Michael J. Travis

A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder

BACKGROUND Accurate recognition of facial expressions is crucial for social functioning. In depressed individuals, implicit and explicit attentional biases away from happy and toward sad stimuli have been demonstrated. These may be associated with the negative cognitions in these individuals. METHODS Using event-related functional magnetic resonance imaging (fMRI), neural responses to happy and sad facial expressions were measured in 14 healthy individuals and 16 individuals with major depressive disorder. RESULTS Healthy but not depressed individuals demonstrated linear increases in response in bilateral fusiform gyri and right putamen to expressions of increasing happiness, while depressed individuals demonstrated linear increases in response in left putamen, left parahippocampal gyrus/amygdala, and right fusiform gyrus to expressions of increasing sadness. There was a negative correlation in depressed individuals between depression severity and magnitude of neural response within right fusiform gyrus to happy expressions. CONCLUSIONS Our findings indicate preferential increases in neural response to sad but not happy facial expressions in neural regions involved in the processing of emotional stimuli in depressed individuals. These findings may be associated with the above pattern of implicit and explicit attentional biases in these individuals and suggest a potential neural basis for the negative cognitions and social dysfunction in major depression.

Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression.

Impaired facial expression recognition has been associated with features of major depression, which could underlie some of the difficulties in social interactions in these patients. Patients with major depressive disorder and age- and gender-matched healthy volunteers judged the emotion of 100 facial stimuli displaying different intensities of sadness and happiness and neutral expressions presented for short (100 ms) and long (2,000 ms) durations. Compared with healthy volunteers, depressed patients demonstrated subtle impairments in discrimination accuracy and a predominant bias away from the identification as happy of mildly happy expressions. The authors suggest that, in depressed patients, the inability to accurately identify subtle changes in facial expression displayed by others in social situations may underlie the impaired interpersonal functioning.

A preferential increase in the extrastriate response to signals of danger

This study examined neural responses in nine right-handed healthy individuals while they viewed mild and intense expressions of four emotions (fear, disgust, happiness, and sadness) contrasted with neutral faces in four event-related functional magnetic resonance imaging experiments. Orthogonal polynomial trend analysis revealed a significant linear increase in the fusiform extrastriate cortical response to increasing intensities of all four emotional expressions, which was significantly greater to increasing intensities of fear and disgust than happiness and sadness, and a significant linear decrease in response to sadness in another extrastriate region. The amygdala was activated by high-intensity fearful expressions, consistent with findings from previous studies, and by low- but not high-intensity sad expressions. Significant linear increases in response to increasing intensities of fear, disgust, and happiness occurred within the hippocampus, anterior insula, and putamen, respectively. Conversely, significant linear decreases in hippocampal and putamen responses occurred to increasing intensities of sadness. We provide the first demonstration of differential increases in extrastriate and limbic responses to signals of increasing danger than to those of other emotions, and significant decreases in these responses to signals of increasing sadness in others. We suggest that this differential pattern of response to different categories of emotional signals allows the preferential direction of visual attention to signals of imminent danger than to other, less-salient emotional stimuli.

A Reversal of the Normal Pattern of Parahippocampal Response to Neutral and Fearful Faces Is Associated with Reality Distortion in Schizophrenia

BACKGROUND Individuals with schizophrenia demonstrate impaired recognition of facial expressions and may misattribute emotional salience to otherwise nonsalient stimuli. The neural mechanisms underlying this deficit and the relationship with different symptoms remain poorly understood. METHODS We used event-related functional magnetic resonance imaging to measure neural responses to neutral, mildly fearful, and prototypically fearful facial expressions. The sample included 15 medicated individuals with chronic schizophrenia (SZ) and 11 healthy control individuals (CON), matched for gender (all male), age, and years of education. RESULTS A repeated measures 3 x 2 analysis of variance (ANOVA) revealed a significant interaction between expression intensity and group in right parahippocampal gyrus (p < .01). Individuals with chronic schizophrenia demonstrated a decrease, whereas CON showed an increase, in right parahippocampal gyrus response to increasingly fearful expressions. Between-group comparison revealed greater activation in SZ than CON in right parahippocampal gyrus to neutral faces. The reality distortion dimension, but not neuroleptic medication dose, was positively associated with the right parahippocampal gyral and right amygdalar response to neutral faces in SZ. CONCLUSIONS An abnormally increased parahippocampal response to neutral faces was positively associated with reality distortion in SZ. This may underlie the previously reported finding of a misattribution of emotional salience to nonsalient social stimuli in schizophrenia.

Estrogen therapy and brain muscarinic receptor density in healthy females: a SPET study.

Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimers disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimers disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term ET and age on brain m(1)/m(4) receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n=2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels.

Aripiprazole in schizophrenia: consensus guidelines

Schizophrenia is a chronic disabling disease which in the majority of cases requires long‐term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Initial evaluation of123I-5-I-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150 or123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary123I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET.

Aripiprazole in schizophrenia

Schizophrenia is a chronic disabling disease which in the majority of cases requires long‐term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

In vivo imaging of muscarinic receptors in the aging female brain with (R,R)[123I]-I-QNB and single photon emission tomography ☆

The effect of age on brain muscarinic receptor density is unclear. Some in vivo neuroimaging studies have reported a large age-related reduction in muscarinic receptor density; however, others have reported increases or no change. The variability in these results most likely arises because of the heterogeneity of the populations studied, differences in quantification methods employed, and a paucity of subtype selective ligands. Thus, we used the m(1)/m(4) selective probe (R,R)[(123)I]-I-QNB to investigate age-related differences in brain muscarinic receptors in healthy females. We included 10 younger subjects (age range 26-37) and 22 older women (age range 57-82 years). The older women had significantly lower (R,R)[(123)I]-I-QNB binding in widespread brain regions including cerebral cortex and hippocampus. Across all subjects, regional binding was significantly negatively correlated with age. Thus, in this population of healthy women, there was an age-related reduction in muscarinic receptor density. This may contribute to age-related differences in cognitive function and risk for Alzheimers disease.

Cost analysis of treating schizophrenia with amisulpride: naturalistic mirror image study.

The aim of the study was to examine the costs of schizophrenia treatment using the atypical antipsychotic amisulpride relative to treatment with other antipsychotics. Service use data were collected for one year of amisulpride treatment. The patients were also assessed with the Global Assessment of Functioning (GAF) scale and scales of Quality of Life. These were compared with retrospectively collected data for the 1-year period prior to the patients commencing amisulpride. The findings indicate that, compared with the year before, the clinical and quality of life scores improved during the year of treatment with amisulpride. There was a numerical reduction of total costs, as well as costs of in- and out-patient service use per patient per year during the year on amisulpride compared with the year before the patients started amisulpride. Patients on amisulpride spent fewer days as acute in-patients, but stayed longer in rehabilitation wards. Amisulpride treatment may lead to a reduction in the cost of treating schizophrenia in comparison with treatment with other antipsychotic medications.