Preliminary Evidence for Heterogeneity of Beliefs About Auditory Verbal Hallucinations Intent.

ABSTRACT: Perceptions of patient's auditory verbal hallucinations (AVHs), commonly termed voices, have important impacts on their everyday lives. Despite research emphasizing the consequences of malevolent voices, preliminary results suggest that beliefs about voices may not be mutually exclusive. As such, we aimed to characterize the heterogeneity of beliefs about AVHs and describe their clinical correlates. We recruited 78 patients referred to a Voices group therapy for refractory and distressing voices. Based on the Revised Beliefs About Voices Questionnaire, clustering analysis yielded four subgroups of patients with distinct pattern of beliefs about AVHs. These subgroups differed significantly in terms of affective disturbances, engagement, and resistance to their voices. Furthermore, no significant changes in beliefs about voices were observed after 6 weeks. Results of the current study suggest that the heterogeneity regarding the beliefs about AVHs should be targeted in treatment to reduce their associated negative outcomes.

A word is worth a thousand pictures: A 20-year comparative analysis of aberrant abstraction in schizophrenia, affective psychosis, and non-psychotic depression.

thinking is a cognitive process that involves the assimilation of concepts reduced from diffuse sensory input, organized, and interpreted in a manner beyond the obvious. There are multiple facets by which abstraction is measured that include semantic, visual-spatial and social comprehension. This study examined the prevalence and course of abstract and concrete responses to semantic proverbs and aberrant abstraction (composite score of semantic, visual-spatial, and social comprehension) over 20 years in 352 participants diagnosed with schizophrenia, affective psychosis, and unipolar non-psychotic depression. We utilized linear models, two-way ANOVA and contrasts to compare groups and change over time. Linear models with Generalized Estimation Equation (GEE) to determine association. Our findings show that regardless of diagnosis, semantic proverb interpretation improves over time. Participants with schizophrenia give more concrete responses to proverbs when compared to affective psychosis and unipolar depressed without psychosis. We also show that the underlying structure of concretism encompasses increased conceptual overinclusion at index hospitalization and idiosyncratic associations at follow-up; whereas, abstract thinking overtime encompasses increased visual-spatial abstraction at index and rich associations with increased social comprehension scores at follow-up. Regardless of diagnosis, premorbid functioning, descriptive characteristics, and IQ were not associated with aberrant abstraction. Delusions are highly and positively related to aberrant abstraction scores, while hallucinations are mildly and positively related to this score. Lastly, our data point to the importance of examining the underlying interconnected structures of 'established' constructs vis-à-vis mixed methods to provide a description of the rich interior world that may not always map onto current quantitative measures.

Neurocognition in Bipolar and Depressive Schizoaffective Disorder: A Comparison with Schizophrenia.

INTRODUCTION: Schizoaffective disorder (SA) is classified into bipolar (bSA) and depressive (dSA) subtypes. Although clinical differences between both have been reported, there is no clear information regarding their specific cognitive profile. OBJECTIVE: To compare neurocognition between SA subtypes and schizophrenia (SC). METHODS: A total of 61 patients were assessed and divided into 3 groups: 35 SC, 16 bSA, and 10 dSA. All participants signed an informed consent letter. The MATRICS Consensus Cognitive Battery, Central and South American version was used to assess neurocognition. The study was performed at the Instituto Nacional de Psiquiatría "Ramón de la Fuente". Participants were identified by specialized psychiatrists. Trained neuropsychologists carried out the clinical and cognitive assessment, which lasted 2 h approximately. RESULTS: The cognitive assessment showed a significant difference in Trail Making Test part A subtest (F[2,58] = 4.043; p = 0.023]. Post hoc analyses indicated that dSA obtained a significantly higher score than SC (MD = -11.523; p = 0.018). The f test showed a large effect size (f = 0.401). No statistical differences were observed regarding other cognitive variables. CONCLUSIONS: The cognitive profile of SA subtypes and SC is similar since no differences were found in most subtests. However, dSA may be less impaired than SC in measures of processing speed. Further research with larger samples must be conducted.

Sex Differences in Verbal Memory Predict Functioning Through Negative Symptoms in Early Psychosis.

