Emotion processing and regulation in bipolar disorder: a review

Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: a review.
Bipolar Disord 2012: 14: 326–339. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BP) is characterized by a dysfunction of mood, alternating between states of mania/hypomania and depression. Thus, the primary abnormality appears to be an inability to regulate emotion, the result of which is emotional extremes. The purpose of this paper is to review the current functional magnetic resonance imaging (fMRI) literature on adult patients with BP using emotion processing or regulation paradigms. Methods: A search was conducted on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression, bipolar euthymia, emotion, and amygdala. Only those studies that were conducted in adult patients using an emotion activation task were included in the final review. Results: Using tasks that assess neural functioning during emotion processing and emotion regulation, many fMRI studies have examined BP subjects during mania and euthymia. Fewer fMRI studies have been conducted during depression, and fewer still have included the same subjects in multiple mood states. Despite these limitations, these studies have demonstrated specific abnormalities in frontal–limbic regions. Using a variety of paradigms, investigators have specifically evaluated the amygdala (a structure within the limbic system known to be critical for emotion) and the prefrontal cortex (PFC) (a region known to have a regulatory function over the limbic system). Conclusions: These investigations reveal that amygdala activation varies as a function of mood state, while the PFC remains persistently hypoactivated across mood states. Emotional dysregulation and lability in mania and depression may reflect disruption of a frontal–limbic functional neuroanatomical network.     

Sex differences in bipolar disorder: a review of neuroimaging findings and new evidence

Jogia J, Dima D, Frangou S. Sex differences in bipolar disorder: a review of neuroimaging findings and new evidence.
Bipolar Disord 2012: 14: 461–471. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The sex of an individual is known to modulate the clinical presentation of bipolar disorder (BD), but little is known as to whether there are significant sex‐by‐diagnosis interactions on the brain structural and functional correlates of BD. Methods: We conducted a literature review of magnetic resonance imaging (MRI) studies in BD, published between January 1990 and December 2010, reporting on the effects of sex and diagnosis. In the absence of any functional MRI (fMRI) studies, this review was supplemented by original data analyses focusing on sex‐by‐diagnosis interactions on patterns of brain activation obtained during tasks of working memory, incentive decision‐making, and facial affect processing. Results: We found no support for a sex‐by‐diagnosis interaction in global gray or white matter volume. Evidence regarding regional volumetric measures is limited, but points to complex interactions between sex and diagnosis with developmental and temperamental factors within limbic and prefrontal regions. Sex‐by‐diagnosis interactions were noted in the pattern of activation within the basal ganglia during incentive decision‐making and within ventral prefrontal regions during facial affect processing. Conclusions: Potential sex‐by‐diagnosis interactions influencing the brain structural and functional correlates of disease expression in BD have received limited attention. Our data suggest that the sex of an individual modulates structure and function within subcortical and cortical regions implicated in disease expression.     

A quantitative meta-analysis of fMRI studies in bipolar disorder

Chen C‐H, Suckling J, Lennox BR, Ooi C, Bullmore ET. A quantitative meta‐analysis of fMRI studies in bipolar disorder.
Bipolar Disord 2011: 13: 1–15. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Functional magnetic resonance imaging (fMRI) has been widely used to identify state and trait markers of brain abnormalities associated with bipolar disorder (BD). However, the primary literature is composed of small‐to‐medium‐sized studies, using diverse activation paradigms on variously characterized patient groups, which can be difficult to synthesize into a coherent account. This review aimed to synthesize current evidence from fMRI studies in midlife adults with BD and to investigate whether there is support for the theoretical models of the disorder. Methods: We used voxel‐based quantitative meta‐analytic methods to combine primary data on anatomical coordinates of activation from 65 fMRI studies comparing normal volunteers (n = 1,074) and patients with BD (n = 1,040). Results: Compared to normal volunteers, patients with BD underactivated the inferior frontal cortex (IFG) and putamen and overactivated limbic areas, including medial temporal structures (parahippocampal gyrus, hippocampus, and amygdala) and basal ganglia. Dividing studies into those using emotional and cognitive paradigms demonstrated that the IFG abnormalities were manifest during both cognitive and emotional processing, while increased limbic activation was mainly related to emotional processing. In further separate comparisons between healthy volunteers and patient subgroups in each clinical state, the IFG was underactive in manic but not in euthymic and depressed states. Limbic structures were not overactive in association with mood states, with the exception of increased amygdala activation in euthymic states when including region‐of‐interest studies. Conclusions: In summary, our results showed abnormal frontal‐limbic activation in BD. There was attenuated activation of the IFG or ventrolateral prefrontal cortex, which was consistent across emotional and cognitive tasks and particularly related to the state of mania, and enhanced limbic activation, which was elicited by emotional and not cognitive tasks, and not clearly related to mood states.     

