The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

BackgroundThe Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.MethodWe employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.ResultsIrrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.ConclusionsOur results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

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Event-related potential examination of facial affect processing in bipolar disorder and schizophrenia

Psychological Medicine ◽

10.1017/s0033291712001006 ◽

2012 ◽

Vol 43 (1) ◽

pp. 109-117 ◽

Cited By ~ 37

Author(s):

J. K. Wynn ◽

C. Jahshan ◽

L. L. Altshuler ◽

D. C. Glahn ◽

M. F. Green

Keyword(s):

Bipolar Disorder ◽

Event Related Potentials ◽

Facial Affect ◽

Event Related Potential ◽

Facial Features ◽

Healthy Controls ◽

Related Potentials ◽

Patient Groups ◽

Bipolar Patients ◽

Affect Processing

BackgroundPatients with bipolar disorder exhibit consistent deficits in facial affect identification at both behavioral and neural levels. However, little is known about which stages of facial affect processing are dysfunctional.MethodEvent-related potentials (ERPs), including amplitude and latency, were used to evaluate two stages of facial affect processing: N170 to examine structural encoding of facial features and N250 to examine decoding of facial features in 57 bipolar disorder patients, 30 schizophrenia patients and 30 healthy controls. Three conditions were administered: participants were asked to identify the emotion of a face, the gender of a face, or whether a building was one or two stories tall.ResultsSchizophrenia patients' emotion identification accuracy was lower than that of bipolar patients and healthy controls. N170 amplitude was significantly smaller in schizophrenia patients compared to bipolar patients and healthy controls, which did not differ from each other. Both patient groups had significantly longer N170 latency compared to healthy controls. For N250, both patient groups showed significantly smaller amplitudes compared with controls, but did not differ from each other. Bipolar patients showed longer N250 latency than healthy controls; patient groups did not differ from each other.ConclusionsBipolar disorder patients have relatively intact structural encoding of faces (N170) but are impaired when decoding facial features for complex judgments about faces (N250 latency and amplitude), such as identifying emotion or gender.

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Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies

Psychological Medicine ◽

10.1017/s0033291712001432 ◽

2012 ◽

Vol 43 (3) ◽

pp. 553-569 ◽

Cited By ~ 78

Author(s):

G. Delvecchio ◽

G. Sugranyes ◽

S. Frangou

Keyword(s):

Bipolar Disorder ◽

Visual Processing ◽

Emotional Regulation ◽

Emotional Processing ◽

Meta Analysis ◽

Likelihood Estimation ◽

Facial Affect ◽

Healthy Individuals ◽

Processing Network ◽

Affect Processing

BackgroundSchizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry.MethodFunctional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE).ResultsCompared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices.ConclusionsDuring facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ.

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The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Journal of Affective Disorders ◽

10.1016/j.jad.2012.03.014 ◽

2012 ◽

Vol 141 (1) ◽

pp. 94-101 ◽

Cited By ~ 25

Author(s):

Márcio Gerhardt Soeiro-de-Souza ◽

Maria Concepción Garcia Otaduy ◽

Carolina Zadres Dias ◽

Danielle S. Bio ◽

Rodrigo Machado-Vieira ◽

...

Keyword(s):

Bipolar Disorder ◽

Risk Allele ◽

Healthy Controls ◽

Limbic Structures ◽

Facial Emotions ◽

The Impact

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The impact of leprosy on the mental wellbeing of leprosy-affected persons and their family members – a systematic review

Global Mental Health ◽

10.1017/gmh.2020.3 ◽

2020 ◽

Vol 7 ◽

Cited By ~ 2

Author(s):

PMW Somar ◽

MM Waltz ◽

WH van Brakel

Keyword(s):

