Transcranial direct current stimulation combined with a brief intervention for smoking cessation: a randomized double-blind clinical trial.

Non-invasive brain stimulation methods are currently being evaluated for treatment of addictive disorders. Some evidence indicates that modulating left and right prefrontal brain activity by transcranial direct current stimulation (tDCS) can reduce craving and relapse rates in tobacco addiction. Therefore, this study investigated the effects of active and sham tDCS as an add-on treatment to a standardized brief intervention for smoking cessation. This randomized, double-blind study included 36 participants (22 women and 14 men) with nicotine dependence according to ICD-10 criteria. At five visits on alternate days, participants underwent a 20-min active or sham tDCS over the left dorsolateral prefrontal cortex and subsequently participated in a 10-min brief intervention for smoking cessation. Patients were followed up after 3 months. On each treatment day and at follow-up, abstinence was assessed as the smoking status nonsmoker and craving was assessed with the German version of the Questionnaire on Smoking Urges. At each visit, the number of cigarettes smoked per day was recorded and carbon monoxide in expired air and cotinine in saliva were measured. At follow-up, a study-specific questionnaire was used to assess tobacco use. All 36 participants completed the treatment sessions, but one participant in each group was lost to follow-up. Abstinence rates were not significantly different between the groups at any of the study visits, but craving was significantly lower in the active group at tDCS session 5 compared with session 1. tDCS combined with a brief intervention may support smoking cessation, but studies need to evaluate whether longer and more intensive treatment can achieve significant, sustainable effects.

Binding potential changes of SERT in patients with depression are associated with remission: A prospective [¹²³I]ß-CIT-SPECT study.

The status of remission in patients with major depressive disorder treated with selective serotonin reuptake inhibitors (SSRIs) is mostly evaluated with clinical rating scales. Morphological correlates of the remission status remain a rare event. Addressing this challenge, we investigated functional correlates of remission by assessment of serotonin and dopamine transporter availability (SERT and DAT) using single-photon emission computed tomography (SPECT). Our purpose was to identify changes in the SERT/DAT binding potential in accordance with the clinical improvement. Nineteen drug-naïve patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of major depression were included. [¹²³I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane(ß-CIT) SPECT was obtained from each participant before (baseline) and after 6 weeks (follow-up) of standardized treatment with escitalopram. The [¹²³I]ß-CIT-SPECT recordings were acquired 4 hr (SERT-weighted) and 20-24 hr p.i (DAT-weighted), and binding potentials (˜BPND: baseline, follow-up, and rate of change) were calculated for thalamus, midbrain, pons (SERT), and striatum (DAT). From all study participants, neuropsychiatric symptoms were assessed using Hamilton depression (HAM-D) and Beck Depression Inventory scores. At follow-up, patients were divided into responders and nonresponders (as well as remitters and nonremitters). Compared to nonremitted, remitted patients showed over the course of 6 weeks a significantly higher loss of SERT binding potential in the thalamus (p = .036) and in the midbrain (p = .019). Additionally, the correlation of HAM-D with SERT binding potential in the thalamus showed a trend toward significance (p = .057) with higher HAM-D scores (at baseline) leading to lower SERT binding potential. No significant associations were identified for the analysis of baseline prediction of therapy response with SERT and DAT. Our results suggest that patients who remit from their depressive symptoms under escitalopram are characterized by stronger decreases of SERT, indicating that escitalopram blocking of SERT leads to clinical improvement. Therefore, this study shows that measuring SERT availability with SPECT could be an efficient and applicable technique to illustrate a possible underlying pathophysiology of symptom remission in response to treatment. In addition, the present results could help to stimulate new treatment approaches based on SERT and DAT binding. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Biobanking in everyday clinical practice in psychiatry-The Munich Mental Health Biobank.

Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biosamples from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy (DPP) and the Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records. The generated data and biosamples are available to both academic and industry researchers. In this manuscript, we outline the workflow and infrastructure of the MMHB, describe the clinical characteristics and representativeness of the sample collected so far, and reveal future plans for expansion and application. As of 31 October 2021, the MMHB contains a continuously growing set of data from 578 patients and 104 healthy controls (46.37% women; median age, 38.31 years). The five most common mental health diagnoses in the MMHB are recurrent depressive disorder (38.78%; ICD-10: F33), alcohol-related disorders (19.88%; ICD-10: F10), schizophrenia (19.69%; ICD-10: F20), depressive episode (15.94%; ICD-10: F32), and personality disorders (13.78%; ICD-10: F60). Compared with the average patient treated at the recruiting hospitals, MMHB participants have significantly more mental health-related contacts, less severe symptoms, and a higher level of functioning. The distribution of diagnoses is also markedly different in MMHB participants compared with individuals who did not participate in the biobank. After establishing the necessary infrastructure and initiating recruitment, the major tasks for the next phase of the MMHB project are to improve the pace of participant enrollment, diversify the sociodemographic and diagnostic characteristics of the sample, and improve the utilization of real-world data generated in routine clinical practice.

