Alzheimer's disease camouflaged by histrionic personality disorder.

A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.

Theory of mind deficits in chronically depressed patients.

BACKGROUND: Poor theory of mind (ToM) performance has been found in patients with mood disorders, but it has not been examined in the subgroup of chronic depression where ToM deficits may be even more persistent than in acute depressive episodes. The aim of this study was to compare the ToM performance of chronically depressed patients with a healthy control group and to clarify the relation of ToM to other cognitive functions. METHODS: ToM performance was assessed in 30 chronically depressed patients and 30 matched healthy controls by two cartoon picture story tests. In addition, logical memory, alertness, and executive functioning were evaluated. RESULTS: Chronically depressed patients were markedly impaired in all ToM- and neuropsychological tasks compared to healthy controls. Performance in the different ToM tests was significantly correlated with at least one other cognitive variable. After controlling for logical memory and working memory, no ToM tasks predicted being a patient. CONCLUSIONS: Patients with chronic depression present significant deficits in "reading" social interactions, which may be associated with general cognitive impairments.

[Development and evaluation of a group therapy for functional memory and attention disorder]. / Konzeption und Erprobung eines gruppentherapeutischen Behandlungskonzepts für die funktionelle Gedächtnis- und Konzentrationsstörung.

OBJECTIVES: Functional Memory and Attention Disorder (FMD) is regularly seen in patients presenting in psychosomatic or memory clinics. The aim of this study was the evaluation of a novel group therapy for FMD in a randomized controlled trial. METHODS: 40 FMD patients were randomly assigned to either the experimental (EG) or the wait-list control group (CG). Out of these 35/31 were analysed (intent to treat vs. observed cases respectively). The intervention consisted of psychoeducation, cognitive restructuring, stress management, relaxation and mindfulness techniques. Data were collected at baseline, three months (post-intervention) and six months (follow-up). Primary outcome was the memory self-efficacy measure of the Metamemory in Adulthood Questionnaire (MSE). Secondary outcomes were the sum scores of the Perceived Stress Questionnaire (PSQ) and the SCL-90-R. RESULTS: The EG showed a significantly higher improvement on MSE at follow-up than the CG. No significant group differences emerged on PSQ or SCL-90-R. The CG showed stable MSE scores during the waiting period without intervention. However, after the CG received their therapy the same pattern on MSE scores as seen in the EG emerged. CONCLUSIONS: This study provides preliminary evidence for an improvement of memory self efficacy in FMD through a newly devised group therapy program consisting of different modules. This result ought to be replicated in larger studies.

Efficacy of Interpersonal Psychotherapy plus pharmacotherapy in chronically depressed inpatients.

BACKGROUND: Clinical guidelines recommend the combination of pharmaco- and psychotherapy for the treatment of chronic depression, although there are only a few studies supporting an additive effect of psychotherapy. METHODS: Forty-five inpatients with a chronic Major Depressive Disorder were randomized to 5 weeks of either Interpersonal Psychotherapy (IPT) modified for an inpatient setting (15 individual and 8 group sessions) plus pharmacotherapy or to medication plus Clinical Management (CM). The 17-item Hamilton Rating Scale for Depression was the primary outcome measure. The study included a prospective naturalistic follow-up, 3- and 12-months after discharge. RESULTS: Intent-to-treat analyses revealed a significantly greater reduction of depressive symptoms as well as better global functioning of patients treated with IPT compared to the CM group at week 5. Response and sustained response rates differed significantly between the two treatment conditions, favouring the IPT group. Remission rates were considerably higher for IPT patients who completed the treatment (67% vs. 32%). Patients who initially responded to IPT exhibited greater treatment gains at 12 months since only 7% of these subjects relapsed compared with 25% of the CM subjects. In the long-term, additional IPT led to a lower symptom level and higher global functioning. LIMITATIONS: The study uses data of a subset of patients from a larger trial. Both treatment groups did not receive comparable amounts of therapeutic attention. Extrapolating the data from this inpatient study to chronically depressed outpatients may not be possible. CONCLUSIONS: Intensive combined treatment provides superior acute and long-term effects over standard treatment in chronically depressed inpatients.

An intensive treatment program of interpersonal psychotherapy plus pharmacotherapy for depressed inpatients: acute and long-term results.

