Associations between disturbed sleep and attenuated psychotic experiences in people at clinical high risk for psychosis.

BACKGROUND: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. METHODS: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. RESULTS: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. CONCLUSION: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

Prediction of transition to psychosis in patients with a clinical high risk for psychosis: a systematic review of methodology and reporting.

BACKGROUND: To enhance indicated prevention in patients with a clinical high risk (CHR) for psychosis, recent research efforts have been increasingly directed towards estimating the risk of developing psychosis on an individual level using multivariable clinical prediction models. The aim of this study was to systematically review the methodological quality and reporting of studies developing or validating such models. METHOD: A systematic literature search was carried out (up to 14 March 2016) to find all studies that developed or validated a clinical prediction model predicting the transition to psychosis in CHR patients. Data were extracted using a comprehensive item list which was based on current methodological recommendations. RESULTS: A total of 91 studies met the inclusion criteria. None of the retrieved studies performed a true external validation of an existing model. Only three studies (3.5%) had an event per variable ratio of at least 10, which is the recommended minimum to avoid overfitting. Internal validation was performed in only 14 studies (15%) and seven of these used biased internal validation strategies. Other frequently observed modeling approaches not recommended by methodologists included univariable screening of candidate predictors, stepwise variable selection, categorization of continuous variables, and poor handling and reporting of missing data. CONCLUSIONS: Our systematic review revealed that poor methods and reporting are widespread in prediction of psychosis research. Since most studies relied on small sample sizes, did not perform internal or external cross-validation, and used poor model development strategies, most published models are probably overfitted and their reported predictive accuracy is likely to be overoptimistic.

[The Basel Interview for Psychosis (BIP): structure, reliability and validity]. / Das Basler Interview für Psychosen (BIP): Struktur, Reliabilität und Validität.

BACKGROUND: Although several instruments have been developed to identify patients with an at-risk mental state (ARMS) for psychosis and first episode of psychosis (FEP), up to now there were no instruments for a detailed assessment of risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span in these patients. We therefore developed the Basle Interview for Psychosis (BIP). The aim of this study is to describe the development of the BIP and to report about its psychometric properties. METHODS: The BIP is a comprehensive semi-structured interview that was developed for the Basel early detection of psychoses (FePsy) study. Its items were derived from the most important risk factors and indicators of psychosis described in the literature and from several existing instruments. It contains the following six sections: 1) social and physical development and family, 2) signs and symptoms, 3) vulnerability, 4) help-seeking behavior, 5) illness insight, 6) evaluation of the interview. To estimate the inter-rater reliabilities of the items of sections 2 and 3, 20 interviews were conducted and rated by 8 well-trained raters. The factorial structure of the BIP section "signs and symptoms" was explored in a sample of 120 ARMS and 77 FEP patients. On the basis of the discovered factorial structure, we created new subscales and assessed their reliabilities and validities. RESULTS: Of the 153 studied items of sections 2 and 3, 150 (98 %) were rated with sufficiently high agreement (inter-rater reliability > 0.4). The items of section "signs and symptoms" could be grouped into 5 subscales with predominantly good to very good internal consistencies, homogeneities, and discriminant and convergent validities. Predictive validities could be demonstrated for the subscales "Positive Psychotic Symptoms", "Disturbance of Thinking" and the total score. DISCUSSION: The BIP is the first interview for comprehensively assessing risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span, which has been validated in ARMS and FEP patients. We could show that the BIP has excellent psychometric properties.

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.

BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis.

BACKGROUND: Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs). METHOD: In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500. RESULTS: Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men. CONCLUSIONS: Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.

[Domestic violence against women of a crisis intervention population - forms of violence and risk factors]. / Häusliche Gewalt bei Frauen einer Kriseninterventionspopulation - Formen der Gewalt und Risikofaktoren.

UNLABELLED: BACKGROUND AND HYPOTHESES: Domestic violence is common and can lead to severe physical and psychological problems. Thus, we have investigated the frequency of occurrence, forms and risk factors of domestic violence against female patients on a crisis intervention ward. METHODS: 115 women were screened with the "screening spouse violence" (SPG) and the "index of spouse abuse" (ISA). RESULTS: The life time prevalence concerning spouse violence was 70 %. Out of 74 women who were currently living in a relationship 28 (38 % )were victims of violence in the last 12 months prior to their admission. Women who experienced violence had a significantly lower level of education. CONCLUSION: Screening for domestic violence in female patients in the field of crisis intervention and psychiatry should become a standard of "good clinical practice".