Impaired sustained attention in euthymic bipolar disorder patients and non‐affected relatives: an fMRI study

Sepede G, De Berardis D, Campanella D, Perrucci MG, Ferretti A, Serroni N, Moschetta FS, Del Gratta C, Salerno RM, Ferro FM, Di Giannantonio M, Onofrj M, Romani GL, Gambi F. Impaired sustained attention in euthymic bipolar disorder patients and non‐affected relatives: an fMRI study. Bipolar Disord 2012: 14: 764–779. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD‐I) and also in non‐affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD‐I patients and non‐affected relatives during a sustained attention task. Methods: Twenty‐four euthymic BD‐I patients, 22 non‐affected first‐degree relatives of BD‐I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event‐related fMRI scanning. Results: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between‐group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule – limited to the higher attention load – and an augmented deactivation of the posterior cingulate/retrosplenial cortex. Conclusions: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD‐I patients and non‐affected first‐degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD‐I.     

Decreased self-reported arousal in schizophrenia during aversive picture viewing compared to bipolar disorder and healthy controls

Both schizophrenia (SCZ) and bipolar disorder (BD) are associated with disturbances in emotion processing. Previous studies suggest that patients with SCZ assess unpleasant pictures as less arousing than healthy controls (HC), while patients with BD assess neutral pictures as more arousing than HC. No previous studies have investigated whether there is a difference in emotional response across all three groups. Our aim was to explore whether there was a difference in the evaluation of valence and in arousal between SCZ, BD and HC for aversive and neutral pictures. We showed 72 pictures (neutral, non-socially aversive and socially aversive) from the International Affective Picture System (IAPS) to 347 subjects. There was a clear interaction effect between the diagnostic group and increasing picture aversiveness for both valence and arousal. There were no significant differences in valence ratings between the different groups or in arousal ratings on any type of stimuli between BD patients and HC. However, SCZ patients reported significantly lower arousal for aversive stimuli, particularly with a social content, when compared to BD patients and HC. This was more pronounced in females. The presence of lifetime psychotic symptoms did not influence emotional responses.     

Structural changes in the hippocampus and amygdala at first episode of psychosis

Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ.     

Effects of childhood trauma on working memory in affective and non-affective psychotic disorders

Childhood trauma is a significant risk factor for the development of psychotic disorders, and may influence executive brain functions. We thus set out to investigate the long-term effects of childhood trauma exposure on brain function of adult chronic patients diagnosed with schizophrenia, schizoaffective disorder and (psychotic) bipolar-I disorder while performing a standard 2/0-back working memory task. Participants were 50 cases diagnosed with schizophrenia/schizoaffective disorder (SCZ), 42 cases with bipolar-I disorder (BD), and 47 healthy controls (HC). Among this sample, 56 clinical cases (SCZ?=?32; BD?=?24) and 17 HC reported significant levels of childhood trauma, while 36 clinical cases (SCZ?=?18; BD?=?18) and 30 HC did not. Effects of childhood trauma on working memory-related brain activation were examined in combined samples of clinical cases (independently of diagnosis) relative to HCs, as well as within each diagnostic category. Case–control analyses revealed increased activation of the left inferior parietal lobule as a main effect of trauma exposure. In addition, trauma exposure interacted with a diagnosis of SCZ or BD to reveal trauma-related increased activation in the cuneus in clinical cases and decreased activation in this region in controls. Disorder-specific functional alterations were also evident in the SCZ sample, but not BD. Childhood trauma exposure elicits aberrant function of parietal regions involved in working memory performance regardless of clinical status, as well as task-relevant visual regions that participates to attentional processes. Childhood trauma may therefore contribute to alterations in attention in SCZ and BD while performing an n-back working memory task.     

Association of MIF and MBL2 gene polymorphisms with attempted suicide in patients diagnosed with schizophrenia or bipolar disorder

The aim of this study to investigate the genetic polymorphisms in macrophage inhibitory factor (MIF) and mannose-binding lectin 2 (MBL2) gene in schizophrenia (SCZ) or bipolar disorder (BD) patients with attempted suicide by comparing with a non-attempted SCZ or BD patients and healthy controls. A sample of 108 patients with SCZ, 100 patients with BD and 100 healthy volunteers were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that included sociodemographic, suicidal behavior and symptom severity information. PCR-RFLP was used to determine MIF and MBL2 gene polymorphisms from DNA material. Our results demonstrated that the distributions of MBL2 genotype (AA, AB, BB), combined genotype (AA, AB/BB) and the allele frequencies (A, B) of attempted suicide patients in SCZ were significantly different from the non-attempted SCZ patients. The distributions of the MBL2 genotype of attempted suicide patients in SCZ were significantly different from the control group. The distributions of MIF genotype (GG, GC, CC), combined genotype (GG, GC/CC) and the allele frequencies (G, C) of attempted suicide patients in BD were significantly different from the non-attempted BD patients or control group. In summary MBL2 gene polymorphism may be associated with attempted suicide in SCZ and MIF gene polymorphism might be associated with attempted suicide in BD. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of these polymorphisms in SCZ or BD.     

