Electroconvulsive Therapy Versus Repetitive Transcranial Magnetic Stimulation in Patients With a Depressive Episode: A Register-Based Study.

OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions. METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively. RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression. CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.

Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

ABSTRACT: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression - A Swedish register-based study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. LIMITATIONS: Retrospective analysis of register data. No comparison group. CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.

Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998-2020.

OBJECTIVES: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence. METHODS: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15-19 and 20-88+, across 1998-2020. RESULTS: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj  = 0.5216 and p < 0.00001, R-squaredadj  = 0.5090, in the 15-19 and 20-88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate. CONCLUSIONS: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.

Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy.

BACKGROUND: The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. AIM: This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. MATERIALS AND METHODS: From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery Åsberg Depression Rating Scale between the Q-ECT and the patient record. RESULTS: A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. CONCLUSIONS: We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.

Plasma Levels of Brain-Derived Neurotrophic Factor and S100B in Relation to Antidepressant Response to Ketamine.

BACKGROUND: Evidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking. METHOD: We evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (n = 20) to a placebo (n = 10) control (saline). Severity of depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Plasma mBDNF and S100B were not significantly changed after 1-2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1-2 weeks of open-label ketamine treatment (rho = 0.495, p = 0.031), though this change did not survive correction for multiple comparisons. CONCLUSION: These findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.

P11 (S100A10) as a potential predictor of ketamine response in patients with SSRI-resistant depression.

BACKGROUND: Ketamine can act as antidepressant in patients with major depressive disorder (MDD) who are treatment-resistant. P11 has been implicated in ketamine's mechanism of action and proposed as biomarker for treatment response to other antidepressants. This study explores the effect of ketamine on peripheral p11 and the potential role for p11 as response marker for ketamine treatment. METHODS: Thirty Selective Serotonin Reuptake Inhibitor resistant MDD patients were randomized to either 0.5 mg/kg ketamine or placebo intravenous treatment. Using multicolor Flow Cytometry, peripheral p11 levels were measured before and 1-2 days after treatment. RESULTS: P11 levels were decreased within the ketamine group in both cytotoxic T cell and T helper cells populations, although this did not significantly differ from changes seen in the placebo group. Baseline p11 levels in cytotoxic T cells were significantly correlated with antidepressant response to ketamine treatment. LIMITATIONS: This study was part of a larger study examining the effect of ketamine on the serotonin system in MDD patients, therefore the number of study subjects was limited to that of the primary study. CONCLUSIONS: High baseline p11 levels in cytotoxic T cells were associated with a stronger reduction of depressive symptoms in MDD patients after ketamine treatment. Future studies should confirm if peripheral p11 levels could be used as a predictor of ketamine treatment response.

Repetitive transcranial magnetic stimulation in major depression: A three-arm parallel-group dose-response randomized pilot trial.

BACKGROUND: The optimal dose (number of pulses per session) of repetitive transcranial magnetic stimulation (rTMS), using the H-coil, in major depressive disorder (MDD) has not previously been reported. OBJECTIVE: To explore the relationship between rTMS dose and antidepressant effect, and collect data for the design of a definitive trial. METHODS: This was a double-blind, three-arm parallel-group, randomized [1:1:1], pilot trial conducted in Stockholm, Sweden (September 2014 to September 2016). The primary outcome was change in depression severity measured with the Montgomery Åsberg Depression Rating Scale (MADRS) after 4 weeks. Participants (n = 29) with MDD were randomized to 1000, 2000, or 4000 pulses of rTMS for 20 sessions during 4 weeks. RESULTS: At 4 weeks, the 3 treatment groups reduced the mean MADRS (95% CI) by 11.6 (4.0-19.2), 9.1 (5.0-13.3), and 11.3 (4.1-18.5) points respectively. Eleven participants met criteria for response and 10 for remission. No serious adverse events occurred. Ratings of subjective memory improved in all groups. Exploring the effect of dose and time, 4000 pulses had the largest reduction in MADRS during the first 2 weeks. A comparison of change in MADRS between 2000 and 4000 pulses after 2 weeks will require a sample size of 66 patients at power .80 and alpha .05. CONCLUSIONS: It is feasible to conduct a definitive trial investigating whether a higher number of magnetic pulses per treatment session gives a more rapid antidepressive response.

A randomized placebo-controlled PET study of ketamine´s effect on serotonin1B receptor binding in patients with SSRI-resistant depression.

