Enhanced detection of feigned cognitive impairment using per item response time measurements in the Word Memory Test.

Response time (RT) is a less obvious outcome measure than conventional accuracy measures used in performance validity tests (PVTs). It is also under less conscious control and is affected by cognitive processes associated with deception. Studies that assessed the utility of RT for the detection of feigned cognitive impairment are however numbered. Moreover, RT variability was not assessed in a clinically used PVT. In the current study, we assessed the utility of RT measures for the detection of feigned cognitive impairment in the Word Memory Test (WMT). Healthy participants (N = 90) were randomly assigned to a simulation or control condition and their per-item RTs were recorded while they performed the WMT's immediate recognition (IR) subtest. Simulators had longer mean RTs and larger RT variance than controls. Combining RT measures and the IR-subtest's accuracy score enabled a highly accurate detection of simulators. Moreover, the combined scale demonstrated incremental value (though slight) in predicting group membership beyond the use of the accuracy score as the sole PVT measure. The findings tentatively point toward the usefulness of RT measures to enhance the detection of feigned cognitive impairment. Further studies are needed, however, in order to explore the utility of these measures in clinical settings.

Factors associated with response after deep transcranial magnetic stimulation in a real-world clinical setting: Results from the first 40 cases of treatment-resistant depression.

BACKGROUND: Deep transcranial magnetic stimulation (dTMS) has been sanctioned by the United States Food and Drug Administration for treatment-resistant depression. In a retrospective cohort study, we evaluated response and effectiveness of dTMS in real-world practice, as an add-on treatment for resistant depression. METHODS: Forty adult outpatients suffering from depression, all taking psychiatric medications, underwent 20 dTMS treatments over a 4-6 week period. At baseline (T0), visit 10 (T1), and visit 20 (T2), the Clinical Global Impression-Severity (CGI-S) scale was administered, and the Clinical Global Impression Improvement (CGI-I) scale was completed at T1 and T2; the Hamilton Depression Rating Scale (HDRS-21) was administrated at T0 and T2 only. The patients also completed the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) at T0, T1, and T2. RESULTS: Depressive symptoms (HDRS-21 total score) decreased significantly following treatment. The HDRS total score decreased from an average of 21.22 (±6.09) at T0, to 13.95 (±7.24) at T2. Correspondingly, at T2, 32.5% were responders to the treatment and 20% were in remission, based on the HDRS-21. Treatment was well tolerated, with a discontinuation rate of 7.5%. While depressive symptoms at baseline did not predict remission/response at T2, higher HDRS scores at T0 were associated with a larger decrease in depressive symptoms during the study. CONCLUSIONS: Significant antidepressant effects were seen following 20 dTMS treatments, given as augmentation to ongoing medications in treatment-resistant depression. The findings suggest that among patients with TRD, the severity of the depressive episode (and not necessarily the number of failed antidepressant medication trials) is associated with a positive therapeutic effect of dTMS. Hence, the initial severity of the depressive episode may guide clinicians in referring patients for dTMS.

Executive dysfunction in bipolar disorder and borderline personality disorder.

OBJECTIVE: The boundary between bipolar disorder (BD) and borderline personality disorder is a controversial one. Despite the importance of the topic, few studies have directly compared these patient groups. The aim of the study was to compare the executive functioning profile of BD and BPD patients. METHOD: Executive functioning (sustained attention, problem-solving, planning, strategy formation, cognitive flexibility and working memory) was assessed in BD (n=30) and BPD outpatients (n=32) using a computerized assessment battery (Cambridge Neuropsychological Test Automated Battery, CANTAB). The groups were compared to one another as well as to healthy controls. RESULTS: BD patients showed deficits in strategy formation and in planning (indicated by longer execution time in the ToL task) in comparison to BPD patients and healthy controls. BPD patients showed deficits in planning (short deliberation time in the ToL task) in comparison to BD patients and in comparison to healthy controls. In comparison to healthy controls, BPD patients displayed deficits in problem-solving. CONCLUSIONS: Differences in executive dysfunction between BD and BPD patients suggest that this cognitive dimension may be relevant for the clarification of the boundary between the disorders.

Remission of positive symptoms according to the "remission in Schizophrenia Working Group" criteria: a longitudinal study of cognitive functioning.