OBJECTIVE: The purpose of this article was to determine the relative efficacy of a psychotherapy program when combined with pharmacotherapy versus medication and clinical management in more severely depressed patients. METHOD: A randomized controlled trial was conducted in 124 hospitalized patients with DSM-IV major depressive disorder that compared 5 weeks of interpersonal psychotherapy modified for depressed inpatients (15 individual and eight group sessions) plus pharmacotherapy with a regimen that involved medication plus intensive clinical management. The study included a prospective, naturalistic follow-up 3 and 12 months after acute treatment in 97 of 105 treatment completers. The 17-item version of the Hamilton Depression Rating Scale (HAM-D) was the primary outcome measure. RESULTS: For the intent-to-treat cohort (N=124), analysis of covariance (ANCOVA) showed that patients treated with interpersonal psychotherapy had a significantly greater reduction of depressive symptoms at week 5. Response rates differed significantly between the two treatment conditions, favoring the group that received adjuvant interpersonal psychotherapy (70%) versus clinical management (51%). Remission rates also tended to be higher for patients in the interpersonal psychotherapy group (49% versus 34%). Patients who initially responded to interpersonal psychotherapy exhibited greater treatment gains at the 3-month follow-up evaluation, since only 3% of these subjects relapsed, compared with 25% of the clinical management subjects. Nine months later, this difference lost statistical significance. CONCLUSIONS: An inpatient treatment program with both brief and intensive psychotherapy plus pharmacotherapy is superior to standard treatment. The results, which add to a growing body of evidence, suggest that this combination treatment may offer an advantage over treatment with medication and clinical management for more severely depressed patients.

Plasmapheresis Responsive Rapid Onset Dementia with Predominantly Frontal Dysfunction in the Context of Hashimoto's Encephalopathy.

BACKGROUND: Hashimoto's encephalopathy (HE) is a rare immunological neuropsychiatric disorder characterized by increased antithyroid antibodies and mixed neurological and psychiatric symptoms. HE has been previously discussed as a differential diagnosis for rapid progressive dementia. However, most of these patients suffered from additional neurological symptoms, like ataxia or seizures. CASE PRESENTATION: Here, we present the case of a 59-year-old female patient suffering rapid onset dementia with salient frontal executive dysfunction. She developed rapid onset symptoms, including apathy, verbal depletion up to a stuporous state, severe working memory deficits, evidence of primitive reflexes, disturbed Luria's three-step test, and micturition disorder. Analysis of her cerebrospinal fluid was normal. The serum analyses showed increased antithyroid (antithyroid peroxidase and antithyroglobulin) antibodies. In the cerebral magnetic resonance imaging, supratentorial deep and peripheral white matter lesions were found; the electroencephalography showed intermittent slowing, and the [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) depicted medial and superior dorsolateral frontal hypometabolism. Several different psychopharmacological therapeutic approaches with various neuroleptics, antidepressants, and high doses of lorazepam were unsuccessful. Due to the organic alterations, including increased antithyroid antibodies, HE was suspected. Against expectations, treatment with high-dose corticosteroids proved to be ineffective and was associated with worsening symptoms. However, escalated treatment with plasmapheresis over 5 days led to significant improvement in all reported symptoms and in psychometric testing. The neuropsychological improvement was stable over a 6-month follow-up period, and the FDG-PET normalized. CONCLUSION: This case report reveals that (1) HE can mimic rapid onset dementia with predominantly frontal dysfunction; (2) this syndrome can be successfully treated in the context of HE; and (3) plasmapheresis can be effective in such a disease constellation. The detection of the immunological causes of rapid onset dementia and other psychiatric syndromes is important because it opens opportunities for new, innovative immunosuppressive treatment options.

Mapping of temporal and parietal cortex in progressive nonfluent aphasia and Alzheimer's disease using chemical shift imaging, voxel-based morphometry and positron emission tomography.

Little and controversial evidence is available from neuroimaging studies in progressive nonfluent aphasia (PNA). The goal of this study was to combine information from different imaging modalities in PNA compared with Alzheimer's disease (AD). Chemical shift imaging (CSI), voxel-based morphometry (VBM) and fluorodeoxyglucose positron emission tomography (FDG-PET) were used in 5 PNA, 10 AD patients and 10 normal subjects. Group comparisons revealed left anterior lateral temporal abnormalities (BA20/21) in PNA using CSI, VBM and PET in comparison to normal subjects. AD patients showed more limited hypometabolism within the same area. In addition left lateral parietal (BA40) abnormalities were demonstrated in our PNA as well as our AD group using PET and VBM (AD group only). Combining information from all imaging modalities on a single case basis revealed pathology within the left anterior lateral temporal and lateral parietal lobe both in PNA and AD. PNA and AD patients differed significantly, however, with respect to the frequency of medial temporal lobe and posterior cingulate/precuneus involvement. Although our results might not be generalizable to all subgroups of PNA, we conclude that medial temporal and posterior cingulate/precuneus cortex pathology as assessed by CSI and VBM or PET distinguish PNA from AD, whereas lateral temporal and parietal areas are involved in both conditions.

