The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Neurofunctional alterations of cognitive down-regulation of craving in quitting motivated smokers.

OBJECTIVE: Cognitive down-regulation of craving involves a neural network within the prefrontal cortex. Tobacco use disorder (TUD) and trait impulsivity have been associated with prefrontal cortex impairments and down-regulation deficits. However, general deficits in down-regulation of craving (regarding non-drug-related cues) compared to never-smokers (NS), differential alterations between drug-related and non-drug-related cues, as well as its links to subject characteristics (smoking severity, trait impulsivity) have so far sparsely been investigated in TUD. METHOD: In this study, 78 subjects (37 TUD & 42 NS) underwent functional magnetic resonance imaging while performing a down-regulation of craving task. Two reward cue-types were presented (drug cues and alternative rewards). Subjects applied down-regulation of craving during a LATER condition and up-regulated their craving during a NOW condition. Subjective craving ratings were assessed after each trial. To evaluate down-regulation of craving, we investigated the LATER versus NOW condition. RESULTS: TUD subjects showed no differences in down-regulation on a behavioral level, neither compared to NS nor between the two reward cue-types. On a neurofunctional level, we found a stronger BOLD response in the middle temporal gyrus in TUD subjects compared to NS in the alternative reward condition. No differences between the two reward cue-types were found within TUD subjects. During down-regulation across both reward cue-types, we identified significant negative associations between activation of control areas and smoking severity. CONCLUSIONS: Results neither indicate evidence for the expected general alterations in down-regulation of craving in TUD, compared to NS, nor specific alterations between drug-related and alternative reward cues on a neurofunctional level. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Evidence for a hijacked brain reward system but no desensitized threat system in quitting-motivated smokers: An fMRI study.

BACKGROUND AND AIMS: Several aspects of how quitting-motivated tobacco use disorder (TUD) subjects and never-smokers differ in terms of reward and threat processing remain unresolved. We aimed to examine aberrant reward and threat processes in TUD and the association with smoking characteristics. DESIGN: A between- and within-subjects functional magnetic resonance imaging (fMRI) experiment with a 2 (groups) × 4 (stimulus type) factorial design. The experimental paradigm had four conditions: pictures of (1) cigarettes served as drug-related-positive cues, (2) food as alternative reward cues, (3) long-term consequences of smoking as drug-related-negative cues and (4) neutral pictures as control. SETTING/PARTICIPANTS: Adult participants (n = 38 TUD subjects and n = 42 never-smokers) were recruited in Berlin, Germany. MEASUREMENTS: As contrasts of primary interest, the interactions of group × stimulus-type were assessed. Significance threshold correction for multiple testing was carried out with the family-wise error method. Correlation analyses were used to test the association with smoking characteristics. FINDINGS: The 2 × 2 interaction of smoking status and stimulus type revealed activations in the brain reward system to drug-related-positive cues in TUD subjects (between-subjects effect: P-values ≤ 0.036). As a response to drug-related-negative cues, TUD subjects showed no reduced activation of the aversive brain network. Within the TUD group, a significant negative association was found between response of the aversive brain system to drug-related-negative cues (within-subjects effect: P-values ≤ 0.021) and the number of cigarettes smoked per day (right insula r = -0.386, P = 0.024; left insula r = -0.351, P = 0.042; right ACC r = -0.359, P = 0.037). CONCLUSIONS: Moderate smokers with tobacco use disorder appear to have altered brain reward processing of drug-related-positive (but not negative) cues compared with never smokers.

Aversive drug cues reduce cigarette craving and increase prefrontal cortex activation during processing of cigarette cues in quitting motivated smokers.

