Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N -acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Magnetic resonance spectroscopy comparing adults with high functioning autism and above average IQ

Electroencephalographic abnormalities in the absence of any other major laboratory or imaging findings are a frequently encountered phenomenon in many psychiatric disorders. In some cases, clear-cut interictal epileptiform EEG abnormalities in patients with classic primary psychiatric disorders lead to referrals to epilepsy departments for diagnostic evaluation. Although video/EEG telemetry in these cases generally proves that there is no direct temporal link between the EEG pathologies and psychiatric symptoms, and therefore the psychiatric syndrome cannot be regarded as epilepsy, the relevance of the EEG abnormalities remains open to discussion. In this article we put forward the model of a paraepileptic pathomechanism, which might explain the pathogenetic role of such EEG pathologies, at least in subgroups of such patients. We propose that ictal or nonictal epileptic neurophysiological activity can lead to local area neuronal network inhibition (LANI). In this model clinical symptoms are related not to the excitatory epileptiform abnormalities themselves, but to the extent, site, and dynamics of the resulting local neuronal network inhibition. The LANI hypothesis is capable of explaining the complex relationship between EEG abnormalities and clinical symptoms in different neuropsychiatric syndromes and can be verified and falsified in empirical research.

The indication for treatment of adult attention-deficit hyperactivity disorder (adult ADHD) is derived not from the diagnosis itself but results from the severity of symptoms, comorbidities, psychosocial consequences, and a lack of defined resources for ADHD. The basis of therapy is psychoeducation that includes teaching about symptoms, models of the disorder, and options for treatment. The combination of pharmacotherapy and psychotherapy is recommended. Methylphenidate is considered the first-line therapy, because of its strong effect and modest side effects, but is not authorized in Germany ("off-label use"). Atomoxetine, which is authorized for continuing treatment into adulthood, is indicated if methylphenidate is insufficient or has unacceptable side effects and in case of comorbid substance use. Various psychotherapeutic interventions using available ADHD-typical resources have demonstrated positive effects. Psychosocial support and self-help groups complete the treatment concept. Persistence of the treatment indication has to be reevaluated at regular intervals. Disorder-specific multimodal therapy of adult ADHD conforms to the complex, primarily neurobiologic etiology and the psychosocial consequences.

Die Behandlungsindikation für die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter (adulte ADHS) ergibt sich nicht allein aus der Diagnose, sondern resultiert aus Symptomausprägungen, komorbiden Störungen, geringer psychosozialer Adaptation sowie eingeschränkten Ressourcen. Grundlage der Therapie ist Psychoedukation mit Vermittlung von Kenntnissen zu Symptomen, Störungsmodellen und Behandlungsoptionen. Die Kombination von Psychopharmako- und Psychotherapie wird empfohlen. Methylphenidat, das aufgrund hoher Effektstärken und geringen Nebenwirkungen die Medikation der ersten Wahl ist, ist in Deutschland nicht zugelassen („off-label use“). Atomoxetin ist zugelassen für die Weiterbehandlung im Erwachsenenalter und indiziert bei unzureichender Wirkung oder Nebenwirkungen von Methylphenidat sowie komorbidem Substanzkonsum. Verschiedene psychotherapeutische Interventionen unter Nutzung vorhandener Ressourcen zeigen positive Effekte. Psychosoziale Beratung und Selbsthilfegruppen ergänzen das Behandlungskonzept. Das Fortbestehen der Behandlungsindikation ist in regelmäßigen Abständen zu überprüfen. Eine störungsspezifische multimodale Therapie entspricht der komplexen überwiegend neurobiologischen Ätiologie und den psychosozialen Folgen der adulten ADHS.

