Brassica napus Plants Gain Improved Salt-Stress Tolerance and Increased Storage Oil Biosynthesis by Interfering with CRL3BPM Activities.

Generating new strategies to improve plant performance and yield in crop plants becomes increasingly relevant with ongoing and predicted global climate changes. E3 ligases that function as key regulators within the ubiquitin proteasome pathway often are involved in abiotic stress responses, development, and metabolism in plants. The aim of this research was to transiently downregulate an E3 ligase that uses BTB/POZ-MATH proteins as substrate adaptors in a tissue-specific manner. Interfering with the E3 ligase at the seedling stage and in developing seeds results in increased salt-stress tolerance and elevated fatty acid levels, respectively. This novel approach can help to improve specific traits in crop plants to maintain sustainable agriculture.

Pyruvate, phosphate dikinase regulatory protein impacts light response of C4 photosynthesis in Setaria viridis.

In C4 plants, the pyruvate (Pyr), phosphate dikinase regulatory protein (PDRP) regulates the activity of the C4 pathway enzyme Pyr, phosphate dikinase (PPDK) in a light-/dark-dependent manner. The importance of this regulatory action to C4 pathway function and overall C4 photosynthesis is unknown. To resolve this question, we assessed in vivo PPDK phospho-regulation and whole leaf photophysiology in a CRISPR-Cas9 PDRP knockout (KO) mutant of the NADP-ME C4 grass green millet (Setaria viridis). PDRP enzyme activity was undetectable in leaf extracts from PDRP KO lines. Likewise, PPDK phosphorylated at the PDRP-regulatory Thr residue was immunologically undetectable in leaf extracts. PPDK enzyme activity in rapid leaf extracts was constitutively high in the PDRP KO lines, irrespective of light or dark pretreatment of leaves. Gas exchange analysis of net CO2 assimilation revealed PDRP KO leaves had markedly slower light induction kinetics when leaves transition from dark to high-light or low-light to high-light. In the initial 30 min of the light induction phase, KO leaves had an ∼15% lower net CO2 assimilation rate versus the wild-type (WT). Despite the impaired slower induction kinetics, we found growth and vigor of the KO lines to be visibly indistinguishable from the WT when grown in normal air and under standard growth chamber conditions. However, the PDRP KO plants grown under a fluctuating light regime exhibited a gradual multi-day decline in Fv/Fm, indicative of progressive photosystem II damage due to the absence of PDRP. Collectively, our results demonstrate that one of PDRP's functions in C4 photosynthesis is to ensure optimal photosynthetic light induction kinetics during dynamic changes in incident light.

Validation of the French Clinical Assessment Interview for Negative Symptoms in a Sample of Stable French Individuals With Schizophrenia.

Objectives: The Clinical Assessment Interview for Negative Symptoms (CAINS) is an interview-based instrument evaluating the existence and severity of negative symptoms in people diagnosed with schizophrenia or schizoaffective disorder. The aim of this study is to translate and validate a French version of the CAINS in a French sample of outpatients diagnosed with schizophrenia or schizoaffective disorder. Methods: In this study, we included 84 outpatients with a diagnosis of schizophrenia from the University Department of Adult Psychiatry in Montpellier, France. All participants were assessed for the severity of negative symptoms as well as level of depression. Psychometric properties of the French CAINS were investigated including its factor structure, internal consistency, and interrater and test-retest reliabilities. We also determined the discriminant and convergent validity. Results: Exploratory factor analysis and parallel analysis reproduced the two-factor model, and explained 43.55% of the total score variation with good internal consistency (Cronbach α of 0.87). Both interrater and test-retest reliabilities were high for the CAINS and its subscales (intraclass correlation coefficient range, 0.89-0.99). The standard errors of measurement and minimal detectable change were also investigated. Convergent validity of the CAINS was underpinned by correlations obtained with various measures of negative symptoms. Adequate discriminant validity was established by showing that the CAINS did not correlate with positive symptoms. Conclusion: Overall, our results obtained were similar to those found in the original study of the CAINS. Structural analyses also replicated the two-factor model of the CAINS. Our results indicate that the French CAINS has robust psychometric properties and is a valid tool for evaluating negative symptoms in French-speaking individuals diagnosed with schizophrenia.

Acquisition and maintenance of disgust reactions in an OCD analogue sample: Efficiency of extinction strategies through a counter-conditioning procedure.

