[Borderline personality disorders: diagnosis and treatment]. / Troubles limites et personnalité "border-line": comment les reconnaître et les traiter?

Borderline personality disorders are complex clinical states with highly polymorphic symptoms and signs, leading to delays in their diagnosis and treatment. All international classifications emphasize certain clinical criteria such as unstable identity and interpersonal relationships, feelings of emptiness or boredom, and pathological impulsiveness. The prevalence is about 2%, with a female-male sex ratio of 2 or 3 to 1. Both adolescents and adults may be affected There is a high risk of suicide, addictive behaviors, eating disorders, and criminality. These individuals frequently have a history of trauma in early childhood, such as separation, loss, physical or sexual abuse, or affective privation. Subjective signs and symptoms are particularly important in the diagnostic and therapeutic evaluation, and this requires an empathic and subtle approach. Standardized and semi-structured interviews may help to identify comorbidities such as thymic disorders, anxiety, addiction, eating disorders, and, in some cases, psychotic symptoms. The psychiatric bio-psycho-social model takes into account multiple pathogenic factors, such as trauma during early development, temperamental instability and other emotional disorders, as well as psychosocial, neurobiological (5HT etc.) and genetic vulnerabilities. Treatment requires optimal integration of psychotherapeutic and pharmacotherapeutic approaches. Emergency intervention must be available in case of delirious or suicidal behavior The clinical course is often lengthy and complex, but outcome may be favorable, provided the principal risk--suicide--is correctly managed,

Therapeutic drug monitoring of clomipramine and amitriptyline in a depressed patient with upper digestive tract resection.

We describe a 55-year-old woman with extensive digestive resection and recurrent depressive disorder resistant to oral clomipramine tablets but not to an oral solution of amitriptyline. In the light of this case report, the potential mechanisms of drug resistance after digestive resection are discussed, including the importance of drug monitoring.

[Diagnosis of bipolar disorder and rationale of early treatment]. / Comment dépister et pourquoi traiter précocement la maladie bipolaire?

The earlier bipolarity is diagnosed and treated, the better the chances of durable recovery The bipolar spectrum consists of a large panel of clinical syndromes with heterogeneous symptoms. Clinical studies show that, on average, a period of nine years elapses between onset of the first mood symptoms and appropriate prescription of mood stabilizers. Tools such as the bipolarity index can help with earlier and more precise diagnosis of bipolarity, and with the choice of the best treatment to prevent complications of bipolar illness.

Self-referential processing and the prefrontal cortex over the course of depression: a pilot study.

BACKGROUND: Depressed patients exhibit cognitive biases, including maladaptive self-focus. In a previous functional magnetic resonance imaging (fMRI) study, the dorsal medial prefrontal cortex (MPFC) activation during self-referential versus semantic processing was unique to patients, as was the left dorsolateral prefrontal cortex (DLPFC) activation. The aim of this pilot study was to examine whether this pattern was stable over the course of depression. METHODS: Sixteen participants (8 depressed inpatients, 8 healthy controls) viewed personality traits during fMRI and judged whether each trait described them or not ('self' condition), or whether it described a socially desirable trait or not ('general' condition). There were 2 scanning sessions with an interval of at least 6weeks, in which patients received an antidepressant treatment. RESULTS: After a mean duration of 9 weeks, depressed patients displayed a more balanced activation of the left DLPFC but a greater activation of the dorsal MPFC in 'self' versus 'general' condition remained. LIMITATIONS: The small sample size and heterogeneous clinical features prevented subgroups analyses between responders and non-responders. CONCLUSIONS: The change of the left DLPFC activation suggests that antidepressants are associated with a more balanced allocation of cognitive control across self-referential and non-self-referential processes. The apparent lack of effect on the dorsal MPFC activity is consistent with the specific effects of antidepressants versus cognitive behavior therapy (CBT) previously demonstrated in depression. Future studies could examine the relationships between the dorsal MPFC activity in depressed patients and the need to reduce self-focus through CBT to achieve remission and prevent relapse.

In search of the depressive self: extended medial prefrontal network during self-referential processing in major depression.

