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ADHD is a serious risk factor for co-occurring psychiatric disorders and negative psychosocial consequences in adulthood. Previous trials on psychotherapeutic concepts for adult ADHD are based on behavioural (cognitive behavioural and dialectical behavioural) psychotherapeutic approaches and showed significant effects. The aim of our study group (COMPAS) is to carry out a first randomized and controlled multicentre study to evaluate the effects of a disorder tailored psychotherapy in adult ADHD compared to clinical management in combination with psychopharmacological treatment or placebo. A total of 448 adults with ADHD according to DSM-IV will be treated at seven university sites in Germany. In a four-arm design, patients are randomized to a manualized dialectical behavioural therapy (DBT) based group programme plus methylphenidate or placebo or clinical management plus methylphenidate or placebo with weekly sessions in the first 12 weeks and monthly sessions thereafter. Therapists are graduated psychologists or physicians. Treatment integrity is established by independent supervision. Primary endpoint (ADHD symptoms measured by the Conners Adult Rating Scale) is rated by interviewers blind to the treatment allocation. Intention-to-treat analysis will be performed within a linear regression model (Current Controlled Trials ISRCTN54096201). The trial is funded by the German Federal Ministry of Research and Education (01GV0606) and is part of the German network for the treatment of ADHD in children and adults (ADHD-NET).

The last decade has seen an increasing interest in the method of magnet resonance spectroscopy (MRS) since this is the only research tool that allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without employing ionising radiation. In this paper we review published MRS results with respect to childhood, adolescence and adult ADHD.We searched the Medline (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of identified articles were also searched for relevant studies. Meta-analyses were performed for the measured metabolites and regions of assessment.Sixteen studies could be identified that used MRS to investigate the neurobiology of ADHD. Two regions could be identified as the focus of spectroscopic investigations--the frontal lobe including anterior cingulate cortex and parts of prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto-striato-thalamo-frontal circuits. As for metabolites, in the majority of studies the ratios to creatine and not absolute concentrations of metabolites were estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to creatine ratios) could be identified as being altered in several studies in ADHD. The meta-analysis showed increased choline compounds in several researched regions.MRS is a promising tool for the non-invasive in vivo assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI) like amygdala, hippocampus, thalamus and cerebellum should be assessed in future studies. Further methodological improvements of MRS are desirable in order to assess the absolute metabolite concentration of several ROIs at the same time. Such developments will open novel perspectives in spectroscopic investigations of ADHD.

BackgroundTo date, nearly all research of subtype differences in ADHD has been performed in children and only two studies, with conflicting results, have covered this subject in adults with ADHD.ObjectiveThis study examined subtype differences in the clinical presentation of ADHD-symptoms, related psychopathological features, psychosocial functioning and comorbid psychiatric disorders in adults with ADHD.MethodOne hundred and eighteen adults with ADHD, diagnosed according to DSM-IV criteria, and a population based control group underwent diagnostic evaluations with clinical interviews for ADHD, DSM-IV disorders and demographic features. Comparisons were made between ADHD combined type (n = 64), predominantly inattentive type (n = 30) and predominantly inattentive type, anamnestically combined type (n = 24), relative to each other and to a community control group (n = 70).ResultsThe four groups did not differ in age and gender composition. All ADHD groups had significantly less education, were significantly more often unemployed and reported significantly more lifetime psychiatric comorbidity than controls. In comparison to each other, the three ADHD groups differed mainly in core symptoms and the pattern of comorbid psychiatric disorders, whereas no prominent differences in associated psychopathological features and most of the assessed psychosocial functions could be found. Patients with ADHD combined type and inattentive, anamnestically combined type both presented with significantly more hyperactive symptoms and also showed more impulsive symptoms than those with the predominantly inattentive type. With a similar overall lifetime psychiatric comorbidity in the three groups, patients with ADHD combined type and inattentive, anamnestically combined type suffered significantly more from lifetime substance use disorders than patients with predominantly inattentive type.ConclusionOur results clearly show impaired psychosocial adjustment and elevated risk for additional psychiatric disorders in adults with all subtypes of ADHD, compared to healthy controls. They provide preliminary evidence that in adult ADHD there might be a subgroup of patients, which is classified as predominantly inattentive subtype according to current diagnostic criteria, but which in its clinical presentation is in between ADHD combined and inattentive type. Further studies are needed to evaluate this finding and to gain a clear picture of its validity.