BACKGROUND: Obsessive-compulsive disorder (OCD) has long been considered as an anxiety disorder, disgust is the dominant emotion in contamination-based OCD. However, disgust seems resistant to exposure with response prevention partly due to the fact that disgust is acquired through evaluative conditioning. AIMS: The present research investigates a counter-conditioning intervention in treating disgust-related emotional responses in two groups of individuals with high (High contamination concerns, HCC, n = 24) and low (Low contamination concerns LCC, n = 23) contamination concerns. METHODS: The two groups completed a differential associative learning task in which neutral images were followed by disgusting images (conditioned stimulus; CS+), or not (CS-). Following this acquisition phase, there was a counter-conditioning procedure in which CS+ was followed by a very pleasant unconditional stimulus while CS- remained unreinforced. RESULTS: Following counter-conditioning, both groups reported significant reduction in their expectancy of US occurrence and reported less disgust with CS+. For both expectancy and disgust, reduction was lower in the HCC group than in the LCC group. Disgust sensitivity was highly correlated with both acquisition and maintenance of the response acquired, while US expectation was predicted by anxiety. CONCLUSION: Counter-conditioning procedure reduces both expectations and conditioned disgust.

Self-Awareness Deficits of Cognitive Impairment in Individuals With Schizophrenia. Really?

OBJECTIVE: Misestimation of cognitive functioning has been largely described in individuals with schizophrenia. There is large evidence that correlations between subjectively assessed cognitive functioning and objectively determined cognitive functioning are weak in non clinical individuals and may be more closely related to other psychoaffective or clinical factors than to objective neuropsychological functioning. Surprisingly, no study to date has compared the associations between cognitive complaint and objective measures of cognitive functioning in individuals with schizophrenia and healthy controls. The main objective of this study was to 1) compare cognitive complaint between individuals with schizophrenia and non clinical controls, 2) explore the relationships between cognitive complaint and psychoaffective and clinical factors in the clinical group and 3) compare the relationships between subjective awareness of cognitive functioning and objective neuropsychological assessment in individuals with schizophrenia and non-clinical participants. METHOD: In this study 30 individuals with schizophrenia and 20 non-clinical matched controls were included. In addition to objective cognitive measures and subjective cognition assessed by the Subjective Scale To Investigate Cognition In Schizophrenia, measures of psychotic symptoms, depression, and anxiety were included. RESULTS: Schizophrenia patients reported higher cognitive complaints in comparison with controls. In individuals with schizophrenia, cognitive complaint subscores were differently associated with depression, anxiety, and negative symptoms. When depression was controlled for, the same number of correlations between self-rated measures of cognition and objective measures of cognition were found in both groups, but accuracy of self-assessment of cognition was lower in the schizophrenia group.When the schizophrenia group was divided into a high cognitive complaint group (SZ High CC) and a low cognitive complaint group (SZ Low CC), findings indicated that self-assessment of cognition in the SZ high CC was highly accurate (correlations with large effect sizes). By contrast the SZ low CC group severely misjudge their cognition. CONCLUSION: A significant proportion of patients with schizophrenia can accurately estimate their cognitive skills. Self-awareness of cognitive deficits in individuals with schizophrenia is an heterogenous phenomenon and misestimation of cognitive functioning might have been overestimated, partly due to secondary psychoaffective factors. Caution is warranted before jumping to the conclusion that all individuals with schizophrenia misjudge their cognitive functioning.

Why you can't be in sync with schizophrenia patients.

Most individuals with schizophrenia will be confronted with some form of stigma. In recent years, clinicians and family members have increasingly contested the term "schizophrenia". Many of them discuss changing this name, as a means to fight stigma. Up until now, surprisingly, most research has been conducted using self-reports and behavioral research is lacking. The aim of our study was to assess through an experimental design if the term "schizophrenia" itself modifies social behaviours. Forty participants were asked to engage in a synchronization task with a dot displayed on a screen and moved by another person. Non-clinicians participants had to synchronize their movements as accurately as possible with either a "schizophrenia" patient, a patient with "neuro-emotional integration disorder" or a "healthy" subject, kept out of sight. Each condition was counterbalanced between participants. In fact, the movements of the dot were pre-recorded (five trajectories) and were therefore identical for all three conditions. Measuring the error between the displayed and performed trajectories, participants exhibited more errors when they thought they were interacting with a patient in comparison to the "healthy" subject. Post-hoc analysis revealed an even higher difference between "schizophrenia" and "healthy" conditions. Altogether, our results show a significant behavioral impact of the term "schizophrenia" with possibly negative consequences on social interactions. The effect of changing the name reduces this impact but remains unclear.