A machine learning approach to risk assessment for alcohol withdrawal syndrome.

At present, risk assessment for alcohol withdrawal syndrome relies on clinical judgment. Our aim was to develop accurate machine learning tools to predict alcohol withdrawal outcomes at the individual subject level using information easily attainable at patients' admission. An observational machine learning analysis using nested cross-validation and out-of-sample validation was applied to alcohol-dependent patients at two major detoxification wards (LMU, n = 389; TU, n = 805). 121 retrospectively derived clinical, blood-derived, and sociodemographic measures were used to predict 1) moderate to severe withdrawal defined by the alcohol withdrawal scale, 2) delirium tremens, and 3) withdrawal seizures. Mild and more severe withdrawal cases could be separated with significant, although highly variable accuracy in both samples (LMU, balanced accuracy [BAC] = 69.4%; TU, BAC = 55.9%). Poor outcome predictions were associated with higher cumulative clomethiazole doses during the withdrawal course. Delirium tremens was predicted in the TU cohort with BAC of 75%. No significant model predicting withdrawal seizures could be found. Our models were unique to each treatment site and thus did not generalize. For both treatment sites and withdrawal outcome different variable sets informed our models' decisions. Besides previously described variables (most notably, thrombocytopenia), we identified new predictors (history of blood pressure abnormalities, urine screening for benzodiazepines and educational attainment). In conclusion, machine learning approaches may facilitate generalizable, individualized predictions for alcohol withdrawal severity. Since predictive patterns highly vary for different outcomes of withdrawal severity and across treatment sites, prediction tools should not be recommended for clinical practice unless adequately validated in specific cohorts.

Acute alcohol withdrawal and recovery in men lead to profound changes in DNA methylation profiles: a longitudinal clinical study.

BACKGROUND AND AIMS: Withdrawal is a serious and sometimes life-threatening event in alcohol-dependent individuals. It has been suggested that epigenetic processes may play a role in this context. This study aimed to identify genes and pathways involved in such processes which hint to relevant mechanisms underlying withdrawal. DESIGN: Cross-sectional case-control study and longitudinal within-cases study during alcohol withdrawal and after 2 weeks of recovery SETTING: Addiction medicine departments in two university hospitals in southern Germany. PARTICIPANTS/CASES: Ninety-nine alcohol-dependent male patients receiving in-patient treatment and suffering from severe withdrawal symptoms during detoxification and 95 age-matched male controls. MEASUREMENTS: Epigenome-wide methylation patterns were analyzed in patients during acute alcohol withdrawal and after 2 weeks of recovery, as well as in age-matched controls using Illumina EPIC bead chips. Methylation levels of patients and controls were tested for association with withdrawal status. Tests were adjusted for technical and batch effects, age, smoking and cell type distribution. Single-site analysis, as well as an analysis of differentially methylated regions and gene ontology analysis, were performed. FINDINGS: We found pronounced epigenome-wide significant [false discovery rate (FDR) < 0.05] differences between patients during withdrawal and after 2 weeks [2876 cytosine-phosphate-guanine (CpG) sites], as well as between patients and controls (9845 and 6094 CpG sites comparing patients at time-point 1 and patients at time-point 2 versus controls, respectively). Analysis of differentially methylated regions and involved pathways revealed an over-representation of gene ontology terms related to the immune system response. Differences between patients and controls diminished after recovery (> 800 CpG sites less), suggesting a partial reversibility of alcohol- and withdrawal-related methylation. CONCLUSIONS: Acute alcohol withdrawal in severely dependent male patients appears to be associated with extensive changes in epigenome-wide methylation patterns. In particular, genes involved in immune system response seem to be affected by this condition.

Epileptic Spikes in EEG and Migraine Attacks in the Course of Cannabis Withdrawal: A Case Report.

