Dorsolateral Prefrontal Cortex Volume Research Articles

Dorsolateral prefrontal cortex volume as a mediator between socioeconomic status and executive function.

Lower socioeconomic status (SES) is related to poorer cognitive performance, but the neural underpinnings of this relation are not fully understood. This study examined whether SES-linked decrements in executive function were mediated by smaller dorsolateral prefrontal cortex (DLPFC) volumes. Given the literature demonstrating that SES-brain relations differ by race, we examined whether race moderated these mediations. Participants were 190 socioeconomically diverse, self-identified African American (AA) and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Regional brain volumes were derived using T1-weighted MP-RAGE images. Adjusting for age and sex, moderated mediation analyses examined if the DLPFC mediated SES-executive function relations differently across racial groups. Executive function was measured using Trail Making Test part B (Trails B), Digit Span Backwards (DSB), and verbal fluency. Moderated mediation demonstrated that DLPFC volume significantly mediated the association between SES and Trails B in Whites (lower confidence interval [CI] = 0.01; upper CI = 0.07), but not in AAs (lower CI = -0.05; upper CI = 0.01). No mediations were found for DSB or verbal fluency, although SES was related to all tests. The DLPFC may be important in the association of SES and mental flexibility for White, but not AA adults. It is possible that the well-replicated advantages of high SES among Whites do not readily translate, on average, to AAs. These findings highlight the importance of brain volume for cognitive functioning, while adding to the literature on sociodemographic health disparities. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study

Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p = 0.037, OR = 0.65, 95% CI = 0.43–0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p = 0.035, Cohen’s d = 0.194), as well as significantly greater DLPFC (p < 0.05, Cohen’s d = −0.21) and parahippocampal volumes (p < 0.01, Cohen’s d = −0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.

Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders

Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.

Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.

ObjectiveThe effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health.MethodsParticipants (aged 42–56 years; 5–36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B–PET (n = 68).ResultsVentricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo.ConclusionsThe effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain.Classification of evidenceThis study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT.

Neuroanatomical correlates of grit: Growth mindset mediates the association between gray matter structure and trait grit in late adolescence.

There is a long-standing interest in exploring the factors related to student achievement. As a newly explored personality trait, grit is defined as a person's tendency to pursue long-term goals with continual perseverance and passion, and grit plays a critical role in student achievement. Increasing evidence has shown that growth mindset, the belief that one's basic abilities are malleable and can be developed through effort, is a potential factor for cultivating grit. However, less is known about the association between grit and the brain and the role of growth mindset in this association. Here, we utilized voxel-based morphometry to examine the neuroanatomical correlates of grit in 231 healthy adolescent students by performing structural magnetic resonance imaging. The whole-brain regression analyses revealed that the regional gray matter volume (rGMV) in the left dorsolateral prefrontal cortex (DLPFC) negatively predicted grit. In contrast, the rGMV in the right putamen positively predicted grit. Furthermore, mediating analyses suggested that growth mindset served as a mediator in the association between left DLPFC volume and grit. Our results persisted even after controlling for the influences of self-control and delayed gratification. Overall, our study presents novel evidence for the neuroanatomical basis of grit and highlights that growth mindset might play an essential role in cultivating a student's grit level.

Examining brain structures associated with dispositional envy and the mediation role of emotional intelligence

Dispositional envy is distinguished by definition and neurally from episodic envy. While the neural correlates of episodic envy have been evaluated by specific tasks in previous studies, little is known about the structural neural basis of dispositional envy. In this study, we investigated the structural neural basis of dispositional envy underlying individual differences across two independent samples comprising a total of 100 young healthy adults. Firstly, 73 subjects’ data (sample 1) was analyzed, and we assessed the association between regional gray matter volume (rGMV) and dispositional envy using voxel-based morphometry (VBM). Furthermore, we explored the role of emotional intelligence in the association between GMV and dispositional envy. VBM indicated that dispositional envy was positively correlated with GMV in the left dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG). We also found that emotional intelligence partially mediated the association between DLPFC volume and dispositional envy. These results were replicated in another independent sample (Sample 2, n = 27). These results provide the first evidence that dispositional envy exhibits a structural neural correlation with the DLPFC and STG, and give a neutral explanation for why individuals with high emotional intelligence exhibit less envy.

Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task

The CNTNAP2 (contactin-associated protein-like 2) gene, highly expressed in the human prefrontal cortex, has been linked with autism and language impairment. Potential relationships between CNTNAP2, dorsolateral prefrontal cortex (DLPFC), and cognition have been suggested by previous clinical studies, but have not been directly examined in the same study. The current study collected structural MRI, genetic, and behavioral data in 317 healthy Chinese adults, and examined associations between CNTNAP2 variants, DLPFC, and cognitive performance (measured by the Stroop task). After controlling for intracranial volume, sex, and age, the CNTNAP2 genetic polymorphism at SNP rs7809486 had the strongest association with bilateral DLPFC volume (p=0.00015 and 0.00014 for left and right DLPFC volumes, respectively), with GG homozygotes having greater bilateral DLPFC volumes and surface areas than the other genotypes. Furthermore, TT homozygotes of CNTNAP2 rs4726946 (a nearby SNP that had moderate linkage disequilibrium with rs7809486) had greater left DLPFC volume and surface area, and better cognitive performance than the other genotypes. Subjects with greater left DLPFC surface area had better cognitive performance. Importantly, the left DLPFC surface area mediated the association between the CNTNAP2 rs4726946 genotype and cognitive performance. This study provides the first evidence for associations among the CNTNAP2 gene, left DLPFC structure, and cognitive control.

Neural correlates of impaired self-awareness of apathy, disinhibition and dysexecutive deficits in cocaine-dependent individuals.

Cocaine addiction is characterized by impaired self-awareness about cognitive and motivational deficits, leading to poor treatment outcomes. However, there is still limited understanding of the neurophysiological underpinnings of this impairment. We aimed to establish if impaired self-awareness is underpinned by brain structural phenotypes among cocaine-dependent individuals (CDI). Sixty-five CDI and 65 designated informants completed the Frontal Systems Behavior Scale, and a subsample of 40 CDI were scanned via magnetic resonance imaging. We applied multiple regression models to establish the association between levels of self-awareness indexed by Frontal Systems Behavior Scale's discrepancy scores (i.e. informant ratings minus self-reports of apathy, disinhibition and dysexecutive deficits) and gray matter volumes indexed by magnetic resonance imaging voxel-based measures within five brain regions of interest: anterior cingulate cortex, orbitofrontal cortex (OFC), striatum, insula and dorsolateral prefrontal cortex (DLPFC). We also examined the neural underpinnings of underestimation versus overestimation of deficits, by splitting the CDI group according to the positive or negative value of their discrepancy scores. We found that poorer self-awareness of apathy deficits was associated with greater gray matter volume in the dorsal striatum, and poorer self-awareness of disinhibition deficits was associated with greater gray matter volume in the OFC in the whole sample. More underestimation and more overestimation of executive deficits were linked to lower DLPFC volume. We show that impaired self-awareness of cognitive and motivational deficits in cocaine addiction has a neural underpinning, implicating striatum, OFC and DLPFC structural phenotypes.

Brain structural anomalies in borderline and avoidant personality disorder patients and their associations with disorder-specific symptoms

BackgroundBorderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature. MethodsIn the present study we investigated group differences among 29 BPD patients, 27 AvPD patients, and 29 healthy controls (HC) in structural brain volumes using voxel-based morphometry (VBM) in five anatomically-defined regions of interest: amygdala, hippocampus, medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). We also examined the relationship between individual differences in brain structure and self-reported anxiety and affective instability in each group. ResultsWe observed reductions in MPFC and ACC volume in BPD relative to HC, with no significant difference among patient groups. No group differences in amygdala volume were found. However, BPD and AvPD patients each showed a positive relationship between right amygdala volume and state-related anxiety. By contrast, in HC there was an inverse relationship between MPFC volume and state and trait-related anxiety as well as between bilateral DLPFC volume and affective instability. LimitationsCurrent sample sizes did not permit examination of gender effects upon structure-symptom correlations. ConclusionsThese results shed light on potentially protective, or compensatory, aspects of brain structure in these populations–namely, relatively reduced amygdala volume or relatively enhanced MPFC and DLPFC volume.

Representation of economic preferences in the structure and function of the amygdala and prefrontal cortex.

