Effect of venlafaxine on anhedonia and amotivation in patients with major depressive disorder.

OBJECTIVE: Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD). METHODS: Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data. RESULTS: At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: -2.73 [-3.63, -1.82], p < 0.0001) and amotivation scores (mean, 95% CI: -0.78 [-1.04, -0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time. CONCLUSION: This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Role of Motivation in the Progression of Problem Gambling: A Comparison of Early and Late Adults.

Motivation plays a dominant role in gambling progression. Most studies using motivational scales have revealed that certain motivations are associated with problem gambling. However, age differences were found to be negligible in gambling motivation. This study aimed to examine the role of motivation associated with age differences in problem gambling in Japan. A total of 160 participants over 20 years of age who had gambled within the past six months were randomly recruited from web monitors. In this study, the Japanese version of the modified Gambling Motivation Scale (J-MGMS) was used which comprises six systematic factors: intellectual challenge, excitement, socialization (coping and sociability), social recognition, monetary gain, and amotivation. The Japanese version of the South Oaks Gambling Screening (J-SOGS) was used to assess participants' gambling-related problems. Demographic data, such as gambling frequency, were solicited. Using linear regression analysis, amotivation in all participants, social recognition in early adults (under 30), and amotivation in late adults (30 or over) were associated with J-SOGS scores (adjusted R2 = 0.170, 0.290, 0.156). Among late adults, social recognition was nearly significant, although negative (p = 0.0503). 1) Self-determinant (autonomous) motivations such as excitement and socialization do not contribute to the progression of problem gambling. 2) Two non-self-determinant (non-autonomous) motivations, social recognition in early adults and amotivation in late adults, are predictors of problem gambling. 3) Social recognition is a dichotomic and paradoxical motivation in the progress of problem gambling according to age.

Academic motivation decreases across adolescence for youth with and without attention-deficit/hyperactivity disorder: Effects of motivation on academic success.

BACKGROUND: This longitudinal study examined growth trajectories of academic motivation in youth with and without attention-deficit/hyperactivity disorder (ADHD) across the important developmental transition from middle school to high school, and associations with academic success. Consistent with self-determination theory (SDT) of motivation, trajectories of amotivation, extrinsic motivation, and intrinsic motivation were modeled. METHODS: The study included a robust multi-method, multi-source assessment of academic outcomes, including homework performance ratings; reading and mathematics standardized test scores; and grade point average (GPA) obtained from school records. Participants included 302 adolescents (ages 12-14; Mage = 13.20) in eighth grade who were specifically recruited so that approximately half (n = 162) were diagnosed with ADHD and 140 adolescents comprising a comparison sample without ADHD. The sample was predominantly White (81.80%), with 7.90% identifying as bi/multiracial, 5.30% identifying as Black/African American, 4.60% identifying as Asian, and 0.30% identifying as Indigenous/Alaskan. RESULTS: Adolescents with ADHD had worse academic motivation at all timepoints. Growth curve analyses indicated the academic motivation of adolescents without ADHD decreased at faster rates across the transition to high school compared to adolescents with ADHD. However, for adolescents with ADHD, amotivation, extrinsic motivation, and intrinsic motivation each predicted GPA, with higher extrinsic and intrinsic motivation also predicting better homework performance and different aspects of math performance, whereas for youth without ADHD, only amotivation and extrinsic motivation predicted GPA. CONCLUSIONS: Intervention and school policy implications are discussed, including the importance of fostering autonomy and internal motivation, and consideration of whether current ADHD interventions primarily foster extrinsic motivation.

The effect of salience of rewards on effort-based decision making in psychotic disorders.

BACKGROUND: Although motivational negative symptoms account for reduced functioning and quality of life in individuals with psychotic disorders, the underlying mechanisms are yet not fully understood. Neuroimaging studies suggest that an impaired perception of reward cues could result in a lack of incentive value that then leads to a decrease in goal-directed behavior. Therefore, the aim of this study was to test the effect of increasing the salience of reward cues on goal-directed behavior. METHODS: We recruited a sample of n = 30 participants with a psychotic disorder and at least mild negative symptoms and n = 30 healthy controls. We used the Balloon Effort Task, an effort-based decision-making paradigm, to assess amotivation on a behavioral level. We manipulated the salience of rewards in the paradigm by highlighting the monetary rewards in half of the trials. RESULTS: Total effort expenditure did not differ between participants with and without psychotic disorders, but participants with psychotic disorders showed a significantly reduced effort allocation to the level of rewards. The salience of rewards manipulation significantly increased effort expenditure both in participants with psychotic disorders and in the healthy controls, but had no impact on effort allocation. CONCLUSIONS: Increasing the salience of reward cues promotes goal-directed behavior. This opens up new possibilities for interventions addressing amotivation in individuals with negative symptoms by facilitating the perception of reward cues.