Schizophrenia patients in positive symptomatic remission (PSR; n=39) were assessed using a longitudinal research design. The patients were found to exhibit widespread cognitive impairments that were stable over the three-year follow-up period. The findings support a generalized and stable cognitive impairment profile among schizophrenia patients in partial symptomatic remission.

Clinical correlates of cannabis use among adolescent psychiatric inpatients.

OBJECTIVES: This study sought to determine the clinical correlates of adolescents with cannabis use and no additional drug use (CU) compared to adolescents with no drug use (NDU) among a group of adolescent psychiatric inpatients in Israel. METHODS: Two hundred and thirty-six patients consecutively admitted to an adolescent inpatient unit at a university-affiliated mental health center in Israel during a 3-year period were screened. Individuals with polydrug use were excluded from the study. RESULTS: Prevalence of cannabis use was 13%. In the CU group, 39% were diagnosed with attention deficit and disruptive behavior disorders compared with 16% in the NDU group. Antipsychotics were the most common medications prescribed in both groups. Mood stabilizers were more frequently prescribed to CU than to NDU patients (39% vs 16%, respectively). A higher prevalence of alcohol abuse and criminal behaviors was found among CU compared to NDU patients (61% and 39% vs 6% and 4%, respectively). CONCLUSIONS: The high prevalence of disruptive behaviors and frequent treatment with antipsychotics and mood stabilizers in the CU group may be related to the strong association between externalizing behavior and cannabis use and the non-specific pharmacological treatment of disruptive behaviors. Formal screening for cannabis use should be considered in psychiatric facilities. Specifically, adolescents with disruptive behaviors could benefit from early interventions, before and after cannabis initiation.

Comparison of insight among schizophrenia and bipolar disorder patients in remission of affective and positive symptoms: analysis and critique.

BACKGROUND: Schizophrenia and bipolar disorder are associated with impairments in insight, leading to a poorer clinical outcome and functioning. Earlier studies comparing the two disorders on the basis of insight included inpatients or patients who were clinically symptomatic. The current study therefore assessed patients in remission of affective symptoms and positive symptoms of schizophrenia. METHODS: Schizophrenia and bipolar disorder patients (n=32, n=34; respectively) underwent clinical and functional evaluations. Insight was assessed using the Scale to assess Unawareness of Mental Disorder (SUMD) and the positive and negative syndrome scale (PANSS). Attention was assessed using a continuous performance task (CANTAB's rapid visual information processing). RESULTS: Schizophrenia patients displayed poorer insight into having a mental disorder and into the social consequences thereof compared to the bipolar disorder patients. They were also less aware of their anhedonia-asociality. Age, however, was significantly correlated with insight and differences in insight between the patient groups became nonsignificant when age was used as a covariate in the statistical analyses. Age was not a moderating variable of the relationship between diagnosis and insight. CONCLUSIONS: Significant differences in insight held by the two patient groups might be related to age disparities between patient groups. Earlier studies did not adequately address these age differences, their cause and their potential effects on findings. These issues are explored with regard to the findings of the current study, as well as earlier studies, emphasizing the need for further research of the relationship between age and insight.

Neurocognitive functions of heavy cannabis using schizophrenia patients.

This current study assessed neurocognitive functioning in a carefully selected sample of schizophrenia patients with and without heavy cannabis use and healthy controls. All subjects were negative for any other substance use. Schizophrenia subjects had impaired neurocognitive functions across a wide range of tasks compared to healthy controls. Cannabis using schizophrenia patients had focused impairments on tasks of attention, and the findings suggest an impulsive pattern of response among these patients.

Divergent maternal behavioral patterns in two genetic animal models of depression.

Maternal behavior was examined in Flinders Sensitive-Line (FSL) and Wistar-Kyoto (WKY) rats, two different genetic animal models of depression. Behavioral patterns were assessed by undisturbed observations in the nest [Post-Partum Days (PPD) 4 and 9] and post-disturbance observations ("retrieval tests") on PPD 10. Litters were randomly allocated to a mild chronic-stress condition (limiting available bedding between PPD 2 and 9) or a standard rearing condition. The findings indicated that FSL dams did not differ from control dams in the undisturbed observations. However, in the post-disturbance observations FSL dams exhibited less pup-directed behaviors, a shorter latency to first pup carrying/retrieval and more self-directed behaviors than controls (the latter effect only in dams' interaction with whole litter). In contrast, WKY dams performed more pup-directed activities (e.g., nursing and licking) and less self-directed activities in both the undisturbed and post-disturbance observations (in both dams' interaction with single-pup and with the whole-litter) compared to controls. Accordingly, WKY dams exhibited a shorter latency for first pup-licking bout (in both post-disturbance observations). The early life mild chronic-stress used in the study ('limited-bedding') had a minor effect on the dams' behavior. Overall, the study investigated for the first time the maternal behavior of WKY dams and suggests that these dams show an almost opposite behavioral pattern to that of FSL dams. The results are discussed with regard to earlier findings in the FSL strain and behavioral patterns documented in depressed human mothers.