Disgust assessment: Factorial structure and psychometric properties of the French version of the Disgust Propension and Sensibility Scale Revised-12.

The present study examined the internal and external validity of the French version of the 12-item Disgust Propensity and Sensitivity Scale-Revised (DPSS-12) in a nonclinical sample from the general population. Two hundred and eighty-two participants completed the DPSSf-12 questionnaire as well as the Anxiety Sensitivity Index (ASI), Anxiety Trait (STAI B), Obsessional Belief Questionnaire 44 items (OBQ 44), Obsessive Compulsive Inventory-Revised (OCI-R) and Positive and Negative Affect Schedule (PANAS). Confirmatory Factor Analysis supported a 2-factor structure after two sensitivity items were removed. The 10-item scale showed good internal consistency, construct validity and test-retest reliability. These adequate psychometric properties make the DPSSf-10 appropriate for use by researchers and practitioners.

Apathy in schizophrenia: A review of neuropsychological and neuroanatomical studies.

Apathy is a multidimensional symptom composed of cognitive, behavioral, and emotional facets including impaired motivation and reduced goal-directed behavior. Apathy belongs to schizophrenia's negative symptomatology which has received increased attention over the last years including a growing interest in the assessment and the consequences of apathy. Nevertheless, the pathological mechanisms are still insufficiently explored as well as the multidimensional aspect of this symptom. The aim of this article is to provide a review of the main measures used to explore apathy in schizophrenia as well as the cognitive and neural correlates of apathy while taking into account the multidimensionality of this symptom. Studies have shown important correlations between apathy, executive functions and specific brain regions such as the anterior cingulate cortex, orbitofrontal cortex and the ventral and dorsal striatum. Nevertheless, most studies have neglected the multidimensional aspect of apathy, which is assessed as a single-dimension concept. These and other limitations are discussed as well as the main strengths of the current evidence on apathy in schizophrenia.

Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

BACKGROUND: Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. METHOD: Data were drawn from 41 patient-parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. RESULTS: Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. CONCLUSIONS: Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions.

Mirror self-face perception in individuals with schizophrenia: Feelings of strangeness associated with one's own image.

Self-face recognition is crucial for sense of identity and for maintaining a coherent sense of self. Most of our daily life experiences with the image of our own face happen when we look at ourselves in the mirror. However, to date, mirror self-perception in schizophrenia has received little attention despite evidence that face recognition deficits and self abnormalities have been described in schizophrenia. Thus, this study aims to investigate mirror self-face perception in schizophrenia patients and its correlation with clinical symptoms. Twenty-four schizophrenia patients and twenty-five healthy controls were explicitly requested to describe their image in detail during 2min whilst looking at themselves in a mirror. Then, they were asked to report whether they experienced any self-face recognition difficulties. Results showed that schizophrenia patients reported more feelings of strangeness towards their face compared to healthy controls (U=209.5, p=0.048, r=0.28), but no statistically significant differences were found regarding misidentification (p=0.111) and failures in recognition (p=0.081). Symptoms such as hallucinations, somatic concerns and depression were also associated with self-face perception abnormalities (all p-values>0.05). Feelings of strangeness toward one's own face in schizophrenia might be part of a familiar face perception deficit or a more global self-disturbance, which is characterized by a loss of self-other boundaries and has been associated with abnormal body experiences and first rank symptoms. Regarding this last hypothesis, multisensorial integration might have an impact on the way patients perceive themselves since it has an important role in mirror self-perception.

Innovative mechanisms of action for pharmaceutical cognitive enhancement: A systematic review.