Effects of Cannabis-Delivered THC on mood and negative attentional bias in the context of positive vs. neutral Alternatives-a pilot study.

OBJECTIVE: To assess: (1) the acute effects of smoked marijuana (MJ) on negative attentional bias (NAB), (2) moderation of these effects by positive versus neutral alternatives, and (3) the associations of tetrahydrocannabinol (THC)-induced changes in NAB with changes in affect. METHODS: Fourteen MJ users (1-4 uses/wk) smoked a THC cigarette on 1 day and a placebo cigarette on the other counterbalanced day. After smoking, participants freely gazed back and forth at a series of two side-by-side pictures pairs presented for 3000 ms (one negative, while the other was either positive or neutral) while eye gaze was tracked. RESULTS: The effects of THC relative to placebo varied across time such that THC increased NAB during the early temporal component of threatening picture viewing, 333-858 ms after dual-picture onset, regardless of alternative picture valance. However, contrary to the attentional bias-causes affect hypothesis, during the early viewing phase THC-enhanced positive affect (PA) correlated positively with THC-induced NAB. In contrast, during the late phase (891-3000 ms) THC-enhanced PA did not correlate significantly with NAB, though THC-induced negative affect (NA) change did correlate positively with THC-induced change in NAB in the positive alternative condition. CONCLUSIONS: We replicated findings of others showing that THC can enhance NAB during the early stages of threatening picture viewing. We extended previous results by demonstrating the THC-induced NAB is associated with increased PA during initial threat viewing, but with increased NA during later processing if positive alternatives are present.

Distinct profiles of psychological and neuropsychological functions underlying goal-directed pursuit in schizophrenia.

OBJECTIVES: Several components are known to underlie goal-directed pursuit, including executive, motivational and volitional functions. These were explored in schizophrenia spectrum disorders in order to identify subgroups with distinct profiles. METHODS: Multiple executive, motivational and volitional tests were administered to a sample of outpatients with schizophrenia spectrum diagnoses (n = 59) and controls (n = 63). Research questions included whether distinct profiles exist and whether some functions are impacted disproportionately. These questions were addressed via cluster analysis and profile analysis, respectively. RESULTS: Some such functions were significantly altered in schizophrenia while others were unaffected. Two distinct profiles emerged, one characterized by energizing deficits, reduced reward sensitivity and few subjective complaints; while another was characterized by markedly increased punishment sensitivity, intact reward sensitivity and substantial subjective reporting of avolitional symptoms and boredom susceptibility. CONCLUSION: These findings highlight the importance of considering distinct patterns of strengths and deficits in functions governing goal-directed pursuit in schizophrenia that demarcate identifiable subtypes. These distinctions have implications for treatment, assessment and research.

How supervisors can support employees' needs and motivation? an experimental study based on SDT.

Supervisors and managers have an increasingly significant role in employees' motivation. The applied framework in this field research was the Self-Determination Theory (SDT). In this way, it was assessed that whether supervisors can be trained in order to support employees' basic psychological needs including autonomy, relatedness, and competence. As a result, their need satisfaction and autonomous motivation were promoted, at the same time, the controlled motivation and amotivation were reduced. The training was provided to 15 supervisors then employees' need satisfaction, amotivation, controlled motivation, and autonomous motivation were investigated, pre- and post-intrvention. Performing a multilevel regression analysis revealed that employees in the intervention group showed an increment in autonomous motivation and need satisfaction, as well as a significant reduction in amotivation than those of the control group. Furthermore, increasing autonomous motivation and decreasing amotivation were moderated via increasing need satisfaction. An added value has been provided for the mentioned theory on need satisfaction by the current study. It was also indicated that a relatively brief intervention for supervisors may affect creating employees need support, and autonomous motivation increment, and amotivation reduction.

Negative symptoms in schizophrenia: reconsidering evidence and focus in clinical trials.

Negative symptoms of schizophrenia have been documented in the literature for over a century. Nevertheless, research has not convincingly produced effective interventions for their treatment. We propose to re-analyse currently published evidence on treatment of negative symptoms, using narrower definitions for symptom dimensions, to better understand what works for whom.