Withdrawal emotional-regulation in infant rats from genetic animal models of depression.

Children of depressed parents exhibit high rates of emotion-dysregulation, characterized by excessive withdrawal or approach strategies toward the mother in infancy. The understanding of factors affecting the establishment of these behavioral deficits is limited. The current study utilized two genetic animal models of depression, the Wistar-Kyoto (WKY) and Flinders Sensitive Line (FSL) rat strains. In addition, in order to assess the interactive effects of depressive vulnerability and exposure to early life stress, the subjects were raised either in a standard rearing condition or exposed to mild chronic-stress on postnatal days (PND) 2-9. On PND 10-11, an isolation test examined the pups' emotion-regulation. WKY pups produced less separation-induced ultrasonic vocalizations (USV) and proximity-seeking behaviors, compared to controls. In addition, WKY pups did not show the expected potentiation effect that was evident in control pups (an increase in USV and pivoting behavior after a short reunion with the dam). FSL pups exhibited less proximity-seeking behaviors compared to controls while showing levels of USV, potentiation of USV, and change in proximity-seeking behaviors that were similar to controls. No differences between the strains were found in self-grooming. The early life chronic-stress paradigm had no effect on the behaviors of the pups, indicating either stress-resilience or a limited effect of the paradigm. Overall, the results tentatively imply a tendency of the WKY and FSL pups towards withdrawal behavior instead of approach-behavior when regulating emotion, with a more pronounced pattern in WKY pups. This behavioral profile is reminiscent of avoidant attachment, a characteristic of many children of depressed parents.

Dehydroepiandrosterone and monoamines in the limbic system of a genetic animal model of childhood depression.

Monoamines and dehydroepiandrosterone (DHEA) levels were measured in a genetic animal model for childhood depression in four subcortical structures: nucleus accumbens (Nac), ventral tegmental area (VTA), amygdala and hypothalamus. The "depressive-like" strain was the Flinders Sensitive Line (FSL), compared to their controls, Sprague-Dawley (SD) rats. Prepubertal FSL rats showed abnormal levels of only a few monoamines and their metabolites in these brain regions. This is in contrast to former studies, in which adult FSL rats exhibited significantly higher levels of all the monoamines and their metabolites measured. These different abnormal monoamine patterns between the "depressed" prepubertal rats and their adults, may help to explain why depressed children and adolescents fail to respond to antidepressant treatment as well as adults do. On the other hand, FSL prepubertal rats exhibited the same pattern of abnormal DHEA basal levels as was found in adults in previous experiments. The results from the current study may imply that treatment with DHEA could be a promising novel therapeutic option for depressed children and adolescents that fail to respond to common (monoaminergic) antidepressant treatments.

Assessment of antidepressant and anxiolytic properties of NK1 antagonists and substance P in Wistar Kyoto rats.

In an attempt to explore the involvement of substance P in depression and anxiety and its' potential therapeutic effects, we measured basal plasma and hypothalamic levels of substance P in a well-studied animal model of depression--adult male Wistar Kyoto (WKY) rats and their controls, Wistar rats. We also studied the influence of a substance P receptor (NK1) antagonist (SPA) on "anxiety-like" and "depressive-like" behaviors exhibited by the WKY rats in the open field and swim test paradigms, compared to controls. WKY rats exhibited lower levels of substance P compared to controls in the hypothalamus. Though the WKY strain exhibited less rearing behavior in the open field compared to controls, SPA did not influence this pattern of behavior. In contrast, SPA had a significant effect on a depressive-like behavior exhibited by the WKY strain--it reduced significantly the immobility duration of WKY rats in the swim test. Thus it seems that depression involves alterations in levels of substance P, and that NK1 antagonists may be effective in the relief of depressive, but not anxiety symptoms.