In order to detect possible links between structural and neurochemical brain abnormalities we applied high resolution morphometric imaging and short-echo time absolute-quantification magnetic resonance spectroscopy (MRS) at the left hand side to the amygdala in 12 patients with borderline personality disorder (BPD) and 10 group-matched healthy controls. Confirming earlier reports we found a significant 11-17% reduction of amygdalar volumes in patients with BPD. In addition there was a significant 17% increase of left amygdalar creatine concentrations in BPD patients. Left amygdalar creatine concentration correlated positively with measures of anxiety and negatively with amygdalar volume. This pilot study of simultaneous amygdalar morphometry and spectroscopy in BPD reveals a possible link between amygdalar volume loss, psychopathology and neurochemical abnormalities in terms of creatine signals.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Ten male patients with type I alcohol dependency fulfilling DSM-IV criteria for alcohol dependency were investigated twice using IBZM-SPECT after alcohol withdrawal (day 2 and day 28 after withdrawal). Five patients had a history of physical withdrawal symptoms, 5 patients had no such history. The group with physical withdrawal symptoms showed higher IBZM binding in both scans indicating differences of dopaminergic neurotransmission in different subtypes of alcohol dependency.

The authors examined the brains of patients with borderline personality disorder (BPD) by using short echo time single voxel spectroscopy and found a significant 19% reduction of absolute N-acetylaspartate concentrations in the dorsolateral prefrontal cortex in BPD (P=0.01) compared with control subjects.

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood and adolescence and in a considerable number of patients it persists into adulthood. A network of brain regions have been shown to be abnormal in ADHD. In the present study we used magnetic resonance volumetry to investigate a possible role of the orbitofrontal cortex (OFC). Eight never medicated male patients fulfilling diagnostic criteria for ADHD and 17 male healthy controls were investigated. There was a significant reduction of the volume of the left OFC in patients with ADHD. It remains unknown whether small volumes are a primary deficit or a result of dysfunctional activation during childhood in terms of a residual deficit or a specific type of adult outcome of the disease.

Attention-deficit hyperactivity disorder (ADHD) in adulthood is a serious health problem with a prevalence of up to 4%. Limbic structures have been implicated in the genesis of ADHD; it has been suggested that they mediate mood and cognitive disturbances in affected individuals. Recently, a large study involving children and adolescents with ADHD reported bilateral enlargement of the hippocampus and indirect evidence of amygdala volume loss in this patient sample. We sought to test the hypothesis that, like in pediatric patients, there might be hippocampus and amygdala volume abnormalities in adult patients with ADHD.We studied 27 adult patients with ADHD and 27 group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements of the regions mentioned.In contrast to previous findings in children and adolescents, we found no significant differences in hippocampus and amygdala volumes among adults with and without the disorder.Findings of hippocampus enlargement and amygdala volume loss are not very stable across different samples of patients with ADHD. Contradictory findings may be related to the different locations of alterations along the complex circuits responsible for the different symptoms of ADHD. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed.

Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that often persists in adulthood. In a pilot study, a structured skills training group program for adult ADHD led to significant symptomatic improvements. The present study evaluated the program's effectiveness, feasibility, and patient acceptability in a multicenter setting. Seventy-two adult ADHD patients were assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy was well tolerated and led to significant improvements of ADHD, depressive symptoms, and personal health status (p < 0.001). The factors treatment site and medication did not contribute to the overall improvement. Patients regarded the program topics "behavioral analyses," "mindfulness," and "emotion regulation" as the most helpful. In this multicenter study, the therapy program showed therapist-independent effects and seemed to be disorder-specific. This warrants the effort of organizing further controlled studies.