In psychiatry, routine EEGs are often abnormal and not very specific, raising questions about the clinical relevance and consequences of potential anomalies. One such question is whether the administration of anticonvulsants would be useful if epileptic discharges are detected in patients without any clinical correlates. With regard to this question, we present a case study in which abnormal EEG patterns were observed in a patient with chronic migraine and cannabis addiction. The patient was a 34-year-old woman with a 14-year history of cannabis abuse who, during withdrawal, showed epileptic spikes, without any corresponding clinical symptoms, and migraine attacks of increasing intensity and frequency. This case study is in line with the new DSM-5 diagnostic tool that for the first time includes the diagnosis of cannabis withdrawal.

Methamphetamine withdrawal and the restoration of cognitive functions - a study over a course of 6 months abstinence.

A continuously rising consumption of methamphetamine (MA) has been suggested to be associated with increasing cognitive dysfunction. The objective of this study was to investigate associations between cognitive functions and gender, drug using patterns and treatment-attending profiles of recently abstinent MA users over the course of six months abstinence. Data were collected from 108 participants in two inpatient rehabilitation centers. The mean duration of MA use was 11.5 years. Interviews and cognitive tests (cognitrone, Stroop, TMT, nback) were performed right after the withdrawal and again after approx. six months of abstinence. Comparisons and explorative analyses between the groups (gender, primary MA/ multidrug users, early dropouts/ completers) regarding cognitive variables were performed. At baseline a significant decline in general neuropsychological functioning and attention/concentration after ongoing years of consumption were found. After a period of six months abstinence, cognitive performances remained stable or improved significantly for cognitrone percentile and cognitive flexibility. Normal cognitive functions were measured in former MA users after acute withdrawal which remained stable and partly improved in those patients who refrained from substance abuse over six months. Continued long-term MA intake was the only identified indicator of poorer cognitive performance. These results point towards a regain of cognitive performance in patients abstinent from MA.

Pain management in opioid maintenance treatment.

Introduction: Opioid addiction is a worldwide disease with a significant impact. A multitude of physical and mental comorbidities are associated with opioid addiction, pain being one of the most relevant. Insufficient pain management may lead to a disruption in medical treatment, self-medication, and subsequent harm to patients. Areas covered: In this review, the authors provide a general overview of opioid addiction. A literature search for pain management and opioid maintenance treatment was conducted. Different settings of acute or chronic pain and situations specific to patients addicted to opioids are described. Pain management therapy in addiction is also addressed with an emphasis on treatment strategies such as the optimization of methadone and buprenorphine medication, additional opioid analgesia, and multimodal pain management. Expert opinion: Opioid addiction is a growing global health concern, and maintenance therapy remains an effective and lifesaving treatment option. However, there remains uncertainty on the appropriate pain management for this patient group. The backbone of pain management in opiate-addicted patients remains maintenance therapy while adjunctive treatment such as regional analgesia, non-opioid analgesia, antidepressants, steps to improve sleep, acceptance and commitment therapy, biofeedback, and hypnosis should be considered. Additional opioid medication is possible as well.

[Adult attention deficit hyperactivity disorder (ADHD) with comorbid addictive disorder. Therapeutic challenges using the example of a survey of clinical practice]. / ADHS im Erwachsenenalter und komorbide Suchterkrankungen : Therapeutische Herausforderungen am Beispiel einer Praxiserhebung.

BACKGROUND: ADHD in childhood and adolescence is characterized by the symptoms hyperactivity, impulsivity, and inattentiveness; these symptoms may persist into adulthood or may manifest as restlessness, emotional instability, and disorganized behavior. In adults ADHD often occurs with increased substance use and is associated with an early onset of substance use, development of severe addiction, and decreased treatment effectiveness. METHOD: This overview will present and critically discuss current study results and evidence-based and consensus-oriented recommendations that ensure the most adequate care for patients with ADHD and addictive disorder. RESULTS AND CONCLUSIONS: For drug therapy, the current S3 guideline recommends methylphenidate, amphetamine salts, and atomoxetine, among others. Treatment of adult patients with ADHD and addiction with stimulants tends to be viewed critically; if required, long-acting medications should be used. Integrated treatment of ADHD and addiction, consisting of a combination of pharmacotherapy and psychotherapy, is recommended.

Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies.

