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Objectives: Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood. Methods: Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C‐reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3‐hydroxykynurenine (3‐HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow‐up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis. Results: Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor‐α and KYN, KYN/TRP, 3‐HK and QA (ρ > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3‐HK, P =.0004) and a strong association between interferon‐y and kynurenine pathway activation (P <.0001). KYNA was low in both patient groups versus controls throughout the whole follow‐up (P =.0008). Conclusions: Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism. [ABSTRACT FROM AUTHOR]

Background: Child molesters form a heterogeneous group, but one generally shared characteristic is maladaptive, rigid behaviour. Impairments in reinforcement learning may explain these maladaptive tendencies, but this has not been systematically investigated. Further, it is not known if such impairments vary with subtype of child molesters.Aims: To investigate the presence of impairments in reinforcement learning among child molesters and to test for differences in patterns of impairment with subtype.Methods: A group of 59 child molesters was recruited from several prisons in a two-stage screening process, the first using records and the second interview; a comparison group of 33 offenders who had never committed a sex offence and who denied paedophile ideation was similarly recruited; 36 nonoffender comparison men were recruited by social media and word of mouth. Each was asked to perform a probabilistic reversal learning task, in which stimulus-outcome contingencies had to be learned.Results: Child molesters, as a group, made significantly more errors on the probabilistic reversal learning task than the nonoffenders; the comparison offenders and the nonoffenders gained similar scores, although findings may have been confounded by older age in the child molester group. Nonpaedophilic child molesters had significantly worse scores than paedophilic child molesters.Conclusions: Child molesters, especially those not diagnosed with paedophilia, have deficits during both the acquisition and reversal of contingencies, suggesting reinforcement learning deficits that may undermine their capacity to benefit maximally from therapy without preliminary work to repair those deficits, possibly in conjunction with extending the offender programmes. Testing before programme entry would enable accurate targeting of scarce resources in this respect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential role of the Maudsley Staging Method (MSM) in the prediction of electroconvulsive therapy (ECT) outcome in severely depressed adults. Method: Between August 2015 and August 2017, 73 consecutive patients with a major depressive episode (DSM‐IV‐TR) scheduled for ECT were recruited. Prior to their first ECT session, the MSM was completed to assess the level of therapy resistance. To determine the reduction in depression severity and response and remission rates, symptom severity was assessed at baseline and within one week after the last ECT session using the 17‐item Hamilton Depression Rating Scale (HDRS17). Results: The percentage of symptom reduction following ECT was best predicted by the MSM episode duration and depression severity factors (R2 completer sample 0.24). Episode duration alone was the best predictor of remission (area under the ROC curve for completers: 0.72). Adding age to the models increased their predictive capacity. Conclusion: An adapted version of the MSM gauging shorter episode duration, more severe depressive symptoms and older age is significantly associated with ECT effectiveness in adults with severe recurrent depression and is thus highly suitable for use in clinical practice, promoting the shared treatment decision‐making process. [ABSTRACT FROM AUTHOR]

Heterogeneity in borderline personality disorder (BPD) drives the search for BPD subtypes to optimize the assessment and treatment of these patients. Therefore, the aims of the present study were (1) to replicate previously identified BPD subtypes based on reactive and regulative temperament; (2) to compare them on symptomatology and coping; and (3) to investigate whether these subtypes show different treatment responses after 3 months of inpatient dialectical behaviour therapy (DBT). A total of 145 BPD inpatients were assessed by means of measures of temperament, symptomatology and coping. Through model‐based clustering on the Behavioural Inhibition and Behavioural Activation Scales (BISBAS) and Effortful Control Scale (ECS), we identified three BPD subtypes: an Emotional/Disinhibited subtype (15%, high BAS and low ECS); a Low Anxiety subtype (41%, low BIS) and an Inhibited subtype (44%, low BAS). After 3 months of DBT, 75 patients completed the measures for a second time. Repeated measure ANOVAs demonstrated a general improvement on all symptoms and coping strategies. In addition, the BPD subtypes showed trajectory differences in clinical and borderline specific symptomatology and dissociation. These findings indicate that BPD subtypes based on temperament demonstrate different treatment responses, which can contribute to the search of more BPD subtype tailored treatment interventions. © 2018 John Wiley & Sons, Ltd. Highlights: Three BPD subtypes were identified based on reactive and regulative temperament: the Emotional/Disinhibited, Inhibited and Low Anxiety subtype.All BPD patients improved in symptomatology and coping after 3 months of DBT.The three BPD subtypes differed in symptom trajectory after 3 months of DBT.In contrast to the other two subtypes, the Low Anxiety subtype did not show a significant decrease in symptomatology. [ABSTRACT FROM AUTHOR]

