P3 event-related potential impairments in antisocial and psychopathic individuals: A meta-analysis

Prior findings on P3 event-related potential deficits in antisocial populations are mixed and it has been suggested that these abnormalities may not apply to psychopaths. A meta-analysis of 38 studies (total N = 2616) was conducted to investigate the relationship of P3 measures to antisocial behavior. Reduced P3 amplitudes (d = 0.252, p < .001) and longer P3 latencies (d = 0.130, p = .019) were significantly associated with antisocial behavior across all electrode sites, and when using both normal and non-normal control groups. A significant moderating effect of electrode site indicated longer latencies at Fz but not Pz. Compared to non-psychopathic offenders, psychopathic offenders showed P3 amplitudes impairments in standard oddball tasks, but not other tasks. Findings suggest that reduced P3 amplitudes and prolonged P3 latencies may reflect inefficient deployment of neural resources in processing cognitive task-relevant information in individuals characterized with generic antisocial behavior (i.e., aggression, antisocial personality disorder, conduct disorder/oppositional-defiant disorder, and psychopathy), whereas this association in psychopaths may be moderated by the type of tasks.     

Apolipoprotein E modulates auditory event-related potentials in healthy aging

42 individuals ranging from 47 to 73 years of age underwent an auditory three-stimulus oddball task while their event-related potentials (ERPs) were recorded. Half were APOE ?3 homozygotes and the remaining participants were either ?3/?4 heterozygotes (n = 13), or ?4 homozygotes (n = 8). Analyses of variance showed that the heterozygotes had lower N1 amplitudes than the ?3 homozygotes, consistent with a previous study of participants with mild cognitive impairment (MCI) [I. Reinvang, T. Espeseth, L. Gjerstad, Cognitive ERPs are related to ApoE allelic variation in mildly cognitively impaired patients, Neuroscience Letters 382 (3) (2005) 346–351]. APOE genotype also significantly modulated N2 latency. ?4 homozygotes had longer N2 latencies, and importantly, longer N2 latencies predicted decline in verbal learning after 3.5 years follow up. These findings indicate a potential clinical significance of individual differences in ERP components N1 and N2.     

Longitudinal associations in adolescence between cortisol and persistent aggressive or rule-breaking behavior

Although several studies have associated antisocial behavior with decreased cortisol awakening responses (CAR), studies in adolescent samples yielded inconsistent results. In adolescence however, the CAR develops and antisocial behavior is heterogeneous in type and persistence. Therefore this longitudinal study compared persistent aggressive and rule-breaking adolescents to low aggressive and rule-breaking adolescents on the development of the CAR from ages 15 to 17 (N = 390). Persistently high aggressive adolescents showed decreased cortisol levels at awakening consistently over the years (Δχ²(1) = 6.655, p = .01) as compared to low aggressive adolescents. No differences between adolescents showing persistent high rule-breaking and low rule-breaking were found. This longitudinal study is the first to show that persistent aggression, but not rule-breaking behavior, is related to neurobiological alterations. Moreover, despite development of the CAR over adolescence, the decrease in cortisol is consistent over time in persistent high aggressive adolescents, which is an important prerequisite for the prediction of persistent aggression.     

Asymmetry of magnetic motor evoked potentials recorded in calf muscles of the dominant and non-dominant lower extremity

The aim of the study was to determine the applicability of magnetic stimulation and magnetic motor evoked potentials (MEPs) in motor asymmetry studies by obtaining quantitative and qualitative measures of efferent activity during low intensity magnetic stimulation of the dominant and non-dominant lower extremities. Magnetic stimulation of the tibial nerve in the popliteal fossa was performed in 10 healthy male right-handed and right-footed young adults. Responses were recorded from the lateral head of the gastrocnemius muscles of the right and left lower extremities. Response characteristics (duration, onset latency, amplitude) were analyzed in relation to the functional dominance of the limbs and in relation to the direction of the current in the magnetic coil by use of the Wilcoxon pair sequence test. The CCW direction of coil current was related to reduced amplitudes of recorded MEPs. Greater amplitudes of evoked potentials were recorded in the non-dominant extremity, both in the CW and CCW coil current directions, with the statistical significance of this effect (p = 0.005). No differences in duration of response were found in the CW current direction, while in CCW the time of the left-side response was prolonged (p = 0.01). In the non-dominant extremity longer onset latencies were recorded in both current directions, but only for the CW direction the side asymmetries showed a statistical significance of p = 0.005. In the dominant extremity the stimulation correlated with stronger paresthesias, especially using the CCW direction of coil current. The results indicate that low intensity magnetic stimulation may be useful in quantitative and qualitative research into the motor asymmetry.     

Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 ± 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p = 0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p = 0.001). Additionally, main effects were observed for condition (p = 0.001), period (p = 0.001) and electrodes (p = 0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli.     

Evaluation of auditory, visual and olfactory event-related potentials for comparing interspersed- and single-stimulus paradigms

Background

An interspersed-stimulus paradigm (ISP) for event-related potential (ERP) recordings in which different sensory modality stimuli are presented within the same test session was developed to minimize recording time and facilitate modality comparison. The present study compared the ISP with a single-stimulus paradigm (SSP), using auditory, visual, and olfactory stimuli.

Method

Normal participants (n = 16) were assessed on two independent test occasions to obtain data on inter-paradigm and test-retest reliability. Peak amplitude/latency and area measures were obtained for the N1, P2 and P3 peaks for each paradigm.

Results

Except for larger auditory and visual P3 peaks and smaller visual P2 peaks in the ISP, no significant differences in amplitudes or latencies were found between the two paradigms. Correlation coefficients between paradigms were generally fairly high (amplitude mean r = 0.76; latency r = 0.42). Test-retest reliability within paradigms for amplitudes (ISP r = 0.70; SSP r = 0.68) and latencies (ISP r = 0.44; SSP r = 0.42) was similar across paradigms.

Conclusion

The findings suggest that the ISP, compared to the SSP, produces, in general, highly comparable auditory, visual, and olfactory peak amplitudes and latencies, and comparable reliability estimates, even though the ISP takes much less time to record (25 vs. 50 min). The larger auditory and visual P3 peaks and smaller visual P2 peaks in the ISP may be attributable to a less predictable stimulus environment. Thus, this method enables systematic comparisons of ERP peaks across sensory modalities while reducing testing time. Practical implications are discussed.     

Enhanced P3 Evoked Potentials and Longer P3 Recovery Times in Psychopaths

A recent study by Raine and Venables (1987) reported increased P3 amplitudes in antisocial adolescents, a replicable result indicating enhanced processing of task-relevant events. The present study assesses whether adult psychopaths similarly show enhanced P3 amplitudes; latency of P3 recovery to baseline was also measured to assess Jutai et al.'s (1987) finding of sustained late positivity in psychopaths. EPs were measured at T₃, T₄, P₃, and P₄ to targets and nontargets during a continuous performance task in 14 psychopathic and 14 nonpsychopathic top-security prisoners. Psychopaths showed larger P3 amplitudes to targets relative to nontargets at parietal but not temporal sites, and larger P3 recovery times. Psychopaths also scored higher on WAIS subtests sensitive to parietal lobe functioning but not on non-parietal subtests. No laterality effects were uncovered to support a left hemisphere dysfunction theory of psychopathy. It is argued that this evidence for proficient information-processing on parietal-related tasks may underlie clinical reports of enhanced short-term attentional ability in psychopaths.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

Cognitive task performance causes impaired maximum force production in human hand flexor muscles

The purpose of this study was to investigate effects of demanding cognitive task performance on intermittent maximum voluntary muscle contraction (MVC) force production. Participants performed either a modified Stroop or control task for 22 min. After the first min and at 3-min intervals thereafter, participants rated fatigue, perceived mental exertion and performed a 4-s MVC handgrip squeeze. A mixed ANOVA showed a significant interaction, F(7, 259) = 2.43, p = .02, with a significant linear reduction in MVC force production over time in the cognitively depleting condition (p = .01) and no change for controls. Ratings of perceived mental exertion, F(7, 252) = 2.39, p < .05, mirrored the force production results with a greater linear increase over time in the cognitive depletion condition (p < .001) compared to controls. Findings support current views that performance of cognitively demanding tasks diminishes central nervous system resources that govern self-regulation of physical tasks requiring maximal voluntary effort.     