Stress hormones and emotion-regulation in two genetic animal models of depression.

Children of depressed parents often exhibit emotion-regulation deficits, characterized by either excessive withdrawal or approach strategies toward the mother. The current study examined behavioral and physiological emotion-regulation in preweanling pups (postnatal day 17-19) belonging to two different genetic animal models of depression, Wistar-Kyoto (WKY) and Flinders Sensitive-Line (FSL) rats. The study also examined the effects of stress on the two animal models, hypothesizing an interactive effect of hereditary vulnerability and exposure to stress. Chronic-stress was simulated by providing limited bedding to the dam and litter for a week, in the early postnatal period. Acute-stress was generated by exposure to an adult male rat, an ethologically valid stressor. Emotion-regulation of the pups was examined using a Y-maze preference test and radioimmunoassay of Hypothalamic-Pituitary-Adrenal (HPA) axis hormones (corticosterone & adreno-corticotropin/ACTH). WKY and FSL pups exhibited reduced approach-behavior toward the dam, an emotion-regulation profile reminiscent of avoidant attachment evident in many children of depressed parents. In contrast, the two animal models did not show similar HPA axis activity. FSL pups exhibited markedly lower ACTH levels compared to controls, while WKY pups did not differ from controls. With regard to the stress manipulations, the limited-bedding condition had no effect, while the acute-stressor induced overall effects on all groups, with more pronounced reactivity evident in the WKY and FSL pups. Taken together, the experiments indicate a similar behavioral profile of the two strains at the preweanling period, while suggesting HPA dysfunction in only one of the strains.

Anxiety-like behaviors in pre-pubertal rats of the Flinders Sensitive Line (FSL) and Wistar-Kyoto (WKY) animal models of depression.

Animal models have been used in understanding the neuro-biological basis of depression and predicting successful treatment strategies. The current study focused on two genetic models of depression, the Flinder's Sensitive Line (FSL) and Wister-Kyoto (WKY). Our laboratory showed depressive symptomatology in pre-pubertal WKY and FSL rats, and the current study focused on the strains' anxiety-like traits. Since human depression-anxiety comorbidity is very common at young ages, it is essential to establish whether FSL and WKY pre-pubertal rats also exhibit such comorbidity. In addition, the effect of different rearing environments was studied using a mild chronic-stress condition (limiting available bedding between post-natal days 2-9). Two well-validated tests of anxiety, the open-field and elevated plus-maze, were used on 40-day-old pups. FSL pups exhibited lower anxiety-like behavior when compared to controls, in traditional open-field and plus-maze measures. A different pattern was observed in the WKY strain, which exhibited heightened anxiety-like behaviours in the FSL strain and affecting WKY's body-weight. Overall, the findings indicate differential expression of anxiety in pre-pubertal rats belonging to the 'depressed' strains, suggesting that these strains may be suitable for modelling different sub-groups of depression at young ages.

Reward and anxiety in genetic animal models of childhood depression.

One of the most important criteria for major depressive disorder in adults and in children and adolescents as well, is the loss of interest in or pleasure from typically enjoyable experiences or activities: anhedonia. Anxiety is frequently co-morbid with depression. We examined reward and anxiety in genetic animal models of childhood depression. Two different "depressed" lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD) rats and the Wistar Kyoto (WKY) line and their controls, Wistar rats. Recently, we found that prepubertal rats (about 35 days old) from these lines exhibited increased immobility in the swim test, and abnormal social play observed after 24-h isolation. We hypothesized that FSL and WKY prepubertal rats will further show anhedonia in two different behavioral assays: the conditioned place preference test (CPP), examining the rewarding aspect of social interaction and the saccharin preference test. Behavior in the open field paradigm and freezing behavior in the CPP apparatus were also used as measures of anxiety. WKY, but not FSL prepubertal rats, consumed less of the saccharin solution compared to their control line. FSL, and WKY prepubertal rats found social interaction to be rewarding to a similar extent as their control lines, in the CPP test. Only the WKY rats showed anxiety in behavior in the open field and freezing behavior in the CPP paradigm. The results suggest that WKY prepubertal rats are anxious and sensitive to stress-induced anhedonia, while FSL prepubertal rats exhibit none of these symptoms.