Objectives Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal cortex in response to biologically salient stimuli in an emotional face matching task (EFMT). Experimental design Amygdala activity and amygdala connectivity during the EFMT were assessed in 51 cocaine using males and 32 non-drug-using healthy males using functional magnetic resonance imaging (fMRI). Within the cocaine use group, we explored whether amygdala activation was associated with age of first use of cocaine and duration of cocaine use to distinguish between amygdala activation alterations as a cause or a consequence of cocaine use. Principal observations We observed hyperactivity of the amygdala, thalamus, and hippocampus and reduced amygdala connectivity with the anterior cingulate gyrus in response to angry and fearful facial expressions in current cocaine users compared to controls. Increased amygdala activation was independently associated with earlier age of first cocaine use and with longer exposure to cocaine. Conclusions Our findings suggest that amygdala hyperactivity to biologically salient stimuli may represent a risk factor for an early onset of cocaine use and that prolonged cocaine use may further sensitize amygdala activation. High amygdala activation to emotional face processing in current cocaine users may result from low prefrontal control of the amygdala response to such stimuli. Hum Brain Mapp 36:4222-4230, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25 μL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10 μL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1 month at room temperature, 4 °C and −18 °C. Lurasidone was unstable when the extract was stored for 12 h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-μL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Apart from mood episodes, many cognitive deficits are present in bipolar disorder ( BD). Performance monitoring is an important aspect of executive functioning and involves continuous monitoring of behavior and making subsequent changes when an error is made. On a neurophysiological level, the error-related negativity ( ERN), an event-related brain potential ( ERP) generated in the anterior cingulate cortex ( ACC), reflects this process of performance monitoring. Abnormal ERN amplitudes have been observed in many major psychiatric disorders. However, despite conflicting evidence regarding the role of the ACC in BD, no studies to date have investigated performance monitoring as reflected in the ERN in BD. Methods Sixteen patients with BD in a euthymic state and 14 matched healthy controls performed a speeded two-choice reaction-time paradigm (Flankers Task) while electroencephalogram ( EEG) measures were obtained. Behavioral and ERP measurements were analyzed for the two groups. Results The patients with BD, although euthymic, scored higher on depressive symptoms than healthy controls. While no behavioral group differences were found, patients with BD displayed lower ERN amplitudes than healthy controls when controlling for effects of residual mood. Conclusions The lower ERN amplitudes in the BD group reflect reduced performance monitoring and extend current knowledge of executive functioning in BD. Importantly, these findings go a long way to resolving the contradictory results regarding ACC involvement in BD by showing that taking into account residual mood may greatly influence error-related ACC activations and is critically important in understanding cognitive deficits in BD. [ABSTRACT FROM AUTHOR]