Verbal memory (VM) is one of the most affected cognitive domains in first-episode psychosis (FEP) and is a robust predictor of functioning. Given that healthy females demonstrate superior VM relative to males and that female patients show less-severe illness courses than male patients, this study examined whether normative sex differences in VM extend to FEP and influence functioning. Four hundred and thirty-five patients (299 males, 136 females) with affective or nonaffective psychosis were recruited from a catchment-based specialized FEP intervention service and 138 nonclinical controls (96 males, 42 females) were recruited from the same community. One of the two neurocognitive batteries comprising six cognitive domains (VM, visual memory, working memory, attention, executive function, processing speed) were administered at baseline. In patients, positive and negative symptoms were evaluated at baseline and functioning was assessed at 1-year follow-up. Patients were more impaired than controls on all cognitive domains, but only VM showed sex differences (both patient and control males performed worse than females), and these results were consistent across batteries. In patients, better baseline VM in females was related to better functioning after 1 year, mediated through fewer baseline negative symptoms. Supplemental analyses revealed these results were not driven by affective psychosis nor by age and parental education. Thus, normative sex differences in VM are preserved in FEP and mediate functioning at 1-year follow-up via negative symptoms. This study highlights the importance of investigating sex effects for understanding VM deficits in early psychosis and suggests that sex may be a disease-modifying variable with important treatment implications.

Affective Disorders with Psychosis in Youth: An Update.

Mood disorders, including major depression and mania, can present with psychotic features. In youth psychotic-like phenomena such as "seeing faces in the dark" or "hearing noises" are fairly common. Rates of lifetime psychotic symptoms are much higher than rates of psychosis during a "current" episode of mania or depression in youth. Psychotic phenomena can be mood congruent or incongruent. A detailed mental status examination and clinical history include questioning to ensure the informants understand the questions being asked. There are interviews that structure how questions are asked, and rating scales that help anchor severity and quality of the mood episode.

Liraglutide and the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis: protocol for a pilot trial.

BACKGROUND: People with severe mental illness (SMI) are two to three times more likely to be overweight and obese than the general population and this is associated with significant morbidity and premature mortality. Although lifestyle interventions can support people with SMI to lose weight, some are unable to make the necessary lifestyle changes or, despite making the changes, continue to gain weight. OBJECTIVE: To assess the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, a once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis. METHODS: Design: a single-centre, double-blind, randomised, placebo-controlled trial. SETTING: mental health facilities within Southern Health NHS Trust. PARTICIPANTS: 60 adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication will be recruited. Participants will be overweight or obese, defined by their baseline BMI which will be: • BMI ≥ 30 kg/m2 or • BMI ≥ 27 kg/m2 to < 30 kg/m2 in the presence of at least one weight-related consequence. This is in concordance with the current EU licence for liraglutide (maximum dosage 3.0 mg). INTERVENTION: participants will be allocated in a 1:1 ratio using a computer-based randomisation programme to either once-daily subcutaneously administered liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. All participants will receive standardised written information about healthy eating and exercise at their randomisation visit. OUTCOMES: the main aim of the study is to gather data on recruitment, consent, retention and adherence. Qualitative interviews with a purposive sub-sample of participants and healthcare workers will provide data on intervention feasibility and acceptability. Secondary clinical outcome measurements will be assessed at 3 and 6 months and will include: weight, fasting plasma glucose, lipid profile, HbA1c level; and the Brief Psychiatric Rating Scale. DISCUSSION: This study should provide evidence of the potential benefits of liraglutide (maximum dosage 3.0 mg daily) on body weight and metabolic variables in people with schizophrenia, schizoaffective disorder and first-episode psychosis. It will also address the feasibility and acceptability of the use of liraglutide in mental health settings. This will inform the design of a longer outcome study that will be needed to determine whether any weight loss can be maintained in the long term. TRIAL REGISTRATION: Universal Trial Number (UTN), ID: U1111-1203-0068. Registered on on 2/10/2017. European Clinical Trials Database (EudraCT), ID: 2017-004064-35. Registered on 3/10/2017.

HPA axis in psychotic major depression and schizophrenia spectrum disorders: Cortisol, clinical symptomatology, and cognition.

