[Hallucinogen Persisting Perception Disorder (HPPD) and Flashback Phenomena ­ Differential Diagnosis and Explanation Models]. / Halluzinogen-induzierte Persistierende Wahrnehmungsstörung (HPPD) und Flashback-Phänomene ­ Differenzialdiagnose und Erklärungsmodelle.

OBJECTIVE: The purpose of this article is to provide an overview of the current research on "Hallucinogen Persisting Perception Disorder" (HPPD) and "Flashback" phenomena. The definition and diagnostic features of "Flashback" and HPPD remained often unclear and since the 1960 s interchangeable. METHODS: Relevant literature was identified by means of a computerized MEDLINE search including the years 1994-2014. Finally 75 journal articles out were included in the review. RESULTS: Consistent with the ICD-10 (F16.70) definition "Flashback" is often used to describe brief visual perceptual, mood, and altered states of consciousness effects reminiscent of acute hallucinogen intoxication effects. Many users regard flashback phenomena as benign and even pleasant. HPPD is described in DSM-5 as a visual perceptual disorder, sometimes persisting for months or years causing severe individual distress. The prevalence of flashback and HPPD is unknown. It is considered to be remarkable in view of the relatively few case reports published out of millions of hallucinogen users since the 1960 s and 1970 s. Despite a multitude of etiological and therapeutic approaches the exact pathophysiological mechanisms underlying HPPD remain elusive. At present HPPD appears to be further a DSM-5-genuine but still puzzling disorder. The different consequences including new therapeutic approaches are discussed in clinical context.

[Substance use associated disorders: frequency in patients with schizophrenic and affective psychoses]. / Substanzbezogene Störungen: Häufigkeit bei Patienten mit schizophrenen oder affektiven Störungsbildern.

BACKGROUND: Alcohol and substance use disorders (ASUD) are considered to be among the most frequent comorbidities in schizophrenic and affective psychoses and have a significant negative influence on their course and prognosis. In the present study patients with diagnosis from the ICD-10 category F2 or F3 were examined regarding a substance use disorder in a multicentre cross-section evaluation at nine psychiatric hospitals in Baden-Württemberg. The aim of this study is to discuss the current research on substance use disorders and psychosis comorbidity regarding the theoretical models by means of collected data. METHODS: The examination of 50 consecutive admissions per centre is based on a shortened version of the European Severity Index (Europ ASI). An initial urine drug screening was carried out with all patients after admission. Statistical assessment was based on percentage distributions, mean values, standard deviations and suitable correlation analysis. RESULTS: The representative sample included 448 patients. A proportion of 169 patients (37.7%) had a dual diagnosis F2 and F1 and a proportion of 144 patients (32.1%) had a dual diagnosis F3 and F1; 64 patients (14.3%) had an F2 diagnosis and 71 patients (15.8%) had an F3 diagnosis without ASUD. Apart from lifetime use of alcohol (n = 268) and tobacco (n = 325) hypnotics/tranquilizers (n = 214), cannabis (n = 156), opioids (n = 71), stimulants (n = 96) and hallucinogens (n = 36) were consumed. The most frequent combination and long-term intake consisted of tobacco, alcohol, hypnotics/tranquilizer, cannabis and psychostimulants especially in men with schizophrenic disorders. Regarding motivation before first substance use general psychological adjustment disorders (51%), peer impact (42%) and unspecific affective symptoms were predominant. CONCLUSIONS: Altogether the present study clearly demonstrates that patients suffering from schizophrenia, affective disorders and ASUD have significantly higher rates of more severe substance use disorders in their psychosocial environment and more suicidal behaviour than patients without substance misuse. The high rate in the cross-sectional prevalence of tobacco, alcohol, cannabis and psychostimulant use calls for more effective drug prevention.

[Lie detection and mind reading: is there a use for fMRI?: A critical survey and reflection]. / MRT als Lügendetektor und Gedankenleser?: Kritische Bestandsaufnahme und Reflexion.

Great efforts have been made in recent years to use functional magnetic resonance imaging (fMRI) in the context of lie detection. In the present paper the pros and cons of such an approach are analyzed and critically discussed.Both epistemological and methodical considerations have shown that all attempts to derive mental states from fMRI findings ("reverse inference") are not valid. Consequently, fMRI scans cannot reveal a person's thoughts and whether (s)he is lying or telling the truth.

