[Psychiatric Patients in Obstetrics in Germany - The Legal Basis and a Thematic Analysis of Case Reports]. / Psychiatrische Patientinnen in der Geburtsmedizin in Deutschland ­ die juristischen Grundlagen und eine thematische Analyse von Fallbeispielen.

The care of adult patients with particularly severe psychiatric illnesses in the daily routine of inpatient obstetrics is rare, but due to its complexity it represents a great challenge for all professions involved. The clinical pictures are very variable. There are a number of interlocking responsibilities in the provision of care. For planning of the birth, the medical-professional cooperation of psychiatry, obstetrics and pediatrics is necessary. Patients are often represented by legal guardians. The Youth Welfare Office is responsible for the welfare of the family and the children. The legal basis is essentially provided by the Civil Code, the Criminal Code and specific state laws, compliance with which is monitored by the courts. Typical psychiatric clinical pictures are presented by means of case reports. Legally defined applications such as accommodation, measures similar to deprivation of liberty, compulsory medical measures and justifiable necessity are explained. In the sense of a thematic analysis, these are applied to the case reports and peripartum management is discussed against the legal background. The precise knowledge of the legal background makes it easier for obstetricians to follow the procedures and interdisciplinary cooperation, especially at perinatalogical centres.

Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.

How do we 'learn' addiction? Risk factors and mechanisms getting addicted to alcohol.

BACKGROUND: Alcohol dependence is one of the leading contributors to the burden of disease in the world. A range of genetic and environmental risk factors has been identified to date, and preclinical and clinical studies including imaging studies have identified neuronal networks involved in the development of alcohol dependence. METHODS: We review genetic and environmental risk factors for the development of alcohol addiction as well as structural and neuronal changes, including their transmitter systems, due to regular alcohol intake. RESULTS: Stress as well as family background and, in juveniles, the peer group could be identified as environmental risk factors for alcohol dependence. Heritability is estimated at around 50%, and it seems to be comparable in women and men. There is ongoing research on a broad range of putative endophenotypes such as tolerance of the effects of alcohol intake or personal traits like 'impulsivity'. On the neurobiological level, chronic alcohol intake seems to render mesolimbic circuits hypersensitive to alcohol and alter the motivational reward system including dopaminergic neurotransmission. CONCLUSION: Environmental and genetic risk factors, and especially their interaction, facilitate the development of alcohol dependence. Ongoing alcohol intake results in profound alterations of neuronal systems crucial for motivation, learning, memory and cognition control. Future studies should further combine the knowledge of neurobiological mechanisms and risk factors to develop new prevention strategies.

Model-based and model-free decisions in alcohol dependence.

BACKGROUND: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. METHODS: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. RESULTS: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. CONCLUSION: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.

Altered representation of expected value in the orbitofrontal cortex in mania.

OBJECTIVE: Increased responsiveness to appetitive and reduced responsiveness to aversive anticipatory cues may be associated with dysfunction of the brain reward system in mania. Here we studied neural correlates of gain and loss expectation in mania using functional magnetic resonance imaging (fMRI). METHOD: Fifteen manic patients and 26 matched healthy control individuals performed a monetary incentive delay task, during which subjects anticipated to win or lose a varying amount of money. Varying both magnitude and valence (win, loss) of anticipatory cues allowed us to isolate the effects of magnitude, valence and expected value (magnitude-by-valence interaction). RESULTS: Response times and total gain amount did not differ significantly between groups. FMRI data indicated that the ventral striatum responded according to cued incentive magnitude in both groups, and this effect did not significantly differ between groups. However, a significant group difference was observed for expected value representation in the left lateral orbitofrontal cortex (OFC; BA 11 and 47). In this region, patients showed increasing BOLD responses during expectation of increasing gain and decreasing responses during expectation of increasing loss, while healthy subjects tended to show the inverse effect. In seven patients retested after remission OFC responses adapted to the response pattern of healthy controls. CONCLUSIONS: The observed alterations are consistent with a state-related affective processing bias during the expectation of gains and losses which may contribute to clinical features of mania, such as the enhanced motivation for seeking rewards and the underestimation of risks and potential punishments.

A preliminary study of increased amygdala activation to positive affective stimuli in mania.

OBJECTIVES: The present study in hypomanic and manic patients explored how amygdala responses to affective stimuli depend on the valence of the stimuli presented. METHODS: We compared 10 patients with 10 matched healthy control subjects. We measured blood oxygen level-dependent (BOLD) responses in the amygdala while subjects passively viewed photographs taken from the International Affective Picture System. After the fMRI session, subjects saw the pictures again and subjectively rated the emotional valence and intensity of each picture. RESULTS: Compared to healthy individuals, hypomanic or manic patients showed higher valence ratings in positive pictures and associated larger BOLD responses in the left amygdala during positive versus neutral picture viewing. This enhanced amygdala activation was correlated with Young Mania Rating Scale scores and with euphoric as opposed to irritable symptom presentation. CONCLUSIONS: Increased valence ratings and amygdala responses to positive affective stimuli may reflect a positive processing bias contributing to elevated mood states characteristic for euphoric mania.

Reward and loss anticipation in panic disorder: An fMRI study.