Mental Health ◽

Systematic Review ◽

Anxiety Disorders ◽

Family Members ◽

Health Impact ◽

Self Esteem ◽

Mental Wellbeing ◽

Primary Data ◽

Current Evidence ◽

The Impact

Abstract Leprosy has long-term consequences related to impairment and stigma. This includes a major impact on mental health. This study aims to consolidate current evidence regarding the mental health impact of leprosy on affected persons and their family members. In addition, determinants influencing mental health outcomes among leprosy-affected persons and effective interventions are examined. A keyword-based search was conducted in PubMed, Web of Science, Scopus, PsycINFO, Infolep and InfoNTD; additional literature was also considered. Articles presenting primary data involving leprosy-affected persons or their family members experiencing mental conditions were included. Independent extraction of articles was executed using predefined data fields. Articles were sorted according to relevance. In total, 65 studies were included in this systematic review. Multiple psychiatric morbidities have been identified among leprosy-affected persons, including depression, anxiety disorders and suicide (attempts). Additional factors were found that may impact mental health. Moreover, studies found that demographic factors, lifestyle and disease-specific factors and stigma and discrimination impact mental health. Depressive symptoms and low self-esteem were identified among children of leprosy-affected persons. In addition, interventions were identified that could improve the mental wellbeing of leprosy patients. Depressive disorders and anxiety disorders were found to be very common among persons affected by leprosy. Feelings such as fear, shame and low self-esteem are also experienced by those affected, and their children. Further research is necessary to ensure that mental health impact is included when determining the burden of disease for leprosy, and to relieve this burden.

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PW01-148 - Effective connectivity within the network of fearful facial affect recognition in patients with bipolar disorder compared to healthy controls

European Psychiatry ◽

10.1016/s0924-9338(10)71547-9 ◽

2010 ◽

Vol 25 ◽

pp. 1564 ◽

Cited By ~ 1

Author(s):

M. Kempton ◽

D. Dima ◽

J. Roiser ◽

K. Stephan ◽

K. Friston ◽

...

Keyword(s):

Bipolar Disorder ◽

Effective Connectivity ◽

Facial Affect ◽

Affect Recognition ◽

Facial Affect Recognition ◽

Healthy Controls

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Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders

The British Journal of Psychiatry ◽

10.1192/bjp.bp.104.007773 ◽

2006 ◽

Vol 189 (1) ◽

pp. 20-25 ◽

Cited By ~ 144

Author(s):

Michael W. Otto ◽

Naomi M. Simon ◽

Stephen R. Wisniewski ◽

David J. Miklowitz ◽

Jane N. Kogan ◽

...

Keyword(s):

Quality Of Life ◽

Bipolar Disorder ◽

Anxiety Disorders ◽

Negative Impact ◽

Mood State ◽

Comorbid Anxiety ◽

Depression Risk ◽

The Impact ◽

A Current

BackgroundThe impact of anxiety disorders has not been well delineated in prospective studies of bipolar disorder.AimsTo examine the association between anxiety and course of bipolar disorder, as defined by mood episodes, quality of life and role functioning.MethodA thousand out-patients with bipolar disorder were followed prospectively for 1 year.ResultsA current comorbid anxiety disorder (present in 31.9% of participants) was associated with fewer days well, a lower likelihood of timely recovery from depression, risk of earlier relapse, lower quality of life and diminished role function over 1 year of prospective study. The negative impact was greater with multiple anxiety disorders.ConclusionsAnxiety disorders, including those present during relative euthymia, predicted a poorer bipolar course. The detrimental effects of anxiety were not simply a feature of mood state. Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course.

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Neural correlates of perception of emotional facial expressions in out-patients with mild-to-moderate depression and anxiety. A multicenter fMRI study

Psychological Medicine ◽

10.1017/s0033291711000596 ◽

2011 ◽

Vol 41 (11) ◽

pp. 2253-2264 ◽

Cited By ~ 47

Author(s):

L. R. Demenescu ◽

R. Renken ◽

R. Kortekaas ◽

M.-J. van Tol ◽

J. B. C. Marsman ◽

...