[Hallucinogen-induced psychological disorders]. / Halluzinogen-induzierte psychische Störungen.

OBJECTIVE: The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults. METHODS: Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 - 2007. As keywords "hallucinogen induced psychosis", "hallucinogen induced flashback", "hallucinogen persisting perception disorder (HPPD)" were used. Finally, 64 journal articles and books out of 103 were included in the review. RESULTS: Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

Response inhibition in borderline personality disorder: event-related potentials in a Go/Nogo task.

Borderline personality disorder (BPD) has been related to a dysfunction of anterior cingulate cortex, amygdala, and prefrontal cortex and has been associated clinically with impulsivity, affective instability, and significant interpersonal distress. We examined 17 patients with BPD and 17 age-, sex-, and education matched control participants with no history of Axis I or II psychopathology using event-related potentials (ERPs). Participants performed a hybrid flanker-Go/Nogo task while multichannel EEG was recorded. Our study focused on two ERP components: the Nogo-N2 and the Nogo-P3, which have been discussed in the context of response inhibition and response conflict. ERPs were computed on correct Go trials (button press) and correct Nogo trials (no button press), separately. Groups did not differ with regard to the Nogo-N2. However, BPD patients showed reduced Nogo-P3 amplitudes. For the entire group (n = 34) we found a negative correlation with the Barratt Impulsiveness Scale (BIS-10) and Becks's depression inventory (BDI). The present study is the first to examine Nogo-N2 and Nogo-P3 in BPD and provides further evidence for impaired response inhibition in BPD patients.

Executive control in obsessive-compulsive disorder: event-related potentials in a Go/Nogo task.

Obsessive-compulsive disorder (OCD) has been related to a hyperactive cortico-striatal-pallidal-thalamic circuitry resulting clinically in an impaired inhibition of repetitive thoughts and behaviors. We examined thirteen patients with OCD and thirteen age-, sex-, and education matched healthy controls using event-related potentials (ERPs). Participants performed a hybrid flanker-Go/Nogo task while multichannel EEG was recorded. Our study focused on two ERP components: the Nogo-N2 and the Nogo-P3, which have been discussed in the context of response inhibition and response conflict. Artifact-free EEG-segments were used to compute ERPs on correct Go trials (button press) and correct Nogo trials (no button press), separately. Patients with OCD showed enhanced (more negative) Nogo-N2 amplitudes than controls, and a significant difference in amplitudes between Nogo-N2 and Go-N2 trials (more negative for Nogo trials) at central midline electrode positions. However, groups did not differ with regard to the Nogo-P3 and Go-P3. The present study replicates and extends previous findings of altered executive control processes in OCD patients.

[Development of the concept of identity in psychiatry and philosophy]. / Zur Entwicklung des Begriffs der Person in Psychiatrie und Philosophie.

The present paper discusses possible solutions to the problem of personal identity and intends to demonstrate criteria enabling us to view a person as the same at different time points in his life. Of special interest are the so-called memory criterion and the criterion of physical identity/continuity: a person remains the same if he is able to remember his past "states" or if he continues to have his former body (brain). The philosophical discussion of the last decades made clear that all attempts to reduce personal identity to memory or physical continuity are contradictory. In this paper we propose regarding personal identity as a normative phenomenon that evades a purely descriptive or neurobiological approach.

[AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders]. / AWMF-Behandlungsleitlinie: Psychische und Verhaltensstörungen durch Kokain, Amphetamine, Ecstasy und Halluzinogene.

Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

Enantio-selective cognitive and brain activation effects of N-ethyl-3,4-methylenedioxyamphetamine in humans.

In a randomised double-blind trial the subjective, neuropsychological and brain activation effects of the two enantiomers of the MDMA (ecstasy-) like drug N-ethyl-3,4-methylenedioxyamphetamine (MDE) were studied in five normal subjects using functional magnetic resonance imaging (fMRI). (S)-MDE produced elevated mood, impairments in conceptually driven cognition and marked right frontal activation. In contrast, (R)-MDE produced increased depression, enhanced visual feature processing, and activation of visual cortical and left frontal areas. Plasma concentrations were higher for the (R)-enantiomer. The so-called entactogenic effects of MDE are likely to be caused by the (S)-enantiomer, whereas (R)-MDE appears to be responsible for neurotoxic effects.

