The Role of Defeatist Performance Beliefs in State Fluctuations of Negative Symptoms in Schizophrenia Measured in Daily Life via Ecological Momentary Assessment.

BACKGROUND AND HYPOTHESIS: The Cognitive Model of Negative Symptoms is a prominent model that posits that defeatist performance beliefs (DPB) are a key psychological mechanism underlying negative symptoms in those with schizophrenia (SZ). However, the ecological validity of the model has not been established, and temporally specific evaluations of the model's hypotheses have not been conducted. This study tested the model's key hypotheses in real-world environments using ecological momentary assessment (EMA). STUDY DESIGN: Fifty-two outpatients with SZ and 55 healthy controls (CN) completed 6 days of EMA. Multilevel models examined concurrent and time-lagged associations between DPB and negative symptoms in daily life. STUDY RESULTS: SZ displayed greater DPB in daily life than CN. Furthermore, greater DPB were associated with greater concurrently assessed negative symptoms (anhedonia, avolition, and asociality) in daily life. Time-lagged analyses indicated that in both groups, greater DPB at time t led to elevations in negative symptoms (anhedonia, avolition, or asociality) at t + 1 above and beyond the effects of negative symptoms at time t. CONCLUSIONS: Results support the ecological validity of the Cognitive Model of Negative Symptoms and identify a temporally specific association between DPB and subsequent negative symptoms that is consistent with the model's hypotheses and a putative mechanistic pathway in Cognitive Behavioral Therapy for negative symptoms. Findings suggest that DPB are a psychological factor contributing to negative symptoms in real-world environments. Implications for measuring DPB in daily life and providing just-in-time mobile health-based interventions to target this mechanism are discussed.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

An exploration of blood-based biomarkers of negative symptoms of psychosis in men.

Negative symptoms in the context of psychosis are still poorly understood and diagnosed, which impairs the treatment efficacy of current therapies and patient's integration in society. In this study, we aimed to test hypothesis-based and exploratory associations of negative symptom domains, as defined by the Brief Negative Symptom Scale (BNSS), with hormonal and hematological variables, and, complementarily, with standard psychological/cognitive and psychopathological measures. Fifty-one male patients diagnosed with a psychotic disorder underwent a structured interview and blood collection. Standard Spearmen bivariate correlations were used for data analysis. We obtained evidence of hypothesis-based associations between specific negative symptoms and oxytocin, thyroid stimulating hormone levels and neutrophil-to-lymphocyte ratio; as well as novel and hypothesis-free associations with erythrocyte and lymphocyte count, mean corpuscular volume and red cell distribution width. Complementarily, we also obtained some validation of previous associations of negative symptoms with illness resolution, cognitive symptom severity and social performance, and a novel association with anger contagion. We hope our results can generate new hypotheses in psychosis research. Our work suggests further avenues in research on erythrocytic, inflammatory, thyroid and oxytocin-related markers and abnormalities in psychosis, especially in regards to specific negative symptoms, towards more precise and comprehensive etiological, diagnostic and therapeutic models.

Blunted ventral striatal reactivity to social reward is associated with more severe motivation and pleasure deficits in psychosis.

Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a key role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences. Here we leveraged parallel social and monetary incentive delay fMRI paradigms to test whether blunted reactivity to social incentives in the ventral striatum-a key component of the distributed neural circuit mediating appetitive motivation and hedonic pleasure-is associated with more severe MAP symptoms in a transdiagnostic sample enriched for psychosis. To maximize ecological validity and translational relevance, we capitalized on naturalistic audiovisual clips of an established social partner expressing positive feedback. Although both paradigms robustly engaged the ventral striatum, only reactivity to social incentives was associated with clinician-rated MAP deficits. This association remained significant when controlling for other symptoms, binary diagnostic status, or ventral striatum reactivity to monetary incentives. Follow-up analyses suggested that this association predominantly reflects diminished striatal activation during the receipt of social reward. These observations provide a neurobiologically grounded framework for conceptualizing the social-anhedonia symptoms and social impairments that characterize many individuals living with psychotic disorders and underscore the need to establish targeted intervention strategies.

Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats.