The glutamate N-methyl-D-aspartate receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine's mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the serotonin (5-HT)1B receptor. Low 5-HT1B receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT1B receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT1B receptor selective radioligand [11C]AZ10419369 and positron emission tomography (PET) before and 24-72 h after treatment. 5-HT1B receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT1B receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT1B receptor binding in VST at baseline correlated with MDD symptom ratings (r = -0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = -0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT1B receptor binding in VST. Further studies examining the role of 5-HT1B receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT1B receptor as an MDD treatment response marker.

The Effect of Pulse Width on Subjective Memory Impairment and Remission Rate 6 Months After Electroconvulsive Therapy.

OBJECTIVES: The aim of this study was to compare the 0.5-millisecond pulse width with broader brief width stimulus and ultrabrief pulse width stimulus in respect to rates of subjective memory impairment and remission 6 months after completion of electroconvulsive therapy (ECT). METHODS: This study used data from the Swedish National Quality Register for ECT. Inclusion criteria were bipolar or unipolar depression with or without psychosis, ECT with unilateral electrode placement, and data on the Montgomery-Åsberg Depression Rating Scale-Self-Assessment and the memory item of the Comprehensive Psychopathological Rating Scale (CPRS-M) before and 6 months after ECT. The primary outcomes were the distributions of patients with a maximum of 10 on the Montgomery-Åsberg Depression Rating Scale-Self-Assessment (remission) and a minimum of 2-step worsening in CPRS-M score according to the ECT pulse widths of <0.5, 0.5, and >0.5 millisecond. RESULT: This study included 312 patients. The distributions of patients with remission or a minimum of 2-step worsening on the CPRS-M 6 months after completion of ECT showed no significant differences between the 3 pulse width groups. Older age was associated with a significantly higher rate of remission 6 months after ECT. CONCLUSIONS: In this cohort of patients, no support was found for the previous research finding of lower rates of subjective memory disturbances 6 months after ultrabrief pulse width ECT in comparison with brief pulse width ECT. Older age was associated with higher remission rate 6 months after ECT. Large randomized studies are required to exclude the possibility of long-term differential effects between pulse widths.

Physician estimated vs. self-reported subjective memory in depressed patients treated with electroconvulsive therapy.

Background: Subjective memory deficits are common in depression and during series of treatment with electroconvulsive therapy (ECT). There is a need for feasible assessment of memory deficit. In the Swedish National Quality Register for ECT, patients' subjective memory function is rated by a clinician. Self-ratings would be easier to administer.Objectives: The aim of this study was to analyze the consistency between self-reported and physician estimated subjective memory in depressed patients treated with ECT.Methods: Fifty-two inpatients treated with ECT for major- or bipolar depression were recruited and 41 of them completed the study protocol. Each patient rated their own subjective memory and had it rated in an interview by a physician both before/in the beginning of the ECT series and after the ECT series. The patients' memory was rated and self-rated with the memory item in the Comprehensive Psychopathological Rating Scale (CPRS). We then analyzed correlations, and differences in distributions, between self-reported assessment and physician estimates of patients' subjective memory.Results: The correlations between the self-reported and the physician estimated ratings of subjective memory were 0.699 (p < .01) in baseline ratings and 0.651 (p < .01) in post-treatment ratings. These correlations were relatively high compared to a previous study on self-reported vs. physician estimated CPRS ratings.Conclusions: Based on the results in this study, we propose that patients' self-ratings of subjective memory in association with ECT can be used instead of a physician's rating of patients' subjective memory.

Electroconvulsive Therapy in Depression: Improvement in Quality of Life Depending on Age and Sex.

OBJECTIVES: It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups. METHODS: This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups. RESULTS: There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients. CONCLUSIONS: Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.

The Incidence of Dental Fracturing in Electroconvulsive Therapy in Sweden.

OBJECTIVES: One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions. METHODS: This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions. RESULTS: Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture. CONCLUSIONS: There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant.

Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use.