Brain activity and connectivity differences in reward value discrimination during effort computation in schizophrenia.

Negative symptoms in the motivational domain are strongly correlated with deficits in social and occupational functioning in schizophrenia. However, the neural substrates underlying these symptoms remain largely unknown. Twenty-eight adults with schizophrenia and twenty healthy volunteers underwent functional magnetic resonance while completing a lottery game designed to capture reward-related cognitive processes. Each trial demanded an initial investment of effort in form of key presses to increase the odds of winning. Brain activity in response to different reward cues (1 euro versus 1 cent) was compared between groups. Whereas controls invested more effort in improving their chances to win 1 euro compared to 1 cent in the lottery game, patients invested similarly high amounts of effort in both reward conditions. The neuroimaging analysis revealed lower neural activity in the bilateral caudate and cingulo-opercular circuits and decreased effective connectivity between reward-associated areas and neural nodes in the frontoparietal and salience network in response to high- versus low-reward conditions in schizophrenia patients compared to controls. Effective connectivity differences across conditions were associated with amotivation symptoms in patients. Overall, our data provide the evidence of alterations in neural activity in the caudate and cingulo-opercular "task maintenance" circuits and frontoparietal effective connectivity with reward-associated nodes as possible underlying mechanisms of reward value discrimination deficits affecting effort computation in schizophrenia.

Relationship of subjective quality of life with symptomatology, neurocognition and psychosocial functioning in first-episode psychosis: a structural equation modelling approach.

Subjective quality of life (SQoL) represents an important outcome of psychotic disorders. However, determinants of SQoL and their complex inter-relationships in the early course of illness remain to be clarified. Association between neurocognitive impairment and SQoL in first-episode psychosis (FEP) is understudied. This study employed structural equation modeling (SEM) to examine relationships among SQoL, depressive, positive and negative symptoms, neurocognition, and psychosocial functioning in FEP patients. Three hundred and forty-seven patients aged 25-55 years presenting with FEP to early intervention program in Hong Kong were recruited. Assessment encompassing symptom profiles, psychosocial functioning and a battery of neurocognitive tests were conducted. SF-12 mental component summary scores were computed as the primary measure of SQoL. Our correlation analyses revealed differential relationships between negative symptom subdomains and SQoL, with amotivation, but not diminished expression, being related to SQoL. Final SEM model yielded a good model fit (comparative fix index = 0.94; root mean square error of approximation = 0.05; standardized root mean square residuals = 0.07) and demonstrated that depression, positive symptoms and psychosocial functioning were directly associated with SQoL, with depression showing the strongest effect. Amotivation, neurocognition and positive symptoms had an indirect effect on SQoL via the mediation of psychosocial functioning. This study affirms depression as a critical determinant of subjective mental wellbeing, and underscores an intermediary role of psychosocial functioning in linking amotivation, neurocognitive impairment and positive symptoms to SQoL in FEP patients. Depression and functional impairment thus constitute as crucial therapeutic targets for improvement of SQoL in the early illness stage.

Inter-relationships among psychopathology, premorbid adjustment, cognition and psychosocial functioning in first-episode psychosis: a network analysis approach.

BACKGROUND: Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP. METHOD: This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses. RESULTS: Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength. CONCLUSION: Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.

Cognitive effort-avoidance in patients with schizophrenia can reflect Amotivation: an event-related potential study.

BACKGROUND: Amotivation is regarded as a core negative symptom in patients with schizophrenia. There are currently no objective methods for assessing and measuring amotivation in the scientific literature, only a trend towards assessing motivation using effort-orientated, decision-making tasks. However, it remains inconclusive as to whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation. Therefore, this study aimed to find out whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation. METHODS: In total, 28 patients with schizophrenia and 27 healthy controls were selected as participants. The demand selection task (DST) was adapted according to the feedback-based Guilty Knowledge Test (GKT) delayed response paradigm, which was combined with the mean amplitude of contingent negative variation (CNV), considered as the criterion of motivation. RESULTS: Our results showed that: (1) patients with schizophrenia showed a lower CNV amplitude for the target stimuli compared to the probe stimuli, whereas the control group showed the opposite trend (P < 0.05); (2) among patients with schizophrenia, the high cognitive effort-avoidance group showed a smaller CNV amplitude for the target stimuli compared to the probe stimuli, whereas the low cognitive effort avoidance group showed a higher CNV amplitude for the target stimuli compared to the probe stimuli; the opposite trend was observed in the control group (P < 0.05). CONCLUSION: These findings support the claim that CNV amplitude can be used as a criterion for detecting amotivation in patients with schizophrenia. Within the context of the DST, the high and low cognitive effort-avoidance of patients with schizophrenia can reflect their state of amotivation; patients with high cognitive effort-avoidance showed severe amotivation.

