Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial - CADOT.

Introduction: Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines. Method: Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity - QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning - GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st - 3rd quartile) of 4 (1-9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11-33) months after remission. Results: At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38-66%]). After DATA step 2, 37 patients were in remission (77% [65-89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78-97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62-95%]). Conclusion: These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s).

Neural basis of impaired narrative discourse comprehension in prodromal and mild dementia with lewy bodies.

Narrative discourse (ND) comprehension is a complex task that implies not only linguistic abilities but also other cognitive abilities, including efficient executive functioning. An executive dysfunction has been described in dementia with Lewy bodies (DLB) from the early stage. Here, we question the link between executive dysfunction in DLB and narrative comprehension. The aim of our study was to evaluate ND comprehension and to investigate the neuroanatomical basis for its impairment in the early stage of DLB. DLB patients (N = 26) and controls (N = 19) underwent the ND comprehension test of the Montreal Protocol for Evaluation of Communication (MEC). An additional, qualitative analysis was conducted on their verbal productions. Cognitive tests assessing verbal episodic memory, executive functions, naming and oral syntactic comprehension were also performed. Brain gray matter correlates of the ND comprehension test were examined using voxel-based morphometry (VBM). An ND comprehension impairment was found for prodromal and mild DLB patients as compared to controls. These difficulties were correlated with the Frontal Assessment Battery (FAB) score. ND comprehension impairment in DLB was further characterized by a deficit in the organization and the logic of the discourse. Moreover, VBM analysis revealed a correlation between striatal gray matter volumes and DLB patients' ability to extract and organize relevant information (p < 0.05, FDR correction, cluster level). The ND comprehension impairment in DLB patients could be related to their executive dysfunction through a deficit of information selection and organization that correlates with the volumetric reduction of striatal gray matter.

A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [-9; +10; +60] and L-LPM [-46; -12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76-100%) and specificity 88% (72-97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.

[Narrative discourse in dementia with Lewy bodies and Alzheimer's disease]. / Le discours narratif dans la maladie à corps de Lewy et la maladie d'Alzheimer.

Dementia with Lewy bodies (DLB) is the second most common form of dementia, after Alzheimer's disease (AD). Subjects with DLB remain under-diagnosed, especially in the early stage of the disease, when they can show subtle neurocognitive disorders similar to subjects with AD. In order to refine the differential diagnosis between these two neurodegenerative diseases and to improve patients' care, our speech therapy study aimed to analyze their ability to tell a story by producing a narrative discourse (ND). METHOD: 25 participants with DLB and 12 participants with AD underwent a ND test based on an illustrated story. The test was selected from the French language assessment corpus GREMOTS. The grading of the ND was done according to the following six parameters: lexicon, syntax, pragmatics, presence of the main actions, quality of discourse and informativeness. RESULTS: In the early stage, a quarter of the participants with DLB are under cut-off score for ND, and this proportion strongly increases in the advanced stage. In contrast, all the participants with AD show a pathological ND in both stages. In the early stage, the ND abilities appear significantly better preserved in participants with DLB than in participants with AD. No difference is found in the advanced stage. This result highlights two distinct language profiles, with the participants with AD being significantly less informative than the participants with DLB in the early stage. Furthermore, the participants with DLB show pathological scores spreading over the six parameters, whereas the participants with AD have more selective impairments. Indeed, the informativeness of participants with AD is 100% pathological while their syntax is 100% preserved. DISCUSSION: These results are encouraging as they could enable speech therapists to better adjust their follow-up according to the linguistic profile of the patients and to educate caregivers more appropriately. Further research on language issues in DLB and AD is essential.

Prospective and retrospective episodic metamemory in posttraumatic stress disorder.

OBJECTIVES: Posttraumatic stress disorder (PTSD) has been consistently associated with episodic memory deficits. To some extent, these deficits could be related to an impairment of metamemory in individuals with PTSD. This research consequently aims at investigating prospective (feeling-of-knowing, FOK) and retrospective (confidence) metamemory judgments for episodic information in PTSD. METHOD: Twenty participants with PTSD and without depression were compared to 30 healthy comparison participants on metamemory judgments during an episodic memory task. The concordance between metamemory judgments and recognition performance was then assessed by gamma correlations. RESULTS: The results confirmed that PTSD is associated with episodic memory impairment. Regarding metamemory, gamma correlations indicated that participants with PTSD failed to accurately predict their future memory performance as compared to the comparison group (mean FOK gamma correlations: .23 vs. .42, respectively). Furthermore, participants with PTSD made less accurate confidence judgments than comparison participants (mean confidence gamma correlations: .62 vs. .74, respectively). CONCLUSION: Our results demonstrate an alteration of both prospective and retrospective metamemory processes in PTSD, which could be of particular relevance to future therapeutic interventions focusing on metacognitive strategies.