Social value orientations (SVOs) are economic preferences for the distribution of resources – prosocial individuals are more cooperative and egalitarian than are proselfs. Despite the social and economic implications of SVOs, no systematic studies have examined their neural correlates. We investigated the amygdala and dorsolateral prefrontal cortex (DLPFC) structures and functions in prosocials and proselfs by functional magnetic resonance imaging and evaluated cooperative behavior in the Prisoner’s Dilemma game. We found for the first time that amygdala volume was larger in prosocials and positively correlated with cooperation, while DLPFC volume was larger in proselfs and negatively correlated with cooperation. Proselfs’ decisions were marked by strong DLPFC and weak amygdala activity, and prosocials’ decisions were marked by strong amygdala activity, with the DLPFC signal increasing only in defection. Our findings suggest that proselfs’ decisions are controlled by DLPFC-mediated deliberative processes, while prosocials’ decisions are initially guided by automatic amygdala processes.

Neuroanatomical correlates of attitudes toward suicide in a large healthy sample: A voxel-based morphometric analysis

Previous studies have indicated that permissive attitudes toward suicide are positively associated with mental illness (e.g., depression and loneliness). Evidence suggests that there are abnormalities in the cognitive and brain functioning of suicidal patients. Nevertheless, there has been no evidence of the correlation between attitudes toward suicide and abnormal brain structure variations in healthy people. Therefore, in this study, we seek to investigate the neuroanatomical differences in healthy participants with regard to attitudes toward suicide. The results show that permissive attitudes toward suicide were significantly correlated with gray matter volume (GMV) in the left dorsolateral prefrontal cortex (DLPFC) and the left cerebellum in the large sample (n=405), which may be related to inefficient inhibitory control of negative emotion. Then, in a subset of healthy individuals with permissive attitudes (n=113), we also observed that stronger permissive attitudes toward suicide were positively related to the larger GMV in the left DLPFC and the left middle temporal gyrus (MTG), which may be associated with sensitivity of emotional feeling. Furthermore, loneliness had a mediating effect on the relation between the DLPFC volume and attitudes toward suicide. Taken together, neuroanatomical differences in healthy participants with permissive attitudes toward suicide may provide a better understanding of permissive attitudes toward suicide as a likely risk factor for suicidal behavior.

Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder.

Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD.

Individual differences in rumination in healthy and depressive samples: association with brain structure, functional connectivity and depression

Rumination is an important cognitive risk factor for onset and relapse of depression. However, no studies have employed a dimensional approach in investigating the neural correlates of rumination and the relationship with depression. Non-clinical healthy subjects (n = 306), who completed the classical rumination and depression scales, were studied using voxel-based morphometry and regional homogeneity (ReHo). Subsequently, mediation analysis was conducted to examine the influence of rumination on the relationship between brain structure and depression. Moreover, depressive patients (n = 60) and a control group (n = 63) of comparable age and education were studied with regions of interest that were identified in the healthy individuals. For healthy individuals, regional grey-matter volume (rGMV) of dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG) were positively correlated with rumination. In addition, rumination had a mediating effect on the relationship between the DLPFC and PHG and depression. Moreover, ReHo analysis showed that rumination had a significantly negative correlation with functional homogeneity of DLPFC. However, compared to the control group, depressed patients showed significant decrease of rGMV in the DLPFC and PHG and there was a significant negative correlation between DLPFC volume and depressive rumination. Increased DLPFC volume (decreased ReHo) in healthy individuals while decreased in depression indicated the trend of DLPFC from inefficient inhibition ('overload state') to impaired regulatory mechanism ('paralysis state'). This finding might elucidate when and why healthy individuals would develop sustained negative mood and depression eventually.

Reflection impulsivity in binge drinking: behavioural and volumetric correlates.

The degree to which an individual accumulates evidence prior to making a decision, also known as reflection impulsivity, can be affected in psychiatric disorders. Here, we study decisional impulsivity in binge drinkers, a group at elevated risk for developing alcohol use disorders, comparing two tasks assessing reflection impulsivity and a delay discounting task, hypothesizing impairments in both subtypes of impulsivity. We also assess volumetric correlates of reflection impulsivity focusing on regions previously implicated in functional magnetic resonance imaging studies. Sixty binge drinkers and healthy volunteers were tested using two different information‐gathering paradigms: the beads task and the Information Sampling Task (IST). The beads task was analysed using a behavioural approach and a Bayesian model of decision making. Delay discounting was assessed using the Monetary Choice Questionnaire. Regression analyses of primary outcomes were conducted with voxel‐based morphometry analyses. Binge drinkers sought less evidence prior to decision in the beads task compared with healthy volunteers in both the behavioural and computational modelling analysis. There were no group differences in the IST or delay discounting task. Greater impulsivity as indexed by lower evidence accumulation in the beads task was associated with smaller dorsolateral prefrontal cortex and inferior parietal volumes. In contrast, greater impulsivity as indexed by lower evidence accumulation in the IST was associated with greater dorsal cingulate and precuneus volumes. Binge drinking is characterized by impaired reflection impulsivity suggesting a deficit in deciding on the basis of future outcomes that are more difficult to represent. These findings emphasize the role of possible therapeutic interventions targeting decision‐making deficits.

Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI

Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation – that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age.

Brain regions associated with risk and resistance for bipolar I disorder: a voxel‐based MRI study of patients with bipolar disorder and their healthy siblings

Bipolar I disorder is a highly heritable disorder but not all siblings manifest with the illness, even though they may share similar genetic and environmental risk factors. Thus, sibling studies may help to identify brain structural endophenotypes associated with risk and resistance for the disorder. Structural magnetic resonance imaging (MRI) scans were acquired for 28 euthymic patients with bipolar disorder, their healthy siblings, and 30 unrelated healthy controls. Statistical Parametric Mapping 8 (SPM8) was used to identify group differences in regional gray matter volume by voxel-based morphometry (VBM). Using analysis of covariance, gray matter analysis of the groups revealed a group effect indicating that the left orbitofrontal cortex [Brodmann area (BA) 11] was smaller in patients with bipolar disorder than in unrelated healthy controls [F=14.83, p<0.05 (family-wise error); 7mm(3) ]. Paired t-tests indicated that the orbitofrontal cortex of patients with bipolar disorder [t=5.19, p<0.05 (family-wise error); 37mm(3) ] and their healthy siblings [t=3.89, p<0.001 (uncorrected); 63mm(3) ] was smaller than in unrelated healthy controls, and that the left dorsolateral prefrontal cortex was larger in healthy siblings than in patients with bipolar disorder [t=4.28, p<0.001 (uncorrected); 323mm(3) ] and unrelated healthy controls [t=4.36, p<0.001 (uncorrected); 245mm(3) ]. Additional region-of-interest analyses also found volume deficits in the right cerebellum of patients with bipolar disorder [t=3.92, p<0.001 (uncorrected); 178mm(3) ] and their healthy siblings [t=4.23, p<0.001 (uncorrected); 489mm(3) ], and in the left precentral gyrus of patients with bipolar disorder [t=3.61, p<0.001 (uncorrected); 115mm(3) ] compared to unrelated healthy controls. The results of this study suggest that a reduction in the volume of the orbitofrontal cortex, which plays a role in the automatic regulation of emotions and is a part of the medial prefrontal network, is associated with the heritability of bipolar disorder. Conversely, increased dorsolateral prefrontal cortex volume may be a neural marker of a resistance factor as it is part of a network of voluntary emotion regulation and balances the effects of the disrupted automatic emotion regulation system.

Visual–spatial working memory performance and temporal gray matter volume predict schizotypal personality disorder group membership

BackgroundPrior work shows individuals with schizotypal personality disorder (SPD) evince temporal lobe volume abnormalities similar to schizophrenia but sparing of prefrontal cortex, which may mitigate psychosis and the severe neurocognitive impairments observed in schizophrenia. This study examined the extent to which frontal–temporal gray matter volume and neurocognitive performance predict: (1) SPD group membership in a demographically-balanced sample of 51 patients and 37 healthy controls; and (2) symptom severity in SPD. MethodsDimensional gray-matter volume (left frontal–temporal regions (Brodmann area (BA) 10, 21, 22)) and neurocognitive performance on key memory tasks (California Verbal Learning Test (CVLT), Dot Test, Paced Auditory Serial Addition Test (PASAT)), all salient to schizophrenia-spectrum disorders were examined in a multi-variable model. ResultsMiddle temporal gyrus (BA21) volume and spatial–working memory (Dot Test) performance were significant predictors of SPD group membership likelihood, with poorer working-memory performance indicating increased probability of SPD membership. Combining across regional volumes or cognitive measures resulted in fair-to-good discrimination of group membership, but including neurocognitive and non-collinear regional volume measures together resulted in a receiver-operating-characteristic (ROC) curve with improved diagnostic discrimination. Larger BA10 volume in dorsolateral prefrontal cortex (DLPFC) significantly predicted less symptom severity in SPD. ConclusionsThese findings suggest that temporal lobe volume and spatial-working memory performance are promising biological/phenotype markers for likelihood of SPD classification, while greater DLPFC volume may serve as a protective factor.