RATIONALE: Motivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and rodents. OBJECTIVES: Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats. METHODS: The present studies compared the effort-related effects of IP injections of the dopamine antagonists ecopipam and haloperidol, and the vesicular monoamine transport-2 inhibitor tetrabenazine (TBZ), in male and female rats using the fixed ratio 5/chow feeding choice task. RESULTS: Ecopipam (0.05-0.2 mg/kg) and haloperidol (0.05-0.15 mg/kg) induced a low-effort bias, decreasing lever pressing and increasing chow intake in males and females in the same dose range. With lever pressing, there was a modest but significant dose x sex interaction after ecopipam injection, but there was no significant interaction after administration of haloperidol. In the first study with TBZ (0.25-1.0 mg/kg), there was a robust sex difference. TBZ shifted choice from lever pressing to chow intake in male rats, but was ineffective in females. In a second experiment, 2.0 mg/kg affected choice behavior in both males and females. TBZ increased accumbens c-Fos immunoreactivity in a sex-dependent manner, with males significantly increasing at 1.0 mg/kg, while females showed augmented immunoreactivity at 2.0 mg/kg. CONCLUSIONS: The neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology.

Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Specific mechanisms underlying executive and emotional apathy: A phenotyping study.

Apathy is a behavioral symptom prevalent both in neuropsychiatric pathologies and in the healthy population. However, the knowledge of the cognitive and neural mechanisms underlying apathy is still very limited, even if clinical and fMRI data support the existence of three forms of apathy (executive, emotional, initiative). These forms could be explained by the alteration of specific mechanisms. This present study's aim is to specify the cognitive and neuronal mechanisms of executive and emotional apathy. We used an EEG study conducted on 68 subjects comprising two groups of young people with specific executive or emotional phenotypes of apathy and one group with no apathy. Despite having symptom of apathy, participants were free of any neurological, metabolic, or psychiatric diagnoses and with high education. Two tasks were used: the DPX for cognitive control and the MID for motivation. Our results showed that distinct mechanisms underlie these two forms of apathy, and, for the first time, we specified these mechanisms. A deficit of the proactive control mode, reflected by a reduced probe-N2 amplitude in AY trials, underlies the executive form of apathy (p < .03), whereas liking motivational blunting, highlighted by a reduced LPP amplitude for financial loss, characterizes the emotional form (p < .04). The main limit of the results is that generalizability to the general population may be reduced since the apathetic samples were chosen for having a specific form of apathy. To conclude, better knowledge of these mechanisms informs new, more targeted treatments, both pharmacological and non-pharmacological, necessary for reducing the debilitating consequences of apathy.

Unraveling depression: Principles and practices of clinical hypnosis.

People struggling with depression are burdened by losses they can't and won't accept. They find themselves at odds not only with their circumstances, but also with symptomatic expressions of their exhausting efforts to shelter from, gird against, and contend with their pain and desolation. Their embattled sense of self gets no respite: Everything, including the depression itself, feels threatening, a violation, other. This article investigates why, and demonstrates how, hypnosis is particularly well suited for treating such self-referential, adversarial entanglements. Fundamentally associational in both structure and function, hypnosis resonates with other long-established, connection-based traditions for altering suffering. In keeping with Taoist, Sufi, and Buddhist ideas and practices, hypnosis introduces a quality of acceptance into the relationship between self and other, between self and pain. Clinical hypnosis establishes and maintains a context of interpersonal and intrapersonal security, a protective space and a relationship in which avolitional experience is not felt to be out-of-control or uncontrollable, but rather not-in-need-of-being-controlled. It thus becomes safe for clients to become curious about, approach, and engage with what in other settings would have the potential of producing a fearful, even panicky, reaction. By altering the boundary between clients and their suffering, clinicians facilitate an effortless rapprochement, making possible the shifting, repurposing, and unraveling of symptoms.

The validity of a therapeutic invigoration task in avolitional schizophrenia outpatients.