Keyword(s):

Anxiety Disorders ◽

Facial Expressions ◽

Emotional Processing ◽

Brain Regions ◽

Neural Activation ◽

Healthy Controls ◽

Depression And Anxiety ◽

Emotional Facial Expressions ◽

Emotional Faces ◽

Depressed Patients

BackgroundDepression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients.MethodAn event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.ResultsFacial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.ConclusionsWe suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.

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Genetics in anxiety disorders - an update

European Psychiatry ◽

10.1016/s0924-9338(11)73800-7 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 2097-2097

Author(s):

K. Domschke

Keyword(s):

Panic Disorder ◽

Anxiety Disorders ◽

Candidate Genes ◽

Genetic Variants ◽

Emotional Processing ◽

Disease Risk ◽

Association Studies ◽

Imaging Genetics ◽

Genome Wide Association Studies ◽

Increased Risk

Twin studies propose a strong genetic contribution to the pathogenesis of anxiety disorders with a heritability of about 50%. The dissection of the complex-genetic underpinnings of anxiety disorders requires a multi-level approach using molecular genetic, imaging genetic, (cognitive)-behavioral genetic and pharmacogenetic techniques linking basic and clinical research.The present talk will first give an overview of results from linkage and association studies yielding support for several candidate genes contributing to the genetic risk for anxiety and panic disorder in particular such as the adenosine 2A receptor, the catechol-O-methyltransferase, the neuropeptide S receptor and the serotonin receptor 1A genes. Results from the first genome-wide association studies in the field of anxiety disorders will be discussed. Additionally, studies on gene-environment interactions between anxiety disorder risk variants and environmental factors will be presented. Imaging genetics approaches have yielded evidence for several risk genes to crucially impact activation in brain regions critical for emotional processing. Gene variation has furthermore been found to potentially confer an increased risk for panic disorder via elevated autonomic arousal and dysfunctional cognitions regarding bodily sensations. Finally, there is first evidence for genetic variants impacting treatment response to antidepressant pharmacotherapy in anxiety disorders.Thus, converging lines of evidence will be presented for several candidate genes of anxiety to exert an increased disease risk potentially via a distorted cortico-limbic interaction during emotional processing, increased physiological arousal or dysfunctional cognition. Additionally, a possible impact of genetic variants on pharmacoresponse in anxiety disorders and its potential clinical implications will be discussed.

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Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2010.10.004 ◽

2011 ◽

Vol 26 (3) ◽

pp. 135-137 ◽

Cited By ~ 62

Author(s):

E. Perrier ◽

F. Pompei ◽

G. Ruberto ◽

E. Vassos ◽

D. Collier ◽

...

Keyword(s):

Bipolar Disorder ◽

Emotional Processing ◽

Risk Allele ◽

Anatomical Variation ◽

Brain Structures ◽

Brain Morphology ◽

Healthy Controls ◽

Subcortical Brain ◽

Increased Risk ◽

Subcortical Regions

AbstractBackgroundThe polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions. Here we sought to investigate the influence of CACNA1C polymorphism on key subcortical brain structures implicated in the pathophysiology of BD.MethodsStructural magnetic resonance imaging scans were acquired from 41 euthymic patients with BD and 40 healthy controls, who were also genotyped for the CACNA1C rs1006737 polymorphism. The effect of diagnosis, genotype and their interaction was examined in predefined volumes of interest in the basal ganglia, hypothalamus and amygdala extracted using SPM5.ResultsCarriers of the CACNA1C rs1006737 risk allele showed increased grey matter density in the right amygdala and right hypothalamus irrespective of diagnosis. An interaction between genotype and diagnosis was observed in the left putamen which was smaller in BD patients carrying the risk allele than in healthy controls.Conclusions:The CACNA1C rs1006737 polymorphism influences anatomical variation within subcortical regions involved in emotional processing.

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