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).

Investigating racing thoughts via ocular temporal windows: deficits in the control of automatic perceptual processes.

BACKGROUND: Racing thoughts have been found in several states of bipolar disorder (BD), but also in healthy populations with subclinical mood alterations. The evaluation of racing thoughts relies on subjective reports, and objective measures are sparse. The current study aims at finding an objective neuropsychological equivalent of racing thoughts in a mixed group of BD patients and healthy controls by using a bistable perception paradigm. METHOD: Eighty-three included participants formed three groups based on participants' levels of racing thoughts reported via the Racing and Crowded Thoughts Questionnaire. Participants reported reversals in their perception during viewing of the bistable Necker cube either spontaneously, while asked to focus on one interpretation of the cube, or while asked to accelerate perceptual reversals. The dynamics of perceptual alternations were studied both at a conscious level (with manual temporal windows reflecting perceptual reversals) and at a more automatic level (with ocular temporal windows derived from ocular fixations). RESULTS: The rate of windows was less modulated by attentional conditions in participants with racing thoughts, and most clearly so for ocular windows. The rate of ocular windows was especially high when participants with racing thoughts were asked to focus on one interpretation of the Necker cube and when they received these instructions for the first time. CONCLUSIONS: Our results indicate that in subjects with racing thoughts automatic perceptual processes escape cognitive control mechanisms. Racing thoughts may involve not only conscious thought mechanisms but also more automatic processes.

Novel method to measure temporal windows based on eye movements during viewing of the Necker cube.

Bistable stimuli can give rise to two different interpretations between which our perception will alternate. Recent results showed a strong coupling between eye movements and reports of perceptual alternations with motion stimuli, which provides useful tools to objectively assess perceptual alternations. However, motion might entrain eye movements, and here we check with a static picture, the Necker cube, whether eye movements and perceptual reports (manual responses) reveal similar or different alternation rates, and similar or different sensitivity to attention manipulations. Using a cluster analysis, ocular temporal windows were defined based on the dynamics of ocular fixations during viewing of the Necker cube and compared to temporal windows extracted from manual responses. Ocular temporal windows were measured also with a control condition, where the physical stimulus presented to viewers alternated between two non-ambiguous versions of the Necker cube. Attention was manipulated by asking subjects to either report spontaneous alternations, focus on one percept, or switch as fast as possible between percepts. The validity of the ocular temporal windows was confirmed by the correspondence between ocular fixations when the physical stimulus changed and when the bistable Necker cube was presented. Ocular movements defined smaller time windows than time windows extracted from manual responses. The number of manual and ocular windows both increased between the spontaneous condition and the switch condition. However, only manual, and not ocular windows, increased in duration in the focus condition. Manual responses involve decisional mechanisms, and they may be decoupled from automatic oscillations between the two percepts, as suggested by the fact that both the number and duration of ocular windows remained stable between the spontaneous and focus conditions. In all, the recording of eye movements provides an objective measure of time windows, and reveals faster perceptual alternations with the Necker cube and less sensitivity to attention manipulations than manual responses.

Racing thoughts revisited: A key dimension of activation in bipolar disorder.

BACKGROUND: Racing and crowded thoughts are frequently reported respectively in manic and mixed episodes of bipolar disorder (BD). However, questionnaires assessing this symptom are lacking. Here we aimed to investigate racing thoughts across different mood episodes of BD through a self-report questionnaire that we developed, the 34-item Racing and Crowded Thoughts Questionnaire (RCTQ). In addition to assessing its factor structure and validity, we were interested in the RCTQ's ability to discriminate mixed and non-mixed depression. METHODS: 221 BD patients and 120 controls were clinically assessed via the YMRS (mania) and the QIDS-C16 (depression), then fulfilled the RCTQ, rumination, worry, and anxiety measures. Three depression groups were operationalized according to YMRS scores: YMRS scores 2 > 6 and YMRS scores = 1 or 2, for respectively mixed and non-pure depression, and YMRS = 0 for pure-depression. RESULTS: Confirmatory factor analysis showed that the three-factor model of the RCTQ yielded the best fit indices, which improved after the removal of redundant items, resulting in a 13-item questionnaire. Hypomanic and anxiety symptoms were the main predictors of scores; rumination was not a significant predictor. RCTQ results were similar between mixed groups and non-pure depression, and both were higher than in pure-depression. LIMITATIONS: Patients' pharmacological treatment might have influenced the results. CONCLUSIONS: The 13-item RCTQ captures different facets of racing thoughts heightened in hypomanic and mixed states, but also in depression with subclinical hypomanic/activation symptoms (e.g. non-pure depression characterized by enhanced subjective irritability), suggesting that it is particularly sensitive to activation symptoms in BD, and could become a valuable tool in the follow-up of patients.

A case study of suicidality presenting as a restricted interest in autism Spectrum disorder.

BACKGROUND: Suicidality has been under-researched in autism spectrum disorders (ASD). Most studies have linked increased suicidality in ASD to psychiatric comorbidities such as depression. Here we investigated, from a neuropsychological and clinical standpoint, the relationship between core ASD symptoms, i.e., restricted behaviors and social and communication impairments, and the suicidal behaviors in an adult male individual with ASD, with no psychiatric comorbidities. CASE PRESENTATION: We report the case of a 21-year-old male with ASD who attempted suicide twice, in the absence of other psychiatric diagnoses. His behavior and communication skills were rigid. His suicidality was characterized by a rigid, detailed, and pervasive thinking pattern, akin to restricted interests. Consistently, from a neuropsychological standpoint, we found below-average planning and attention skills, and mind-reading skills were rigid and lacked spontaneity. CONCLUSIONS: Our case-study suggests that specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD. Clinically, the repetitive and rigid suicide-oriented thinking of our patient was not part of a depressive episode. Instead, it followed a purely logical, inflexible, and pervasive reasoning pattern focused on a topic that fascinated him - i.e., suicide --, akin to restricted behaviors. From a neuropsychological standpoint, restrictive suicide-oriented thinking in our patient seems to be related to attention and executive anomalies that have been linked to repetitive and restricted behaviors in ASD. New tools need to be developed to assess persistent suicidal thoughts in this population, as they might be related to intrinsic features of ASD.