Major depression is associated with an excessive self-focus, a tendency to engage oneself in self-referential processing. The medial frontal gyrus (MFG) is central to self-referential processing. This study aimed to explore the neural bases of this excessive self-focus and to disambiguate the role of the MFG in the pathophysiology of major depression. We presented 15 depressed patients and 15 healthy subjects with personality traits during functional magnetic resonance imaging and asked them to judge whether each trait described them ('self' condition) or a generally desirable trait ('general' condition). Both patients and healthy subjects activated the MFG in 'self' vs 'general' condition. However, the activation of the dorsal part of the MFG and of the dorsolateral prefrontal cortex (DLPFC) in 'self' vs 'general' condition was unique to patients. Additionally, patients displayed an increased functional connectivity between the MFG, the dorsal anterior cingulate cortex and the DLPFC. These results provide evidence for an extended medial prefrontal network during self-referential processing in major depression, suggesting the involvement of a greater cognitive control.

Cognitive avoidance of intrusive memories and autobiographical memory: specificity, autonoetic consciousness, and self-perspective.

Autobiographical memory (AM) specificity is impaired in depression and post-traumatic stress disorder. Previous studies emphasised the role of cognitive avoidance of intrusive memories in this impairment. This study aimed to examine the association of cognitive avoidance of intrusive memories with specificity, autonoetic consciousness, and self-perspective. A total of 38 healthy participants were given the revised Impact of Event Scale (IES-R) and an AM task designed to assess positive and negative memories regarding specificity, autonoetic consciousness (remember/know procedure), and self-perspective (field/observer procedure). Taking into account age, verbal IQ, mood, harm avoidance, and executive resources, the IES-R avoidance subscale was negatively correlated with specificity and remember responses for positive memories, and with remember and field responses for negative memories. These findings suggest that cognitive avoidance of intrusive memories is associated with a decrease of the episodic components of AM retrieval.

[Adult depressive disorder: clinical aspects, nosography and psychiatrics comorbidity]. / Dépression de l'adulte, manifestations cliniques, nosographie et comorbidités.

Depressed mood and anhedonia are the main symptoms of depressive disorder. With other symptoms, it is responsible for a real break with premorbid patient's way of life. Several clinicals forms, caracterised by melancholia intensity, psychotic symptoms and cognitive troubles, must be identified to adapt treatment and to prevent patients from particular risks. The short and middle term prognosis is linked to the suicidal risk and the socioprofessionnal and familial consequences. Long term risk is the disease chronicisation, recurrence and bipolarity. The existence of other psychiatric comorbidity, such as alcoholism, personality disorder, anxiety disorder, is frequent and must be envisaged, despite the difficulty linked with symptoms intrication.

Field perspective deficit for positive memories characterizes autobiographical memory in euthymic depressed patients.

Research on autobiographical memory (AM) and the ability to retrieve specific autobiographical events in euthymic depressed patients yielded divergent results. The main goal of the present study was to further explore episodic specificity of AM among fully remitted depressed patients. Twenty euthymic depressed patients and 20 matched healthy controls were given a semi-structured interview, which assesses episodic specificity of positive and negative autobiographical memories regarding event and details' specificity, autonoetic consciousness (remember/know procedure) and visual perspective (field/observer procedure). Results showed an impairment of episodic specificity of AM in euthymic depressed patients. This impairment was explained by a field perspective deficit for positive memories only. These results suggest that euthymic patients continue to exhibit discrepancy between their current self and their self for positive past behaviors, which maintains an unfavorable view of their current self. Specific cognitive interventions may improve the self-relevance of their positive memories.

[Babinski and hysteria]. / Babinski et l'hystérie.

Babinski made important contributions to both psychiatry and neurology. He disagreed with Charcot's theatrical interpretation of hysteria and made a subtle distinction between Suggestion and Persuasion, thereby differentiating Hysteria from Pithiatism. This paper examines Charcot's concepts and the way in which Babinski refined and honed his master's theories.

Validating the bipolar spectrum in the French National EPIDEP Study: overview of the phenomenology and relative prevalence of its clinical prototypes.