Association of GPR50, an X-linked orphan G protein-coupled receptor,and affective disorder in an independent sample of the Scottish population

A recent report detected association between GPR50, an orphan G protein-coupled receptor, and bipolar disorder (BD) in the Scottish population [29]. We sought to replicate this study in a second sample from the same population, consisting of 338 patients with BD, 359 patients with major depressive disorder (MDD) and 913 control individuals. In addition, the effect of GPR50 genotype on clinical phenotype and treatment response was assessed in a subset of 56 patients with early onset MDD (eoMDD). We identified an association with BD in women with an intronic SNP, rs1202874, that withstood correction for multiple testing (p = 0.0035, permuted p = 0.037, OR = 1.9, 95%CI 1.2–3.0). However, we failed to find an association with the previously associated Δ502-505 polymorphism (p = 0.2). Combined analysis of this and the original samples did detect association between the deletion and susceptibility to BD in females, but with a reduced effect size (p = 0.0006, permuted p = 0.0024, OR = 1.41, 95%CI 1.16–1.71). In the highly phenotyped eoMDD subgroup, we found an association between the Δ502-505 deletion polymorphism and age of onset (p = 0.049), number of episodes (p = 0.044), hypomanic symptoms (p = 0.019), and initial thinking time (p = 0.027), in women; and in family history of depression in men (p = 0.038), uncorrected for multiple testing. No association was seen between Δ502-505 genotype and treatment response at 3 months. To our knowledge this is the first association of rs1202874 with BD and is the second positive association at the GPR50 locus.     

Treatment effects of serotonergic and noradrenergic antidepressants on the intensity dependence of auditory ERP components in major depression

The intensity dependent amplitude change of auditory evoked potentials (IDAP), an assumed indicator of the level of central nervous serotonergic neurotransmission, was measured in major depressive disorder (MDD, DSM-IV: 296.2, 296.3; APA 1994) before and after treatment with either a selective serotonin reuptake inhibitor or a selective noradrenaline reuptake inhibitor antidepressant and compared with the results of a healthy control group. Auditory evoked P1, N1, P2, P1/N1 and N1/P2 peak-to-peak amplitudes were evaluated in 26 in-patients with MDD prior to and after antidepressant treatment with citalopram (24 days, n = 14) or reboxetine (25 days, n = 12), and in 43 healthy control subjects. Clinical symptoms of MDD were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). The IDAP within the control group remained stable over 24 days (N1 amplitude slope retest ANOVA p = .79). Neither applied antidepressants nor decrease of HDRS total score during treatment had a significant effect on the IDAP in the patients’ sample. The conclusion that the IDAP does not reflect the temporary depressive state in MDD is discussed.     

Can interactive skills-based seminars with standardized patients enhance clinicians’ prevention skills? Measuring the impact of a CME program

Objective

Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction.

Methods

Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests.

Results

OSCE scores (n = 15) revealed significant improvements in communication skills overall (p = 0.004) and within specific domains (data gathering: p = 0.003; rapport building: p = 0.01; patient education: p = 0.02), but no change in case-specific knowledge (p = 0.1). Participants (n = 14) reported high satisfaction with program methods (mean = 4.6/5) and content (mean = 4.7/5), 70% planning to alter their clinical practice. Chart audits (pre = 96, post = 103) showed increased screening for smoking (RR 1.65, p = 0.03), depressed mood (RR 1.40, p = 0.04), anhedonia (RR 1.47, p = 0.01), sexual activity (RR 1.73, p = 0.002) and drinking (RR 1.77, p = 0.04). Sampling of satisfaction among participants’ patients (pre n = 689, post n = 383) detected no increase in already high baseline satisfaction.

Conclusion

This curriculum improved clinicians’ relevant skills and screening behavior.

Practice implications

Skills-oriented CME can improve clinicians’ communication skills and screening and counseling practices.     