Background: Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. However, so far there is limited direct evidence of altered in vivo glutamate concentrations in the brains of patients with schizophrenia. To test the hypothesis that altered glutamatergic neurotransmission might play a role in the pathogenesis of schizophrenia, we measured glutamate and glutamine concentrations in the prefrontal cortex and the hippocampus of patients with chronic schizophrenia using high-field magnetic resonance spectroscopy.Methods. Twenty-one patients with schizophrenia and 32 healthy volunteers were examined clinically and by means of short echo time single voxel magnetic resonance spectroscopy of the dorsolateral prefrontal cortex and the hippocampus. Absolute concentrations of neurometabolites were calculated.Results: Absolute concentrations of glutamate were significantly higher in the prefrontal cortex and the hippocampus in the patient group. Factorial analysis of variance (ANOVA) revealed no significant interactions between duration of schizophrenia, number of hospitalizations, or hype of antipsychotic medication and glutamate concentrations. Increased prefrontal glutamate concentrations were associated with poorer global mental functioning.Conclusions: This is the first study that reports increased levels of glutamate in prefrontal and limbic areas in patients with schizophrenia. Our data support the hypothesis of glutamatergic dysfunction in schizophrenia.

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.

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. (c) 2006 Elsevier Ltd. All rights reserved.

Aims: Fronto-striato-cerebellar networks (FSCN) are widely accepted to play a major role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Recent studies point to a possible contribution of the visual cortex in regulating visuo-spatial attention. To our knowledge there are no morphometric imaging studies that particulary address the question of a possible involvement of visual brain areas in the pathogenesis of adult ADHD.

Continuous recording of Visual Evoked Potentials (VEPs) and functional Magnetic Resonance Imaging (fMRI) exploits the VEPs high temporal resolution and the fMRI high spatial resolution. In this work, we present a new method of continuous VEPs/fMRI recording to study visual function in seven normal subjects. Our real-time artifact filtering is characterized by a procedure based on an analytical study of echo-planar imaging (EPI) sequence parameters related electro-encephalogram (EEG)-artifact shapes. The magnetic field artifacts were minimized by using a dedicated amagnetic device and by a subtraction algorithm that takes into account the EPI sequence parameters. No significant decrease in signal-to-noise ratio was observed in case of EEG recording simultaneously with MR acquisition; similarly, transient and steady-state VEPs parameters were comparable during fMRI acquisition and in the off-phase of fMRI recording. We also applied this method to one patient with optic neuritis, and, compared with controls, found different results. We suggest that our technique can be reliably used to investigate the function of human visual cortex and properly correlate the electrophysiological and functional neuroimaging related changes.

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-II 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.

BACKGROUND Recently amygdala enlargement has been reported in patients with schizophrenia like psychosis of epilepsy. The effect of antipsychotic medication on amygdala structure has not been investigated so far. There is theoretical evidence to support the assumption that dopaminergic neurotransmission might affect neuronal plasticity. METHODS In order to analyze the influence of chronic antidopaminergic medication on amygdala structure we compared amygdala volumes in patients with schizophrenia like psychosis of epilepsy (POE) treated with neuroleptic medication (n = 11) to patients with POE not treated with such medication (n = 15), patients with epilepsy alone (n = 24) and healthy control subjects (n = 20). RESULTS Analyzing our data with a factorial ANOVA approach, we found a significant effect of the factor medication in that patients treated with antipsychotic medication displayed a "normalization" of the increased amygdala volumes observed in the untreated patient group. CONCLUSION This observation supports the assumption that antidopaminergic medication might affect the amygdala structure.

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.

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.

Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible causal element in various neuropsychiatric disorders, in particular depressive disorder and schizophrenia. To test the hypothesis that bilateral symmetrical severe volume loss of the hippocampi is of causal relevance to these psychiatric syndromes rather than an epiphenomenon we assessed the psychopathology in a group of patients with temporal lobe epilepsy (TLE) and very severe bilateral symmetrical hippocampal atrophy and compared it with that of a patient control group. Patients with TLE and hippocampal volumes smaller than three standard deviations below the mean of a control population were identified and compared with a matched patient population with normal hippocampal volumes. Psychopathology was assessed by blinded trained psychiatrists using the Present State Examination and Neurobehavioral Inventory. The prevalence of psychiatric syndromes was high in both patient groups; however, there was no significant difference between the two groups. With use of the more specific Neurobehavioral Inventory a psychopathological pattern reminiscent of the Geschwind syndrome emerged when patients with BHA were characterized by caregivers. While BHA does not result in an increased prevalence of specific psychiatric syndromes, specific symptoms that characterize the Geschwind syndrome like hypergraphia and hyposexuality might be pathogenically related to hippocampal atrophy.