Hemispheric asymmetries of hypometabolism associated with semantic memory impairment in Alzheimer's disease: a study using positron emission tomography with fluorodeoxyglucose-F18.

Considerable disagreement exists about the neuroanatomical basis of conceptual-semantic impairments observed in a subgroup of patients with Alzheimer's disease (AD) at mild to moderate stages of the disease. Several studies of groups of patients have shown correlations between focal hypometabolism or hypoperfusion in left hemispheric areas and measures of verbal semantic memory impairment in AD patients. The question remains, however, whether left hemispheric hypometabolism is sufficient to produce such impairment in the single case and whether nonverbal semantic knowledge is also affected. We used positron emission tomography (PET) with fluorodeoxyglucose-F18 (FDG), statistical parametric mapping (SPM), and tests of verbal and nonverbal semantic memory in 11 AD patients with a mean score on the Mini-Mental State Examination of 22.6 (+/-2.8). Naming impairment was significantly associated with left hemispheric asymmetry of hypometabolism on a single-case basis. Our correlation analysis showed that metabolism in left anterior temporal, posterior inferior temporal, inferior parietal and medial occipital areas (Brodmann areas: 21/38, 37, 40 and 19) correlated with both verbal and nonverbal semantic performance. We conclude that left hemispheric synaptic dysfunction, as measured by regional glucose hypometabolism, was sufficient to produce semantic impairments in our patients. The majority of areas affected in our patients with semantic impairments were involved in multimodal or supramodal (verbal and nonverbal) semantic knowledge.

Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients.

Discrepancies between scores on the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI), as well as differences regarding their sensitivity to detect change, have been reported. This study investigates discrepancies and their potential prediction on the basis of demographic, personality, and clinical factors in depressed inpatients and analyzes the sensitivity to change. The HAMD and the BDI were administered to 105 inpatients with major depressive disorder randomized to 5 weeks of either interpersonal psychotherapy or clinical management. Personality was assessed with the NEO Five-Factor Inventory. Low extraversion and high neuroticism were associated with relatively higher endorsement of depressive symptoms on the BDI compared with the HAMD. The HAMD presented a greater reduction of symptom scores than the BDI. Patients with high BDI scores, high HAMD scores or both revealed the greatest change, possibly due to a statistical effect of regression to the mean. Restricted by sample size, analyses were not differentiated by treatment condition. Regression to the mean cannot be tested directly, but it might be considered as a possible explanation. The HAMD and the BDI should be regarded as two complementary rather than redundant or competing instruments as the discrepancy is associated with personality characteristics. Attributing large effect sizes solely to effective treatment and a sensitive measure may be misleading.

Cognitive behavioral analysis system of psychotherapy versus interpersonal psychotherapy for early-onset chronic depression: a randomized pilot study.

BACKGROUND: The only psychotherapy specifically designed and evaluated for the treatment of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), has never been directly compared to another depression-specific psychological method. METHODS: Thirty patients with early-onset chronic depression were randomized to 22 sessions of CBASP or Interpersonal Psychotherapy (IPT) provided in 16 weeks. Primary outcome was the score on the 24-item Hamilton Rating Scale for Depression (HRSD) assessed posttreatment by an independent blinded evaluator. Secondary endpoints were, among others, remission (HRSD≤8) rates and the Beck Depression Inventory (BDI). The study included a prospective naturalistic 12-month follow-up. RESULTS: Intent-to-treat analyses of covariance (ANCOVA) revealed that there was no significant difference in posttreatment HRSD scores between the CBASP and the IPT condition, but in self-rated BDI scores. We found significantly higher remission rates in the CBASP (57%) as compared to the IPT (20%) group. One year posttreatment, no significant differences were found in the self-reported symptom level (BDI) using ANCOVA. LIMITATIONS: The study used only a small sample size and no placebo control. The generalizability of the results may be limited to patients with a preference for psychological treatment. CONCLUSIONS: While the primary outcome was not significant, secondary measures showed relevant benefits of CBASP over IPT. We found preliminary evidence that in early-onset chronic depression, an approach specifically designed for this patient population was superior to a method originally developed for the treatment of acute depressive episodes. Long-term results suggest that chronically depressed patients may need extended treatment courses.