How to preserve the antidepressive effect of sleep deprivation: A comparison of sleep phase advance and sleep phase delay.

Total sleep deprivation (TSD) leads to an immediate amelioration of depressed mood in approximately 70 % of patients with the melancholic subtype of depression. The clinical utility of this procedure is limited, as the improvement usually subsides after the next night of sleep. In the present study, 40 depressed inpatients, being free of psychoactive medication for at least 7 days and who had responded to a TSD were then distributed (according to a matched-pair design) to a sleep phase advance (SPA = time in bed scheduled from 1700-2400 hrs) or a sleep phase delay (SPD = time in bed from 0200-0700 hrs) with a succeeding shift back (for one hour in the SPA group per day) respectively shift forward (for 30 minutes in the SPD group per day), until the initial sleep phase (2300-0600 hrs) was reached after seven days again. Based on previous observations it was hypothesized that a phase advance of the sleep period should prevent responders to TSD from relapsing. Whereas 75% of the TSD responders were stabilized by the phase advanced condition and did not relapse over a period of seven days, only 40% of the patients in the phase delayed condition did not relapse. Polysomnography during the course of the study gave no evidence that the unusual sleep schedules caused prolonged sleep deprivation. Abnormalities of REM sleep persisted both in the clinical responders and non-responders after the sleep wake manipulation. It is concluded that the clinical effectiveness of TSD can be significantly improved by combining TSD with a following phase advance of the sleep period.

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study.

The aim of this study was to contribute to the characterization of the entactogen (ecstasy) substance group. The psychopathological, neuroendocrine and autonomic effects of common recreational doses of the entactogen 3,4-methylenedioxyethylamphetamine (MDE), the hallucinogen psilocybin, the stimulant d-methamphetamine and placebo were investigated in a double-blind study with healthy volunteers (n = 32). Psychological effects of the drugs were assessed by means of standardized rating scales, self assessment inventories and free descriptions. The most characteristic effects of MDE were pleasant emotional experiences of relaxation, peacefulness, content and closeness to others. However, significant stimulant and hallucinogen-like effects were also present, although the latter were weaker than the effects of psilocybin. MDE elicited the strongest endocrine and autonomic effects among the three drugs, including robust rises of serum cortisol and prolactin, elevations of blood pressure and heart rate, and a moderate, but significant rise of body temperature. The apparent contrast between psychological and autonomic effects (subjective relaxation versus physical activation) was a unique feature of the MDE state. Our findings are in line with both users' reports and results from previous experimental studies, and support the view that entactogens constitute a distinct psychoactive substance class taking an intermediate position between hallucinogens and stimulants.

History, rationale and potential of human experimental hallucinogenic drug research in psychiatry.

Systematic scientific interest in psychedelic substances has a tradition of about 100 years. Numerous human experimental studies have confirmed the existence of a common nucleus of experiences in hallucinogen-induced states and the acute stages of schizophrenic psychoses. However, the degree of resemblance between endogenous and drug-induced psychotic states has been an issue of controversial debate. After the scheduling of psychedelics in the 1960s, human research became highly restricted worldwide and scientific interest in this field faded. The debate about the appropriateness of the psychedelic state as a model for endogenous psychosis therefore seemed to have little practical relevance. Currently there is a revival of scientific interest in human experimental psychedelic research. Consequently, the appropriateness of hallucinogen-induced states as models for psychosis needs to be reappraised. The arguments for and against are summarized in this paper. In conclusion, the drug-induced model psychosis is shown to be a useful model for acute psychotic stages, but not for the nosological entity schizophrenia.

Blood flow and cerebral laterality in the mescaline model of psychosis.

The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal male volunteers. Between 3 1/2 and 4 hours after drug intake, mescaline produced an acute psychotomimetic state, as measured by the BPRS and PDS-P. The APZ questionnaire revealed the specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/non-face decision task with known right hemisphere advantage, in which mescaline induced a decrease in functioning of the right hemisphere. In functional brain imaging using SPECT, mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotomimetic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for acute psychotic symptomatology.