BACKGROUND: Few studies have been undertaken to ascertain the feasibility of using the bipolar (BP) spectrum in clinical practice. The only systematic national study is the French EPIDEP Study of consecutive inpatients and outpatients presenting with major depressive episodes (MDE). The protocol was developed in 1994 and implemented in 1995; publication of its first data began in 1998. This report provides the complete data set of the EPIDEP. METHODS: Forty-eight psychiatrists, practicing in 15 sites in four regions of France (Paris, Besançon, Bordeaux and Marseille), were all trained on a common protocol based on DSM-IV criteria for MDE (n=537) subdivided into BP-I (history of mania), BP-II (history of hypomania), as well as extended definitions of the "softer spectrum" beyond BP-I and BP-II. Measures tapping into this spectrum included the Hypomania Checklist (HCA), the cyclothymic (CT), depressive (DT) and hyperthymic (HT) temperament scales. These measures and course permitted post-hoc assignment of MDE in the bipolar spectrum, based in part on the Akiskal, H.S., Pinto, O., 1999. [The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22, 517-534] proposal: depression with history of spontaneous hypomanic episodes (DSM-IV, BP-II), cyclothymic depressions (BP-II(1/2)), antidepressant-associated hypomania (BP-III) and hyperthymic depressions (BP-IV). <> was thereby limited to an exclusion diagnosis for the remainder of MDE. LIMITATION: In the clinical setting, psychiatrists cannot be entirely blind to the observations in the various clinical evaluations and instruments. However, the systematic multisite collection of such data tended to minimize any such biases. RESULTS: After excluding patients lost to follow-up, among 493 presenting with MDE with complete data files, the BP-II rate was estimated at index at 20%; 1 month later, systematic probing for hypomania doubled the rate of BP-II to 39%. The comparison between BP-II and UP showed differential phenomenology, such as hypersomnia, increased psychomotor activation, guilt feelings and suicidal thoughts in BP-II. Related data demonstrated the importance of CT in further qualifying of MDE to define a distinct, more severe ("darker") BP-II(1/2) variant of BP-II. Moreover, BP-III, arising from DT and associated with antidepressants, emerged as a valid soft bipolar variant on the basis of the phenomenology of hypomania and bipolar family history. Finally, we found preliminary evidence for the inclusion of BP-IV into the bipolar spectrum, its total hypomania score falling intermediate between BP-II and strict UP. Using this broader diagnostic framework, the bipolar spectrum (the combined "hard" BP-I phenotype, BP-II and the soft spectrum) accounted for 65% of MDE. CONCLUSION: The EPIDEP study achieved its objectives by demonstrating the feasibility of identifying the bipolar spectrum at a national level, and refining its phenomenology through rigorous clinical characterization and validation of bipolar spectrum subtypes, including MDE with brief hypomanias, cyclothymia and hyperthymia. The spectrum accounted for two out of three MDE, making "strict UP" less prevalent than BP as redefined herein. Our findings were anticipated by Falret, who in 1854 had predicted that many melancholic patients in the community would 1 day be classified in his circular group. We also confirmed Baillarger's observation in the same year that episodes (in this study, hypomanic episodes) could last as short as 2 days. Our findings deriving from a systematic French national database a century and a half later invite major shifts in clinical and public health services, as well as in the future conduct of psychopharmacologic trials. In this respect, the systematic training of clinicians in four regions of France represents a national resource for affective disorders and can serve as a model to effect change in diagnostic practice in other countries.

Episodic autobiographical memory in depression: Specificity, autonoetic consciousness, and self-perspective.

Autobiographical memory (AM) and the self are closely linked. AM retrieval in depression is characterized by a lack of specificity, suggesting an impairment of episodic AM. Autonoetic consciousness and self-perspective, which are critical to episodic AM, have never been addressed in depression. Twenty-one depressed inpatients and 21 matched controls were given an episodic AM task designed to assess positive and negative memories regarding specificity, autonoetic consciousness (remember/know procedure), and self-perspective (field/observer procedure). For specificity, "remember", and "field" responses, ANOVAs revealed a main group effect and a group x valence interaction. Between groups, patients showed lower scores than controls for positive memories. Within groups, patients showed greater scores for negative memories, and controls showed greater scores for positive memories. There is a global episodic AM impairment of positive memories in depression regarding specificity, autonoetic consciousness, and self-perspective. Our results suggest new cognitive interventions to improve the self-relevance of positive memories in depression.

Cognitive control and brain resources in major depression: an fMRI study using the n-back task.