Time course of response to antidepressants: predictive value of early improvement and effect of additional psychotherapy.

BACKGROUND: The full response to antidepressant pharmacotherapy is evident only after several weeks, but considerable improvements may already be visible within the first two weeks. Little is known about the potential influence of additional psychotherapy on the speed of response to antidepressant treatment. We have analysed in more severely depressed inpatients treated with antidepressants i) the predictive value of early improvement for later response and ii) the impact of additional psychotherapy on the time course of response. METHODS: 124 patients with a major depression referred for hospitalized care were randomized to 5 weeks of sertraline (or amitriptyline as a second choice) plus either additional Interpersonal Psychotherapy modified for inpatients (IPT) or Clinical Management (CM). "Improvement" was defined as a decrease of > or = 20% on the 17-item Hamilton Rating Scale for Depression (HAMD). "Onset of response" was defined as sustained improvement (without any subsequent increase in the HAMD) culminating in 50% decrease on the HAMD by week 5. RESULTS: Early improvement within two weeks was highly predictive of later stable response (> or = 50% decrease on the HAMD at weeks 4 and 5) or stable remission (HAMD score of < or = 7 at weeks 4 and 5), irrespective of the type of medication or additional IPT or CM. Survival analysis of the ITT sample revealed that patients of the IPT group had a shorter time to "onset of response" than patients in the CM group (median: 12 vs. 30 days; p=0.041, Log Rank). However, there was no significant difference in the time to onset of response, when more stringent conditions were used. LIMITATIONS: Due to ethical restrictions a comparison with an untreated placebo group could not be performed. CONCLUSIONS: Early improvement is highly predictive for later stable response or remission in more severely depressed inpatients. In combination therapy, the additional benefit of psychotherapy occurs at least as rapid as the response to antidepressants.

Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in Alzheimer's disease.

The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used a semantic verification task and resting 18-fluorodeoxyglucose positron emission tomography in a group of mild to moderate AD patients to investigate this issue. The four task conditions required semantic knowledge of (1) visual, (2) functional properties of living objects, and (3) visual or (4) functional properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for non-living objects largely overlapped in the left anterior temporal (BA 38/20) and bilateral premotor areas (BA 6), with the visual condition extending more into left lateral precentral areas. There were no associations with functional property verification for living concepts. Our results provide strong support for anatomically separable representations of living and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas.

Psychotherapy of attention deficit hyperactivity disorder in adults--a pilot study using a structured skills training program.

In clinical practice many adult patients with attention deficit hyperactivity disorder (ADHD) ask for an additional psychotherapeutic intervention besides the medical therapy. In this paper we present a structured skill training program particularly tailored for adult patients with ADHD. The program is based on the principles of cognitive-behavioral treatment for borderline personality disorder developed by M. Linehan. It was modified to suit the special needs of adult patients with ADHD. In this exploratory pilot study we tested this program in a group setting. The following elements were presented: neurobiology of ADHD, mindfulness, chaos and control, behavior analysis, emotion regulation, depression, medication in ADHD, impulse control, stress management, dependency, ADHD in relationship and self respect. In an open study design patients were assessed clinically using psychometric scales (Attention Deficit Hyperactivity Disorder Checklist according to DSM-IV, 16 items of the SCL-90-R, Beck-Depression Inventory, visual analogue scale) prior to and following group therapy. This treatment resulted in positive outcomes in that patients improved on all psychometric scales.

On the role of quantitative brain imaging in the differential diagnosis of speech disorders.

We present the case of a 71-year-old woman with an 11-year history of slowly progressive decline of motor speech. Normal clinical investigations including routine magnetic resonance imaging (MRI) at 7, 8 and 10 years after the onset of speech dysfunction led to the suggestion of a psychogenic disorder. Extensive clinical, neuropsychological and neuroimaging investigations including 18F-desoxyglucose-positron emission tomography (PET), quantitative MRI and MR spectroscopy were performed to look for subtle brain pathology. Quantitative assessment of 3D-MRI, F-desoxyglucose-PET and magnetic resonance spectroscopy all demonstrated clear evidence of multifocal frontotemporal brain pathology that had not been picked up on routine MRI investigations on previous admissions. This is the longest benign history of slowly progressive anarthria reported so far. It demonstrates a possible role of quantitative neuroimaging techniques in the diagnosis of complex neuropsychiatric disorders.