Benchmarking Treatment Response in Tourette’s Disorder: A Psychometric Evaluation and Signal Detection Analysis of the Parent Tic Questionnaire

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions – Improvement (CGI-I) scale. Cronbach’s alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment.     

Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus

The NMDA receptor (NMDAR) subunit GluN1 is an obligatory component of NMDARs without a known functional homolog and is expressed in almost every neuronal cell type. The NMDAR system is a coincidence detector with critical roles in spatial learning and synaptic plasticity. Its coincidence detection property is crucial for the induction of hippocampal long-term potentiation (LTP). We have generated a mutant mouse model expressing a hypomorph of the Grin1^N598R allele, which leads to a minority (about 10%) of coincidence detection-impaired NMDARs. Surprisingly, these animals revealed specific functional changes in the dentate gyrus (DG) of the hippocampal formation. Early LTP was expressed normally in area CA1 in vivo, but was completely suppressed at perforant path-granule cell synapses in the DG. In addition, there was a pronounced reduction in the amplitude of the evoked population spike in the DG. These specific changes were accompanied by behavioral impairments in spatial recognition, spatial learning, reversal learning, and retention. Our data show that minor changes in GluN1-dependent NMDAR physiology can cause dramatic consequences in synaptic signaling in a subregion-specific fashion despite the nonredundant nature of the GluN1 gene and its global expression.According to Hebb''s postulate, neurons require a molecular mechanism to detect synchronous activity in order to change the strength of synaptic connectivity (Hebb 1949). NMDA receptors (NMDARs) are molecular coincidence detectors, and selective NMDAR antagonists block the induction of long-term potentiation (LTP) in both the dentate gyrus (DG) and CA1 regions of the hippocampus (Bliss and Collingridge 1993; Martin et al. 2000). NMDARs have been long known for their role in spatial learning, but more recently have been implicated in other forms of cognitive function and dysfunction (Gruart et al. 2006; Whitlock et al. 2006; Castner and Williams 2007; Kristiansen et al. 2007; Wilson and Linster 2008).Neuronal NMDARs are hetero-tetrameric ligand-gated ion channels typically comprised of two types of subunits. Two copies of the mandatory GluN1 subunit (or NR1 subunit [Collingridge et al. 2009] encoded by Grin1) are associated with two copies from the GluN2 family, GluN2A–D (or NR2A–D). The GluN1 subunit is expressed ubiquitously both spatially and temporally throughout the developing and adult brain. Global knockout mice models of the GluN1 subunit are postnatally lethal within hours after birth (Forrest et al. 1994; Li et al. 1994), and cell-specific GluN1 mice knockouts (Tsien et al. 1996; Nakazawa et al. 2002; McHugh et al. 2007; Niewoehner et al. 2007) have provided insights on how specific synapses and regional neuronal networks are dependent on NMDAR function.The early postnatal lethality of the global GluN1 knockout is in contrast to the null mutants of the four AMPA receptor genes and other major synaptic proteins, such as αCaMKII (Silva et al. 1992a,b; Jia et al. 1996; Zamanillo et al. 1999; Meng et al. 2003). This can be at least partially explained by the absence of any close GluN1 homologs, which could functionally compensate for the absence of the GluN1 subunit. Recombinant expression studies defined the GluN1 subunit as a mandatory component of NMDARs. This constellation provides a specific opportunity to test whether different local neuronal subnetworks are affected differentially by mutant Grin1 alleles associated with subtle alterations of the functional properties of NMDARs.GluN1 subunits with the N598R point mutation (GluN1^R) yield functional NMDARs that are Mg²⁺ insensitive and Ca²⁺ impermeable (Burnashev et al. 1992; Mori et al. 1992). The Grin1^N598R allele that codes for GluN1^R subunits is a gain-of-function mutation that is dominant lethal, even in heterozygous and hemizygous lines (Single et al. 2000; Rudhard et al. 2003). NMDARs with GluN1^R subunits do not act as coincidence detectors and, interestingly, mice expressing exclusively the GluN1^R allele lack whisker-related pattern formation in the neonate brainstem (Rudhard et al. 2003).To investigate the functional importance of GluN1 subunits with the N598R point mutation, we took advantage of the generation of a variant mutant line of mice (GluN1^Rneo/+) expressing a minority (around 10%) of these mutant NMDARs. Even though the majority of the NMDARs are normal, all neurons expressing NMDARs will contain a subset of receptors carrying this mutation.Therefore, this mouse model is an ideal candidate to study the impact of subtle alterations of NMDAR function on different neuronal networks, such as those comprising the hippocampal formation.Studies examining region-specific targeted disruption of GluN1 expression in subregions of the hippocampus have revealed subtle yet important contributions of this NMDAR subunit in synaptic plasticity and spatial learning and memory. CA1-restricted knockout of GluN1 expression in the hippocampus caused impaired spatial learning and memory as well as reduced CA1-LTP (Tsien et al. 1996). In the case of the disruption of GluN1 expression in the DG region of the hippocampus, more subtle behavioral impairments were apparent, including the inability to discriminate between two similar contexts (pattern separation) and deficits in spatial working memory despite normal LTP in the CA1 region (McHugh et al. 2007; Niewoehner et al. 2007).Our GluN1^Rneo/+ mice differ from the region-specific GluN1 mutant mice in that they express the mutant hypomorph at the same level in different subregions of the hippocampus. Interestingly, we found that this allele leads to substantial differences in short- and long-term plasticity between area CA1 and the DG of the hippocampus. The specific impairment in the DG was accompanied by impaired spatial recognition, spatial learning, reversal learning, and retention. Our data establish the possibility of a circuit-specific phenotype caused by a mutant variant of a globally expressed major nonredundant synaptic protein.     

