Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Quality Review in Psychiatry.

This position paper has been substantially revised by the Canadian Psychiatric Association's Professional Standards and Practice Committee and approved for republication by the CPA's Board of Directors on August 31, 2016. The original position paper1 was developed by the Professional Standards and Practice Council and approved by the Board of Directors on April 9, 1994.

Second-Generation Antidepressants and Hyponatremia Risk: A Population-Based Cohort Study of Older Adults.

BACKGROUND: Hyponatremia may occur after initiation of a second-generation antidepressant drug. However, the magnitude of this risk among older adults in routine care is not well characterized. STUDY DESIGN: Retrospective, population-based, matched-cohort study. SETTING & PARTICIPANTS: In Ontario, Canada, 2003 to 2012, we compared older adults with a mood or anxiety disorder who were dispensed 1 of 9 second-generation antidepressant drugs with matched adults with comparable indicators of baseline health who were not dispensed an antidepressant drug (n=138,246 per group). A similar comparison was made in a subpopulation with available laboratory data (n=4,186 per group). PREDICTOR: Second-generation antidepressant prescription versus no antidepressant prescription. OUTCOMES: The primary outcome was hospitalization with hyponatremia. A secondary outcome was hospitalization with both hyponatremia and delirium. MEASUREMENTS: We assessed hospitalization with hyponatremia using a diagnosis code and, in the subpopulation, serum sodium values. We assessed hospitalization with hyponatremia and delirium using a combination of diagnosis codes. RESULTS: Second-generation antidepressant use versus nonuse was associated with higher 30-day risk for hospitalization with hyponatremia (450/138,246 [0.33%] vs 84/138,246 [0.06%]; relative risk [RR], 5.46 [95% CI, 4.32-6.91]). This association was consistent in the subpopulation with serum sodium values (73/4,186 [1.74%] vs 18/4,186 [0.43%]; RR, 4.23 [95% CI, 2.50-7.19]; absolute risk increase, 1.31% [95% CI, 0.87%-1.75%]). Second-generation antidepressant use versus nonuse was also associated with higher 30-day risk for hospitalization with both hyponatremia and delirium (28/138,246 [0.02%] vs 7/138,246 [0.005%]; RR, 4.00 [95% CI, 1.75-9.16]). LIMITATIONS: Measures of serum sodium could be ascertained in only a subpopulation. CONCLUSIONS: Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.

Atypical antipsychotic medications and hyponatremia in older adults: a population-based cohort study.

BACKGROUND: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. OBJECTIVE: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. DESIGN: The design of this study was a retrospective, population-based cohort study. SETTING: The setting of this study was in Ontario, Canada, from 2003 to 2012. PATIENTS: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. MEASUREMENTS: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs) was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. METHODS: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group). We used conditional logistic regression to compare outcomes among the matched users and non-users. RESULTS: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 %) versus 53/58,008 (0.09 %); relative risk 1.62 (95 % confidence interval (CI) 1.15 to 2.29); absolute risk increase 0.06 % (95 % CI 0.02 to 0.10)). The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical antipsychotic use compared to non-use was not associated with hospitalization with bowel obstruction within 30 days (55/58,008 (0.09 %) versus 44/58,008 (0.08 %); relative risk 1.25 (95 % CI 0.84 to 1.86)). LIMITATIONS: We could only study older adults within our data sources. CONCLUSIONS: In this study, the use of an atypical antipsychotic was associated with a modest but statistically significant increase in the 30-day risk of a hospitalization with hyponatremia. The association was less pronounced than that described with other psychotropic drugs.