Pharmacological cognitive enhancement refers to improvement in cognitive functions after drug use in healthy individuals. This popular topic attracts attention both from the general public and the scientific community. The objective was to explore innovative mechanisms of psychostimulant's action, whose potential effectiveness was assessed in randomized placebo-controlled trials (RCTs). A systematic review was carried out, using the words "attention", "memory", "learning", "executive functions", and "vigilance/wakefulness" combined to "cognitive enhancer" or "smart drug". Methylphenidate, amphetamines, modafinil, nicotine, acetylcholine esterase inhibitors and antidepressants were extensively studied in previous meta-analyses and were not included in the present work. Drugs were classified according to their primary mode of action, namely catecholaminergic drugs (tolcapone, pramipexole, guanfacine), cholinergic drugs (anticholinergics), glutamatergic drugs (ampakines), histaminergic drugs, and non-specified (glucocorticoids). Overall, 50 RCTs were included in the present review. In conclusion, a number of new active drugs were found to improve some cognitive functions, in particular verbal episodic memory. However the number of RCTs was limited, and most of the studies found negative results. Future studies should assess both effectiveness and tolerance of repeated doses administration, and individual variability in dose response (including baseline characteristics and potential genetic polymorphisms). One explanation for the limited number of recent RCTs with new psychostimulants seems to be the ethical debate surrounding pharmaceutical cognitive enhancement in healthy subjects.

Insight of patients and their parents into schizophrenia: Exploring agreement and the influence of parental factors.

Poor insight is found in up to 80% of schizophrenia patients and has been associated with multiple factors of which cognitive functioning, social and environmental factors. Few studies have explored associations between patient insight and that of their biological parents', and the influence of parental factors. Insight was assessed in 41 patients and their biological parents with Amador's Scale for the assessment of Unawareness of Mental Disorder (SUMD). Parents' knowledge about schizophrenia and critical attitudes were assessed with validated self-report questionnaires. Both groups underwent cognitive assessments for working memory and executive functioning. Insight in patients and their parents was not associated for any of the SUMD dimensions but a significant correlation was found between patient and parent awareness of treatment effect for patient-parent dyads with frequent daily contact. Low parental critical attitude was associated with higher patient awareness of symptoms and a high parental memory task score with high patient insight. Our study is the first to suggest a possible influence of parental factors such as critical attitudes and cognitive performance on patient insight.

Prevalence and smoking behavior characteristics of nonselected smokers with childhood and/or adult self-reported ADHD symptoms in a smoking-cessation program: a cross-sectional study.

BACKGROUND: ADHD involves impairing core symptoms of inattention and hyperactivity/impulsivity in children (childhood ADHD = CH) that may persist in adulthood (adult ADHD = AD). Conflicting findings have been found regarding AD prevalences among adult smokers, and it is unclear whether AD is associated with a more severe smoking behavior in adulthood. OBJECTIVE: The aim of this article is (a) to determine CH and AD prevalences in a nonselected sample of adult smokers, (b) to describe the characteristics of smokers with ADHD symptoms versus those without, and (c) to determine whether CH and/or AD symptoms are risk factors for more severe smoking in adulthood. METHOD: Three hundred and seventy-three participants aged 18 years and over were prospectively recruited in a smoking-cessation unit. Participants were classified as "no ADHD symptoms," "CH symptoms," or "AD symptoms" according to their baseline score on the Wender Utah Rating Scale (WURS) alone (for CH symptoms) and WURS combined to the Adult Self Report Scale (ASRS) for AD symptoms. Other clinical variables were reported at first consultation. RESULTS: (a) CH symptoms were reported in 15.3% (57/373) of the total sample, 42.1% (24/57) of whom also had persistent ADHD symptoms in adulthood (prevalence of AD was 24/373 = 6.4%). (b) In comparison with participants without ADHD symptoms, smokers with ADHD symptoms consume significantly more tobacco, but ADHD symptoms were no longer significantly associated with the daily number of smoked cigarettes after adjustment for sociodemographic variables. No significant association was found between the two groups and age at the first cigarette, age at onset daily smoking, and nicotine dependence. (c) Participants were categorized into three groups: Group 1 without ADHD symptoms lifetime (NH; n = 316), Group 2 with childhood history of ADHD symptoms (CH; n = 33), and Group 3 with Adult ADHD symptoms (AD; n = 24). The association with tobacco consumption (>20 cigarettes/day) was significant for CH only (p = .02). After adjustment for gender, age, professional status, and educational level, this association was not longer significant. CONCLUSION: Childhood and adult ADHD symptoms are both highly prevalent among nonselected smokers but our study failed to show more severe smoking characteristics among these participants after adjustment with sociodemographic variables.