How stable is sense of coherence? Changes following an intervention for unemployed individuals

The present investigation was concerned with the changeability of sense of coherence. We examined changes in sense of coherence (SOC) over a six-month period in a sample of Finnish unemployed individuals ( n = 74) participating in an intervention program designed to boost re-employment. Over the study period, participants' sense of coherence improved significantly and re-employed individuals reported the greatest changes. Different changes in the subcomponents of SOC, comprehensibility, manageability and meaningfulness, were found. Contrary to expectations, participants younger than 30 years of age did not show greater changes in their SOC. Initial personal resources were predictors of both positive and negative changes in SOC.     

Suicide in group therapy: trauma and possibility

Abstract This paper compares and contrasts the experiences of two different long term psychodynamic psychotherapy groups in which a patient suicided. The acute reactions and longer term process of each group is described in detail and discussed. The reactions of the two leaders, married to each other and in a shared supervisory group with the late Anne Alonso, and their own working through of the traumatic losses are explored. Their experiences highlight the importance of open discussion of the suicides in the groups, consultation with senior colleagues, and continual processing of their own reactions as a means of fostering posttraumatic growth. The authors discuss their experience in light of the literature on trauma in groups and the emerging literature on posttraumatic growth and they reflect on implications for the community of group therapists.     

On the early left-anterior negativity (ELAN) in syntax studies

Within the framework of Friederici’s (2002) neurocognitive model of sentence processing, the early left anterior negativity (ELAN) in event-related potentials (ERPs) has been claimed to be a brain marker of syntactic first-pass parsing. As ELAN components seem to be exclusively elicited by word category violations (phrase structure violations), they have been taken as strong empirical support for syntax-first models of sentence processing and have gained considerable impact on psycholinguistic theory in a variety of domains. The present article reviews relevant ELAN studies and raises a number of serious issues concerning the reliability and validity of the findings. We also discuss how baseline problems and contextual factors can contribute to early ERP effects in studies examining word category violations. We conclude that - despite the apparent wealth of ELAN data - the functional significance of these findings remains largely unclear. The present paper does not claim to have falsified the existence of ELANs or syntax-related early frontal negativities. However, by separating facts from myths, the paper attempts to make a constructive contribution to how future ERP research in the area of syntax processing may better advance our understanding of online sentence comprehension.     

Morningness‐eveningness and educational outcomes: the lark has an advantage over the owl at high school

Background. Chronotype refers to individuals’ preference for morning or evening activities. Its two dimensions (morningness and eveningness) are related to a number of academic outcomes. Aims. The main goal of the study was to investigate the incremental validity of chronotype as a predictor of academic achievement after controlling for a number of traditional predictors. In so doing, a further aim was ongoing validation of a chronotype questionnaire, the Lark‐Owl Chronotype Indicator. Sample. The sample comprised 272 students attending 9th and 10th grades at five German high schools. Data was also obtained from 132 parents of these students. Method. Students were assessed in class via self‐report questionnaires and a standardized cognitive test. Parents filled out a questionnaire at home. The incremental validity of chronotype was investigated using hierarchical linear regression. Validity of the chronotype questionnaire was assessed by correlating student ratings of their chronotype with behavioural data on sleep, food intake, and drug consumption and with parent ratings of chronotype. Results. Eveningness was a significant (negative) predictor of overall grade point average (GPA), math–science GPA, and language GPA, after cognitive ability, conscientiousness, need for cognition, achievement motivation, and gender were held constant. Validity evidence for the chronotype measure was established by significant correlations with parent‐ratings and behavioural data. Conclusions. Results point to the possible discrimination of adolescents with a proclivity towards eveningness at school. Possible explanations for the relationship between chronotype and academic achievement are presented. Implications for educational practice are also discussed.