[Prediction of psychosis by stepwise multilevel assessment--the Basel FePsy (Early Recognition of Psychosis)-Project]. / Vorhersage von Psychosen durch stufenweise Mehrebenenabklärung--Das Basler FePsy(Früherkennung von Psychosen)-Projekt.

BACKGROUND: We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Früherkennung von Psychosen, FePsy). METHODS: From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc. RESULTS: Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6%) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81% by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction. CONCLUSIONS: The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre.

Insular volume abnormalities associated with different transition probabilities to psychosis.

BACKGROUND: Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). METHOD: We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. RESULTS: The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. CONCLUSIONS: GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.

[Can cannabis use increase the risk for schizophrenic psychoses?]. / Kann Cannabis das Risiko für schizophrene Psychosen erhöhen?

BACKGROUND: In recent years, cannabis has been increasingly discussed as one of the most important environmental risk factors for developing schizophrenic psychoses. This is mainly due to the following observations. (i) Cannabis at high doses can cause acute transient psychotic symptoms even in healthy individuals. (ii) Patients with schizophrenia abuse cannabis more often than age-matched healthy controls. OBJECTIVES: It is still controversial whether cannabis use can cause schizophrenic psychoses that would not have occurred otherwise. In our review, we have critically evaluated the evidence for a causal link between cannabis use and schizophrenic psychoses. METHODS: A systematic literature review in PubMed, ISI Web of Science and PsycINFO was carried out using the following keywords: cannabis, marijuana, THC, hashish, psychosis, schizophrenia. CONCLUSIONS: We have concluded that although a causal relationship between cannabis use and schizophrenic psychoses cannot be definitely proven, the available evidence strongly supports its plausibility. Furthermore, the results of the review indicate that cannabis might cause psychosis especially in individuals with a predisposition for schizophrenia and in adolescents with an early onset of cannabis use.

[Professional misconduct in therapeutic relationships: developing critical attitudes in the medical community]. / Missbrauch in therapeutischen Beziehungen : Möglichkeiten zur kritischen Positionierung der Ärzteschaft.

Already the Hippocratic Oath defines maintaining boundaries in the physician-patient relationship as an essential part of medical care: "…In every house where I come I will enter only for the good of my patients, keeping myself far from all intentional ill-doing and all seduction and especially from the pleasures of love with women or men, be they free or slaves…". The World Psychiatric Association's Declaration of Madrid 1996 specifically comments on boundary issues of physician-patient relationships in psychiatry. Boundary violations in any kind of therapeutic relationship - not only regarding psychotherapy - are both relevant and tabooed. There are hardly any options for patients concerned to find appropriate therapeutic and legal support. A public positioning of the medical profession seems to be very important. Apart from raising awareness, further important goals are prevention, guidelines for appropriate handling of victims and offenders, as well as integration of the issue in education and public discourse.

[Patients in intensive care after a suicide attempt with legal drugs - risk profile and course]. / Patienten mit Intensivpflichtigen Medikamentösen Suizidversuchen - Risikoprofil und Verlauf.

Little is known about the risk profile and the further history of patients who attempted suicide by severe medicinal intoxication.All patients residing in Basel (n = 190) admitted to the intensive care unit between 01/01/1998 and 12/31/2001 because of a suicide attempt with legal drugs were investigated regarding psychopathology and sociodemographic features. Also, until the end of 2005, further suicide attempts as well as potential cases of death were followed up.All 190 patients had psychiatric disorders. Compared to the general population, female sex, single status, low educational level, unemployment and invalidity were found significantly more often. Until the end of 2005 almost half of 118 patients followed up in our outpatient department committed further suicide attempts. 28 patients died, 6 of these by suicide.These patients should preferably not be prescribed medication with a low therapeutic range and they should receive intensive follow-up care.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

[Depression during pregnancy and its treatment]. / Schwangerschaftsdepression und deren Behandlung.

Approximately 11% of pregnant women suffer from major depression which requires treatment and if left untreated there are risks of preterm delivery or low birth weight. The initial difficulty lies in diagnosing the depression itself, as many symptoms of depression can be ascribed to the pregnancy. A further challenge is choosing the appropriate therapy. Treatment options are psychotherapy, antidepressants, electroconvulsive therapy (ECT) or the new possibility of light therapy. A growing number of reports on the side effects of antidepressants in pregnancy have led to uncertainties as to how to proceed. Thus, choosing the most suitable treatment needs to be made together with the pregnant woman and a careful clarification of possible risks attendant on each treatment option is essential.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

["Self-screen prodrome"--self-rating for the early detection of mental disorders and psychoses]. / "Selbstscreen-Prodrom"--Ein Selbstbeurteilungsinstrument zur Früherkennung von psychischen Erkrankungen und Psychosen.