The Hypothalamic Pituitary Adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance, and a potential role of HPA axis genetic variation in cognition. In schizophrenia differential HPA activity has been found, including higher rates of non-suppression to dexamethasone challenge and higher salivary cortisol levels, which have been a premonitory risk factor for conversion to psychosis in adolescents at risk for developing schizophrenia. The present study investigated the simultaneous roles HPA axis activity and clinical symptomatology play in poor cognitive performance. Patients with major depression with psychosis (PMD) or schizophrenia spectrum disorder (SCZ) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, and overnight hourly blood sampling for cortisol. Cognitive performance did not differ between the clinical groups, though they both performed more poorly than the HC's across a variety of cognitive domains. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher evening cortisol levels than did SCZ and HCs. Cortisol and clinical symptoms, as well as age, sex, and antipsychotic use predicted cognitive performance. Diathesis stress models and their links to symptomatology, cognition, and HPA function are discussed.

Sixth Kraepelin Symposium-Understanding and Treating Cognitive Impairment and Depression in Schizophrenia and Affective Disorders.

The Sixth Kraepelin Symposium was held at the Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich in October 2018, covering reports from 12 working groups (Keith H. Nuechterlein, Ph.D., University of California, Los Angeles; Kim T. Mueser, Ph.D., Center for Psychiatric Rehabilitation, Boston University, U.S.A.; Dominic Dwyer, Ph.D, Hospital LMU, Munich; David Fowler, Ph.D. University of Sussex, Brighton, U.K.; Martin Hautzinger, Ph.D., University of Tübingen; Nikolaos Koutsouleris, M.D., Hospital LMU, Munich; Stephan Leucht, M.D., Technical University Munich, Munich; David Miklowitz, Ph.D., UCLA School of Medicine, Los Angeles. U.S.A.; Cornelius Schüle, M.D., Hospital LMU, Munich; Florian Seemüller. M.D., kbo-Lech-Mangfall Clinics for Psychiatry and Psychotherapy, Garmisch Partenkirchen; Carla Torrent, Ph.D., Institute of Neuroscience, University of Barcelona, Barcelona, Spain.) from the United States and Europe on understanding and treating cognitive impairment and depression in schizophrenia and affective disorders. Current psychological interventions to improve outcome in schizophrenia and affective disorder such as cognitive remediation, illness management, psychoeducational and cognitive therapy were focused on, as were evidence-based psychological and pharmacological treatment options, guidelines for treating cognitive deficits and depression in schizophrenia, Cochrane-meta-analysis of acute therapies, relapse prevention as well as supported withdrawal from medication. Prevention of cognitive dysfunction and symptom exacerbation was approached in terms of machine learning methods to revisit Kraepelin's illness distinctions, application of new strategies in order to increase the rate of social recovery in patients with first-episode psychosis as well as in terms of state of the art psychosocial interventions for bipolar disorder in adolescents. Finally, the dissemination of information to consumers and the contribution to the reduction of stereotypes in psychiatry was also part of the symposiums aims.

An association between YKL-40 and type 2 diabetes in psychotic disorders.

OBJECTIVE: This study examines if YKL-40 is increased in individuals with psychotic disorders and if elevated YKL-40 levels at baseline is associated with subsequent development of type 2 diabetes. METHOD: A total of 1383 patients with a diagnosis of schizophrenia or affective psychosis and 799 healthy controls were recruited in the period 2002-2015. Plasma YKL-40 and metabolic risk factors were measured and medication was recorded. Using national registry data, association between baseline risk factors and later development of type 2 diabetes was assessed using Cox proportional hazards models. RESULTS: Plasma YKL-40 was higher in patients vs. healthy controls also after adjusting for metabolic risk factors, with no difference between the schizophrenia and affective psychosis groups. Patients were diagnosed with type 2 diabetes at a significantly younger age. Multivariate Cox regression analyses showed that elevated YKL-40 (hazard ratio (HR) = 5.6, P = 0.001), elevated glucose (HR = 3.6, P = 0.001), and schizophrenia diagnosis (HR = 3.0, P = 0.014) at baseline were associated with subsequent development of type 2 diabetes. CONCLUSIONS: Patients with psychotic disorders have at baseline increased levels of YKL-40 beyond the effect of comorbid type 2 diabetes and metabolic risk factors. Elevated YKL-40 level at baseline is associated with later development of type 2 diabetes.

Working Memory Impairment Across Psychotic disorders.