Background The dopaminergic system is thought to be essentially involved in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). However, there is also evidence for abnormalities in the glutamatergic system and recent theories focus on a disturbed interaction between the two systems as the essential pathogenetic mechanism of ADHD. In the present study, we wanted to test the hypothesis that prefrontal glutamate signals indirectly indicate dopaminergic dysfunction in adult patients with ADHD. Methods Twenty-eight adult patients with ADHD and 28 group-matched healthy volunteers were studied clinically and using chemical-shift MR spectroscopy (MRS) of the prefrontal cortex covering the anterior cingulate gyrus. Results A significant reduction of the combined glutamate/glutamine to creatine ratio in the right anterior cingulate cortex in patients with ADHD was found. Discussion Glutamatergic alterations as measured with MRS might play a role in the pathogenesis of adult patients with ADHD.

We report the case of a patient developing psychosis after the addition of mirtazapine, a novel antidepressant enhancing serotonergic neurotransmission, to a chronic levodopa regimen. There was complete and rapid recovery upon low-dose clozapine treatment. To our knowledge, this is the first published case of a mirtazapine-levodopa interaction and the second case report of a psychosis induced by a serotonergic antidepressant in a patient with Parkinson's disease (PD). This phenomenon might be due to a postsynaptic serotonin receptor supersensitization caused by low central serotonin levels in treated PD.

Study Objectives: Previous studies in children with attention-deficit/hyperactivity disorder and attention deficit disorder (ADHD/ADD) have shown impaired sleep quality with increased nocturnal motor activity. However, polysomnographic findings are not unequivocal. Up to now, in adults with ADHD, only 1 case-control polysomnographic study with small sample size has been performed. We investigated objective and subjective sleep quality in adult ADHD, including an electroencephalogram spectral power analysis. Design: Single-blind comparative study. Setting: University medical center. Participants: Twenty adult unmedicated ADHD patients without current comorbid major depression, drug abuse, or comorbid axis-ll disorder and 20 sex- and age-matched control subjects. Interventions: N/A. Measurements: Conventional polysomnographic parameters and sleep electroencephalogram spectral power analysis was calculated for the 2 laboratory nights. Subjective sleep parameters were estimated by sleep questionnaires to assess the relationship between objective and subjective sleep measurements. Results: Adult ADHD patients showed increased nocturnal motor activity (as indicated by heightened indexes of periodic leg movements in sleep), which was significantly inversely correlated with subjective total sleep time. Although ADHD patients displayed significantly increased objective total sleep time, the subjective ratings documented impaired sleep quality in those with ADHD. Other polysomnographic sleep patterns and spectral electroencephalogram parameters did not differ between ADHD patients and normal controls. Conclusions: Similar to children, adults with ADHD show increased nocturnal motor activity. Otherwise, sleep does not seem to be impaired in ADHD patients. However, the dissociation between objective and subjective sleep parameters points to a misinterpretation of sleep quality in patients with ADHD.

There are some reports in the literature about the comorbidity of Darier's Disease (keratosis follicularis) and psychiatric illness (e.g. mental retardation or affective disorders). Here we present evidence that schizophreniform psychosis may also be associated with Darier's Disease.

The new antiepileptic lamotrigine has been shown to be effective in the treatment of focal epilepsies with or without secondary generalization and has also been suggested to be efficacious in the treatment and prophylaxis of affective disorders. Therefore, we analyzed its possible benefit in a patient with refractory bipolar affective disorder. Lamotrigine (up to 150 mg/d) was added to valproate (2700 mg/d), substituting previously administered neuroleptics. A considerable improvement of the patient's condition was achieved several days after the beginning of lamotrigine co-administration, and lasted over the total follow-up period of more than one year. The plasma concentrations after total remission were in the range of 1.9 to 6.2 mg/l for lamotrigine and 57.1 to 95.2 mg/l for valproate. This positive action of lamotrigine is discussed in the context of the drug's elementary effects on sodium and calcium channels.

