Evaluating major depressive episodes through the algorithmically structured systematic exploration of subject's state of mind.

BACKGROUND/AIMS: Whereas instruments are available to diagnose depression and to rate its severity, there is a lack of instruments to assess the phenomenology of depression, i.e. a set of mental phenomena that constitute subjective experience. The Algorithmically Structured Systematic Exploration of Subject's State of Mind (Assess_Mind) is based on open questions asked via a structured algorithm. Here, we evaluated its reliability and its validity to assess the phenomenology of major depressive episodes. METHODS: Scales were constructed to evaluate various aspects of major depressive episodes, and an Assess_Mind score was derived from these scales. Thirty-five patients presenting a major depressive episode were assessed with the Hamilton Depression Rating Scale, Clinical Global Impressions (CGI) scale, Beck Depression Inventory and Symptom Checklist-90R. Two series of assessments were conducted, separated by 3 weeks. RESULTS: Interrater reliability was good to excellent and test-retest reliability was acceptable. Whereas construct validity was poor at the first time point (first day of the patient's inclusion), it was adequate for the second day and 3 weeks later. The change in the Assess_Mind score predicted the change in the CGI rating as well as the other instruments did. These results should be confirmed in larger samples. CONCLUSION: The Assess_Mind provided a useful assessment of the phenomenology of depression and of the course of major depressive episodes.

[Pseudo-dementia conversion and post-traumatic stress disorder]. / Pseudo-démence conversive et état de stress post-traumatique.

BACKGROUND: Post-traumatic stress disorder (PTSD) is often associated with other psychiatric syndromes. However, studies exploring conversion and PTSD comorbidity are scarce. CASE-REPORT: This paper reports the case of a 45 year-old patient without medical or psychiatric history. In 2003, he suddenly started suffering from amnesia and symptoms of delirium: he was at his office with a cup of coffee but he did not remember why. Aphasia, trembling, behavioural disorders appeared over the next hours and days. Numerous neurological examinations and laboratory tests (including cerebral imagery) were performed without evidence of any physical disease. Three psychiatric examinations were also negative, even if a possible psychogenic origin was hypothesized. Neurological or psychiatric diagnoses were discussed but without definitive conclusion. One year later, the symptoms were unchanged until the patient watched a movie ("Mystic River") that described the story of a man with sexual abuse in childhood. He suddenly remembered that he lived the same experience when he was 8 years old. At the end of the movie, his wife surprisingly noticed that he was walking and speaking normally. All the neurological symptoms disappeared. Unfortunately, symptoms of a severe PTSD appeared, as well as a major depressive disorder. The patient and his parents remembered that he had been more irritable, depressed and anxious at school and during the night, between 8 and 13 years of age, with a possible PTSD during this period. He always refused to talk with his parents about the traumatic event. When he was 13, the family moved house, the patient seemed to forget everything and the symptoms disappeared. About thirty years later, the symptoms were similar with the reexperien of the traumatic event through unwanted recollections, distressing images, nightmares, or flashbacks. He had also symptoms of hyperarousal with physiological manifestations, such as irritability, insomnia, impaired concentration, hypervigilance, and increased startle reactions. Hospitalisation became necessary because of a severe depressive disorder with suicidal ideation and suicidal attempt by hanging. After two failed treatments with SSRI antidepressants, the administration of clomipramine (200 mg/d) and a combined therapy with Eyes Movement Desensitization and Reprocessing (EMDR) led to a significant improvement of PTSD and depression symptoms. DISCUSSION: Even if PTSD and conversion may share common dissociative mechanisms, the links between both syndromes have not yet been sufficiently explored. Our clinical case raises specifically the question of the initial manifestations of pseudo-dementia (why this type of symptoms, and why at this particular moment of his life, without any targeting events). Moreover, the case of this patient is particularly interesting because of the very long amnesia period between the traumatic event and the onset of PTSD. CONCLUSION: The different phases of this case warrant more precise exploration of the links between PTSD and conversion, with clinical, epidemiological and cerebral imagery perspectives.

[Dimensional approach of emotion in psychiatry: validation of the Positive and Negative Emotionality scale (EPN-31)]. / Evaluation dimensionnelle des émotions en psychiatrie: validation du questionnaire Emotionnalité positive et négative à 31 items (EPN-31).