Anticipatory anxiety and harm avoidance are essential features of panic disorder (PD) and may involve deficits in the reward system of the brain, in particular in the ventral striatum. While neuroimaging studies on PD have focused on fearful and negative affective stimulus processing, no investigations have directly addressed deficits in reward and loss anticipation. To determine whether the ventral striatum shows abnormal neural activity in PD patients during anticipation of loss or gain, an event-related functional magnetic resonance imaging experiment using a monetary incentive delay task was employed in 10 patients with PD and 10 healthy controls. A repeated-measures ANOVA to identify effects of group (PD vs. Control) and condition (anticipation of loss vs. gain vs. neutral outcome) revealed that patients with PD showed significantly reduced bilateral ventral striatal activation during reward anticipation but increased activity during loss anticipation. Within the patient group, the degree of activation in the ventral striatum during loss-anticipation was positively correlated with harm avoidance and negatively correlated with novelty seeking. These findings suggest that behavioural impairments in panic disorder may be related to abnormal neural processing of motivational cues.

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.

Diagnostic classification of schizophrenia patients on the basis of regional reward-related FMRI signal patterns.

Functional neuroimaging has provided evidence for altered function of mesolimbic circuits implicated in reward processing, first and foremost the ventral striatum, in patients with schizophrenia. While such findings based on significant group differences in brain activations can provide important insights into the pathomechanisms of mental disorders, the use of neuroimaging results from standard univariate statistical analysis for individual diagnosis has proven difficult. In this proof of concept study, we tested whether the predictive accuracy for the diagnostic classification of schizophrenia patients vs. healthy controls could be improved using multivariate pattern analysis (MVPA) of regional functional magnetic resonance imaging (fMRI) activation patterns for the anticipation of monetary reward. With a searchlight MVPA approach using support vector machine classification, we found that the diagnostic category could be predicted from local activation patterns in frontal, temporal, occipital and midbrain regions, with a maximal cluster peak classification accuracy of 93% for the right pallidum. Region-of-interest based MVPA for the ventral striatum achieved a maximal cluster peak accuracy of 88%, whereas the classification accuracy on the basis of standard univariate analysis reached only 75%. Moreover, using support vector regression we could additionally predict the severity of negative symptoms from ventral striatal activation patterns. These results show that MVPA can be used to substantially increase the accuracy of diagnostic classification on the basis of task-related fMRI signal patterns in a regionally specific way.

Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders.

RATIONALE: A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries. OBJECTIVES: We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment. METHODS: We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation. RESULTS: During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation. CONCLUSION: Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.

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.

Attentional modulation of emotional stimulus processing in patients with major depression--alterations in prefrontal cortical regions.

Patients with depression show an impaired ability to modulate emotional states and to process positive emotional information. Here we examined expectancy-induced modulation of emotional picture processing in major depression. We hypothesized alterations in the medial prefrontal cortex. During fMRI, 15 depressed and 21 healthy control subjects passively viewed affective photographs. Half of the pictures were preceded by an expectancy cue signaling whether an emotionally salient or neutral picture would follow. The contrast 'cued versus uncued emotional picture viewing' was used to study modulation of emotional picture processing by preceding attention. Healthy individuals showed enhanced activation in the dorsomedial prefrontal cortex and decreased activation in the dorsolateral prefrontal cortex during cued compared to uncued emotional picture perception. The group comparison revealed that these modulatory effects were significantly attenuated in depressed patients. This attenuation was particularly observed in the positive compared to the negative picture condition and tended to normalize in the dorsomedial prefrontal cortex after remission of symptoms. Altered prefrontal modulation in depression may contribute to impaired affect modulation and related clinical symptoms, such as anhedonia.

Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics.

BACKGROUND: Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects. METHODS: Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10). RESULTS: Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects. CONCLUSIONS: This study suggests that reduced ventral striatal recruitment during anticipation of conventional rewards in alcoholics may be related to their increased impulsivity and indicate possibilities for enhanced treatment approaches in alcohol dependence.

5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls.

RATIONALE: In major depression, prefrontal regulation of limbic brain areas may be a key mechanism that is impaired during the processing of affective information. This prefrontal-limbic interaction has been shown to be modulated by serotonin (5-HTT) genotype, indicating a higher risk for major depressive disorder (MDD) with increasing number of 5-HTT low-expression alleles. OBJECTIVE: Functional magnetic resonance imaging was used to assess neural response to uncued unpleasant affective pictures in 21 unmedicated patients with MDD compared to 21 matched healthy controls, taking into account genetic influences of the 5-HTT (SCL6A4) high- and low-expression genotype. RESULTS: Healthy controls displayed greater prefrontal activation (BA10) to uncued negative pictures compared to patients with MDD. While in healthy controls prefrontal (BA10) activation and BA10-amygdala coupling increased with the number of 5-HTT low-expression risk alleles, this effect was abolished, and even reversed, in patients with MDD. In MDD, connectivity decreased with severity of depressive symptoms (HAMD total score). CONCLUSION: These findings suggest that increased medial prefrontal (BA10) activation and BA10-amygdala connectivity may counteract the risk for MDD in healthy carriers of 5-HTT low-expression alleles, while this protective factor might be lost in patients who actually suffer from MDD. Prefrontal-limbic regulation in risk populations could be a target of early interventions and should be the focus of further research.