Fronto-limbic function in unaffected offspring at familial risk for bipolar disorder during an emotional working memory paradigm

Evidence from neuroimaging studies indicate that individuals with bipolar disorder (BD) exhibit altered functioning of fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for BD exhibit such alterations. Using an fMRI emotional working memory paradigm, we investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8–17 years old) with at least one parent diagnosed with BD (HBO), and 16 age-matched healthy control (HC) participants. Neural activity and functional connectivity analyses focused on a priori neural regions supporting emotion processing (amygdala and ventral striatum) and voluntary emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC)). Relative to HC, HBO exhibited greater right VLPFC (BA47) activation in response to positive emotional distracters and reduced VLPFC modulation of the amygdala to both the positive and negative emotional distracters; there were no group differences in connectivity for the neutral distracters. These findings suggest that alterations in the functioning of fronto-limbic systems implicated in voluntary emotion regulation are present in unaffected bipolar offspring. Future longitudinal studies are needed to determine the extent to which such alterations represent neurodevelopmental markers of risk for future onset of BD.     

Addressing reverse inference in psychiatric neuroimaging: Meta‐analyses of task‐related brain activation in common mental disorders

Functional magnetic resonance imaging (fMRI) studies in psychiatry use various tasks to identify case‐control differences in the patterns of task‐related brain activation. Differently activated regions are often ascribed disorder‐specific functions in an attempt to link disease expression and brain function. We undertook a systematic meta‐analysis of data from task‐fMRI studies to examine the effect of diagnosis and study design on the spatial distribution and direction of case‐control differences on brain activation. We mapped to atlas regions coordinates of case‐control differences derived from 537 task‐fMRI studies in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder comprising observations derived from 21,427 participants. The fMRI tasks were classified according to the Research Domain Criteria (RDoC). We investigated whether diagnosis, RDoC domain or construct and use of regions‐of‐interest or whole‐brain analyses influenced the neuroanatomical pattern of results. When considering all primary studies, we found an effect of diagnosis for the amygdala and caudate nucleus and an effect of RDoC domains and constructs for the amygdala, hippocampus, putamen and nucleus accumbens. In contrast, whole‐brain studies did not identify any significant effect of diagnosis or RDoC domain or construct. These results resonate with prior reports of common brain structural and genetic underpinnings across these disorders and caution against attributing undue specificity to brain functional changes when forming explanatory models of psychiatric disorders. Hum Brain Mapp 38:1846–1864, 2017. © 2017 Wiley Periodicals, Inc.     

Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study

Shi X‐F, Kondo DG, Sung Y‐H, Hellem TL, Fiedler KK, Jeong E‐K, Huber RS, Renshaw PF. Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus‐31 magnetic resonance spectroscopy study. Bipolar Disord 2012: 14: 607–617. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: To compare the concentrations of high‐energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC). Methods: We used in vivo phosphorus‐31 magnetic resonance spectroscopy (³¹P‐MRS) at 3 Tesla to measure phosphocreatine (PCr), beta‐nucleoside triphosphate (β‐NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs. Results: Analysis of covariance, including age as a covariate, revealed differences in PCr (p = 0.037), Pi (p = 0.017), and PCr/Pi (p = 0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post‐hoc Tukey–Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p = 0.038) and medicated BD (24%; p = 0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p = 0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p = 0.013) and with medicated BD (39%; p = 0.002). No differences in β‐NTP or pH were observed. Conclusions: Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n‐acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD.     

A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states

Cerullo MA, Fleck DE, Eliassen JC, Smith MS, DelBello MP, Adler CM, Strakowski SM. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 2012: 14: 175–184. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally. Methods: fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole‐brain functional connectivity analysis was performed using the left and right amygdala as seed regions. Results: Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group. Conclusions: In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical–amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.     