Lebanese students' motivation in medical school: does it change throughout the years? A cross-sectional study.

BACKGROUND: Students entering medical school are driven by different types of motivation: autonomous motivation, controlled motivation, or amotivation. Motivation types can influence students' performance, outcome and well-being. To our knowledge, this topic has never been studied in Lebanese medical students. This study aims to identify students' motivation types in the first 5 years of medical school at two Lebanese universities (USJ and USEK). It also aims to determine the predominant motivation type of the whole sample. Results may be the first step towards raising awareness about this topic and implementing actions that enhance autonomous motivation. METHODS: A cross-sectional study was performed between January and June 2017. A questionnaire was sent to medical students by e-mail. The students' academic motivation was assessed using the Academic Motivation Scale. RESULTS: A higher mean autonomous motivation score was found in each academic year, as compared to the mean controlled motivation and amotivation scores. The highest mean autonomous motivation score was seen among second year students, whereas the lowest score was noted in fifth year students. The highest scores for controlled motivation and amotivation belonged to the fourth-year students, and the lowest to the first-year students. Students who were still satisfied with medical studies had a higher autonomous motivation score. Finally, USJ students who were satisfied with their second year training had a higher mean autonomous motivation score than those who were not. CONCLUSION: This study showed high levels of autonomous motivation in the first five years of medical school. Autonomous motivation was the predominant type in the whole sample. The highest scores of controlled motivation and amotivation were noted in the fourth year. Moreover, high levels of self-determination were seen in students who enjoyed their early contacts with patients through trainings. Actions should be implemented in medical schools to enhance and maintain autonomous motivation, and consequently students' outcome and health-care quality.

Executive dysfunctions differentially predict amotivation in first-episode schizophrenia-spectrum disorder: a prospective 1-year follow-up study.

Amotivation is a major determinant of functional outcome in schizophrenia but it is understudied in the early course of illness. There is a paucity of longitudinal research investigating predictors of amotivation. In this study, we aimed to examine baseline cognitive and clinical predictors of amotivation at 6 and 12 months of follow-up in patients aged 18-55 years presenting with first-episode DSM-IV schizophrenia-spectrum disorder (FES). Of 145 patients recruited at intake, 116 and 113 completed assessments at 6- and 12-month follow-up, respectively. Amotivation was measured by avolition-apathy and anhedonia-asociality subscale scores of the Scale of the Assessment of Negative Symptoms. Cognitive assessment was administered at baseline. As executive dysfunction has been more consistently found to be associated with negative symptoms and amotivation in prior literature, we adopted fractionated approach to subdivide executive function into distinct components encompassing switching and flexibility, response initiation, response inhibition, planning and strategy allocation, sustained attention and working memory. Our results showed that baseline amotivation (p = 0.01) and switching and flexibility (p = 0.01) were found to independently predict amotivation at 6 months follow-up. Baseline amotivation (p < 0.01) and switching and flexibility (albeit with trend-wise significance, p = 0.06) were also retained in final multivariate regression model for 12-month amotivation prediction. No other executive components or cognitive domains predicted amotivation at follow-up. Findings of our study thus indicate amotivation at initial presentation as a critical determinant of subsequent motivational deficits over 1 year of treatment for FES patients. Cognitive flexibility might be specifically related to the development of amotivation in the early stage of illness.

The Development of Motivation and Amotivation to Study and Work across Age-Graded Transitions in Adolescence and Young Adulthood.

