de alteraciones neuropsicológicas puede variar en los pacientes con TAB según la fase anímica en que se encuentren, con una gran influencia de los síntomas depresivos en la variabilidad cognitiva de los pacientes respecto a la población general y diferencias respecto a los pacientes en fase maniaca. En pacientes eutímicos, los dominios cognitivos más afectados son los de memoria, atención y función ejecutiva, asociados con una enfermedad más grave, factores sociodemográficos de vulne rabilidad y sin interacción con el tiempo de evolución. Se ha encontrado una relación entre el mal rendimiento cognitivo, especialmente la disfunción ejecutiva y el déficit funcional objetivo; además, se han perfilado diferencias cognitivas entre el TAB y otras enfermedades mentales graves que se describen en la revisión.

ABSTRACT Bipolar disorder (BD) is a chronic condition with serious consequences on the health and functionality of patients who suffer from it, with a high heritability and segregation, and a prevalence of between 1% and 2%. Neuropsychological deficits have been implicated as a very important issue related to BD prognosis, so a review was conducted of these deficits, the related factors and their functional consequences. It has been determined that the presence of neuropsychological deficits can vary in patients with BD according to their mood state, with a great influence of depressive symptoms on the cognitive variability of patients with respect to the general population and differences with respect to patients in the manic phase. In euthymic patients, the most affected cognitive domains are those of memory, attention, and executive function, associated with a more severe disease, sociodemographic vulnerability factors, and stable over time. A relationship has been found between poor cognitive performance, especially executive dysfunction, and objective functional deficit. Furthermore, cognitive differences have been outlined between BD and other serious mental illnesses that are described in the review.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.

Differences of affective and non-affective psychoses in early intervention services from Latin America.

BACKGROUND: Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample. METHODS: Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status. RESULTS: A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up. LIMITATIONS: The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases. CONCLUSIONS: This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.

Smartphone-based interventions in bipolar disorder: Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force.

BACKGROUND: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. OBJECTIVES: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. METHODS: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). RESULTS: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. CONCLUSION: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.

Resting-state functional nuclear magnetic resonance imaging in patients with bipolar disorder: Beyond euthymia.

INTRODUCTION: Functional nuclear magnetic resonance imaging in the resting state (R-fMRI) allows the identification of complete functional connectivity networks and the possible neuronal correlations of psychiatric disorders. The literature on R-fMRI and bipolar disorder (BD) will be reviewed, emphasising the findings in the phases of mania, hypomania and depression. METHODS: It is a narrative review of the literature in which articles were searched in PubMed and Embase, with the key words in English "bipolar disorder" AND "resting state", without limit on the date of publication. RESULTS: The studies of BD patients in the mania and hypomania phases who underwent R-fMRI show concordant results in terms of decreased functional cerebral connectivity between the amygdala and some cortical regions, which indicates that this functional connection would have some implication in the normal affect regulation. Patients in the depressive phase show a decrease in functional brain connectivity, but as there are several anatomical structures involved and neural networks reported in the studies, it is not possible to compare them. CONCLUSIONS: There is a decrease in functional connectivity in patients with BD, but current evidence does not allow establishing specific changes in specific functional brain connectivity networks. However, there are already some findings that show correlation with the patients' symptoms.

Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular.

Structural neuroimaging and predominant polarity in patients with type 1 bipolar disorder from Antioquia.

INTRODUCTION: Predominant polarity (PP) has been proposed as a specifier of bipolar disorder (BD) due to its relationship with clinical and prognostic variables. It is possible that this is due to a different underlying neurobiology, in such a way that the changes found by structural nuclear magnetic resonance imaging (sMRI) in BD are different and specific. OBJECTIVES: To explore findings of structural neuroimaging in patients with BD type I (BD-I) according to PP. METHODS: Cross-sectional study that evaluated 77 patients with BD-I using the DIGS interview. PP was established using the operative definition of two-thirds of all affective episodes throughout life to classify PP as manic (MPP), depressive (DPP) or indeterminate (IPP). MRI was performed during the euthymia phase to measure intracranial structures. The data obtained was analysed using a linear regression model adjusted for confounding variables (drug use, alcohol use, psychoactive substance use) and were compared between the three groups finding the standardised mean difference (SMD). RESULTS: Differences with adequate effect size were found in three brain structures after adjusting for confounding variables, specifically in the right fusiform gyrus and the left lingual gyrus, which were greater in the DPP group than in the MPP group (SMD = 0.92; 95% CI = 0.34-1.49 and SMD = 0.78; 95% CI = 0.21-1.35). Likewise, in the right thalamus, it was shown to be greater in the IPP group compared to MPP group (SMD 0.89, 95% CI = 0.31-1.46). CONCLUSIONS: A reduction in the thickness of the right fusiform gyrus and the left lingual gyrus, as well as the right thalamic volume was observed in patients with BD-I with PPM, which supports the hypothesis that PP has a plausible neurobiological correlate and could have potential utility as a BD specifier.

Correlation between cognitive performance and structural neuroanatomy in patients with type I bipolar affective disorder treated with and without lithium.

INTRODUCTION: Lithium treatment of bipolar disorder (BD) has been associated with less cognitive impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. METHODS: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propensity score, and the Spearman correlation coefficient (ρ) was used to assess the relationship between cognitive performance and neuroanatomical regions. RESULTS: Compared to the group without lithium, the group with lithium had fewer perseverative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amygdala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD = .67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (ρ = -0.78), the volume of the right thalamus (ρ = -0.44), and the right amygdala (ρ = 0.6). CONCLUSIONS: The lithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.