Quantitative analysis of the 4977-bp common deletion of mitochondrial DNA in postmortem frontal cortex from patients with bipolar disorder and schizophrenia

Several reports have suggested a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder and schizophrenia. We have focused on the relationship between deleted mitochondrial DNA (mtDNA) and bipolar disorder. To investigate this relationship, we developed a methodology for quantification of the common 4977-bp deletion of mtDNA based on real-time polymerase chain reaction with SYBR Green. In this study, we assessed accumulation of the common deletion in postmortem frontal cortex from 147 individuals (48 controls, 49 patients with bipolar disorder, 50 patients with schizophrenia). We demonstrated age-dependent accumulation of the common deletion of mtDNA (p = 1.09E−10). Females showed significantly higher accumulation of the deletion than did males (p = 0.002). There was no significant association between accumulation and the two studied major mental disorders in the frontal cortex (p > 0.2). However, there was no statistically significant correlation between the common deletion and aging in female patients with bipolar disorder (p = 0.133), and no significant sex difference in patients with bipolar disorder (p = 0.509). These results indicate that aging and sex have effect on accumulation of the common deletion of mtDNA in the prefrontal cortex depending on the diagnosis.     

Effectiveness of the Incredible Years parent training to modify disruptive and prosocial child behavior: A meta-analytic review

The present meta-analytic review examined effectiveness of the Incredible Years parent training (IYPT) regarding disruptive and prosocial child behavior, and aimed to explain variability in intervention outcomes. Fifty studies, in which an intervention group receiving the IYPT was compared to a comparison group immediately after intervention, were included in the analyses. Results showed that the IYPT is an effective intervention. Positive effects for distinct outcomes and distinct informants were found, including a mean effect size of d = .27 concerning disruptive child behavior across informants. For parental report, treatment studies were associated with larger effects (d = .50) than indicated (d = .20) and selective (d = .13) prevention studies. Furthermore, initial severity of child behavior revealed to be the strongest predictor of intervention effects, with larger effects for studies including more severe cases. Findings indicate that the IYPT is successful in improving child behavior in a diverse range of families, and that the parent program may be considered well-established.     

Association study on the NAPG gene and bipolar disorder in the Chinese Han population

Background: Bipolar disorder is a mental health problem throughout the world. Chromosome 18p11 has been identified by several studies as a susceptiblilty region for bipolar disorder and NAPG, located on 18p11, has been suggested as being associated with bipolar disorder in European population. Methods: Our study employed five SNPs (rs2290279, rs495484, rs510110, rs617040 and rs473938) to investigate the role of NAPG in the Chinese Han population based on a sample of 465 controls vs. 499 bipolar patients. Results: Rs617040 was excluded from further analysis because of deviation from Hardy–Weinberg equilibrium. Rs473938 and rs2290279 showed significant association in both allele and genotype frequencies (rs473938: allele p = 0.0028 after 100,000 permutations, genotype p = 0.0018; rs2290279: allele p = 0.0042 after 100,000 permutations, genotype p = 0.0028). Several combinations of haplotype were found to be associated with bipolar disorder. Haplotype T–A–T of rs473938–rs2290279–rs495484 was defined by confidence intervals algorithm and had a p value of 0.0038 after 100,000 permutations. Conclusions: Our study supports NAPG as a candidate for susceptibility to bipolar disorder.     

Shared decision-making to improve attention-deficit hyperactivity disorder care

Objective

To examine the effect of a shared decision-making intervention with parents of children newly diagnosed with attention-deficit/hyperactivity disorder.

Methods

Seven pediatricians participated in a pre/post open trial of decision aids for use before and during the office visit to discuss diagnosis and develop a treatment plan. Encounters pre- (n = 21, control group) and post-intervention implementation (n = 33, intervention group) were compared. We video-recorded encounters and surveyed parents.

Results

Compared to controls, intervention group parents were more involved in shared decision-making (31.2 vs. 43.8 on OPTION score, p < 0.01), more knowledgeable (6.4 vs. 8.1 questions correct, p < 0.01), and less conflicted about treatment options (16.2 vs. 10.7 on decisional conflict total score, p = 0.06). Visit duration was unchanged (41.0 vs. 41.6 min, p = 0.75). There were no significant differences in the median number of follow-up visits (0 vs. 1 visits, p = 0.08), or the proportion of children with medication titration (62% vs. 76%, p = 0.28), or parent-completed behavior rating scale to assess treatment response (24% vs. 39%, p = 0.36).