BACKGROUND: This paper reports the first validation study of the EPN-31 scale (Positive and Negative Emotionality scale, 31 items) in a French psychiatric sample. This questionnaire has been adapted by Rolland from an emotion inventory developed by Diener, and is also in accordance with Watson and Clark's tripartite model of affects. METHODOLOGICAL ASPECTS: Respondents were asked to rate the frequency with which they had experienced each affect (31 basic emotional states) during the last month. The answer format was a 7-point scale, ranging from 1 "Not experienced at all" to 7 "Experienced this affect several times each day". Three main scores were calculated (positive affects, negative affects, and surprise affects), as well as six sub-scores (joy, tenderness, anger, fear, sadness, shame). Four hundred psychiatric patients were included in this study, and completed the EPN-31 scale and the Hospital Anxiety and Depression (HAD) scale. The Global Assessment of Functioning (GAF) scale was rated, as well as DSM IV diagnostic criteria. We performed a principal component analysis, with Varimax orthogonal transformation, and explored the factorial structure of the questionnaire, the internal consistency of each dimension, and the correlations between EPN-31 scores and HAD scores. RESULTS: The factorial structure of the EPN-31 was well-defined as expected, with a three-factor (positive, negative and surprise affects) solution accounting for 58.2% of the variance of the questionnaire. No correlation was obtained between positive and negative affects EPN-31 scores (r=0.006). All alpha Cronbach coefficients were between 0.80 and 0.95 for main scores, and between 0.72 and 0.90 for sub-scores. GAF scores were significantly correlated with EPN-31 positive affects scores (r=0.21; p=0.001) and with EPN-31 negative affects scores (r=- 0.45; p=0.001). We obtained significant correlations between positive affects score and HAD depression score (r=- 0.45; p<0.001), and between negative affects score and HAD anxiety (r=0.56; p<0.001) and depression (r=0.45; p<0.001) scores. This pattern of correlation was in accordance with the Watson tripartite model of emotionality. Significantly higher EPN-31 positive affect mean scores were observed in females when compared to males (p<0.001). The third factor of the EPN-31 is less robust than the others and, the validity of the surprise score could hence be discussed. CONCLUSION: In all, this study confirmed the validity and the interest of the EPN-31 use in psychiatric patients. Various clinical and research applications can be considered, such as infra-symptomatic studies of emotions in affective disorders and during treatment protocols or definition of phenotypic markers in genetic or neuro-imagery studies.

[Episodic autobiographical memory in depression: a review]. / Mémoire autobiographique épisodique et dépression.

