Felix Segmiller

Repeated S-ketamine infusions in therapy resistant depression: a case series.

Keywords: analgesiology/pain management (ANA); psychopharmacology (PSP); psychiatry (PSY); pharmacology (PHA); clinical trials (CTR)

Dopaminergic mechanisms of target detection - P300 event related potential and striatal dopamine.

The P300 is a cortically generated event related potential (ERP) widely used in neurophysiological research since it is related to cognitive functions and central information processing. Intracerebral recordings and functional neuroimaging studies have demonstrated that this potential is generated by various brain regions including frontal, temporal and parietal cortices. Regarding the neurochemical background, clinical and genetic investigations suggest that dopaminergic neurons could be involved in the generation of the P300. However, there is no direct evidence in vivo that P300 amplitudes and latencies are related to dopaminergic parameters. The aim of this study was to further elucidate dopaminergic aspects of the P300 ERP by combining neurophysiological and nuclear medicine assessments in vivo. Patients with a major depressive episode underwent both P300 recordings and dynamic [¹²³I] IBZM SPECT for the evaluation of striatal dopamine D₂/D₃-receptor availability. There were statistically significant positive correlations of the striatal dopamine D₂/D₃-receptor status with P300 amplitudes and significant negative correlations with P300 latencies. Using this combined approach, the study presents direct evidence in vivo that the central dopaminergic system might play an important role in the generation of the P300 and that central dopaminergic activity could be involved in the modulation of P300 parameters. This association might be of relevance for the interpretation of P300 studies in psychiatric disorders.

Driving Performance and Psychomotor Function in Depressed Patients Treated with Agomelatine or Venlafaxine

OBJECTIVE We conducted a randomized case-control study in depressive inpatients to assess the effects of agomelatine and venlafaxine on psychomotor functions related to driving skills and on driving performance in an on-road driving test. METHOD 40 depressed inpatients treated with agomelatine (n = 20) or venlafaxine (n = 20) were tested before pharmacological treatment (t0), and on days 14 (t1) and 28 (t2). 20 healthy subjects were examined in the same time schedule to control for retest effects in psychomotor measures. Additionally, participants were rated in a standardized on-road driving test on day 28 by a licensed driving instructor, who was blind with respect to treatment, diagnosis and test results. RESULTS After 4 weeks of treatment (t2) with agomelatine or venlafaxine, patients showed a significant reduction in depressive symptoms, and a distinct improvement in psychomotor functions. Controlling for retest effects in psychomotor measures, data indicate, that both patient groups significantly improved in tests measuring reactivity and stress-tolerance. Furthermore, prior discharge to outpatient treatment (day 28), 72.5% of patients were labeled abundantly fit to drive in the on-road driving test by a licensed driving instructor. However, patients did not reach the performance level of healthy controls in functional domains tested. Significant differences between treatment groups were not observed. CONCLUSION Our results indicate that depressed inpatients treated with agomelatine or venlafaxine show a better test performance on tasks related to driving skills than do untreated depressives and could predominantly be rated as fit to drive on an actual driving test prior discharge to outpatient treatment.

Loudness dependence of auditory evoked potentials in patients with borderline personality disorder—Impact of psychopathology

Alterations of the central serotonergic system are considered to be involved in the pathophysiology of borderline personality disorder (BPD). The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been shown to indirectly reflect central serotonergic activity. The aim of this study was to investigate LD in patients with BPD compared to healthy controls, and to evaluate the association between LD and psychopathology such as anxiety, anger or impulsiveness. Female patients with BPD were included and compared to age- and sex-matched healthy subjects. Self-rating instruments, such as the State-Trait Anxiety Inventory (STAI), State-Trait Anger Expression Inventory (STAXI), and the Barratt Impulsiveness Scale (BIS) were used to assess clinical scores of anxiety, anger, and impulsiveness. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analysed using dipole source analysis. The mean LD was significantly higher in patients with BPD compared to controls. In the entire sample there were significant positive correlations of LD with state anxiety scores and STAXI subscores. The data contribute to the knowledge of neurophysiological alterations in patients with BPD, supporting the hypothesis of serotonergic dysregulation in the pathophysiology of the disorder. The significant clinical correlations suggest monoaminergic modulations of psychopathology on the symptom level.