Evidence for altered cell membrane lipid composition in postmortem prefrontal white matter in bipolar disorder and schizophrenia

Brain imaging suggests that white matter abnormalities, including compromised white matter integrity in the frontal lobe, are shared across bipolar disorder (BD) and schizophrenia (SCZ). However, the precise molecular and cellular correlates remain to be elucidated. Given evidence for widespread alterations in cell membrane lipid composition in both disorders, we sought to investigate whether lipid composition is disturbed in frontal white matter in SCZ and BD. The phospholipids phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were quantified in white matter adjacent to the dorsolateral prefrontal cortex in subjects with BD (n = 34), SCZ (n = 35), and non-psychiatric controls (n = 35) using high-pressure liquid chromatography. Individual fatty acid species and plasmalogens were then quantified separately in PE and PC fractions by gas liquid chromatography. PC was significantly lower in the BD group, compared to controls. The fatty acids PE22:0, PE24:1 and PE20:2n6 were higher, and PC20:4n6, PE22:5n6 and PC22:5n6 lower in the BD group, relative to the control group. PE22:1 was higher and PC20:3n6, PE22:5n6 and PC22:5n6 lower in the SCZ group, compared to the control group. These data provide evidence for altered lipid composition in white matter in both BD and SCZ. Changes in white matter lipid composition could ultimately contribute to dysfunction of frontal white matter circuits in SCZ and BD.     

Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder

Perlman SB, Almeida JRC, Kronhaus DM, Versace A, LaBarbara EJ, Klein CR, Phillips ML. Amygdala activity and prefrontal cortex–amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder. Bipolar Disord 2012: 14: 162–174. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Methods: Thirty‐one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block‐design emotion processing task requiring color‐labeling of a color flash superimposed on a task‐irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top‐down) and following (bottom‐up) activity between the PFC and the left and right amygdalae. Results: Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted‐BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed‐BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted‐BD and depressed‐BD subjects. Discussion: EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala–PFC circuitry, supporting implicit emotion processing between remitted‐BD and depressed‐BD subjects, which may underlie changes from remission to depression in BD.     

Processing of social emotion in patients with schizophrenia and substance use disorder: An fMRI study

Abstract

The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the aetiology of this comorbid condition remains unknown. Mounting evidence suggests that dual-diagnosis patients have fewer negative symptoms and better social skills, compared to non-abusing patients. We hypothesized that schizophrenia patients with substance use disorder (SCZ–SUD) would display increased cerebral activations in response to socioemotional stimuli, relative to patients with no SUD (SCZ). Schizophrenia patients (DSM-IV criteria) were divided into two groups: patients with (n=12) and without (n=11) substance use (alcohol and/or cannabis). Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of an emotional film excerpt with social content. Loci of activation were identified in the right mPFC (BA 10) and the right supramarginal gyrus (BA 40) in SCZ–SUD patients, and in the left pons in SCZ patients. Relative to SCZ patients, increased loci of activation were found in the right superior parietal cortex (BA 7) and the left medial prefrontal cortex (BA 10) in SCZ–SUD patients, who reported higher subjective emotional experience on a self-report scale. To our knowledge, this is the first fMRI study to assess social emotions in dual-diagnosis schizophrenia. Our results suggest that socioemotional processing may be less impaired in dual diagnosis, which recruited brain regions seemingly involved in “social cognition.” Further studies on the topic are warranted.     

Social cognition in bipolar disorder versus schizophrenia: comparability in mental state decoding deficits

Donohoe G, Duignan A, Hargreaves A, Morris DW, Rose E, Robertson D, Cummings E, Moore S, Gill M, Corvin A. Social cognition in bipolar disorder versus schizophrenia: comparability in mental state decoding deficits. Bipolar Disord 2012: 14: 743–748. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Neuropsychological studies comparing patients with bipolar disorder (BD) to patients with schizophrenia (SZ) suggest milder cognitive deficits in BD patients and across a smaller range of functions. The present study investigated whether this pattern is also true for social cognition – a range of socially relevant abilities, including emotion perception and recognition, theory of mind, and social attributions – by comparing performance on measures of social cognition in patients with BD, SZ, and healthy participants. Methods: One hundred and two patients with BD, 208 patients with SZ, and 132 healthy participants were assessed using a battery of tasks measuring basic neuropsychological and social cognition. Results: We observed significant differences between patients with BD and healthy participants in a test of mental state decoding (‘eyes task’) that was at a level comparable to deficits seen in patients with SZ. By comparison, BD patients showed more subtle deficits in mental state reasoning (‘hinting task’) than those shown by patients with SZ. Conclusions: Mental state decoding difficulties are significant in BD. An important direction for further research will be to establish to what extent these deficits affect social and occupational functioning as a potential target for therapeutic intervention.     