INTRODUCTION: Autobiographical memory and personal identity (self) are linked by a reciprocal relationship. Autobiographical memory is critical for both grounding and changing the self. Individuals' current self-views, beliefs, and goals influence their recollections of the past. According to Tulving, episodic memory is characterized by autonoetic consciousness, which is associated with a sense of the self in the past (emotions and goals) and mental reliving of an experience. Its close relationship with self and emotion strongly involves episodic autobiographical memory in the psychopathology of depression. However, due to methodological and conceptual issues, little attention has been paid to episodic autobiographical memory in depression. Since the seminal work of Williams et al. 15 years ago, there is now growing interest around this issue. LITERATURE FINDINGS: We reviewed the evidence for three major features of autobiographical memory functioning in depression: an increase in general memory retrieval (overgenerality), a mood-congruent memory effect and the high occurrence of intrusive memories of stressful events. Although it was first observed among suicidal patients, overgenerality is actually associated with both depression and post-traumatic stress disorder. Overgenerality is not associated with anxious disorders other than post-traumatic stress disorder, obsessive-compulsive disorder, or borderline personality disorder. Most of controlled studies carried out on autobiographical memory in depression rely on the Williams' Autobiographical Memory Test (AMT). When presented with positive and negative cue words and asked to retrieve specific personal events, depressed patients (unlike matched controls) are less specific in their memories. They tend to recall repeated events (categorical overgeneral memories) rather than single episodes (specific memories). Overgenerality in depression is: 1) more evident with positive than with negative events (mood-congruent memory effect); 2) related to avoidance of intrusive memories; 3) quite stable over time, ie, remaining after remission; and 4) related to short-term prognosis in depression. Although it is not clear whether overgenerality is a cause or an effect of depression, there is some evidence to suggest that overgenerality is a trait marker indicating vulnerability to persistent depression. Mood-congruent effect, a well-known effect in depression, has been addressed in both autobio-graphical and non-autobiographical memory. Depressed patients spontaneously recall more negative than positive memories. With the AMT, depressed patients take longer to respond to positive than to negative cues, whereas controls do the opposite. Depression is also associated with a high occurrence of spontaneous intrusive memories of stressful life events. Studies found intrusions and related avoidance, as measured by the Impact of Event Scale, to be positively correlated with overgenerality, whereas there was no direct link between performance on the Autobiographical Memory Test and stressful life events per se. Both Williams' mnemonic interlock model and Conway's self-memory system are useful models to address the complexity of findings regarding autobiographical memory and depression. DISCUSSION: According to Williams, repeated avoidance of stressful memories leads depressed patients to have an autobiographical memory functioning characterized by iterative retrievals of categorical overgeneral memories, producing an enduring overgeneral retrieval style. According to Conway, the recollection of autobiographical memories requires a retrieval process that provides access to sensory/perceptual event-specific knowledge (ie perceptions and feelings) via a personal semantic knowledge base (ie lifetime periods and generic events). This retrieval process (generative retrieval mode) relies on both executive functioning and current self-view, namely the working-self. Spontaneous memories, usually vivid, result from a direct retrieval mode in which event-specific knowledge is directly triggered. In line with this model, episodic autobiographical memory impairment in state depression may arise from the working self rather than from autobiographical knowledge. The mood-congruent effect may be explained by the current (depressed) self. The high occurrence of intrusive memories may be explained by lack of executive control during direct retrieval. Overgenerality may rely on the interaction of both executive dysfunction and current (depressed) self, within the working-self, during generative retrieval. Our review suggests that further evidence is needed to address the relationship between executive functioning, self and autobiographical memory in depression.

Association between the tryptophan hydroxylase gene and manic-depressive illness.

BACKGROUND: Genes encoding proteins involved in serotonergic metabolism are major candidates in association studies of mood disorders and suicidal behavior. This association study explores whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a susceptibility factor for manic-depressive illness, with or without a history of suicide attempts. METHODS: The TPH intron 7 A218C polymorphism was determined using a polymerase chain reaction-based method in DNA samples from 152 patients with bipolar disorder and 94 healthy control subjects. RESULTS: There was a significant association between TPH genotypes and manic-depressive illness. Among patients with bipolar disorder, no association was found between TPH alleles and suicidal behavior. CONCLUSIONS: This result suggests the involvement of the TPH gene in susceptibility to manic-depressive illness. This preliminary result requires confirmation in further groups of patients and controls.

Validating affective temperaments in their subaffective and socially positive attributes: psychometric, clinical and familial data from a French national study.

BACKGROUND: One of the major objectives of the French National EPIDEP Study was to show the feasibility of systematic assessment of bipolar II (BP-II) disorder and beyond. In this report we focus on the utility of the affective temperament scales (ATS) in delineating this spectrum in its clinical as well as socially desirable expressions. METHODS: Forty-two psychiatrists working in 15 sites in four regions of France made semi-structured diagnoses based on DSM IV criteria in a sample of 452 consecutive major depressive episode (MDE) patients (from which bipolar I had been removed). At least 1 month after entry into the study (when the acute depressive phase had abated), they assessed affective temperaments by using a French version of the precursor of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Principal component analyses (PCA) were conducted on hyperthymic (HYP-T), depressive (DEP-T) and cyclothymic (CYC-T) temperament subscales as assessed by clinicians, and on a self-rated cyclothymic temperament (CYC-TSR). Scores on each of the temperament subscales were compared in unipolar (UP) major depressive disorder versus BP-II patients, and in the entire sample subdivided on the basis of family history of bipolarity. RESULTS: PCAs showed the presence of a global major factor for each clinician-rated subscale with respective eigenvalues of the correlation matrices as follows: 7.1 for HYP-T, 6.0 for DEP-T, and 4.7 for CYC-T. Likewise, on the self-rated CYC-TSR, the PCA revealed one global factor (with an eigenvalue of 6.6). Each of these factors represented a melange of both affect-laden and adaptive traits. The scores obtained on clinician and self-ratings of CYC-T were highly correlated (r=0.71). The scores of HYP-T and CYC-T were significantly higher in the BP-II group, and DEP-T in the UP group (P<0.001). Finally, CYC-T scores were significantly higher in patients with a family history of bipolarity. CONCLUSION: These data uphold the validity of the affective temperaments under investigation in terms of face, construct, clinical and family history validity. Despite uniformity of depressive severity at entry into the EPIDEP study, significant differences on ATS assessment were observed between UP and BP-II patients in this large national cohort. Self-rating of cyclothymia proved reliable. Adding the affective temperaments-in particular, the cyclothymic-to conventional assessment methods of depression, a more enriched portrait of mood disorders emerges. More provocatively, our data reveal socially positive traits in clinically recovering patients with mood disorders.

