Markus Zedler

Comorbidity of alcohol and substance dependence with attention-deficit/hyperactivity disorder (ADHD).

AIMS Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high prevalence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. METHODS We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. RESULTS 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in childhood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of ADHD persisting in adulthood. CONCLUSIONS These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.

Genuine and drug-induced synesthesia: A comparison

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed. Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Disinhibited feedback as a cause of synesthesia: evidence from a functional connectivity study on auditory-visual synesthetes.

In synesthesia, certain stimuli to one sensory modality lead to sensory perception in another unstimulated modality. In addition to other models, a two-stage model is discussed to explain this phenomenon, which combines two previously formulated hypotheses regarding synesthesia: direct cross-activation and hyperbinding. The direct cross-activation model postulates that direct connections between sensory-specific areas are responsible for co-activation and synesthetic perception. The hyperbinding hypothesis suggests that the inducing stimulus and the synesthetic sensation are coupled by a sensory nexus area, which may be located in the parietal cortex. This latter hypothesis is compatible with the disinhibited feedback model, which suggests unusual feedback from multimodal convergence areas as the cause of synesthesia. In this study, the relevance of these models was tested in a group (n=14) of auditory-visual synesthetes by performing a functional connectivity analysis on functional magnetic resonance imaging (fMRI) data. Different simple and complex sounds were used as stimuli, and functionally defined seed areas in the bilateral auditory cortex (AC) and the left inferior parietal cortex (IPC) were used for the connectivity calculations. We found no differences in the connectivity of the AC and the visual areas between synesthetes and controls. The main finding of the study was stronger connectivity of the left IPC with the left primary auditory and right primary visual cortex in the group of auditory-visual synesthetes. The results support the model of disinhibited feedback as a cause of synesthetic perception but do not suggest direct cross-activation.

Inside a synesthete's head: A functional connectivity analysis with grapheme-color synesthetes

Grapheme-color synesthesia is a condition in which letters are perceived with an additional color dimension. To identify brain regions involved in this type of synesthesia and to analyze functional connectivity of these areas, 18 grapheme-color synesthetes and 18 matched controls were stimulated with letters and pseudo-letters presented in black and color in an event-related fMRI experiment. Based on the activation-differences between synesthetes and non-synesthetic controls regions of interest were defined. In a second analysis step functional connectivity was calculated using beta series correlation analysis for these seed regions. First we identified one seed region in the left inferior parietal (IPL) cortex (BA7) showing activation differences between grapheme-color synesthetes and controls. Furthermore, we found activation differences in brain areas involved in processing of letters and pseudo-letters, in particular the right IPL cortex (BA7), but also two more clusters in the right hemispheric BA 18 and BA 40. Functional connectivity analysis revealed an increased connectivity between the left IPL seed region and primary/secondary visual areas (BA 18) in synesthetes. Also the right BA 7 showed a stronger connectivity with primary/secondary visual areas (BA 18) in grapheme-color synesthetes. The results of this study support the idea that the parietal lobe plays an important role in synesthetic experience. The data suggest furthermore that the information flow in grapheme-color synesthetes was already modulated at the level of the primary visual cortex which is different than previously thought. Therefore, the current models of grapheme-color synesthesia have to be refined as the unusual communication flow in synesthetes is not restricted to V4, fusiform cortex and the parietal lobe but rather involves a more extended network.

Pathological Internet use and psychiatric disorders: A cross-sectional study on psychiatric phenomenology and clinical relevance of Internet dependency

Background and Objectives: With the Cyberspaces exponential growth of influence questions arise about its mental impacts. The presented study examines the question whether the dependent use of the Internet can be understood as an impulse con- trol disorder, an addiction or as a symptom of other psychiatric conditions. Methods: Internet dependent patients seeking for psychiatric assistance and fulfilling the criteria for pathological Internet use (PIU) were examined with the Structured Clinical Inter- view according to DSM-IV (SCID), and a variety of questionnaires including the Barratt Im- pulsiveness Scale (BIS), the Beck Depression Inventory (BDI) and the Dissociative Experi- ence Scale (DES). The patient group was compared to a matched group of healthy controls. Results: The adult patient-group consisted of 25 subjects, 76% male, with a mean age of 29.36 years. Average time spent in Cyberspace was 6.47 h/d, mostly in online-role- playing games. According to SCID I and BDI, 19 patients (76%) suffered from a depres- sive syndrome, with 10 cases of major depressive disorder (40%) and 8 cases of adjust- ment disorder with depression (32%). Six patients (24%) suffered from a comorbid anxiety disorder. Compared to controls, the patient group presented significantly higher levels of depression (BDI), impulsivity (BIS) and dissociation (DES). Conclusions: PIU shares common psychopathological features and comorbidities with substance related disorders. Therefore, it might be seen as a diagnostic entity in itself in a spectrum of behavioural and substance dependencies. Especially Internet role play may contain an addictive potential for adolescents and adults with subclinical psychopathology.