MISE EN CONTEXTE: De nombreux exposés de cas font état d'une possible corrélation entre la prise de médicaments antipsychotiques atypiques et l'hyponatrémie. Or actuellement, il n'existe aucune évaluation fiable qui vienne corroborer cette association. OBJECTIFS DE L'ÉTUDE: L'étude visait à évaluer le risque, sur une période de 30 jours, d'hospitalisation pour cause d'hyponatrémie chez des patients adultes sous ordonnance d'un antipsychotique atypique, par rapport à un groupe de patients qui n'en consommaient pas. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte, représentative de la population et rétrospective, qui s'est tenue en Ontario, au Canada, de 2003 à 2012. PARTICIPANTS: L'étude a porté sur un groupe d'adultes de plus de 65 ans avec un trouble psychiatrique établi et qui débutaient un traitement par risperidone, olanzapine ou quétiapine en milieu communautaire. Ils ont été comparés à un groupe d'individus ayant des indicateurs de santé initiaux équivalents, mais ne prenant pas d'antipsychotiques atypiques. MESURES: Le critère de jugement principal était le risque d'hospitalisation pour cause d'hyponatrémie à l'intérieur d'une période de 30 jours. À titre de traceur (événement sur lequel le médicament administré ne devait avoir aucune influence), on a utilisé le risque d'hospitalisation pour occlusion intestinale. Ces résultats ont été évalués en utilisant les codes de diagnostic des hôpitaux. MÉTHODOLOGIE: À l'aide des données administratives de la santé, la méthode statistique de l'appariement par scores de propension a été utilisée pour jumeler chaque patient sous médication antipsychotique avec un patient n'en consommant pas (58,008 patients dans chacun des groupes). On a eu recours à une régression logistique conditionnelle pour comparer les résultats observés au sein des couples de patients ainsi jumelés. RÉSULTATS: On a identifié 104 caractéristiques initiales bien balancées entre les deux groupes de participants. La prise d'antipsychotiques atypiques a été associée à un risque accru d'hospitalisation pour cause d'hyponatrémie à l'intérieur d'une période de 30 jours, lorsque comparée à la non-consommation (86/58 008 [0,15 %] contre 53/58 008 [0,09 %] ; risque relatif de 1,62 [95 % intervalle de confiance [IC] entre 1,15 et 2,29] ; augmentation absolue du risque à 0,06 % [95 % IC entre 0,02 et 0,10]. Le nombre limité d'événements empêche quelques analyses complémentaires qui permettraient de confirmer la robustesse de l'association entre l'hospitalisation pour hyponatrémie et la médication. Par ailleurs, la prise d'antipsychotiques atypiques n'a pas été associée à une hospitalisation pour obstruction intestinale pour la même période de 30 jours lorsque comparée au groupe de patients n'en consommant pas [55/58 008 [0,09 %] contre 44/58 008 [0,08 %] ; risque relatif de 1,25 [95 % IC entre 0,84 et 1,86]]. LIMITES DE L'ÉTUDE: Les sources de données consultées n'ont permis que d'étudier les cas de patients adultes et âgés. CONCLUSIONS: Dans la présente étude, la consommation d'un médicament antipsychotique atypique a été associée à une légère, quoique significative, augmentation du risque d'être hospitalisé pour cause d'hyponatrémie, à l'intérieur d'une période de 30 jours. Toutefois, l'association s'est avérée moins marquée que pour d'autres médicaments psychotropes.

The neural basis of humour comprehension and humour appreciation: The roles of the temporoparietal junction and superior frontal gyrus.

Psychological well-being and social acumen benefit from the recognition of humourous intent and its enjoyment. The enjoyment of humour requires recognition, but humour recognition is not necessarily accompanied by humour enjoyment. Humour recognition is crucial during social interactions, while the associated enjoyment is less critical. Few neuroimaging studies have explicitly differentiated between the neural foundations of humour comprehension and humour appreciation. Among such studies, design limitations have obscured the specification of neural correlates to humour comprehension or appreciation. We implemented a trichotomous response option to address these design limitations. Twenty-four participants rated 120 comics (90 unaltered with humourous intent and 30 caption-altered without humourous intent) as either funny jokes (FJ), not funny jokes but intended to be funny (NFJ), or not intended to be funny or non-jokes (NJ). We defined humour comprehension by NFJ minus NJ and humour appreciation by FJ minus NFJ. We measured localized blood oxygen level dependent (BOLD) neural responses with a 3T MRI scanner. We tested for BOLD responses in humour comprehension brain regions of interest (ROIs), humour appreciation ROIs, and across the whole-brain. We found significant NFJ-NJ BOLD responses in our humour comprehension ROIs and significant FJ-NFJ BOLD responses in select humour appreciation ROIs. One key finding is that comprehension accuracy levels correlated with humour-comprehension responses in the left temporo-parietal junction (TPJ). This finding represents a novel and precise neural linkage to humour comprehension. A second key finding is that the superior frontal gyrus (SFG) was uniquely associated with humour-appreciation. The SFG response suggests that complex cognitive processing underlies humour appreciation and that current models of humour appreciation be revised. Finally, our research design provides an operational distinction between humour comprehension and appreciation and a sensitive measure of individual differences in humour comprehension accuracy.

Client perceptions of the mental health engagement network: a qualitative analysis of an electronic personal health record.