BACKGROUND: Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor availability within the striatum. METHODS: This work focuses on influences of stimulant use on dopaminergic function assessed using nuclear-medicine imaging (PET/SPECT). Included are 39 studies on 655 cocaine, amphetamine, methamphetamine or nicotine users, as well as 690 healthy controls. Metaanalyses were conducted separately for D2/D3 receptors and dopamine transporters of the entire striatum, its subregions caudate and putamen respectively. RESULTS: Meta-analyses results regarding nicotine did not show significant effects between smokers and nonsmokers. In cocaine users there was a significant decrease in dopamine receptor availability in all regions. The striatal DAT availability was significantly increased in cocaine users. Methamphetamine users showed a significantly decreased dopamine receptor and transporter density in all regions. Significant results also indicate a lower transporter availability in all regions. Amphetamine users showed reduced DAT availability in the striatum, as well as in the sub regions. CONCLUSION: This meta-analysis provides evidence that there are ongoing changes in the dopaminergic system associated with the use of stimulants. Especially the results of cocaine, methamphetamine and amphetamine use mainly showed a downregulation. In addition, this meta-analysis is the first to include nicotine. This subset of studies showed evidence for a decreased receptor and DAT availability but no significant results were found in the metaanalyses.

Effects of sedative drug use on the dopamine system: a systematic review and meta-analysis of in vivo neuroimaging studies.

Use of alcohol, cannabis and opioids is highly prevalent and is associated with global disease burden and high economic costs. The exact pathophysiology of abuse or addiction associated with these sedative substances is not completely understood, but previous research implicates the important role of the striatal dopamine system in the addiction process. Multiple studies investigated changes in the striatal dopamine systems of users of sedative substances, but currently these results are very heterogeneous. Therefore, we conducted a meta-analysis of in vivo neuroimaging studies investigating dopaminergic alterations in the striatum of users of alcohol, opioids or cannabis. Analyses for each substance were conducted separately for the availability of D2/D3 dopamine receptors, dopamine transporters and dopamine synthesis capacity. In total, 723 substance users and 752 healthy controls were included. The results indicated a significant lower striatal D2/D3 receptor availability in alcohol users compared to controls (g = 0.46) but no difference in dopamine transporter availability or dopamine synthesis capacity. Our analysis indicated that changes of dopamine receptors and transporters are moderated by the duration of abstinence. Comparing opioid users with controls revealed a significant lower D2/D3 receptor availability (g = 1.17) and a significantly lower transporter availability (g = 1.55) in opioid users. For cannabis users, there was no significant difference in receptor availability compared to controls and too few studies provided information on dopamine transporter availability or synthesis capacity. Our analysis provides strong evidence for a central role of the striatal dopamine system in use of alcohol or opioids. Further studies are needed to clarify the impact of the dopamine system in cannabis users.

Cognitive Deficits in Methamphetamine Users: How Strong is The Evidence?

Methamphetamine use has spread in many European countries and the United States. The current review provides a summary and critical analysis of research on cognitive deficits associated with methamphetamine, also known as "crystal meth." The literature search performed for this review led us to the hypothesis that methamphetamine use is associated with persistent changes in brain metabolism that result in various impairments, such as deficits in memory, attention, and concentration. The dopaminergic system in particular seems to be affected. Some studies indicate that cognitive impairments may improve when users become abstinent, but results of other studies are conflicting. This review discusses these findings and the consequences for the development of a specific addiction treatment for methamphetamine.

[Prevalence and Therapy of Crystal Methamphetamine Dependence]. / Prävalenz und Therapie bei Abhängigkeit von Methamphetamin ("Crystal").

Following a short overview on the epidemiology and clinical correlates of amphetamine abuse and dependence, with special emphasis on metamphetamine ("crystal"), current treatment concepts and recent results of therapy research are discussed. The efficacy of two inpatient treatment models for methamphetamine dependence are currently studied in a study funded by the German Ministry of health. The study concept is given and possible implications are discussed.

Modulation of Craving Related Brain Responses Using Real-Time fMRI in Patients with Alcohol Use Disorder.