Differential relations between fronto‐limbic metabolism and executive function in patients with remitted bipolar I and bipolar II disorder

Li C‐T, Hsieh J‐C, Wang S‐J, Yang B‐H, Bai Y‐M, Lin W‐C, Lan C‐C, Su T‐P. Differential relations between fronto‐limbic metabolism and executive function in patients with remitted bipolar I and bipolar II disorder.
Bipolar Disord 2012: 14: 831–842. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Objectives: The aim of this study was to investigate the relationship between resting brain glucose metabolism and cognitive profiles in patients with remitted bipolar I disorder (BD‐I) and bipolar II disorder (BD‐II). We hypothesized that BD‐I patients (compared to BD‐II patients) would perform worse on tests of cognitive function because of abnormal metabolism in the prefrontal cortex and other mood‐related brain areas. Methods: Thirty‐four patients with remitted bipolar disorder (BD) (BD‐I = 17, BD‐II = 17) under treatment and 17 well‐matched healthy controls received both fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography (PET) and neuropsychological tests of attention, memory, and executive function. Results: Clinical features in patients with BD‐I and BD‐II were comparable. Executive function, as indicated by performance on the Wisconsin Card Sorting Test, was significantly worse (i.e., higher percentage of errors, lower percentage of conceptual level responses, and fewer categories completed) in BD‐I patients than in BD‐II patients and healthy subjects. No difference in attention and memory tests was found among these three groups. Brain PET analysis showed that BD‐I patients (compared to BD‐II patients) had significantly lower glucose uptake in the bilateral anterior cingulum, insula, striatum, and part of the prefrontal cortex, and higher glucose uptake in the left parahippocampus. Further analyses revealed significant correlations between poor executive function and abnormal glucose uptake in other brain areas in BD‐I patients. Conclusions: There are neurobiological differences between subtypes of BD. BD‐I is associated with more impaired fronto‐limbic circuitry, which might account for reduced executive function in BD‐I patients during remission.     

Processing of social emotion in patients with schizophrenia and substance use disorder: an fMRI study

The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the aetiology of this comorbid condition remains unknown. Mounting evidence suggests that dual-diagnosis patients have fewer negative symptoms and better social skills, compared to non-abusing patients. We hypothesized that schizophrenia patients with substance use disorder (SCZ-SUD) would display increased cerebral activations in response to socioemotional stimuli, relative to patients with no SUD (SCZ). Schizophrenia patients (DSM-IV criteria) were divided into two groups: patients with (n=12) and without (n=11) substance use (alcohol and/or cannabis). Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of an emotional film excerpt with social content. Loci of activation were identified in the right mPFC (BA 10) and the right supramarginal gyrus (BA 40) in SCZ-SUD patients, and in the left pons in SCZ patients. Relative to SCZ patients, increased loci of activation were found in the right superior parietal cortex (BA 7) and the left medial prefrontal cortex (BA 10) in SCZ-SUD patients, who reported higher subjective emotional experience on a self-report scale. To our knowledge, this is the first fMRI study to assess social emotions in dual-diagnosis schizophrenia. Our results suggest that socioemotional processing may be less impaired in dual diagnosis, which recruited brain regions seemingly involved in "social cognition." Further studies on the topic are warranted.     

Functional imaging of emotional memory in bipolar disorder and schizophrenia

Objectives: Although in current diagnostic criteria there exists a distinction between bipolar disorder and schizophrenia, many patients manifest features of both disorders, and it is unclear which aspects, if any, confer diagnostic specificity. In the present study, we investigate whether there are differences in medial temporal lobe (MTL) activation in bipolar disorder and schizophrenia. We also investigate associations between activation levels and symptom severity across the disorders. Methods: Functional magnetic resonance imaging scans were conducted on 14 healthy controls, 14 patients with bipolar disorder, and 15 patients with schizophrenia undergoing an emotional memory paradigm. Results: All groups demonstrated the expected pattern of behavioural responses during encoding and retrieval, and there were no significant group differences in performance. Robust MTL activation was seen in all three groups during viewing of emotional scenes, which correlated significantly with recognition memory for emotional stimuli. The bipolar group demonstrated relatively greater increases in activation for emotional versus neutral scenes in the left hippocampus than both controls and patients with schizophrenia. There was a significant positive correlation between mania scores and activation in the anterior cingulate, and a significant negative correlation between depression scores and activation in the dorsolateral prefrontal cortex. Conclusion: These results provide evidence that there are distinct patterns of activation in the MTL during an emotional memory task in bipolar disorder and schizophrenia. They also demonstrate that different mood states are associated with different neurobiological responses to emotion across the patient groups.     

Disrupted Intersubject Variability Architecture in Functional Connectomes in Schizophrenia

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.