OBJECTIVE: In the past years, the significance of early detection of psychoses has been increasingly recognized. Screening for the onset of disorders should focus on individuals seeking treatment in an outpatient setting and should preferably operate stepwise. Within a prospective study for the early detection of psychoses (FePsy = Früh Erkennung von PSYchosen) the self-rating instrument "Self-screen Prodrome" was developed to differentiate between healthy individuals, individuals with psychosis or an at-risk mental state for psychosis and patients with other ICD-10 diagnoses. METHOD: The "Self-screen Prodrome" was developed by taking established risk factors and early signs of disease into account. In particular, prodromes and pre-psychotic symptoms were captured. A total score and a subscale were analyzed with regard to validity and reliability. RESULTS: The total score "Self-screen Prodrome" distinguished between outpatients with a mental disorder and healthy individuals (Cut-off > or = 6; sensitivity: 85 % specificity: 91 %). Additionally the subscale distinguished between psychosis-(risk)-individuals and outpatients with other ICD-10 psychiatric diagnoses (Cut-off > or = 2; sensitivity: 85 % specificity: 39 %). CONCLUSION: The "Self-screen Prodrome" is a useful instrument that a) separates mentally ill patients from healthy individuals and b) filters individuals with a risk of developing psychoses from patients with other ICD-10 diagnoses for further screening. The next step in the early detection of psychoses for identified individuals should be a detailed psychiatric exploration by experts.

NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Impact of polygenic schizophrenia-related risk and hippocampal volumes on the onset of psychosis.

Alterations in hippocampal volume are a known marker for first-episode psychosis (FEP) as well as for the clinical high-risk state. The Polygenic Schizophrenia-related Risk Score (PSRS), derived from a large case-control study, indicates the polygenic predisposition for schizophrenia in our clinical sample. A total of 65 at-risk mental state (ARMS) and FEP patients underwent structural magnetic resonance imaging. We used automatic segmentation of hippocampal volumes using the FSL-FIRST software and an odds-ratio-weighted PSRS based on the publicly available top single-nucleotide polymorphisms from the Psychiatric Genomics Consortium genome-wide association study (GWAS). We observed a negative association between the PSRS and hippocampal volumes (ß=-0.42, P=0.01, 95% confidence interval (CI)=(-0.72 to -0.12)) across FEP and ARMS patients. Moreover, a higher PSRS was significantly associated with a higher probability of an individual being assigned to the FEP group relative to the ARMS group (ß=0.64, P=0.03, 95% CI=(0.08-1.29)). These findings provide evidence that a subset of schizophrenia risk variants is negatively associated with hippocampal volumes, and higher values of this PSRS are significantly associated with FEP compared with the ARMS. This implies that FEP patients have a higher genetic risk for schizophrenia than the total cohort of ARMS patients. The identification of associations between genetic risk variants and structural brain alterations will increase our understanding of the neurobiology underlying the transition to psychosis.

Sex differences in cognitive functioning in at-risk mental state for psychosis, first episode psychosis and healthy control subjects.

BACKGROUND: Several sex differences in schizophrenia have been reported including differences in cognitive functioning. Studies with schizophrenia patients and healthy controls (HC) indicate that the sex advantage for women in verbal domains is also present in schizophrenia patients. However, findings have been inconsistent. No study focused on sex-related cognitive performance differences in at-risk mental state for psychosis (ARMS) individuals yet. Thus, the aim of the present study was to investigate sex differences in cognitive functioning in ARMS, first episode psychosis (FEP) and HC subjects. We expected a better verbal learning and memory performance of women in all groups. METHODS: The neuropsychological data analysed in this study were collected within the prospective Früherkennung von Psychosen (FePsy) study. In total, 118 ARMS, 88 FEP individuals and 86 HC completed a cognitive test battery covering the domains of executive functions, attention, working memory, verbal learning and memory, IQ and speed of processing. RESULTS: Women performed better in verbal learning and memory regardless of diagnostic group. By contrast, men as compared to women showed a shorter reaction time during the working memory task across all groups. CONCLUSION: The results provide evidence that women generally perform better in verbal learning and memory, independent of diagnostic group (ARMS, FEP, HC). The finding of a shorter reaction time for men in the working memory task could indicate that men have a superior working memory performance since they responded faster during the target trials, while maintaining a comparable overall working memory performance level.

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.