BACKGROUND: Working memory (WM) has been a central focus of cognitive neuroscience research because WM is a resource that is involved in many different cognitive operations. The goal of this study was to evaluate the clinical utility of WM paradigms developed in the basic cognitive neuroscience literature, including methods designed to estimate storage capacity without contamination by lapses of attention. METHODS: A total of 61 people with schizophrenia, 49 with schizoaffective disorder, 47 with bipolar disorder with psychosis, and 59 healthy volunteers were recruited. Participants received multiple WM tasks, including two versions each of a multiple Change Detection paradigm, a visual Change Localization paradigm, and a Running Span task. RESULTS: Healthy volunteers performed better than the combined patient group on the visual Change Localization and running span measures. The multiple Change Detection tasks provided mixed evidence about WM capacity reduction in the patient groups, but a mathematical model of performance suggested that the patient groups differed from controls in their rate of attention lapsing. The 3 patient groups performed similarly on the WM tasks. Capacity estimates from the Change Detection and Localization tasks showed significant correlations with functional capacity and functional outcome. CONCLUSIONS: The patient groups generally performed in a similarly impaired fashion across tasks, suggesting that WM impairment and attention lapsing are general features of psychotic disorders. Capacity estimates from the Change Localization and Detection tasks were related to functional capacity and outcome, suggesting that these methods may be useful in a clinical context.

Cognitive reserve as an outcome predictor: first-episode affective versus non-affective psychosis.

OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education-occupation; leisure activities). The groups were divided into high and low CR. RESULTS: In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CONCLUSION: CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.

Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis.

OBJECTIVES: Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery. METHODS: Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report. RESULTS: A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings. CONCLUSIONS: We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2018, 24, 382-390).

Olfactory Functioning in First-Episode Psychosis.

Background: Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. Method: FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Results: Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. Conclusions: These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder.

Background: Context processing may reflect a specific cognitive impairment in schizophrenia. Whether impaired context processing is observed across psychotic disorders or among relatives of affected individuals, and whether it is a deficit that is independent from the generalized neuropsychological deficits seen in psychotic disorders, are less established. Methods: Schizophrenia, schizoaffective, and psychotic bipolar probands (n = 660), their first-degree relatives (n = 741), and healthy individuals (n = 308) studied by the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium performed an expectancy task requiring use of contextual information to overcome a pre-potent response. Sensitivity for target detection and false alarm rates on trials requiring inhibition or goal maintenance were measured. Results: Proband groups and relatives with psychosis spectrum personality traits demonstrated reduced target sensitivity and elevated false alarm rates. False alarm rate was higher under inhibition vs goal maintenance conditions although this difference was attenuated in schizophrenia and schizoaffective proband groups. After accounting for global neuropsychological impairment, as reflected by the composite score from the Brief Assessment of Cognition in Schizophrenia neuropsychological battery, deficits in schizophrenia and bipolar proband groups were no longer significant. Performance measures were moderately familial. Conclusion: Reduced target detection, but not a specific deficit in context processing, is observed across psychotic disorders. Impairments in both goal maintenance and response inhibition appear to contribute comparably to deficits in schizophrenia and schizoaffective disorder, whereas greater difficulty with response inhibition underlies deficits in bipolar disorder. Yet, these deficits are not independent from the generalized neurocognitive impairment observed in schizophrenia and psychotic bipolar disorder.

Auditory Vigilance and Working Memory in Youth at Familial Risk for Schizophrenia or Affective Psychosis in the Harvard Adolescent Family High Risk Study.