People's motivation to engage in studying and working is an important precursor of participation and attainment. However, little is known about how motivation and the lack of motivation develops normatively across adolescence and young adulthood. Furthermore, there is no comparison of motivation and amotivation development across sequential age-graded transitions such as the mid-schooling transition in adolescence and the school-to-work transition in young adulthood. The current study explored trajectories of motivation and amotivation development in Finland, using piecewise growth curve modelling to analyze five waves of data (age 15-22 years) from a sample of 878 youth (52% male). Indicators of amotivation (disinterest, futility and inertia) decreased, whilst the indicator of motivation (attainment value) increased across both transitions. Reductions in disinterest and inertia were steeper for youth transferring into vocational education at the mid-schooling transition and for youth transferring from an academic track to higher education at the school-to-work transition. Amotivation and motivation shifted most at the school-to-work transition, signaling the importance of this period for motivation development. Overall, the results suggest that young people became more motivated and less amotivated as they aged from adolescence through young adulthood, in line with normative maturational and gradual social changes and transfer into increasingly personalized environments.

Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia.

OBJECTIVE: Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long-term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3 R) blockade by antipsychotics. METHODS: Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D2/3 R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. RESULTS: Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: ß = -.38, t = -2.48, P = .01; left: ß = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (ß = -.43, t = -0.26, P = .03). CONCLUSION: We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D2/3 R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit.

Negative symptoms, anxiety, and depression as mechanisms of change of a 12-month trial of assertive community treatment as part of integrated care in patients with first- and multi-episode schizophrenia spectrum disorders (ACCESS I trial).

Assertive community treatment (ACT) has shown to be effective in improving both functional deficits and quality of life (QoL) in patients with severe mental illness. However, the mechanisms of this beneficial effect remained unclear. We examined mechanisms of change by testing potential mediators including two subdomains of negative symptoms, i.e. social amotivation as well as expressive negative symptoms, anxiety, and depression within a therapeutic ACT model (ACCESS I trial) in a sample of 120 first- and multi-episode patients with a schizophrenia spectrum disorder (DSM-IV). Path modelling served to test the postulated relationship between the respective treatment condition, i.e. 12-month ACT as part of integrated care versus standard care, and changes in functioning and QoL. The final path model resulted in 3 differential pathways that were all significant. Treatment-induced changes in social amotivation served as a starting point for all pathways, and had a direct beneficial effect on functioning and an additional indirect effect on it through changes in anxiety. Expressive negative symptoms were not related to functioning but served as a mediator between changes in social amotivation and depressive symptoms, which subsequently resulted in improvements in QoL. Our results suggest that social amotivation, expressive negative symptoms, depression, and anxiety functioned as mechanisms of change of ACCESS. An integrated and sequential treatment focusing on these mediators may optimise the generalisation effects on functioning as well as on QoL by targeting the most powerful mechanism of change that fits best to the individual patient.

Motivational impairment predicts functional remission in first-episode psychosis: 3-Year follow-up of the randomized controlled trial on extended early intervention.

OBJECTIVE: Functional remission represents an intermediate functional milestone toward recovery. Differential relationships of negative symptom sub-domains with functional remission in first-episode psychosis are understudied. We aimed to examine rate and predictors of functional remission in people with first-episode psychosis in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention (i.e. 3-year early intervention) with step-down psychiatric care (i.e. 2-year early intervention). METHOD: A total of 160 participants were recruited upon completion of a 2-year specialized early intervention program for first-episode psychosis in Hong Kong and underwent a 1-year randomized controlled trial comparing 1-year extended early intervention with step-down care. Participants were followed up and reassessed 3 years after inclusion to the trial (i.e. 3-year follow-up). Functional remission was operationalized as simultaneous fulfillment of attaining adequate functioning (measured by Social and Occupational Functioning Scale and Role Functioning Scale) at 3-year follow-up and sustained employment in the last 6 months of 3-year study period. Negative symptom measure was delineated into amotivation (i.e. motivational impairment) and diminished expression (i.e. reduced affect and speech output). Data analysis was based on 143 participants who completed follow-up functional assessments. RESULTS: A total of 31 (21.7%) participants achieved functional remission status at 3-year follow-up. Multivariate regression analysis showed that lower levels of amotivation (p = 0.010) and better functioning at study intake (p = 0.004) independently predicted functional remission (Final model: Nagelkerke R2 = 0.40, χ2 = 42.9, p < 0.001). Extended early intervention, duration of untreated psychosis and diminished expression did not predict functional remission. CONCLUSION: Only approximately one-fifths of early psychosis patients were found to achieve functional remission. Functional impairment remains an unmet treatment need in the early stage of psychotic illness. Our results further suggest that amotivation may represent a critical therapeutic target for functional remission attainment in early psychosis.

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity.

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [(11)C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [(11)C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.

Neurocognitive impairment in the deficit subtype of schizophrenia.

Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.