Decreased serotonin transporter binding in unaffected relatives of manic depressive patients.

BACKGROUND: There are numerous reports of decreased binding to platelet serotonin transporter (5-HTT) in depression, suggesting that it might be considered a trait marker of depression. To further investigate whether reduced 5-HTT function could be an endophenotype in manic depressive illness, we looked for abnormalities of platelet 5-HTT among subjects who are potential carriers of genetic vulnerability to manic depressive illness (MDI). METHODS: Blood samples were obtained from 20 unaffected relatives from families with at least two individuals with bipolar disorder and from 19 control participants. Plasma 5-HIAA, platelet 5-HT, and [3H] imipramine binding were measured. RESULTS: Unaffected relatives manifested lower platelet 5-HTT function than control participants as revealed both by reduced number and diminished affinity of imipramine binding sites and diminished platelet 5-HT content. CONCLUSIONS: These preliminary results suggest that reduced 5-HTT function could be considered a trait marker or an endophenotype in MDI.

Depression as a dynamical disease.

Mathematical models are helpful in the understanding of diseases through the use of dynamical indicators. A previous study has shown that brain activity can be characterized by a decrease of dynamical complexity in depressive subjects. The present paper confirms and extends these conclusions through the use of recent methodological advances: first episode and recurrent patients strongly differ in their dynamical response to therapeutic interventions. These results emphasize the need for clinical follow-ups to avoid recurrence and the necessity of specific therapeutic intervention in the case of recurrent patients.

Absence of cognitive impairment at long-term follow-up in adolescents treated with ECT for severe mood disorder.

OBJECTIVE: Cognitive functions of adolescents treated with ECT for mood disorder were evaluated at long-term follow-up. METHOD: At an average of 3.5 years (SD=1.7) after the last ECT, 10 subjects treated during adolescence with bilateral ECT for severe mood disorder completed a clinical and cognitive evaluation, including the California Verbal Learning Test and Squire's Subjective Memory Questionnaire. The same assessments were given to 10 psychiatric comparison subjects matched for sex, age, and diagnosis. RESULTS: All cognitive test scores of the patients treated with ECT were similar to those of the comparison subjects and did not differ from norms from the community. Six of the 10 ECT-treated patients reported having had memory losses immediately after the ECT course, but only one complained of subjective memory impairment at follow-up. CONCLUSIONS: The results suggest that adolescents given ECT for severe mood disorder do not suffer measurable cognitive impairment at long-term follow-up.

CAG repeat sequences in bipolar affective disorder: no evidence for association in a French population.

Anticipation has been described in bipolar affective disorder (BPAD). However, there are conflicting results from association studies screening for a link between BPAD and CAG/CTG repeat expansions, the molecular basis of anticipation in several hereditary neurodegenerative disorders. Here, the repeat expansion detection (RED) method was used to screen for CAG repeat expansion in 119 French BPAD patients. Western blotting was also used to search for polyglutamine stretches, encoded by CAG expansion, among proteins, extracted from lymphoblastoid cell lines, from six selected familial cases. Maximum CAG/CTG repeat length did not differ significantly (P = 0.38) between the 119 BPAD patients and the 88 controls included in the study. Several categories of subgroups were used, none of which showed significant association with a long repeat. Nor was a specific protein with an unusually long polyglutamine stretch (lower detection limit, approximately 33 polyglutamines) detected in cell lysates from the familial cases studied. In conclusion, an association between a long CAG/CTG repeat and BPAD in the French population sample studied was not found. Nonetheless, a short repeat (<40 repeats) might still be implicated, and this possibility warrants further study.