BACKGROUND: Information technologies such as websites, mobile phone applications, and virtual reality programs have been shown to deliver innovative and effective treatments for mental illness. Much of the research studying electronic mental health interventions focuses on symptom reduction; however, to facilitate the implementation of electronic interventions in usual mental health care, it is also important to investigate the perceptions of clients who will be using the technologies. To this end, a qualitative analysis of focus group discussions regarding the Mental Health Engagement Network, a web-based personal health record and smartphone intervention, is presented here. METHODS: Individuals living in the community with a mood or psychotic disorder (n = 394) were provided with a smartphone and access to an electronic personal health record, the Lawson SMART Record, for 12 to 18 months to manage their mental health. This study employed a delayed-implementation design and obtained both quantitative and qualitative data through individual interviews and focus group sessions. Participants had the opportunity to participate in voluntary focus group sessions at three points throughout the study to discuss their perceptions of the technologies. Qualitative data from 95 focus group participants were analysed using a thematic analysis. RESULTS: Four overarching themes emerged from focus group discussions: 1) Versatile functionality of the Lawson SMART Record and smartphone facilitated use; 2) Aspects of the technologies as barriers to use; 3) Use of the Mental health Engagement Network technologies resulted in perceived positive outcomes; 4) Future enhancement of the Lawson SMART Record and intervention is recommended. DISCUSSION: These qualitative data provide a valuable contribution to the understanding of how smarttechnologies can be integrated into usual mental health care. Smartphones are extremely portable andcommonplace in society. Therefore, clients can use these devices to manage and track mental health issuesin any place at almost any time without feeling stigmatized. CONCLUSIONS: Assessing clients' perspectives regarding the use of smart technologies in mental health care provides an invaluable addition to the current literature. Qualitative findings support the feasibility of implementing a smartphone and electronic personal health record intervention with individuals who are living in the community and experiencing a mental illness, and provide considerations for future development and implementation.

Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study.

BACKGROUND: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis. OBJECTIVE: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2003 to 2012. PATIENTS: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription. MEASUREMENTS: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs. RESULTS: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]). LIMITATION: Only older adults were included in the study. CONCLUSION: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults. PRIMARY FUNDING SOURCE: Academic Medical Organization of Southwestern Ontario.

Effect of direct eye contact in PTSD related to interpersonal trauma: an fMRI study of activation of an innate alarm system.

In healthy individuals, direct eye contact initially leads to activation of a fast subcortical pathway, which then modulates a cortical route eliciting social cognitive processes. The aim of this study was to gain insight into the neurobiological effects of direct eye-to-eye contact using a virtual reality paradigm in individuals with posttraumatic stress disorder (PTSD) related to prolonged childhood abuse. We examined 16 healthy comparison subjects and 16 patients with a primary diagnosis of PTSD using a virtual reality functional magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad, neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed emotion, controls exhibited an increased blood oxygenation level-dependent response during direct vs averted gaze within the dorsomedial prefrontal cortex, left temporoparietal junction and right temporal pole. Under the same conditions, individuals with PTSD showed increased activation within the superior colliculus (SC)/periaqueductal gray (PAG) and locus coeruleus. Our findings suggest that healthy controls react to the exposure of direct gaze with an activation of a cortical route that enhances evaluative 'top-down' processes underlying social interactions. In individuals with PTSD, however, direct gaze leads to sustained activation of a subcortical route of eye-contact processing, an innate alarm system involving the SC and the underlying circuits of the PAG.

Development of a Childhood Attachment and Relational Trauma Screen (CARTS): a relational-socioecological framework for surveying attachment security and childhood trauma history.

BACKGROUND: Current psychometric measures of childhood trauma history generally fail to assess the relational-socioecological context within which childhood maltreatment occurs, including the relationship of abusers to abused persons, the emotional availability of caregivers, and the respondent's own thoughts, feelings, and actions in response to maltreatment. OBJECTIVE: To evaluate a computerized approach to measuring the relational-socioecological context within which childhood maltreatment occurs. METHOD: The psychometric properties of a Childhood Attachment and Relational Trauma Screen (CARTS) were evaluated as a retrospective survey of childhood maltreatment history designed to be appropriate for completion by adults. Participants were undergraduates (n=222), an internet sample (n=123), and psychiatric outpatients (n=30). RESULTS: The internal reliability, convergent, and concurrent validity of the CARTS were supported across samples. Paired differences in means and correlations between rated item-descriptiveness to self, mothers, and fathers also accorded with findings of prior attachment and maltreatment research, illustrating the utility of assessing the occurrence and effects of maltreatment within a relational-socioecological framework. CONCLUSIONS: Results preliminarily support a new survey methodology for assessing childhood maltreatment within a relational-socioecological framework. Further psychometric evaluation of the CARTS is warranted.