Background Differences in clinical characteristics between early and late onset alcohol dependent patients have been examined intensively, but little is known about the differences in neuropsychological functioning between these patient groups. Clinical characteristics and neuropsychological functions of inpatients with early onset and late onset alcohol dependence are therefore investigated in this study. Methods Ninety-three abstinent alcohol dependent inpatients meeting a current diagnosis of DSM- IV alcohol dependence were divided into early onset alcohol dependent patients ( EOA; ≤25 years; n = 36) and late onset alcohol dependent patients (LOA; >25 years; n = 57). Patients using psychoactive medication and patients dependent on other substances than alcohol (and nicotine) were excluded. A comprehensive neuropsychological test battery was administered. Results EOA reported higher trait impulsivity, antisocial traits, and attention deficit hyperactivity disorder-related traits and exhibited an impulsive reflection style, especially in a high-risk context, compared with LOA. Against expectations, EOA performed significantly better on measures of planning, cognitive control, visual memory, and delayed recognition memory than LOA, whereas no significant group differences occurred on measures of delay discounting, digit span, and attention. Better Stroop interference, better visual memory, and a more impulsive reflection style was predictive of an early age of onset, and explained a significant and additional amount of variance (18.8%) on top of the clinical characteristics, together explaining 53.4% of the variance. Conclusions Both clinical characteristics and neuropsychological variables contributed independently to the age of onset of problematic alcohol use. Results indicate that especially an impulsive reflection style, besides higher trait impulsivity, may be the core feature of early onset alcohol dependence. However, the contribution of the neuropsychological variables is complex and more research is needed to clarify the role of psychiatric comorbidity and poly-substance abuse in an unselected sample of alcohol dependent patients. [ABSTRACT FROM AUTHOR]

Background: Autopsy and neuroimaging research in stably abstinent alcoholics illuminated structural and functional abnormalities in brain areas that organize and coordinate motor functioning. Researchers that used behavioural tasks to measure motor functioning found that abstinent alcoholics perform worse than healthy controls. These researchers however did not analyze timed responses into their cognitive and motor components. They thus were unable to decide which aspects of information processing are impaired. We here used a Fitts’ task to examine differences in cognitive and motor components between abstinent alcoholics and healthy controls. Methods: Fifty-two abstinent alcoholics and 52 healthy controls participated in this research design. Fine motor functioning was assessed by means of the Fitts’ task. Results: Abstinent alcoholics needed more time to perform timed responses than healthy controls. As both reaction and movement times were higher in abstinent alcoholics, both cognitive and motor processes seem to be impaired. When the task became more difficult (small targets instead of large targets) abstinent alcoholics needed proportionally more time to give the correct response than healthy controls. This phenomenon solely applied to movement times. Conclusions: These research data indicate that abstinent alcoholics are somewhat impaired on a behavioral level. The execution of timed responses indeed was lengthier in abstinent alcoholics than in healthy controls. As both cognitive and motor processes were impaired, we here assume that both central and peripheral processes are affected by progressive alcohol intake. Abstinent alcoholics also have more difficulties to adapt their motor responses to changing task conditions. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that experiences of trauma and victimization during childhood are associated with an increased risk to develop clinical and subclinical psychosis in adulthood. A recent cross-sectional study showed a significant association between trauma and psychotic experiences in adolescents. The current study aimed to extend these findings by investigating the longitudinal effects of negative life experiences on the risk for subclinical psychotic symptoms 2 years later in an adolescent general community sample. Methods: Data were derived from the standard health screenings of the Youth Health Care Divisions of the Public Health Services, in the South of the Netherlands. A total of 1129 adolescents filled out a self-report questionnaire at age 13/14 years and 2 years later (15/16 years), assessing psychotic experiences, as well as experiences of being bullied, sexual trauma, and negative life events. Results: Logistic regression analyses revealed that sexual trauma increased the risk for psychotic symptoms 2 years later. Life events contributed to the risk for psychosis over time and psychosis in turn gave rise to new life events. No significant association with bullying was found after controlling for confounders. Conclusion: The results provide further evidence for an association between childhood environment and psychosis in the crucial developmental period of early adolescence. Early and later psychological stress, if severe, may impact on the risk for psychosis in adolescence through mechanisms of person–environment interaction and correlation. [ABSTRACT FROM AUTHOR]