Conclusions

Our intervention increased shared decision-making with parents. Parents were better informed about treatment options without increasing visit duration.

Practice implications

Interventions are available to prepare parents for visits and enable physicians to elicit parent preferences and involvement in decision-making.     

The efficacy of short-term psychodynamic psychotherapy for depression: A meta-analysis

Objectives

It remains largely unclear, firstly whether short-term psychodynamic psychotherapy (STPP) is an effective treatment for depression, and secondly, which study, participant, or intervention characteristics may moderate treatment effects. The purpose of this study is to assess the efficacy of STPP for depression and to identify treatment moderators.

Results

After a thorough literature search, 23 studies totaling 1365 subjects were included. STPP was found to be significantly more effective than control conditions at post-treatment (d = 0.69). STPP pre-treatment to post-treatment changes in depression level were large (d = 1.34), and these changes were maintained until 1-year follow-up. Compared to other psychotherapies, a small but significant effect size (d = − 0.30) was found, indicating the superiority of other treatments immediately post-treatment, but no significant differences were found at 3-month (d = − 0.05) and 12-month (d = − 0.29) follow-up. Studies employing STPP in groups (d = 0.83) found significantly lower pre-treatment to post-treatment effect sizes than studies using an individual format (d = 1.48). Supportive and expressive STPP modes were found to be equally efficacious (d = 1.36 and d = 1.30, respectively).

Conclusion

We found clear indications that STPP is effective in the treatment of depression in adults. Although more high-quality RCTs are necessary to assess the efficacy of the STPP variants, the current findings add to the evidence-base of STPP for depression.     

Brain-derived neurotrophic factor serum levels before and after treatment for acute mania

Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p = 0.013) but this difference was no longer significant after treatment (p = 0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p = 0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.     

Significance of association of HLA-C and HLA-E with psoriatic arthritis

Psoriatic arthritis (PsA) is a complex genetic disorder that results from an interplay between multiple genetic and environmental factors. The aim of the study was to assess the significance of the association between the HLA-C and HLA-E allelic groups and PsA. Our results confirm the association between HLA-C^∗06 and PsA (OR = 5.16, p < 0.0001). Furthermore, HLA-C^∗06-positive patients develop more severe disease (p < 0.01) and more frequently present with polyarticular pattern of PsA (p = 0.08). Additionally our study revealed that the HLA-C^∗02 allele was more frequently observed in PsA patients (OR = 5.40, p < 0.0005) and also that the HLA-E^∗01:01 allele was significantly over-represented among HLA-C^∗02-negative patients in comparison to healthy individuals (OR = 6.44, p = 0.045). Therefore these results suggest that the HLA-E and HLA-C^∗02 molecules may also play an important role in determination immune response contributing to the PsA development.     

Autonomic nervous system reactivity to positive and negative mood induction: the role of acute psychological responses and frontal electrocortical activity

The differential effects of positive versus negative emotions on autonomic nervous system activity are insufficiently understood. This study examined the role of acute mood responses and central nervous system activity on heart rate variability (HRV) using 5-min event recall tasks (happiness and anger recall) and a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25 ± 4 years, 55% female). HRV was measured in high frequency (HF) and low frequency (LF) domains, and frontal brain activity using electroencephalography (EEG) in the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF-HRV (p = 0.005) but not HF-HRV (p = 0.71). Anger Recall did not change HRV (p-values > 0.10). The SCWT produced decreases in HF-HRV (p = 0.001) as well as LF-HRV (p = 0.001). The magnitude of feeling “happy” during Happiness Recall was positively correlated with ΔHF-HRV (p = 0.050), whereas an incongruent mood state (“frustrated”) was associated with smaller ΔHF-HRV (p = 0.070). Associations between frontal EEG activation and HRV responses were mostly non-significant, except for increased right frontal activation during Happiness Recall which was associated with a decrease in LF/HF ratio (p = 0.009). It is concluded that positive and negative mood induction result in differential HRV responses, which is related to both task valence and the intensity of task-induced emotions.