Aversive drug cues can be used to support smoking cessation and create awareness of negative health consequences of smoking. Better understanding of the effects of aversive drug cues on craving and the processing of appetitive drug cues in abstinence motivated smokers is important to further improve their use in cessation therapy and smoking-related public health measures. In this study, 38 quitting motivated smokers underwent functional magnetic resonance imaging (fMRI) scanning while performing a novel extended cue-reactivity paradigm. Pictures of cigarettes served as appetitive drug cues, which were preceded by either aversive drug cues (e.g., smokers' leg) or other cues (neutral or alternative reward cues). Participants were instructed to rate their craving for cigarettes after presentation of drug cues. When aversive drug cues preceded the presentation of appetitive drug cues, behavioural craving was reduced and activations in prefrontal (dorsolateral prefrontal cortex) and paralimbic (dorsal anterior cingulate cortex [dACC] and anterior insulae) areas were enhanced. A positive association between behavioural craving reduction and neurofunctional activation changes was shown for the right dACC. Our results suggest that aversive drug cues have an impact on the processing of appetitive drug cues, both on a neurofunctional and a behavioural level. A proposed model states that aversive drug-related cues activate control-associated brain areas (e.g., dACC), leading to increased inhibitory control on reward-associated brain areas (e.g., putamen) and a reduction in subjective cravings.

Brain-derived neurotrophic factor, depressive symptoms and somatic comorbidity in patients with coronary heart disease.

OBJECTIVE: Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF). METHODS: The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment. RESULTS: Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS. CONCLUSION: Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.

Association between heart-focused anxiety, depressive symptoms, health behaviors and healthcare utilization in patients with coronary heart disease.

OBJECTIVE: To analyze the association between heart-focused anxiety, depressive symptoms, health behaviors and healthcare utilization in patients with coronary heart disease (CHD). METHODS: N = 1007 patients with CHD were recruited in hospital and followed for one year in a two-site cohort study. Heart focused anxiety (Cardiac Anxiety Questionnaire [CAQ] with the three subscales fear, attention, and avoidance), depressive symptoms (depression module from the Patient Health Questionnaire [PHQ-9]), health behaviors and healthcare utilization (smoking status, alcohol consumption, physical activity, outpatient physician/psychotherapist visits) were assessed six months after the initial hospitalization. Multiple regression models were used for statistical analysis. RESULTS: About one third of the sample exhibited clinically significant CAQ scores. Higher CAQ-avoidance scores were associated with current smoking (OR = 1.62; 95%CI: 1.33-1.98), reduced alcohol intake (OR = 0.83; 95%CI: 0.71-0.98), non-participation in a coronary exercise group (OR = 1.76; 95%CI: 1.42-2.17), less regular physical activity (OR = 2.69; 95%CI: 2.32-3.12), and more frequent contact to general practitioners (GPs; b = 0.07, SE: 0.03). CAQ-attention was associated with non-smoking (OR = 0.51; 95%CI: 0.37-0.70), exercise group participation (OR = 0.69; 95%CI: 0.51-0.94), more frequent regular physical activity (OR = 0.55; 95%CI: 0.44-0.68), and more frequent contact to specialists for internal medicine (b = 0.09, SE: 0.04). CAQ-fear was not associated with any of the health behavior or healthcare use measures. Depressive symptoms were associated with reduced regular physical activity (OR = 1.05; 95%CI: 1.02-1.08) and increased contact to mental care specialists (b = 0.03, SE: 0.01) and GPs (b = 0.02, SE: 0.01). CONCLUSIONS: Heart-focused anxiety and depressive symptoms may impede secondary prevention in patients with CHD and increase outpatient healthcare utilization.

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)-From trajectories to mechanisms and interventions.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

'Higher education' - substance use among Berlin college students.

Berlin is internationally known for its intense nightlife associated with high rates of psychoactive substance use. Previous studies conducted in other cities indicated college students as a group at high risk for substance (mis-)use that was associated with individual psychological and cognitive impairments as well as lower academic performance. The aim of this study was to provide detailed data about the substance use patterns of Berlin college students. In addition, major protective and risk factors were analysed. An online questionnaire assessing sociodemographic data and various relevant aspects of both legal and illegal substance use such as consumption pattern and frequency as well as risk-taking behaviour was developed and distributed among colleges in Berlin. A sample of 9351 participants from 17 different colleges in Berlin completed the questionnaire. The study revealed high lifetime (69.3%), past year (45.9%) and past month (28.3%) prevalence of illicit substance use in the sample. Daily tobacco-smoking, a mental disorder diagnosis, a positive screening for problematic consumption (Cage-AID), bisexual orientation and living in open relationship were main factors positively associated with the prevalence and the extent of illicit substance use. Students in Berlin appear to show higher rates of illicit substance use than was previously reported for age-matched individuals in the general German population and college students in other cities. Thus, they are a relevant target group for early prevention and intervention concerning substance use and abuse.