Several neuroimaging studies have reported 'hypofrontality' in depressed patients performing a cognitive challenge compared to control subjects. Hypofrontality in depression is likely associated with an impaired behavioral performance. It is unclear whether this impaired performance is the consequence or the cause of hypofrontality. Consequently, we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning. The working memory load was manipulated across the experiment (1,2,3-back) to increase the cognitive demands. fMRI data were acquired on a 1.5-T GE scanner and analyzed using SPM99 software. We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task. Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex, anterior cingulate and parietal cortex. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects. This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task. Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain resources than controls during cognitive control.

[Stress, depression and cerebral plasticity: an update of clinical and experimental findings]. / Stress, dépression et plasticité cérébrale: mise au point a partir des etudes cliniques et expérimentales.

Recent studies of neuroplasticity in stress and depression have given rise to new hypotheses on the neural bases of these disorders. Based on data from imaging studies, cellular and molecular biology, and animal models, this approach could help to understand certain clinical findings, and especially cognitive impairments. Some antidepressants have effects on neuroplasticity, in addition to their symptomatic effects on depression.

[Bipolarity: from manic-depressive disease to bipolar disorder]. / Bipolarité: de la maladie maniaco-dépressive au trouble bipolaire.

Until recently, bipolar disorder was viewed as a relatively rare condition characterized by periods of euphoric excitement and depressive retardation which was easy to diagnose, and easy to treat thanks with lithium and new prophylactic treatments. In fact, bipolar disorder encompasses a variety of conditions, whose overall lifetime prevalence in the general population may be between 5 and 8%. Long term with lithium and other compounds are very effective but must be combined with non pharmacological therapies. Over the past two decades, advances in genetic, brain imagings, and biochemical have improved our knowledge on the pathophysiological mechanisms underlying these disorders.

Verbal memory performance of patients with a first depressive episode and patients with unipolar and bipolar recurrent depression.

Depression is usually associated with episodic memory impairment. The main clinical features of depression associated with that memory impairment are not clearly defined. The main goal of that study was to assess the role of the diagnostic subtypes and the number of depressive episodes on the memory performance of acute unipolar (UP) and bipolar (BP) depressed patients.Twenty-three patients with a first major depressive episode (FE), 28 patients meeting DSM-IV criteria for UP recurrent depression (UR) and 18 BP patients with recurrent depression were compared with 88 healthy subjects on a verbal episodic memory task. Patients suffering from a first depressive episode did not show verbal memory impairment as compared to normal controls. Unlike FE patients, UR and BP patients exhibited verbal memory deficits with impaired free recall and normal cued recall and recognition. The memory deficits of the UR and BP patients was present in the first free recall trial. Depressed patients improved their memory performance across the three trials of the task at the same rate than normal controls. Our results suggest that the number of depressive episodes has a negative influence on verbal memory performance of acute depressed patients. The effects of the repetition of the depressive episodes are not modulated by the subtypes of depression and may reflect sensitization to the cognitive impact of depression associated with increasing prefrontal dysfunction.

Implicit and explicit emotional memory for melodies in Alzheimer's disease and depression.

The present study investigates the impact of emotional deficits on implicit and explicit memory for musical stimuli in patients with Alzheimer's disease and elderly depressed patients. Results showed that unlike Alzheimer's patients, depressed patients were unable to develop a positive affective bias of judgment for previously heard melodies.

Qualitative analysis of verbal fluency in depression.

The aim of this study was to analyze qualitative aspects of verbal fluency in depression. Phonemic and semantic output was scored for word clustering and switching between clusters in depressed patients and normal control subjects. Depressed patients (n=25) and normal control subjects (n=19) were administered both phonemic and semantic fluency tasks. All patients were also evaluated with executive card sorting tests. Patients with depression produced fewer words on the semantic fluency task than controls and showed normal performance on the phonemic fluency tasks. The deficit on semantic fluency of depressed patients was related to a reduced number of switches with normal cluster sizes. The number of switches in depression was associated with a reduced ability to shift mental set on card sorting tests, suggesting that verbal fluency impairment reflects general executive problems in depression.

Bipolar II with and without cyclothymic temperament: "dark" and "sunny" expressions of soft bipolarity.