Hallucinogenic drug induced states resemble acute endogenous psychoses: results of an empirical study.

Clinical evidence suggests that hallucinogenic drug-induced altered states of consciousness (ASCs) and the incipient, acute stages of endogenous psychoses share many common phenomenological features. The aim of our study was to assess hallucinogen-like phenomena in endogenous psychotic patients using standardised methods. We examined 93 endogenous psychotic patients, 50 healthy controls and a small group of drug induced psychotic patients (n = 7) with two ASC self-assessment scales (questionnaire APZ = Abnormer Psychischer Zustand = Altered State of Consciousness [Dittrich et al, 1985]; and questionnaire OAV = Abbreviation of the three subscales: Oceanic Boundlessness/Angst = Dread of Ego Dissolution/Visionary Restructuralisation [Bodmer 1989]). Patients were examined shortly after remission of their last acute psychotic episode and they answered the questionnaires referring to the early phase of this episode. Differences in the questionnaire scores were significant between psychotic patients and controls. Drug induced patients had numerically higher scores than endogenous psychotic patients, however these differences were only significant for the APZ total score and the undifferentiated items of the APZ, but not for the three APZ subscale and the OAV scores. More than 50% of the endogenous psychotic patients answered 26% of the APZ-and 43% of the OAV-items with "yes". The OAV total score and the OSE (Ozeanische Selbstentgrenzung = oceanic boundlessness) scores of both questionnaires correlated significantly with BPRS Factor 3 (thought disturbance). Our results support the hypothesis that hallucinogen-like experiences represent common phenomena during the acute stages of endogenous psychoses. Remarkably, these phenomena include subjectively pleasant experiences of the OSE dimension. In the routine clinical assessment of endogenous psychotic patients experiences of this dimension may be more easily overlooked than the negative experiences of the AIA dimension (AIA: Angst vor der Ich-Auflösung = dread of ego dissolution).

[Metachromatic leukodystrophy simulating schizophrenia-like psychosis]. / Metachromatische Leukodystrophie mit dem klinischen Erscheinungsbild einer schizophrenieähnlichen Psychose.

A case of late onset metachromatic leukodystrophy with a clinical picture of paranoid hallucinatory psychosis and severe dyskinesia is described. The problem of diagnostic recognition is discussed. In the case, diagnostic procedures were initiated after atypical clinical course, and established on the basis of MRI and specific biochemical tests.

The Stroop effect in schizophrenic patients.

Schizophrenic patients (n = 44) and normal controls (n = 50) performed a computerized version of the Stroop color-word interference task. Schizophrenic patients generally showed more Stroop interference than normal subjects. The effect was neither related to demographic variables, nor to actual psychopathology. However, the course of the disorder was related to the Stroop effect, in that acute, chronic, and schizoaffective patients displayed a larger interference effect than patients with a recurrent episode. From a methodological perspective, the computerized version of the Stroop task proved to be more sensitive to interference effects in the patient group. The finding of enhanced reverse Stroop interference in patients strongly preoccupied with colors is discussed within the framework of MacLeod and Dunbar's (MacLeod and Dunbar, 1988) theory of Stroop interference involving differential practice effects.

[Hallucinogen induced psychic disorders. Subjective experiences, psychopathology and differential diagnosis]. / Halluzinogen-induzierte psychische Störungen. Subjektives Erleben, Psychopathologie und Differentialdiagnose.

The concepts of intoxication, intoxication psychosis, and drug-induced psychosis are frequently used to refer to psychopathological states caused by the intake of hallucinogenic substances. The considerable increase of intoxications with substances of the chemical class of amphetamines (in particular, "Ecstasy") in western countries should cause major concern. Moreover, the number of schizophrenic patients who also use hallucinogenic drugs is increasing. High incidence and comorbidity cause clinical problems and call for detailed knowledge of the drug related acute and chronic effects of the various agents currently in use. Clinical findings and subjective reports from research in experimental psychoses are used to discuss differential diagnosis and types of drug-induced mental disorders within the framework of present day classificatory systems, such as DSM-IV and ICD-10.