[Diagnostic Accuracy of German Depression Screenings in Patients with Coronary Heart Disease]. / Erkennungsgüte dreier deutschsprachiger Screeninginstrumente für Depression bei hospitalisierten Patienten mit koronarer Herzerkrankung.

OBJECTIVE: To compare the diagnostic accuracy of German depression screening instruments in patients with coronary heart disease (CHD). METHODS: 1019 CHD patients completed the Patient Health Questionnaire (PHQ-9 and PHQ-2) and the Hospital Anxiety and Depression Scale (HADS-D). The Composite International Diagnostic Interview served as reference standard for "any depressive disorder" and "major depression". RESULTS: The accuracy of the PHQ-9 and the HADS-D was comparable according to the area under the curve, and both were superior to the PHQ-2. The optimal cut-off according to the Youden index (maximum sum of sensitivity and specificity) was 7 for both instruments. At this optimal cut-off, the PHQ-9 had a higher sensitivity compared to the HADS-D, but a lower specificity (below 68). Results remained similar when patients who reported that they currently underwent treatment for depression were excluded. CONCLUSION: The PHQ-9 and the HADS-D have comparable overall diagnostic accuracy in CHD patients. In line with previous screening studies with CHD patients, the optimal cut-offs were below the cut-offs that are recommended in the literature.

Increasing physical activity and healthy diet in outpatients with mental disorders: a randomized-controlled evaluation of two psychological interventions.

INTRODUCTION: While physical activity (PA) can play an important role in the treatment of mental disorders (MD), large proportions of patients with MD do not meet PA recommendations. The aim of this trial was to evaluate whether structured psychological intervention (MoVo-LISA) is effective in helping outpatients with MD to increase their level of PA. As active control group (CG) we modified MoVo-LISA to target healthy diet behavior. METHODS: N = 83 outpatients with MD (F1-F4) were randomized to the two conditions. PA (self-report and accelerometry), dietary behavior, social-cognitive determinants of health behavior change, psychiatric symptoms and health-related quality of life were assessed at baseline, 1 and 12 weeks after the intervention. RESULTS: Significant time*group interaction effects for objectively measured PA, dietary behavior and fruit and vegetable consumption indicated differential effects of the interventions on these outcomes. PA increased in the MoVo-LISA group (IG) from baseline to follow-up while it decreased in CG. IG showed a significant higher level of objectively measured PA at follow-up compared to CG. Dietary behavior and fruit and vegetable consumption significantly increased from baseline to follow-up in CG, but not IG. IG showed a significant increase in some, but not all social cognitive determinants of health behavior change. CONCLUSIONS: MoVo-LISA is effective in helping outpatients with MD to increase their level of PA in short- and mid-term. The used intervention strategies are effective for the promotion of healthy diet in patients with MD as well.

Serum brain-derived neurotrophic factor and stability of depressive symptoms in coronary heart disease patients: A prospective study.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) supports neurogenesis, angiogenesis, and promotes the survival of various cell types in the brain and the coronary system. Moreover, BDNF is associated with both coronary heart disease (CHD) and depression. The current study aims to investigate whether serum BDNF levels are associated with the course of depressive symptoms in CHD patients. METHODS: At baseline, N=225 CHD patients were enrolled while hospitalized. Of these, N=190 (84%) could be followed up 6 months later. Depressive symptoms were assessed both at baseline and at the 6-months follow-up using the Patient Health Questionnaire (PHQ-9). Serum BDNF concentrations were measured using fluorometric Enzyme-linked immunosorbent assays (ELISA). RESULTS: Logistic regression models showed that lower BDNF levels were associated with persistent depressive symptoms, even after adjustment for age, sex, smoking and potential medical confounders. The incidence of depressive symptoms was not related to lower BDNF levels. However, somatic comorbidity (as measured by the Charlson Comorbidity Index) was significantly associated with the incidence of depressive symptoms. CONCLUSIONS: Our findings suggest a role of BDNF in the link between CHD and depressive symptoms. Particularly, low serum BDNF levels could be considered as a valuable biomarker for the persistence of depressive symptoms among depressed CHD patients.