Larger amygdala volume in first-degree relatives of patients with major depression.

ObjectiveAlthough a heritable contribution to risk for major depressive disorder (MDD) has been established and neural alterations in patients have been identified through neuroimaging, it is unclear which brain abnormalities are related to genetic risk. Studies on brain structure of high-risk subjects – such as individuals carrying a familial liability for the development of MDD – can provide information on the potential usefulness of these measures as intermediate phenotypes of MDD.Methods63 healthy first-degree relatives of patients with MDD and 63 healthy controls underwent structural magnetic resonance imaging. Regional gray matter volumes were analyzed via voxel-based morphometry (VBM).ResultsWhole-brain analysis revealed significantly larger gray matter volume in the bilateral amygdala in first-degree relatives of patients with MDD. Furthermore, relatives showed significantly larger gray matter volume in anatomical structures found relevant to MDD in previous literature, specifically in the bilateral hippocampus and amygdala as well as the left dorsolateral prefrontal cortex (DLPFC). Bilateral DLPFC volume correlated positively with the experience of negative affect.ConclusionsLarger gray matter volume in healthy relatives of MDD patients point to a possible vulnerability mechanism in MDD etiology and therefore extend knowledge in the field of high-risk approaches in MDD.

Smoking status as a potential confounder in the study of brain structure in schizophrenia

Several but not all MRI studies have reported volume reductions in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. Given the high prevalence of smoking among schizophrenia patients and the fact that smoking has also been associated with alterations in brain morphology, this study evaluated whether a proportion of the known gray matter reductions in key brain regions may be attributed to smoking rather than to schizophrenia alone.We examined structural MRI data of 112 schizophrenia patients (53 smokers and 59 non-smokers) and 77 healthy non-smoker controls collected by the MCIC study of schizophrenia. An automated atlas based probabilistic method was used to generate volumetric measures of the hippocampus and DLPFC. The two patient groups were matched with respect to demographic and clinical variables.Smoker schizophrenia patients showed significantly lower hippocampal and DLPFC volumes than non-smoker schizophrenia patients. Gray matter volume reductions associated with smoking status ranged between 2.2% and 2.8%. Furthermore, we found significant volume differences between smoker patients and healthy controls in the hippocampus and DLPFC, but not between non-smoker patients and healthy controls.Our data suggest that a proportion of the volume reduction seen in the hippocampus and DLPFC in schizophrenia is associated with smoking rather than with the diagnosis of schizophrenia. These results may have important implications for brain imaging studies comparing schizophrenia patients and other groups with a lower smoking prevalence.

Relationship between frontostriatal morphology and executive function deficits in bipolar I disorder following a first manic episode: data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM)

Executive function impairments are a core feature of bipolar I disorder (BD-I), not only present during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions in healthy subjects, research into morphological abnormalities underlying the deficits in BD-I is lacking. Patients with BD-I within three months of sustained remission from their first manic episode (n=41) underwent neuropsychological testing and a 3T magnetic resonance imaging scan and were compared to healthy subjects matched for age, sex, and premorbid IQ (n=30). Group dorsolateral prefrontal cortex (DLPFC; Brodmann areas 9 and 46) and caudate volumes were examined and analyzed for relationships with the average score from three computerized tests of executive function: Spatial Working Memory, Stockings of Cambridge, and Intradimensional/Extradimensional Shift. Right caudate volumes were enlarged in patients (z=3.57, p<0.05 corrected). No differences in DLPFC volumes were found. Patients showed large deficits in executive function relative to healthy subjects (d=-0.92, p<0.001). While in healthy subjects, a larger right (r = +0.39, p<0.05) and left (r = +0.44, p<0.05) caudate was associated with better executive function score, in patients, larger right (r=-0.36, p<0.05) and left (r=-0.34, p<0.05) volumes correlated with poorer performance. Although the etiology of gray matter changes is unknown, volume increases in the right caudate may be an important factor underlying executive function impairments during remission in patients with BD-I.