Temporal order and spatial memory in schizophrenia: a parametric study.

Spatial working memory has been shown to be impaired in schizophrenia. In contrast, memory for temporal order has been poorly studied in patients with schizophrenia. The aim of this study was to compare and to further characterize spatial working memory and sequence reproduction deficits in patients with schizophrenia under stable medication by manipulating cues (pattern versus sequence), delay, set-size and response type in various recall and recognition tasks. This allowed us to dissociate processes as encoding, retention and retrieval and to compare the performance of patients with schizophrenia to the performance of patients with prefrontal lesions, who have been previously tested in the same tasks. Our results show that increase of the set-size and of the delay decreased performance of both groups, and that these factors had larger detrimental effects in patients with schizophrenia than in controls. Furthermore, comparison between tasks revealed retention and retrieval deficits in schizophrenia. Finally, patients with schizophrenia showed impairments not only in recall but also in sequence recognition tasks with delay. This is in contrast to patients with prefrontal lesions, who have previously been shown to have intact recognition of sequences after a delay. These results suggest that the working memory deficit in schizophrenia cannot be restricted to a prefrontal dysfunction.

Decrease of complexity in EEG as a symptom of depression.

Nonlinear dynamic analysis provides new methods for the processing of the electroencephalogram (EEG). We demonstrate here that the EEG dynamics of major depressive subjects is more predictable, that is less complex, than that of control subjects. Moreover, the consequence of treatment upon the EEG dynamics seems to be dependent on the appearance of the illness. Although the specificity of this dynamic signature for different stages of depression is to be confirmed, the assumption of a strong link between a healthy system and a high level of complexity in dynamics is further supported.

Experimental evidence for two dimensions of cognitive disorders in depressives.

Three neuropsychological tests (Rey's auditory verbal learning test, word fluency and signal detection test for words) were administered to 36 depressed patients (medicated and non-medicated) and 26 controls and compared to scale scores for depression severity and psychomotor retardation to examine how retardation was related to cognitive performance. As expected, compared to controls depressives exhibited non-specific "cognitive inefficiency", that is, consistently deficient performance in all cognitive tasks. Results on all three tests were correlated with one other and with depressive severity (measured by the Montgomery & Asberg Depression Rating Scale, MADRS). One notable exception, however, was the score for commission errors ("false alarms") in the signal detection test, which correlated negatively with psychomotor retardation (measured by a subscale of the Salpétrière Retardation Rating Scale, SRRS) but not at all with depressive severity. Lack of commission errors thus seemed to index a dimension of retardation of ideation that seemed distinct from the non-specific cognitive inefficiency dimension. Conversely, omission errors in the same test strongly correlated with the other two cognitive tests and with depressive severity but not with psychomotor retardation. Cognitive performance in depressives might thus be explainable in terms of two overlapping dimensions of depressive pathology (global cognitive impairment vs. specific effect of retardation). Further studies with non-medicated patients are needed to determine to what extent these findings may be due to medication effects.

Executive functions and updating of the contents of working memory in unipolar depression.

BACKGROUND: Depression is characterized by cognitive impairments, including executive dysfunctions. These executive deficits could reflect impairments of more basic executive processes, such as updating, set shifting and inhibition. While shifting and inhibition impairments are often reported, studies on depression have been somewhat obscure about specific deficits of the updating process. The main goal of that study was to assess the updating process in young in-patients with depression. METHODS: We used a verbal n-back task to assess updating process. Load and mental manipulation within working memory (WM) were incremented by using three different levels of complexity (1,2,3-back). Neuropsychological tests and an attentional task (0-back) were also administered to subjects. Twenty-two individuals meeting DSM-IV criteria for Major Unipolar Depression and 22 healthy control subjects, matched on age, verbal IQ and education, were included in the study. RESULTS: Subjects with depression showed significant deficits at the n-back task compared to control subjects. They were normal in tasks assessing the short-term maintenance in WM and attention. This suggests that depressed patients exhibit impairment in the updating process. Depressed patients also showed set shifting and inhibition deficits. Only the n-back task was correlated with the number of hospitalizations and the longitudinal course of the illness. CONCLUSIONS: Our results suggest that young depressed in-patients have widespread executive dysfunctions, including updating, shifting and inhibition processes. We also found a correlation between a longitudinal measure of depression severity and an updating task performance. We suggest that using multiple executive tasks gives the opportunity to distinguish the specific influence of various executive processes on clinical dimensions in depression.