BACKGROUND: The degree of overlap between schizophrenia (SCZ) and affective psychosis (AFF) has been a recurring question since Kraepelin's subdivision of the major psychoses. Studying nonpsychotic relatives allows a comparison of disorder-associated phenotypes, without potential confounds that can obscure distinctive features of the disorder. Because attention and working memory have been proposed as potential endophenotypes for SCZ and AFF, we compared these cognitive features in individuals at familial high-risk (FHR) for the disorders. METHODS: Young, unmedicated, first-degree relatives (ages, 13-25 years) at FHR-SCZ (n=41) and FHR-AFF (n=24) and community controls (CCs, n=54) were tested using attention and working memory versions of the Auditory Continuous Performance Test. To determine if schizotypal traits or current psychopathology accounted for cognitive deficits, we evaluated psychosis proneness using three Chapman Scales, Revised Physical Anhedonia, Perceptual Aberration, and Magical Ideation, and assessed psychopathology using the Hopkins Symptom Checklist -90 Revised. RESULTS: Compared to controls, the FHR-AFF sample was significantly impaired in auditory vigilance, while the FHR-SCZ sample was significantly worse in working memory. Both FHR groups showed significantly higher levels of physical anhedonia and some psychopathological dimensions than controls. Adjusting for physical anhedonia, phobic anxiety, depression, psychoticism, and obsessive-compulsive symptoms eliminated the FHR-AFF vigilance effects but not the working memory deficits in FHR-SCZ. CONCLUSIONS: The working memory deficit in FHR-SZ was the more robust of the cognitive impairments after accounting for psychopathological confounds and is supported as an endophenotype. Examination of larger samples of people at familial risk for different psychoses remains necessary to confirm these findings and to clarify the role of vigilance in FHR-AFF. (JINS, 2016, 22, 1026-1037).

Impact of psychotic symptoms on cognitive functioning in child and adolescent psychiatric inpatients with severe mood disorders.

Despite established differences in cognitive functioning of adults with mood disorder-related psychosis and those with non-affective psychotic disorders, there is limited evidence of the impact of psychotic symptoms on the cognitive functioning of children and adolescents with mood disorders. This study investigates IQ, working memory, and processing speed scores in 80 child and adolescent inpatients discharged from an intermediate care state psychiatric hospital, using a retrospective chart review. Associations between diagnosis based on DSM-IV criteria (7 with Major Depression- MDD; 43 with Bipolar Disorders-BD, and 30 with Mood Disorders Not Otherwise Specified-NOS), presence of current psychotic features, and cognitive functioning (WISC-IV IQ, Coding, Symbol Search, and Digit Span) were investigated using Multivariate Analyses of Variance. No differences were found in cognitive functioning between patients with MDD and BD, or between those with severe Mood Disorders (MDD or BD) and those with NOS, when controlling for age, gender, and presence of psychotic features. However, patients with severe mood disorders and psychotic features showed lower IQs and greater working memory deficits than those without psychotic features or NOS. Results are discussed in terms of treatment planning for children and adolescents at risk for developing psychotic symptoms and severe mood disorders.

Cognitive Function in Individuals With Psychosis: Moderation by Adolescent Cannabis Use.

Prior cannabis use, compared to nonuse, is reported to be associated with less cognitive impairment in schizophrenia. The age of cannabis use and the persistent influence of cannabis use on cognitive function has not been examined across the psychosis dimension. Ninety-seven volunteers with psychosis (schizophrenia, schizoaffective, or bipolar psychosis) and 64 controls were recruited at the Dallas site of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Cannabis use history obtained in a semi-structured manner was used to categorize subjects into nonusers, adolescent-onset users, and late-onset users. The a priori hypothesis tested was that individuals with psychosis and a history of adolescent cannabis use (ACU) would have better global neuropsychological performance, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) battery, compared to those with psychosis and no cannabis use history. BACS Composite scores were significantly higher in individuals with psychosis with ACU compared to individuals with psychosis and no prior cannabis use. In subgroup analyses, ACU influenced global cognition in the schizophrenia/schizoaffective (SCZ) subgroup but not the bipolar psychosis subgroup. Exploratory analyses within the SCZ group, suggest that ACU was associated with better performance in specific domains compared to non-ACU groups. There are distinct associations between age of cannabis use and neuropsychological function across psychotic illnesses. Specifically, ACU is associated with better cognitive function in SCZ but not bipolar psychosis. This age-dependent and diagnosis-specific influence of cannabis may need to be factored into the design of future cognitive studies in SCZ.

Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders.

BACKGROUND: There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. METHODS: Resting-state functional magnetic resonance imaging was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early-stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions of interest (ROIs) on the basis of connectivity with six a priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxelwise seed-based analyses to further localize thalamic dysconnectivity. RESULTS: ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early-stage psychosis patients. PFC hypoconnectivity and motor cortex hyperconnectivity correlated in patients, suggesting that they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypoconnectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described executive control network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. CONCLUSIONS: Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment.

Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients.

OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (ß=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (ß=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. CONCLUSIONS: DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.