Affective responses across psychiatric disorders-A dimensional approach.

Studying psychiatric disorders across nosological boundaries aims at a better understanding of mental disorders by identifying comprehensive signatures of core symptoms. Here, we studied neurobiological correlates of emotion processing in several major psychiatric disorders. We assessed differences between diagnostic groups, and investigated whether there is a psychopathological correlate of emotion processing that transcends disorder categories. 135 patient with psychiatric disorders (alcohol dependence, n=29; schizophrenia, n=37; major depressive disorder (MDD), n=25; acute manic episode of bipolar disorder, n=12; panic disorder, n=12, attention deficit/hyperactivity disorder (ADHD), n=20) and healthy controls (n=40) underwent an functional magnetic resonance imaging (fMRI) experiment with affectively positive, aversive and neutral pictures from the International Affective Picture System (IAPS). Between-group differences were assessed with full-factorial ANOVAs, with age, gender and smoking habits as covariates. Self-ratings of depressed mood and anxiety were correlated with activation clusters showing significant stimulus-evoked fMRI activation. Furthermore, we examined functional connectivity with the amygdala as seed region during the processing of aversive pictures. During the presentation of pleasant stimuli, we observed across all subjects significant activation of the ventromedial prefrontal cortex (vmPFC), bilateral middle temporal gyrus and right precuneus, while a significant activation of the left amygdala and the bilateral middle temporal gyrus was found during the presentation of aversive stimuli. We did neither find any significant interaction with diagnostic group, nor any correlation with depression and anxiety scores at the activated clusters or with amygdala connectivity. Positive and aversive IAPS-stimuli were consistently processed in limbic and prefrontal brain areas, irrespective of diagnostic category. A dimensional correlate of these neural activation patterns was not found.

From mother to child: orbitofrontal cortex gyrification and changes of drinking behaviour during adolescence.

Adolescence is a common time for initiation of alcohol use and alcohol use disorders. Importantly, the neuro-anatomical foundation for later alcohol-related problems may already manifest pre-natally, particularly due to smoking and alcohol consumption during pregnancy. In this context, cortical gyrification is an interesting marker of neuronal development but has not been investigated as a risk factor for adolescent alcohol use. On magnetic resonance imaging scans of 595 14-year-old adolescents from the IMAGEN sample, we computed whole-brain mean curvature indices to predict change in alcohol-related problems over the following 2 years. Change of alcohol use-related problems was significantly predicted from mean curvature in left orbitofrontal cortex (OFC). Less gyrification of OFC was associated with an increase in alcohol use-related problems over the next 2 years. Moreover, lower gyrification in left OFC was related to pre-natal alcohol exposure, whereas maternal smoking during pregnancy had no effect. Current alcohol use-related problems of the biological mother had no effect on offsprings' OFC gyrification or drinking behaviour. The data support the idea that alcohol consumption during pregnancy mediates the development of neuro-anatomical phenotypes, which in turn constitute a risk factor for increasing problems due to alcohol consumption in a vulnerable stage of life. Maternal smoking during pregnancy or current maternal alcohol/nicotine consumption had no significant effect. The OFC mediates behaviours known to be disturbed in addiction, namely impulse control and reward processing. The results stress the importance of pre-natal alcohol exposure for later increases in alcohol use-related problems, mediated by structural brain characteristics.

Neuropsychosocial profiles of current and future adolescent alcohol misusers.