Increased gamma oscillations during voluntary selection processes in adult patients with attention deficit/hyperactivity disorder

Executive dysfunctions (regarding behavioural inhibition, decision making, flexibility or voluntary selection) rank among the core symptoms of attention deficit/hyperactivity disorder. Several studies demonstrated functional variations in patients with ADHD especially during response inhibition and flexibility. However, information about functional correlates of other aspects of executive functions such as voluntary selection processes is limited. A group of thirty adult patients with attention deficit/hyperactivity disorder (ADHD) and 30 healthy controls, matched for age and education, participated in the present study. Electrophysiological responses (event-related potentials, gamma oscillations) and behavioural data were acquired during the voluntary selection between various response alternatives. ADHD patients demonstrated increased responses in the gamma frequency band especially in frontal and fronto-central brain areas during voluntary response selection processes compared to healthy subjects. In addition, the error rate was increased in patients. Given that gamma-band responses have been related to GABAergic and glutamatergic responses these results may indicate accordant dysfunction in patients with ADHD.

Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). Significance: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior.

Psychosis during treatment with isotretinoin

Isotretinoin, the 13-cis isomer of all-trans-retinoic acid, is a retinoid and thus a derivative of vitamin A. It has been used successfully since the 1980s to treat severe recalcitrant nodular acne [Sundstrom et al. 2010], but various case reports have suggested that isotretinoin is associated with depression and suicidal behaviour [Citrome, 1998; Hazen et al. 1983; Wysowski and Swartz, 2005] and manic psychosis [Barak et al. 2005]. To the best of the authors’ knowledge, there have been hardly any reports of psychosis during treatment with isotretinoin.

Mobility behaviour and driving status of patients with mental disorders - an exploratory study.

Abstract Background Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. Method Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. Results 67% of PPs (89% NPs) reported to have a valid drivers licence and 77% of them (92% NPs) reported to regularly use their cars. Within drivers license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. Conclusion Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.

Driving ability according to German guidelines in stabilized bipolar I and II outpatients receiving lithium or lamotrigine

Mobility is pivotal in modern societies to maintain independence and take part in activities of daily life. Health issues may have a functional impact on mobility behavior. A meta‐analysis pointed out an almost doubled risk for psychiatric patients being involved in road‐traffic accidents. Moreover, it has been estimated that about 10% of killed or injured victims in road‐traffic accidents were under the influence of psychotropic medication. The disorder itself may impair driving behavior. Several studies reported cognitive deficits in bipolar disorder not only during manic or depressive episodes but also during periods of euthymia with distinct impairments of executive function, verbal memory, psychomotor speed, and sustained attention. The causes of these impairments seem to be multifactorial. Amongst others, neuroimaging studies hint at the enlargement of the lateral ventricles and changes in hippocampal and temporal lobe volume. Treatment with mood stabilizers also may affect cognitive functions. Lithium for example impairs short‐ and long‐term memory and psychomotor functions not only in healthy controls but also in bipolar patients. However, a recent meta‐analysis delineated only few negative effects of lithium on cognition and no increased risk of traffic accidents was found in subjects after being exposed to lithium, except for young female drivers. The newer anticonvulsant lamotrigine seems to have a better neurocognitive profile especially when compared with other anticonvulsants. So far, there is only little research available on bipolar patients’ fitness to drive under mood stabilizers. Hence it would be important to examine the driving ability of stable bipolar patients receiving lithium or lamotrigine.

The Effects of Transcranial Direct Current Stimulation (tDCS) on Psychomotor and Visual Perception Functions Related to Driving Skills

Objective: It could be demonstrated that anodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) enhances accuracy in working memory tasks and reaction time in healthy adults and thus may also have an influence on complex everyday tasks like driving a car. However, no studies have applied tDCS to psychomotor skills related to a standard driving test so far. Methods: 10 female and 5 male healthy adults without any medication and history of psychiatric or neurological illness were randomly assigned to two groups receiving active and sham stimulation in a double blind, cross-over study design. Standardized computerized psychomotor tests according to the German guidelines for road and traffic safety were administered at baseline. Then they performed the same tests during an anodal or sham tDCS of the left DLPFC in two separated sessions. Results: No significant improvements in skills related to driving performance like visual perception, stress tolerance, concentration, and vigilance could be shown after left anodal prefrontal tDCS. Side effects were low and did not differ between active and sham stimulation. Conclusions: The findings of our study indicate that left prefrontal tDCS may not alter driving skills affording more automated action patterns but as shown in previous studies may have an influence on driving behavior requiring executive control processes. This however has to be proved in future studies and within greater samples.