A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Sex Hormone Therapy.

BACKGROUND: To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. METHODS: Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. RESULTS: The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. CONCLUSIONS: Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.

Age-related differences in episodic feeling-of-knowing arise from differences in memory performance.

Previous studies about the effects of ageing on the episodic feeling-of-knowing (FOK) accuracy and its underlying processes have yielded conflicting results. Recent work suggests that using alternative measures to gamma correlations might allow more accurate and informative interpretations of metamemory performance in ageing. We therefore investigated this issue with a large sample of 59 young and 61 older participants using alternative signal-detection theory (SDT) measures. These measures (receiver operating characteristic curves and Brier score) are recommended in the literature and able to reveal the characteristic profile of impairment in ageing. Our results suggest that the FOK accuracy deficit observed in the literature arises from differences in memory performance. This observation provides a convenient explanation to the previous discrepancies and furthermore supports the interest of the use of SDT-derived measures in the frame of metamemory.

Impaired emotional memory enhancement on recognition of pictorial stimuli in Alzheimer's disease: no influence of the nature of encoding.

OBJECTIVES: There is some discrepancy in the results regarding emotional enhancement of memory (EEM) in Alzheimer's disease (AD). Some studies report better retrieval of emotional information, especially positive, than neutral information. This observation is similar to the positivity effect reported in healthy older adults. It was suggested that this effect is due to privileged, deeper and more controlled processing of positive information. One way of testing this is to control both the intention to encode the information and the cognitive resources involved during encoding. Studies investigating EEM in AD patients did not systematically control the nature of encoding. Consequently, the purpose of our study was to examine EEM in AD while manipulating the nature of encoding. METHODS: Two experiments were conducted. In Experiment 1 the intention to encode stimuli was manipulated by giving or not giving instructions to participants about the subsequent retrieval. In Experiment 2 cognitive resources involved during encoding were varied (low vs high). In both experiments participants performed immediate recognition task of negative, positive and neutral pictures. 41 mild AD patients and 44 older healthy adults participated in Exp. 1, and 17 mild AD patients and 20 older healthy adults participated in Exp. 2. RESULTS: AD patients did not present EEM. Positivity effect, better performance for positive than neutral and negative pictures was observed with older healthy adults. CONCLUSION: The data suggest that EEM is disturbed in mild AD patients, with respect to both negative and positive stimuli, at least concerning laboratory, not real-life material. They also suggest there is a positivity effect in healthy older adults and lend support to the idea that this effect is due to preferential cognitive processing of positive information in this population.

Effects of emotionally-rated material on visual memory in Alzheimer's disease in relation to medial temporal atrophy.

Emotional material tends to be better retrieved in memory than neutral material. This emotional enhancement of memory may be related to the attentional effects of the amygdala's response to emotional stimuli. Because early neuropathological changes in Alzheimer's disease involve the amygdala and the hippocampus, it has been suggested that this effect is impaired in patients. However inconsistent results have been reported. The goal of our study was to evaluate the effects of emotion on picture recognition in patients affected by Alzheimer's disease, and to explore the link between this effect and the degree of amygdalar and hippocampal atrophy. Mild Alzheimer's disease patients (n = 15) and control participants (n = 20) performed an Old/New recognition task using pictures of negative, neutral, and positive emotional valence. Automated segmentation of their high-resolution T1 MRI scans was performed in order to obtain amygdalar and hippocampal volumes. Correlation analyses were then performed between volumetric data, memory, and the emotional effect on memory. An effect of emotion on memory was found for control participants (with positive items being better recognized than neutral and negative ones), with no correlation between this effect and medial temporal volumes, and a significant correlation between overall recognition scores and hippocampal volumes. Conversely, no emotional effect on memory was found across the group of patients; however, significant correlations were found between the loss of this effect and amygdalar and hippocampal volumes. These results tend to confirm a link between the loss of emotional effect on memory and neuropathological change in medial temporal structures during the course of Alzheimer's disease.