The epidemiology and pathophysiology of pseudobulbar affect and its association with neurodegeneration.

Pseudobulbar affect is a disorder resulting from neurologic damage manifesting as sudden, stereotyped affective outbursts that are not reflective of internal emotion. A literature review was completed to examine the current understanding of the epidemiology, characterization, diagnosis, pathophysiology, and treatment of pseudobulbar affect. This review revealed that it is common in neurodegenerative disorders but is poorly recognized, placing significant impacts on patients and their families. The disorder appears to result from a disruption of the cortico-limbic-subcortical-thalamic-pontocerebellar network involved in emotional expression and regulation with resulting disruptions of neurotransmitter systems. Effective treatment is available with agents such as selective serotonin reuptake inhibitors and dextromethorphan combined with quinidine, but further well-designed comparative studies are needed. Advances in technology such as neuroimaging may enhance knowledge about the pathophysiology of this disorder, and help guide future interventions.

Diminished humour perception in schizophrenia: relationship to social and cognitive functioning.

This study attempted to confirm that humour recognition deficits previously found in schizophrenia are specific to the condition and not attributable to other parameters such as depression or anxiety. Secondarily, we explored any possible cognitive or social functioning correlates to humour recognition deficits. A total of 60 participants (20 outpatients with schizophrenia, 20 psychiatric control participants and 20 control participants) underwent a 64-question humour task in addition to a battery of standard cognitive tests and Social Functioning Scales. In order to compare the three groups of participants, we conducted an analysis of variance (ANOVA) and post-hoc t-tests on neuropsychological measures, social functioning measures, and the primary outcome, humour recognition. The schizophrenia group showed significant and substantial deficits in humour recognition compared to the healthy control group, t(38)=5.1, P<0.001, ES=-1.55 and the psychiatric control group, t(38)=3.6, P=0.001. In the schizophrenia group, humour recognition correlated positively with general intellectual functioning (NART) r=.45, P=0.04, social reasoning (WAIS-III Comprehension) r=.54, P=0.01, executive functioning (WCST-CC) r=.69, P=0.001 and social adjustment ratings (SASS scores), r=.54, P=0.02. These findings support the assertion that humour recognition deficits in schizophrenia are specific to the condition and not attributable to other factors such as depression or anxiety. Furthermore, humour recognition deficits in schizophrenia may perhaps be preferentially associated with deficiencies in set shifting and semantic cognition.

Time-varying amygdala response to emotional faces in generalized social phobia.

BACKGROUND: Individuals with social phobia (SP) have altered behavioral and neural responses to emotional faces and are hypothesized to have deficits in inhibiting emotion-related amygdala responses. We tested for such amygdala deficits to emotional faces in a sample of individuals with SP. METHOD: We used functional magnetic resonance imaging (fMRI) to examine the neural substrates of emotional face processing in 14 generalized SP (gSP) and 14 healthy comparison (HC) participants. Analyses focused on the temporal dynamics of the amygdala, prefrontal cortex (PFC), and fusiform face area (FFA) across blocks of neutral, fear, contempt, anger, and happy faces in gSP versus HC participants. RESULTS: Amygdala responses in participants with gSP occurred later than the HC participants to fear, angry, and happy faces. Parallel PFC responses were found for happy and fear faces. There were no group differences in temporal response patterns in the FFA. CONCLUSIONS: This finding might reflect a neural correlate of atypical orienting responses among individuals with gSP. Commonly reported SP deficits in habituation might reflect neural regions associated with emotional self-evaluations rather than the amygdala. This study highlights the importance of considering time-varying modulation when examining emotion-related processing in individuals with gSP.

Striatal function in generalized social phobia: a functional magnetic resonance imaging study.