Background: Impairments in decision making are a consistent finding in substance use disorder (SUD) populations. However, decision-making deficits are not specific for SUDs and are also reported in the context of other psychiatric disorders such as antisocial and borderline personality disorders (PDs). Given the frequent comorbidity between SUD and cluster B PD, it might be questioned whether the decision-making impairments typically reported in SUD populations reflect the addictive disorder, the cluster B PD, or a combination of the 2. Methods: In the current study, we compare the decision-making performance of non–substance-abusing controls ( n=53) on the Iowa Gambling Task (IGT) with the decision-making performance of 3 abstinent alcohol-dependent samples, i.e., alcoholic patients without any PD ( n=38), alcoholic patients with a cluster A or C PD ( n=19), and alcoholic patients with a cluster B PD ( n=23). Results: Overall, all 3 alcohol-dependent subsamples performed inferior compared with controls. Between alcoholic subsamples, the alcoholic patients with a cluster A or C PD had the highest IGT score, followed by the alcoholic patients without a PD, while the cluster B alcoholic patients were the most impaired. Conclusion: These findings suggest that impairments in decision making underlie both alcohol dependence and cluster B PD, and alcoholic patients with a comorbid cluster B PD are particularly impaired in their decision making. These deficits may underlie the severe problems that characterize cluster B alcoholic patients specifically in inappropriate behaviors (e.g., poly substance abuse, legal, and professional dysfunction). [ABSTRACT FROM AUTHOR]

This pilot study investigated the benefits of discussion groups for patients with chronic pain and their family members. Nineteen patients with chronic pain and 41 relatives participated in four consecutive groups. Most patients and family members found their participation clearly helpful for themselves and for the family. The group helped them to improve communication, support and mutual relationships, and to better cope with the pain. Reported beneficial factors were experiencing communality, having a place to discuss things with each other, gaining insights, and learning from fellow-sufferers and their own family. Post treatment, patients also felt less distressed by the pain, less depressed, less insufficient1 and showed an increase in life-control1 and social activities. Moreover, some aspects of the family climate improved, but only in the perception of the family members. The present study points to the value of a multifamily format in chronic pain therapy and suggests the appropriateness of further controlled investigation. [ABSTRACT FROM AUTHOR]

This paper reports a pilot investigation of the perception of helpful events by the therapeutic team and the families in two family discussion groups (FDGs) of a psychiatric day clinic. All participants of the FDG, including therapists and observers, filled in questionnaires measuring events helpful for the individual, for the family and for the group after each FDG session. The results showed that the therapeutic team and the families diverged in their overall perception of which factors were important in family discussion group therapy. The therapeutic team saw the relational climate and the structural aspects of the group (including group involvement and support from the group), and specific therapeutic interventions as more helpful than the families. The process aspects in the group members (including the experiencing of communality and gaining insight) were, on the other hand, more frequently mentioned by the families than by the therapeutic team. The clinical implications of these findings and suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "What came first? Comment on Dom et al," by W. K. Bickel and R. Yi in a previous issue of the publication.

Objective: To investigate the potential role of the Maudsley Staging Method (MSM) in the prediction of electroconvulsive therapy (ECT) outcome in severely depressed adults., Method: Between August 2015 and August 2017, 73 consecutive patients with a major depressive episode (DSM-IV-TR) scheduled for ECT were recruited. Prior to their first ECT session, the MSM was completed to assess the level of therapy resistance. To determine the reduction in depression severity and response and remission rates, symptom severity was assessed at baseline and within one week after the last ECT session using the 17-item Hamilton Depression Rating Scale (HDRS17)., Results: The percentage of symptom reduction following ECT was best predicted by the MSM episode duration and depression severity factors (R 2 completer sample 0.24). Episode duration alone was the best predictor of remission (area under the ROC curve for completers: 0.72). Adding age to the models increased their predictive capacity., Conclusion: An adapted version of the MSM gauging shorter episode duration, more severe depressive symptoms and older age is significantly associated with ECT effectiveness in adults with severe recurrent depression and is thus highly suitable for use in clinical practice, promoting the shared treatment decision-making process., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)