Emotional enhancement of immediate memory: Positive pictorial stimuli are better recognized than neutral or negative pictorial stimuli.

We examined emotional memory enhancement (EEM) for negative and positive pictures while manipulating encoding and retrieval conditions. Two groups of 40 participants took part in this study. Both groups performed immediate implicit (categorization task) and explicit (recognition task) retrieval, but for one group the tasks were preceded by incidental encoding and for the other group by intentional encoding. As indicated by the sensitivity index (d'), after incidental encoding positive stimuli were easier to recognize than negative and neutral stimuli. Participants' response criterion was more liberal for negative stimuli than for both positive and neutral ones, independent of encoding condition. In the implicit retrieval task, participants were slower in categorizing positive than negative and neutral stimuli. However, the priming effect was larger for emotional than for neutral stimuli. These results are discussed in the context of the idea that the effect of emotion on immediate memory enhancement may depend on the intentionality to encode and retrieve information.

Working memory processing of traumatic material in women with posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with medial frontal and amygdala functional alterations during the processing of traumatic material and frontoparietal dysfunctions during working memory tasks. This functional magnetic resonance imaging (fMRI) study investigated the effects of trauma-related words processing on working memory in patients with PTSD. METHODS: We obtained fMRI scans during a 3-back task and an identity task on both neutral and trauma-related words in women with PTSD who had been sexually abused and in healthy, nonexposed pair-matched controls. RESULTS: Seventeen women with PTSD and 17 controls participated in the study. We found no behavioural working memory deficit for the PTSD group. In both tasks, deactivation of posterior parietal midline regions was more pronounced in patients than controls. Additionally, patients with PTSD recruited the left dorsolateral frontal sites to a greater extent during the processing of trauma-related material than neutral material. LIMITATIONS: This study included only women and did not include a trauma-exposed non-PTSD control group; the results may, therefore, have been influenced by sex or by effects specific to trauma exposure. CONCLUSION: Our results broadly confirm frontal and parietal functional variations in women with PTSD and suggest a compensatory nature of these variations with regard to the retreival of traumatic memories and global attentional deficits, respectively, during cognitively challenging tasks.

Preserved subcortical volumes and cortical thickness in women with sexual abuse-related PTSD.

Posttraumatic stress disorder (PTSD) has been frequently associated with volumetric reductions of grey matter structures (e.g. hippocampus and anterior cingulate), but these results remain controversial, especially in female non-combat-related samples. The present study aimed at exploring whole-brain structures in women with sexual abuse-related PTSD on the basis of cortical and subcortical structure comparisons to a matched pair sample that was well-controlled. Seventeen young women who had experienced sexual abuse and who had a diagnosis of chronic PTSD based on the Clinician Administered PTSD Scale for DSM-IV and 17 healthy controls individually matched for age and years of education were consecutively recruited. Both groups underwent structural magnetic resonance imaging and psychiatric assessment of the main disorders according to Axis I of DSM-IV. The resulting scans were analyzed using automated cortical and subcortical volumetric quantifications. Compared with controls, PTSD subjects displayed normal global and regional brain volumes and cortical thicknesses. Our results indicate preserved subcortical volumes and cortical thickness in a sample of female survivors of sexual abuse with PTSD. The authors discuss potential differences between neural mechanisms of sexual abuse-related PTSD and war-related PTSD.

Effects of level of processing at encoding and types of retrieval task in mild cognitive impairment and normal aging.

A total of 16 young (M = 27.25 years), 13 healthy elderly (M = 75.38 years), and 10 older adults with probable mild cognitive impairment (MCI; M = 78.6 years) carried out a task under two different encoding conditions (shallow vs. semantic) and two retrieval conditions (free recall vs. recognition). For the shallow condition, participants had to decide whether the first or last letter of each word in a list was "E." For the semantic condition, they had to decide whether each word represented a concrete or abstract entity. The MCI group was only able to benefit from semantic encoding to the same extent as the healthy older adults in the recognition task, whereas the younger and healthy older adults benefited in both retrieval tasks. These results suggest that the MCI group required cognitive support at retrieval to make effective use of semantic processing carried out at encoding. In the discussion, we suggest that adults with MCI engage more in deep processing, using the semantic network, than hitherto thought.