BACKGROUND: Bipolar disorder (BD) is a highly heritable psychiatric disorder characterized by episodes of manic and depressed mood states and associated with cortical brain abnormalities. Although the course of BD is often progressive, longitudinal brain imaging studies are scarce. It remains unknown whether brain abnormalities are static traits of BD or result from pathological changes over time. Moreover, the genetic effect on implicated brain regions remains unknown. METHODS: Patients with BD and healthy control (HC) subjects underwent structural magnetic resonance imaging at baseline (123 patients, 83 HC subjects) and after 6 years (90 patients, 61 HC subjects). Cortical thickness maps were generated using FreeSurfer. Using linear mixed effects models, we compared longitudinal changes in cortical thickness between patients with BD and HC subjects across the whole brain. We related our findings to genetic risk for BD and tested for effects of demographic and clinical variables. RESULTS: Patients showed abnormal cortical thinning of temporal cortices and thickness increases in visual/somatosensory brain areas. Thickness increases were related to genetic risk and lithium use. Patients who experienced hypomanic or manic episodes between time points showed abnormal thinning in inferior frontal cortices. Cortical changes did not differ between diagnostic BD subtypes I and II. CONCLUSIONS: In the largest longitudinal BD study to date, we detected abnormal cortical changes with high anatomical resolution. We delineated regional effects of clinical symptoms, genetic factors, and medication that may explain progressive brain changes in BD. Our study yields important insights into disease mechanisms and suggests that neuroprogression plays a role in BD.

Classification of cognitive performance in bipolar disorder.

OBJECTIVE: To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls. METHOD: Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques. RESULTS: A distinct subgroup (∼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics. CONCLUSIONS: Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.

Markers of neuroinflammation and neuronal injury in bipolar disorder: Relation to prospective clinical outcomes.

Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression.

A History of Psychosis in Bipolar Disorder is Associated With Gray Matter Volume Reduction.

Psychotic symptoms are prevalent in schizophrenia, bipolar disorder, and other psychiatric and neurological disorders, yet the neurobiological underpinnings of psychosis remain obscure. In the last decade, a large number of magnetic resonance imaging studies have shown differences in local gray matter volume between patients with different psychiatric syndromes and healthy controls. Few studies have focused on the symptoms, which these syndromes are constituted of. Here, we test the association between psychosis and gray matter volume by using a sample of 167 subjects with bipolar disorder, with and without a history of psychosis, and 102 healthy controls. Magnetic resonance images were analyzed on group level using a voxel-wise mass univariate analysis (Voxel-Based Morphometry). We found that patients with a history of psychosis had smaller gray matter volume in left fusiform gyrus, the right rostral dorsolateral prefrontal cortex, and the left inferior frontal gyrus compared with patients without psychosis and with healthy controls. There was no volume difference in these areas between the no-psychosis group and healthy controls. These areas have previously been structurally and functionally coupled to delusions and hallucinations. Our finding adds further evidence to the probability of these regions as key areas in the development of psychotic symptoms.

Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.

INTRODUCTION: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737. METHODS: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N = 114) and sex- and age-matched population controls (N = 104). RESULTS: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls. CONCLUSIONS: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.

Cortical thickness, volume and surface area in patients with bipolar disorder types I and II.

BACKGROUND: Bipolar disorder (BD) is a common chronic psychiatric disorder mainly characterized by episodes of mania, hypomania and depression. The disorder is associated with cognitive impairments and structural brain abnormalities, such as lower cortical volumes in primarily frontal brain regions than healthy controls. Although bipolar disorder types I (BDI) and II (BDII) exhibit different symptoms and severity, previous studies have focused on BDI. Furthermore, the most frequently investigated measure in this population is cortical volume. The aim of our study was to investigate abnormalities in patients with BDI and BDII by simultaneously analyzing cortical volume, thickness and surface area, which yields more information about disease- and symptom-related neurobiology. METHODS: We used MRI to measure cortical volume, thickness and area in patients with BDI and BDII as well as in healthy controls. The large study cohort enabled us to adjust for important confounding factors. RESULTS: We included 81 patients with BDI, 59 with BDII and 85 controls in our analyses. Cortical volume, thickness and surface area abnormalities were present in frontal, temporal and medial occipital regions in patients with BD. Lithium and antiepileptic drug use had an effect on the observed differences in medial occipital regions. Patients with the subtypes BDI and BDII displayed common cortical abnormalities, such as lower volume, thickness and surface area than healthy controls in frontal brain regions but differed in temporal and medial prefrontal regions, where only those with BDI had abnormally low cortical volume and thickness. LIMITATIONS: The group differences can be explained by progressive changes, but also by premorbid conditions. They could also have been influenced by unknown factors, such as social, environmental or genetic factors. CONCLUSION: Our findings suggest diagnosis-related neurobiological differences between the BD subtypes, which could explain distinct symptoms and point to potential biomarkers that could inform the subtype diagnosis of BD.