Characteristics explaining performance in downhill mountain biking.

PURPOSE: To identify physiological, psychological, and skill characteristics that explain performance in downhill (DH) mountain-bike racing. METHODS: Four studies were used to (1) identify factors potentially contributing to DH performance (using an expert focus group), (2) develop and validate a measure of rider skill (using video analysis and expert judge evaluation), (3) evaluate whether physiological, psychological, and skill variables contribute to performance at a DH competition, and (4) test the specific contribution of aerobic capacity to DH performance. RESULTS: STUDY 1 identified aerobic capacity, handgrip endurance, anaerobic power, rider skill, and self-confidence as potentially important for DH. In study 2 the rider-skill measure displayed good interrater reliability. Study 3 found that rider skill and handgrip endurance were significantly related to DH ride time (ß=-0.76 and -0.14, respectively; R2=.73), with exploratory analyses suggesting that DH ride time may also be influenced by self-confidence and aerobic capacity. Study 4 confirmed aerobic capacity as an important variable influencing DH performance (for a DH ride, mean oxygen uptake was 49±5 mL·kg(-1)·min(-1), and 90% of the ride was completed above the 1st ventilatory threshold). CONCLUSIONS: In order of importance, rider skill, handgrip endurance, self-confidence, and aerobic capacity were identified as variables influencing DH performance. Practically, this study provides a novel assessment of rider skill that could be used by coaches to monitor training and identify talent. Novel intervention targets to enhance DH performance were also identified, including self-confidence and aerobic capacity.

Cognitive insight in schizophrenia patients and their biological parents: a pilot study.

BACKGROUND: Clinical insight in schizophrenia patients is partly associated with familial environment but has been poorly studied to date. We aimed to explore (1) the relationship between parents' cognitive insight and their offspring's; (2) the relationship between parents' cognitive insight and their clinical insight into the disease of their offspring; and (3) the clinical and cognitive determinants of cognitive insight in parents. METHODS: Cognitive insight was assessed in 37 patient-biological parent pairs/dyads with the Beck Cognitive Insight Scale (BCIS). Other measures included the Scale to assess Unawareness of Mental Disorder and cognitive assessments. RESULTS: We found no significant association between parents' cognitive insight and their offspring's. Conversely, a positive association between parents' cognitive insight and parents' insight into their offspring's symptoms was found. Better awareness of their offspring's specific symptoms was associated with lower levels of overconfidence in one's beliefs and with BCIS total score. BCIS Self-Certainty and BCIS total score were associated with better executive functioning and verbal comprehension. CONCLUSIONS: Better insight into their offspring's symptoms is associated with cognitive insight in biological parents of schizophrenia patients. Our results support the integration of cognitive intervention targeting parents' cognitive flexibility in family psychoeducational programs and provide an important first step towards developing a more refined understanding of the factors involved in insight into symptoms of illness in parents of schizophrenia patients.

Ketamine administration in depressive disorders: a systematic review and meta-analysis.