Attention deficit hyperactivity disorder (ADHD) is a severe and often debilitating mental disorder, which begins in childhood and can persist into adulthood. Both major classificatory systems, ICD-10 and DSM-IV, include the age-of-onset criterion (AOC) requiring clinically relevant symptoms before the age of 7 years. In clinical practice, particularly in adult psychiatry, it is often difficult to establish this AOC when ADHD remained unrecognized in childhood. In the literature, there is controversy about the validity of this criterion. In order to explore the validity of the AOC, we performed a retrospective study in adult patients with ADHD. Fifty consecutively diagnosed patients were subjected to a standardized diagnostic procedure. Depending on the onset of clinical symptoms, patients were divided in an early onset and in a late onset ADHD subgroup. Fourteen patients (28%) described late onset ADHD. In four of these patients (8% of the total sample), this assessment was confirmed by parent ratings. There was no difference between early onset and late onset ADHD groups in terms of psychopathology or psychiatric comorbidity.

Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder.Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls.We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes.While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Objective: Clinical and epidemiological observations and neurobiological data suggest that there might be an inherent link between attention deficit hyperactivity disorder (ADHD) and recurrent brief depression (RBD). In this psychopathological study, we investigated the comorbidity between these two conditions. Method: Using an index patient approach 40 adult out-patients fulfilling the criteria for ADHD were investigated for lifetime history of RBD and another 40 out-patients with the primary diagnosis of RBD were investigated for a lifetime history of ADHD. Results: We found a high prevalence of RBD in patients with ADHD (70%) while the prevalence of ADHD in the index sample with RBD was smaller (about 40%). Conclusion: In terms of comorbidity ADHD was the second commonest psychiatric disorder in patients with RBD next to other affective disorders. The psychopathological pattern of lifetime comorbidity might be of clinical relevance in terms of medical treatment.

The objective of this study was to compare the effects of carbamazepine (CBZ) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this controlled clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia (N = 24) or schizoaffective disorder (N = 3) were randomly assigned to receive 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ, or haloperidol with VPA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels. Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy. VPA had no significant effect on either plasma levels or on psychopathology. Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure. This might be a result of a pharmacokinetic interaction on the hepatic level. The concomitant use of VPA with neuroleptic therapy is not impaired by clinically significant drug interactions, but it is not associated with a better outcome under our conditions.

1. This is a report of a patient who developed an acute organic psychosis due to neurotoxicity of lithium several days after tapering off a long-lasting clozapine therapy. 2. The organic brain syndrome with initial illusionary misperceptions, a confusional state and a lapse into a pre-coma developed three days after the end of clozapine therapy and seven days after the beginning of haloperidol addition. 3. Possible pharmacokinetic and pharmacodynamic factors responsible for the severe neurotoxicity of lithium after withdrawal of clozapine and addition of haloperidol are discussed.

Catatonia is a rare but difficult-to-treat disorder. Here, we report on the case of a schizophrenic patient who developed several episodes of severe catatonia after suffering from adequately treated Lyme disease with encephalitis. The catatonic stupor was not responsive to typical neuroleptics and benzodiazepines. After the medication was changed to risperidone, there was a dramatic and persistent improvement of the patient's condition. Two relapses during the follow-up period over five years were caused by dose reductions. Risperidone might be a promising drug in the treatment of acute catatonia and in preventing further episodes.

Adult attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) share several clinical features, e.g. emotional lability and impulsivity. This study aimed to delineate differences and similarities between ADHD and BPD with respect to borderline typical symptomatology and gender specifics. Borderline symptomatology was assessed in 60 adult patients with ADHD with the borderline symptom list (BSL) and compared to both 60 gender- and age-matched BPD patients and control subjects. The BSL is a standardized instrument including 95 items on 7 subscales (self-perception, affect regulation, self-destruction, dysphoria, loneliness, intrusions and hostility). Adult ADHD patients showed significantly higher BSL total scores and all of the seven subscales compared to healthy controls (p < 0.001) but lower scores than BPD patients (p < 0.001). With respect to the seven subscales, the largest differences between ADHD and BPD patients were found with respect to self-destruction (d = 1.12) and affect dysregulation (d = 0.90), whereas the smallest difference was found with respect to loneliness (d = 0.36). In females, the BSL subscales “loneliness” and “hostility” did not differentiate between BPD and ADHD. Borderline typical symptoms are common in adult patients with ADHD but seem to be less pronounced than in patients with BPD. Females with ADHD and BPD share more clinical features than males. However, symptoms of self-destruction and affect dysregulation appear to be more severe in BPD patients.