Toward a refined phenomenology of mania: combining clinician-assessment and self-report in the French EPIMAN study.

BACKGROUND: Because manic patients lack insight, they are generally considered unreliable observers of their own psychopathology. The present analyses sought to examine to what extent patient reports could improve formal diagnostic criteria for mania--and be validated against the Carroll-Klein (CK) psychobiological model of bipolarity. METHOD: 104 DSM-IV acutely manic (hospitalized) patients provided self-assessment on the Ahearn--Carroll scale, the Multiple Visual Analogue Scales of Bipolarity (MVAS-BP). A principal component analysis (PCA) was performed on MVAS-BP, and the data on factorial scores were then compared to dimensional scores according to the CK model and to factors on the Beigel-Murphy Manic State Rating Scale (MSRS) completed by psychiatrists. RESULTS: The PCA identified a general factor accounting for 33% of the total variance; after varimax rotation, seven independent factors emerged, essentially in coherence with the signs and symptoms of DSM-IV mania, except for the 'social disinhibition' factor, which does not figure out as a distinct criterion in DSM-IV. Strong correlations were obtained (r > or = 0.80) between the four major factors of MVAS-BP and the four dimensional categories of the CK model: 'Consummatory Reward' with F1 'Elation and Inflated Self-esteem' (r=0.93), 'Incentive Reward' with F2 'Activation' (r=0.84), 'Psychomotor Pressure' with F3 'Acceleration' (r=0.85), and 'Central Pain' with F4 'Anxiety-Depression' (r=0.84). The F2 'Activation' appeared to be strongly correlated (r > or = 0.70) to all categories of the CK model. Correlational analysis between the factor structure of MVAS-BP and the MSRS showed significant coefficients on the scores assessing the emotional factors of 'Elation' and 'Depression.' Among the MVAS-BP factors, only 'Activation' was correlated to the majority of clinician ratings as obtained by the MSRS. CONCLUSIONS: These findings provide overall construct validity to the DSM-IV criteria for mania. Self-assessment of this disorder appears feasible and potentially useful in practice; lack of insight, poor judgment, and distractibility obviously require assessment by a clinician. Although our data are correlational and require prospective validation, they nonetheless suggest that (1) activation should be raised to the status of the stem criterion for mania, (2) to specify mood as elated, depressive, anxious, or irritable, and (3) to give individual status to social disinhibition (indiscriminate gregariousness) as a core pathological behavior in mania. Combining clinician- and self-observation thus produces a more precise and complete phenomenology of mania. We finally submit that the foregoing reformulation provides a psychobiological basis to the manic construct as formulated in the Carroll-Klein model.

Early and late onset bipolar disorders: two different forms of manic-depressive illness?

BACKGROUND: Conflicting results in genetic studies of bipolar disorders may be due to the clinical and genetic heterogeneity of the disease. Age at onset of bipolar disorders may be a key indicator for identifying more homogeneous clinical subtypes. We tested whether early onset and late onset bipolar illness represent two different forms of bipolar illness in terms of clinical features, comorbidity and familial risk. METHODS: Among a consecutively recruited sample of 210 bipolar patients, we compared early onset (n=58) and late onset (n=39) bipolar patients; the cut-off points were age at onset before 18 years and after 40 years for the two subgroups. The subgroups were compared by independent t tests and a contingency table by raw chi-square test. Morbid risk among first-degree relatives was measured by the survival analysis method. RESULTS: The early onset group had the most severe form of bipolar disorder with more psychotic features (P=0.03), more mixed episodes (P=0.01), greater comorbidity with panic disorder (P=0.01) and poorer prophylactic lithium response (P=0.04). First degree relatives of early onset patients also had a higher risk of affective disorders (P=0.0002), and exhibit the more severe phenotype, i.e bipolar disorder. CONCLUSION: Our data suggest that early and late onset bipolar disorders differ in clinical expression and familial risk and may therefore be considered to be different subforms of manic-depressive illness.