INTRODUCTION: Ketamine's efficacy in depressive disorders has been established in several controlled trials. The aim of the present study was to determine whether or not ketamine administration significantly improves depressive symptomatology in depression and more specifically in major depressive disorder (MDD), bipolar depression, resistant depression (non-ECT studies), and as an anesthetic agent in electroconvulsive therapy (ECT) for resistant depression (ECT studies). Secondary outcomes were the duration of ketamine's effect, the efficacy on suicidal ideations, the existence of a dose effect, and the safety/tolerance of the treatment. METHODS: Studies were included if they met the following criteria (without any language or date restriction): design: randomized controlled trials, intervention: ketamine administration, participants: diagnosis of depression, and evaluation of severity based on a validated scale. We calculated standardized mean differences (SMDs) with 95 % confidence intervals (CIs) for each study. We used fixed and random effects models. Heterogeneity was assessed using the I2 statistic. RESULTS: We included nine non-ECT studies in our quantitative analysis (192 patients with major depressive disorder and 34 patients with bipolar depression). Overall, depression scores were significantly decreased in the ketamine groups compared to those in the control groups (SMD = -0.99; 95 % CI -1.23, -0.75; p < 0.01). Ketamine's efficacy was confirmed in MDD (resistant to previous pharmacological treatments or not) (SMD = -0.91; 95 % CI -1.19,-0.64; p < 0.01), in bipolar depression (SMD = -1.34; 95 % CI -1.94, -0.75), and in drug-free patients as well as patients under medication. Four ECT trials (118 patients) were included in our quantitative analysis. One hundred and three patients were diagnosed with major depressive disorder and 15 with bipolar depression. Overall, depression scores were significantly improved in the 58 patients receiving ketamine in ECT anesthesia induction compared to the 60 patients (SMD = -0.56; 95 % CI -1.10, -0.02; p = 0.04; I2 = 52.4 %). The duration of ketamine's effects was assessed in only two non-ECT studies and seemed to persist for 2-3 days; this result needs to be confirmed. Three of four studies found significant decrease of suicidal thoughts and one found no difference between groups, but suicidal ideations were only studied by the suicide item of the depressive scales. It was not possible to determine a dose effect; 0.5 mg/kg was used in the majority of the studies. Some cardiovascular events were described (mostly transient blood pressure elevation that may require treatment), and ketamine's use should remain cautious in patients with a cardiovascular history. CONCLUSION: The present meta-analysis confirms ketamine's efficacy in depressive disorders in non-ECT studies, as well as in ECT studies. The results of this first meta-analysis are encouraging, and further studies are warranted to detail efficacy in bipolar disorders and other specific depressed populations. Middle- and long-term efficacy and safety have yet to be explored. Extrapolation should be cautious: Patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy.

Smoking behavior characteristics of non-selected smokers with childhood attention-deficit/hyperactivity disorder (AD/HD) history: a systematic review and meta-analysis.

It is unclear whether adult smokers with childhood attention-deficit/hyperactivity disorder history (CH) have more severe smoking behavior than non-CH smokers, while it is clearly suggested that CH adolescents have more severe smoking behavior than CH adolescents. The aim of the present comprehensive meta-analysis is to determine whether CH smokers have more severe smoking behavior characteristics than those without and the effect of age on the association between CH and smoking behavior. We included all case-control studies and first round data collection of observational studies addressing the difference in smoking behavior characteristics of CH smokers versus non-CH smokers, with validated scales or structured interviews, without any language or date restriction. Nine studies (including 365 smokers with CH and 1,708 smokers without) were included. Compared to non-CH smokers, CH smokers smoked significantly more cigarettes [standardized mean differences (SMD) = 0.15, 95 % CI 0.01-0.28, p = 0.04] and began to regularly smoke earlier (SMD = -0.28, 95 % CI -0.49; -0.07, p = 0.01) but were not significantly more nicotine dependent (SMD = 0.23, 95 % CI -0.04 to 0.48, p = 0.08). After removing the single adolescent study, the significant association between CH and number of daily smoked cigarettes disappeared, and subgroups analyses confirmed that the significant association between CH and number of daily smoked cigarettes disappeared as age increased. Our meta-analysis illustrates a clinically important link between CH and tobacco smoking in adolescence but not later in life. Further high-quality studies are needed to confirm this finding, as only two studies included participants with a mean age below 20 years.

Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder.

We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

D2 and D3 dopamine receptor affinity predicts effectiveness of antipsychotic drugs in obsessive-compulsive disorders: a metaregression analysis.

RATIONALE AND OBJECTIVE: The relationship between clinically effective antipsychotic drugs in obsessive-compulsive disorders (OCD) and binding affinities to cloned dopamine and serotonin receptor subtypes was analyzed in an effort to clarify the contribution of individual receptor subtypes to medication response. METHODS: Meta-analysis was used to update previous meta-analyses of effectiveness data of add-on antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) in OCD. Twelve previously analyzed randomized controlled trials (RCTs) and one new RCT were included. We performed a metaregression using a mixed-effect model to examine the association between antipsychotic's effectiveness and receptor affinity. RESULTS: A total of 5 treatment arms obtained from 13 RCTs (431 patients) were included in our study. The results of our metaregression showed a significant association between D2 and D3 dopamine receptor affinities and effectiveness in OCD (respectively, slope = -0.36, p = 0.01; and slope = -0.50, p = 0.01) whereas other dopamine receptors and serotonin receptors were not significantly associated. CONCLUSIONS: These observations suggest that increasing D2 and D3 dopamine receptor binding affinities enhances antipsychotics' effectiveness in obsessive-compulsive disorders.