LITERATURE: One prominent symptom in addiction disorders is the strong desire to consume a particular substance or to display a certain behaviour (craving). Especially the strong association between craving and the probability of relapse emphasises the importance of craving in the therapeutic process. Neuroimaging studies have shown that craving is associated with increased responses, predominantly in fronto-striatal areas. AIM AND METHODS: The aim of the present study is the modification of craving-related neuronal responses in patients with alcohol addiction using fMRI real-time neurofeedback. For that purpose, patients with alcohol use disorder and healthy controls participated once in neurofeedback training; during the sessions neuronal activity within an individualized cortical region of interest (ROI) (anterior cingulate cortex, insula, dorsolateral prefrontal cortex) was evaluated. In addition, variations regarding the connectivity between brain regions were assessed in the resting state. RESULTS AND DISCUSSION: The results showed a significant reduction of neuronal activity in patients at the end of the training compared to the beginning, especially in the anterior cingulate cortex, the insula, the inferior temporal gyrus and the medial frontal gyrus. Furthermore, the results show that patients were able to regulate their neuronal activities in the ROI, whereas healthy subjects achieved no significant reduction. However, there was a wide variability regarding the effects of the training within the group of patients. After the neurofeedback-sessions, individual craving was slightly reduced compared to baseline. The results demonstrate that it seems feasible for patients with alcohol dependency to reduce their neuronal activity using rtfMRI neurofeedback. In addition, there is some evidence that craving can be influenced with the help of this technique. FUTURE PROSPECTS: In future, real-time fMRI might be a complementary neurophysiological-based strategy for the psychotherapy of patients with psychiatric or psychosomatic diseases. For that purpose, the stability of this effect and the generalizability needs to be assessed.

Alcohol-Dependent Subjects Show Different Personality Traits Compared With Subjects With Multiple Substance Dependence: Preliminary Data.

METHODS: We compared personality traits of 27 persons with multiple substance dependence with personality data of 52 alcohol-dependent persons regarding their personality traits and disorders (obtained by using SCID-II, TCI and NEO FFI). Both patient groups were free of any other mental disorder. RESULTS: In SKD-II, we found significant differences in the male group in dependent and scizotypic personality disorder. There were no significant differences in the female group, but sample was very small. We also found significant differences between alcohol-dependent and multiple substance-dependent persons in extraversion and novelty seeking. CONCLUSIONS: We detected significant differences in personality disorders evaluated by SCID-II. Temperament and character items­as evaluated by NEO FFI and TCI­showed also significant differences in personality traits. Given the limited number of subjects, the data should be regarded as preliminary until replicated in a larger sample. Nevertheless, the findings may be of clinical relevance with respect to prognosis or individualized treatment. These findings should be treated with caution until replicated.

Val158Met COMT polymorphism and risk of aggression in alcohol dependence.

Aggression, violence and antisocial behavior are common in alcoholism, but their biological basis is poorly understood. Several studies and recent meta-analyses indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT) Val158Met genotype may be associated with aggression, most often in methionine allele carriers. We tested this hypothesis in a sample of treatment-seeking alcohol-dependent in-patients (293 German patients and 499 controls, and additional 190 Polish patients as replication sample). As expected, patients with a history of violent or non-violent crime were more often male, had an earlier onset of alcoholism and more withdrawal seizures and delirium tremens, and were more likely to have a history of suicide attempts. COMT genotype was not associated with a history of violent or non-violent crime. More studies are needed on the neurobiological basis of aggression and violence in alcoholism.

Low level of harm avoidance is associated with serotonin transporter functional haplotype in alcohol-dependent individuals.

BACKGROUND: The serotonin transporter gene (SLC6A4) encodes a trans-membrane protein (5-HTT) that plays an important role in regulating serotonergic neurotransmission, which is known to be involved in many psychiatric disorders. A polymorphism in the transcriptional control region containing long (L) and short (S) variants (5-HTTLPR) as well as alleles of the variable number tandem repeats (VNTR) region were demonstrated. Higher serotonin levels among carriers of the S allele might exhibit increased liability of serotonin-mediated, psychopathology-like anxiety and depression and may impair social skills reflected by harm avoidance. OBJECTIVE: To analyze the data of alcohol-dependent, unrelated German individuals for a significant association between serotonin transporter gene and history of depression as well as TCI scales. METHODS: We characterized 368 alcohol-dependent participants by TCI and SSAGA/history of depression. HHT and VNTR genes were amplified by polymerase chain reaction. MAIN RESULTS: No significant association was found between history of depression and 5-HTTLPR (F=0.42, P=0.65, d.f.=2) as well as between history of depression and VNTR (F=0.24, P=0.91, d.f.=2). As harm avoidance is often associated with history of depression, the TCI was used. Regarding the TCI temperament and character scale scores, no significant association was found between harm avoidance and this genetic variant 5-HTTLPR (F=0.55, P=0.57, d.f.=2), and between harm avoidance and VNTR (F=0.39, P=0.81, d.f.=2). Haplotype analysis showed significant relationship between low level of harm avoidance and haplotype S/12 (chi=7.01, P=0.00). Haplotype analysis of history of depression (chi=2.04, P=0.742) showed no significant result. CONCLUSION: Our results indicate an association between S/12 haplotype of SLC6A4 and low level of harm avoidance.