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

Gender-specific association of variants in the AKR1C1 gene with dimensional anxiety in patients with panic disorder: additional evidence for the importance of neurosteroids in anxiety?

BACKGROUND: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders. METHODS: We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115). RESULTS: Case-control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female-specific effect of the associations of both SNPs. CONCLUSIONS: These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender-specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results.

Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.

IMPORTANCE: Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offspring's brain response during reward processing. OBJECTIVE: To determine whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward. DESIGN: An observational case-control study. SETTING: Data were obtained from the IMAGEN Study, a European multicenter study of impulsivity, reinforcement sensitivity, and emotional reactivity in adolescents. The IMAGEN sample consists of 2078 healthy adolescents (age range, 13-15 years) recruited from March 1, 2008, through December 31, 2011, in local schools. PARTICIPANTS: We assessed an IMAGEN subsample of 177 adolescents with prenatal exposure to maternal cigarette smoking and 177 nonexposed peers (age range, 13-15 years) matched by sex, maternal educational level, and imaging site. MAIN OUTCOME AND MEASURE: Response to reward in the ventral striatum measured with functional magnetic resonance imaging. RESULTS: In prenatally exposed adolescents, we observed a weaker response in the ventral striatum during reward anticipation (left side, F = 14.98 [P < .001]; right side, F = 15.95 [P < .001]) compared with their nonexposed peers. No differences were found regarding the responsivity of the ventral striatum to the receipt of a reward (left side, F = 0.21 [P = .65]; right side, F = 0.47 [P = .49]). CONCLUSIONS: The weaker responsivity of the ventral striatum to reward anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive measures to reduce smoking during pregnancy. Future analyses should assess whether prenatally exposed adolescents develop an increased risk for substance use and addiction and which role the reported neuronal differences during reward anticipation plays in this development.

Exercise and physical activity in mental disorders: clinical and experimental evidence.

Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

Exercise and physical activity in the therapy of substance use disorders.

Exercise and physical activity are constantly gaining attention as adjuvant treatment for substance use disorders, supplementing classical pharmacological and psychotherapeutic approaches. The present work reviews studies addressing the therapeutic effects of exercise in alcohol abuse/dependence, nicotine abuse/dependence, and illicit drug abuse/dependence. In the field of smoking cessation, evidence is strong for exercise as an effective adjuvant treatment, whereas no generalizable and methodologically strong studies have been published for alcohol and drug treatment so far, allowing only preliminary conclusions about the effectiveness of exercise in these disorders. A couple of potential mechanisms are discussed, by which exercise may act as an effective treatment, as well as future directions for studies investigating exercise as a treatment strategy for substance use disorders.

Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram.

Major Depressive Disorder (MDD) involves deficits in the reward system. While neuroimaging studies have focused on affective stimulus processing, few investigations have directly addressed deficits in the anticipation of incentives. We examined neural responses during gain and loss anticipation in patients with MDD before and after treatment with a selective serotonin reuptake inhibitor (SSRI). Fifteen adults with MDD and 15 healthy participants, matched for age, verbal IQ and smoking habits, were investigated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay task. Patients were scanned drug-free and after 6 weeks of open-label treatment with escitalopram; controls were scanned twice at corresponding time points. We compared the blood oxygenation level dependent (BOLD) response during the anticipation of gain and loss with a neutral condition. A repeated measures ANOVA was calculated to identify effects of group (MDD vs. controls), time (first vs. second scan) and group-by-time interaction. Severity of depression was measured with the Hamilton Rating Scale of Depression and the Beck Depression Inventory. MDD patients showed significantly less ventral striatal activation during anticipation of gain and loss compared with controls before, but not after, treatment. There was a significant group-by-time interaction during anticipation of loss in the left ventral striatum due to a signal increase in patients after treatment. Ventral striatal hyporesponsiveness was associated with the severity of depression and in particular anhedonic symptoms. These findings suggest that MDD patients show ventral striatal hyporesponsiveness during incentive cue processing, which normalizes after successful treatment.