BACKGROUND: In the present report deriving from the French national multi-site EPIDEP study, we focus on the characteristics of Bipolar II (BP-II), divided on the basis of cyclothymic temperament (CT). In our companion article (Hantouche et al., this issue), we found that this temperament in its self-rated version correlated significantly with hypomanic behavior of a risk-taking nature. Our aim in the present analyses is to further test the hypothesis that such patients-assigned to CT on the basis of clinical interview-represent a more "unstable" variant of BP-II. METHODS: From a total major depressive population of 537 psychiatric patients, 493 were re-examined on average a month later; after excluding 256 DSM-IV MDD and 41 with history of mania, the remaining 196 were placed in the BP-II spectrum. As mounting international evidence indicates that hypomania associated with antidepressants belongs to this spectrum, such association per se did not constitute a ground for exclusion. CT was assessed by clinicians using a semi-structured interview based on in its French version; as two files did not contain full interview data on CT, the critical clinical variable in the present analyses, this left us with an analysis sample of 194 BP-II. Socio-demographic, psychometric, clinical, familial and historical parameters were compared between BP-II subdivided by CT. Psychometric measures included self-rated CT and hypomania scales, as well as Hamilton and Rosenthal scales for depression. RESULTS: BP-II cases categorically assigned to CT (n=74) versus those without CT (n=120), were differentiated as follows: (1). younger age at onset (P=0.005) and age at seeking help (P=0.05); (2). higher scores on HAM-D (P=0.03) and Rosenthal (atypical depressive) scale (P=0.007); (3). longer delay between onset of illness and recognition of bipolarity (P=0.0002); (4). higher rate of psychiatric comorbidity (P=0.04); (5). different profiles on axis II (i.e., more histrionic, passive-aggressive and less obsessive-compulsive personality disorders). Family history for depressive and bipolar disorders did not significantly distinguish the two groups; however, chronic affective syndromes were significantly higher in BP-II with CT. Finally, cyclothymic BP-II scored significantly much higher on irritable-risk-taking than "classic" driven-euphoric items of hypomania. CONCLUSION: Depressions arising from a cyclothymic temperament-even when meeting full criteria for hypomania-are likely to be misdiagnosed as personality disorders. Their high familial load for affective disorders (including that for bipolar disorder) validate the bipolar nature of these "cyclothymic depressions." Our data support their inclusion as a more "unstable" variant of BP-II, which we have elsewhere termed "BP-II 1/2." These patients can best be characterized as the "darker" expression of the more prototypical "sunny" BP-II phenotype. Coupled with the data from our companion paper (Hantouche et al., 2003, this issue), the present findings indicate that screening for cyclothymia in major depressive patients represents a viable approach for detecting a bipolar subtype that could otherwise be mistaken for an erratic personality disorder. Overall, our findings support recent international consensus in favoring the diagnosis of cyclothymic and bipolar II disorders over erratic and borderline personality disorders when criteria for both sets of disorders are concurrently met.

Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II).

BACKGROUND: According to DSM-IV and ICD-10, hypomania which occurs solely during antidepressant treatment does not belong to the category of bipolar II (BP-II). METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 144 (29.2%) fulfilled the criteria for bipolar II with spontaneous hypomania (BP-II Sp), and 52 (10.5%) had hypomania associated solely with antidepressants (BP-H AA). RESULTS: BP-II Sp group had earlier age at onset, more hypomanic episodes, and higher ratings on cyclothymic and hyperthymic temperaments, and abused alcohol more often. The two groups were indistinguishable on the hypomania checklist score (12.2+/-4.0 vs. 11.4+/-4.4, respectively, P=0.25) and on rates of familial bipolarity (14.1% vs. 11.8%, respectively, P=0.68). But BP-H AA had significantly more family history of suicide, had higher ratings on depressive temperament, with greater chronicity of depression, were more likely to be admitted to the hospital for suicidal depressions, and were more likely to have psychotic features; finally, clinicians were more likely to treat them with ECT, lithium and mood stabilizing anticonvulsants. LIMITATION: Naturalistic study, where treatment was uncontrolled. CONCLUSION: BP-H AA emerges as a disorder with depressive temperamental instability, manifesting hypomania later in life (and, by definition, during pharmacotherapy only). By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone phenotype of this disorder, and which is susceptible to destabilization under antidepressant treatment. These considerations argue for revisions of DSM-IV and ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression of BP-II; phenotypically; it might provisionally be categorized as bipolar III.