Reduced audio-visual integration in synaesthetes indicated by the double-flash illusion.

It has been suggested that synaesthesia is the result of a hyper-sensitive multimodal binding-mechanism. To address the question whether multi-modal integration is altered in synaesthetes in general, grapheme-colour and auditory-visual synaesthetes were studied using the double-flash illusion. This illusion is induced by a single light flash presented together with multiple beep sounds, which is then perceived as multiple flashes. By varying the separation of auditory and visual stimuli, the hypothesis of a widened temporal window of audio-visual integration in synaesthetes was tested. As hypothesised, the results show differences between synaesthetes and controls concerning multisensory integration, but surprisingly other than expected synaesthetes perceive a reduced number of illusions and have a smaller time-window of audio-visual integration compared to controls. This indicates that they do not have a hyper-sensitive binding mechanism. On the contrary, synaesthetes seem to integrate even less than controls between vision and audition.

Is synesthesia more common in patients with Asperger syndrome

There is increasing evidence from case reports that synesthesia is more common in individuals with autism spectrum conditions (ASC). Further, genes related to synesthesia have also been found to be linked to ASC and, similar to synaesthetes, individuals with ASC show altered brain connectivity and unusual brain activation during sensory processing. However, up to now a systematic investigation of whether synesthesia is more common in ASC patients is missing. The aim of the current pilot study was to test this hypothesis by investigating a group of patients diagnosed with Asperger Syndrome (AS) using questionnaires and standard consistency tests in order to classify them as grapheme-color synaesthetes. The results indicate that there are indeed many more grapheme-color synaesthetes among AS patients. This finding is discussed in relation to different theories regarding the development of synesthesia as well as altered sensory processing in autism.

Acamprosate Reduces Motor Cortex Excitability Determined by Transcranial Magnetic Stimulation

Acamprosate is effective in reducing alcohol intake in weaned alcoholics. We were interested if acamprosate had an effect on the excitability of cortical motoneurons determined by transcranial magnetic stimulation (TMS). We studied 12 male healthy volunteers (mean age 29.5 years, SD = 4.8) who were either treated with 6 tablets of acamprosate (each containing 333 mg verum) per day or placebo (randomized cross-over design) for 1 week. TMS was performed after each treatment session including a paired stimulation paradigm. Motor evoked potentials (MEPs) of the placebo and verum group did not differ with respect to paired stimulation. However, motor threshold increased in the acamprosate group (verum: 61.5% (SD = 7.9) vs. placebo: 58.9% (SD = 8.8), p = 0.036). We conclude that acamprosate leads to a hypoexcitability of the motor cortex. This might be due to subcortical mechanisms, e.g. thalamocortical pathways since intracortical inhibition and facilitation was not affected.

Reduced audiovisual integration in synesthesia – evidence from bimodal speech perception

Recent research suggests synesthesia as a result of a hypersensitive multimodal binding mechanism. To address the question whether multimodal integration is altered in synesthetes in general, grapheme-colour and auditory-visual synesthetes were investigated using speech-related stimulation in two behavioural experiments. First, we used the McGurk illusion to test the strength and number of illusory perceptions in synesthesia. In a second step, we analysed the gain in speech perception coming from seen articulatory movements under acoustically noisy conditions. We used disyllabic nouns as stimulation and varied signal-to-noise ratio of the auditory stream presented concurrently to a matching video of the speaker. We hypothesized that if synesthesia is due to a general hyperbinding mechanism this group of subjects should be more susceptible to McGurk illusions and profit more from the visual information during audiovisual speech perception. The results indicate that there are differences between synesthetes and controls concerning multisensory integration--but in the opposite direction as hypothesized. Synesthetes showed a reduced number of illusions and had a reduced gain in comprehension by viewing matching articulatory movements in comparison to control subjects. Our results indicate that rather than having a hypersensitive binding mechanism, synesthetes show weaker integration of vision and audition.

Effects of methylphenidate in ADHD adults on target evaluation processing reflected by event-related potentials

Attention deficit/hyperactivity disorder (ADHD) is a widely examined disease in childhood. There is evidence that the disease responds well to medication with methylphenidate (MPH). The effect of MPH in adults with ADHD is a question that is often raised, because many adults request such therapy today. As yet, there is a lack of studies on event-related potentials (ERPs) and MPH in ADHD adults. In the present study we examined 10 adults diagnosed with ADHD, with and without MPH medication (30 mg daily), by means of ERP in a visual Go/NoGo experiment to gain information about target evaluation processing in these patients and about the effects on these attentional processes during medication with MPH. Visually, there seem to be differences in the frontal electrodes for the N2 and in the parietal electrodes for the P300. But these differences do not achieve statistical significance. There are also no statistically relevant differences for the N1 or the slow wave. MPH does not seem to have an effect on target evaluation processing, when comparing the ERPs of non-medicated and medicated ADHD adults. Especially the P3 does not appear to be modulated by medication with MPH in these ADHD adults, in contrast to findings in ADHD children.