ABSTRACT
OBJECTIVES: Cognitive dysfunction affects a substantial proportion of patients with bipolar disorder (BD), and genetic-imaging paradigms may aid in the elucidation of mechanisms implicated in this symptomatic domain. The Val allele of the functional Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working memory in BD. METHODS: Sixty-four outpatients with BD in full or partial remission were stratified according to COMT Val158Met genotype (ValVal [n=13], ValMet [n=34], and MetMet [n=17]). The patients completed a spatial n-back working memory task during fMRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory test outside the scanner. RESULTS: During high working memory load (2-back vs 1-back), Val homozygotes displayed decreased activity relative to ValMet individuals, with Met homozygotes displaying intermediate levels of activity in the right dorsolateral prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. CONCLUSIONS: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive impairments in BD.
Subject(s)
Bipolar Disorder , Catechol O-Methyltransferase/genetics , Cognition/physiology , Memory, Short-Term/physiology , Prefrontal Cortex , Adult , Bipolar Disorder/diagnosis , Bipolar Disorder/genetics , Bipolar Disorder/physiopathology , Dopamine/metabolism , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Polymorphism, Genetic , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Statistics as TopicABSTRACT
BACKGROUND: Negative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting. METHODS: Healthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping. RESULTS: Unexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping. CONCLUSIONS: Less susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.
Subject(s)
Brain Mapping/methods , Cerebral Cortex/physiopathology , Depressive Disorder, Major/physiopathology , Facial Expression , Facial Recognition/physiology , Fear/physiology , Adult , Cerebral Cortex/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Female , Genetic Predisposition to Disease , Happiness , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Risk , Twins, DizygoticABSTRACT
INTRODUCTION: The aim of this article is to present the qualitative focus group interview as a useful method of evaluating psycho- and milieu therapeutic treatment. MATERIAL AND METHODS: We conducted two focus group interviews with former inpatients of a psychiatric ward specialising in group therapy. To enhance the quality of the data by triangulation, the staff, representing both milieu- and psychotherapists, were also interviewed. RESULTS: Analysis of the results revealed the following dominant themes: The continuation of the treatment was jeopardised by the existence of a welcome group. There was a need for further information as soon as the patient came into contact with the hospital. Moreover, an earlier and increased involvement of the family was required. After their own interview, the staff participated in deciding which results should lead to alterations in treatment procedures, thereby becoming involved in implementing the results. DISCUSSION: The focus group interview is a valuable method of evaluating psycho- and milieu therapeutic treatment. Interviewing the staff served as triangulation and eased the implementation of the results remarkably.