BACKGROUND: Although evidence suggests the involvement of the amygdala in generalized social phobia (GSP), few studies have examined other neural regions. Clinical, preclinical, and dopamine receptor imaging studies demonstrating altered dopaminergic functioning in GSP suggest an association with striatal dysfunction. This is the first functional magnetic resonance imaging (fMRI) study to use a cognitive task known to involve the striatum to examine the neural correlates of GSP. We examined whether subjects with GSP had differential activation in striatal regions compared with healthy control subjects while engaged in a cognitive task that has been shown to activate striatal regions reliably. METHODS: Ten adult, unmedicated subjects with a primary DSM-IV diagnosis of GSP and 10 age-, gender-, and education-matched healthy comparison subjects underwent fMRI while performing the implicit sequence learning task. RESULTS: The GSP and healthy comparison subjects did not differ significantly on the behavioral performance of the task. Subjects with GSP, however, had significantly reduced neural activation related to implicit learning compared with healthy comparison subjects in the left caudate head, left inferior parietal lobe, and bilateral insula. CONCLUSIONS: These findings support the hypothesis that GSP is associated with striatal dysfunction and further the neurobiological understanding of this complex anxiety disorder.

Deficit in schizophrenia to recruit the striatum in implicit learning: a functional magnetic resonance imaging investigation.

In schizophrenia, explicit learning deficits have been well established although it is less clear whether these patients have deficits in implicit learning (IL). IL is thought to depend on intact striatal functioning. This study examined the hypothesis that schizophrenia patients show deficient recruitment of striatal activation during an IL paradigm, relative to performance-matched healthy comparison subjects. Ten subjects with schizophrenia on atypical antipsychotic medication and 10 age, gender, education, and performance matched healthy comparison subjects underwent fMRI while performing an IL task. On the basis of whole-brain and striatal region-of-interest analyses, we found a relative lack of striatal activation in schizophrenia patients. This result is consistent with convergent evidence of striatal dysfunction in schizophrenia.

Genital anaesthesia persisting six years after sertraline discontinuation.

Sexual side-effects, in general, are common with selective serotonin-reuptake inhibitors (SSRIs). Genital anaesthesia is a rare side-effect previously described with sertraline and fluoxetine use. With SSRI discontinuation, the sexual side-effects are expected to resolve. We report a case of a 26-year-old male who experienced genital anaesthesia during sertraline treatment and continued to be symptomatic despite medication discontinuation 6 years previously. To date, there have been no published reports of SSRI-induced sexual side-effects persisting beyond SSRI discontinuation. This case highlights the complex interplay of psychopharmacologic and psychodynamic factors that can occur in patients with sexual dysfunction.

Psychosis in multiple sclerosis associated with left temporal lobe lesions on serial MRI scans.

There is retrospective evidence of a correlation between psychosis in multiple sclerosis (MS) patients and temporal lobe pathology. A 35-year-old woman with MS presented with psychosis. There was no concurrent history of medication/substance use or family history. Comparison with previous MRI scans showed significant progression of lesions within the periventricular white matter of the left temporal lobe. This case highlights the association of psychosis and MS progression with worsening of left temporal lobe lesions. Prospective studies are required to ascertain the extent to which left temporal lobe lesions are predictive of future psychosis.

A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone.

OBJECTIVE: Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks. METHOD: After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone. RESULTS: Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy. CONCLUSIONS: All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.

Humor perception deficits in schizophrenia.

Humor is a complex cognitive process that could be used to elucidate subtle cognitive deficits. Significant deficits in humor perception were observed among 23 outpatients with schizophrenia compared with 20 controls matched for age, gender and education, using a 128-item humor test.

The role of the striatum in implicit learning: a functional magnetic resonance imaging study.

Previous research has posited striatal involvement in implicit learning. However, imaging studies have not directly compared learners with non-learners. Using functional magnetic resonance imaging with 15 study participants, we used an implicit learning task previously associated with striatal recruitment. Dorsal and ventral striatum activation was observed in the eight participants who demonstrated implicit learning. Ventral striatum activations occurred to a greater extent in implicit learning versus non-implicit learning participants, and were correlated with the degree of reaction time advantage in implicit learning participants, even after controlling for general decreases in reaction time over time. These findings strengthen the specificity of the striatum in implicit learning and are suggestive of a dissociation of striatal regions relative to elements of implicit learning performance.

Could obsessive-compulsive disorder have originated as a group-selected adaptive trait in traditional societies?

Obsessive-compulsive disorder (OCD) possesses distinctive characteristics inviting evolutionary and anthropological explanations. A genetically based condition with low fecundity persisting through generations is paradoxical. The concept of group selection is an evolutionary principle capable of clarifying the perplexing epidemiology of OCD. Using a group-selection paradigm, the authors propose that OCD reflects an ancient form of behavioural specialization. The majority of compulsions such as checking, washing, counting, needing to confess, hoarding and requiring precision, all carry the potential to benefit society. Focussing primarily on hunting and gathering cultures, the potential evolutionary advantages of OCD are explored.