BACKGROUND AND OBJECTIVES: Avolition is associated with much morbidity and functional impairment in schizophrenia patients. Vigor may be taken as, in part, the inverse of avolition, but it has not been investigated as a therapeutic pursuit before. To this end, a therapeutic invigoration task was developed drawing on cognitive-behavioral and guided imagery therapies. This study investigated the validity and reliability of a therapeutic invigoration task in avolitional residual phase schizophrenia outpatients. METHODS: In a proof-of-concept quasi-experimental one-group sequentially repeated pretest/posttest study design, patients (n = 76) participated in a structured invigoration task that was repeated after 1 month (n = 70). RESULTS: Patients' vigor during the preceding 7 days measured on the Vigor Assessment Scale increased highly significantly in anticipation of the subsequent 7 days on both occasions with respectively very large (Cohen's δ with Hedges' correction [δ] = 1.46) and large (δ = 1.04) effect sizes. The anticipated vigor after the first occasion was partially consummated during the subsequent month in that vigor during the 7 days preceding the second occasion was lower than participants had anticipated but still significantly higher than at baseline (p < 0.001; δ = 0.70). Repeating the task a month later, together with homework, had a cumulative effect as indicated by a very large effect size (δ = 1.61). CONCLUSION: Results suggest that the invigoration task did what it was supposed do, and did so consistently, in patients with avolitional residual schizophrenia. These results warrant a subsequent randomized controlled trial to establish the efficacy of the invigoration task.

Evaluation of a new intrinsic and extrinsic motivation scale in youth with psychosis spectrum symptoms.

BACKGROUND: Impairment in intrinsic motivation (IM), the drive to satisfy internal desires like mastery, may play a key role in disability in psychosis. However, we have limited knowledge regarding relative impairments in IM compared to extrinsic motivation (EM) or general motivation (GM), in part due to limitations in existing measures. METHODS: Here we address this gap using a novel Trait Intrinsic and Extrinsic Motivation self-report scale in a sample of n = 243 participants including those with schizophrenia, psychosis-risk, and healthy controls. Each of the 7 IM and 6 EM items used a 7-point Likert scale assessing endorsement of dispositional statements. Bifactor analyses of these items yielded distinct IM, EM, and GM factor scores. Convergent and discriminant validity were examined in relation to General Causality Orientation Scale (GCOS-CP) and Quality of Life 3-item IM measure (QLS-IM). Utility was assessed in relation to psychosis-spectrum (PS) status and CAINS clinical amotivation. RESULTS: IM and EM showed acceptable inter-item consistency (IM: α = 0.88; EM: α = 0.66); the bifactor model exhibited fit that varied from good to borderline to inadequate depending on the specific fit metric (SRMR = 0.038, CFI = 0.94, RMSEA = 0.106 ± 0.014). IM scores correlated with established IM measures: GCOS-CP Autonomy (rho = 0.38, p < 0.01) and QLS-IM (rho = 0.29, p < 0.01). Supporting discriminant validity, IM did not correlate with GCOS-CP Control (rho = -0.14, p > 0.05). Two-year stability in an available longitudinal subset (n = 35) was strong (IM: rho = 0.64, p < 0.01; EM: rho = 0.55, p < 0.01). Trait IM was lower in PS youth (t = 4.24, p < 0.01), and correlated with clinical amotivation (rho = -0.36, p < 0.01); EM did not show significant clinical associations. CONCLUSIONS: These results demonstrate the clinical relevance of IM in psychosis risk. They also provide preliminary support for the reliability, validity and utility of this new Trait IM-EM scale, which addresses a measurement gap and can facilitate identification of neurobehavioral and clinical correlates of IM deficits.

Effort-related effects of chronic administration of the DA D2 receptor antagonist haloperidol via subcutaneous programmable minipumps: Reversal by co-administration of the adenosine A2A antagonist istradefylline.

RATIONALE: Long-acting antipsychotics such as haloperidol decanoate are becoming more commonly used. Long-acting depot formulations have several advantages, but secondary negative effects of prolonged delivery, including motivational dysfunctions, could have debilitating effects. Assessing the behavioral changes that emerge during chronic antipsychotic administration in rats could provide insight regarding the development of motivational dysfunctions and drug tolerance. OBJECTIVES: Acute administration of dopamine D2 antagonists such as haloperidol induce motivational deficits in rats, as marked by a shift towards a low-effort bias during effort-based choice tasks. In the present studies, programmable subcutaneous infusion pumps provided continuous and controlled drug delivery of haloperidol. Animals were assessed using a fixed ratio (FR) 5 lever pressing schedule and the FR5/chow feeding test of effort-based choice. The adenosine A2A antagonist istradefylline was studied for its ability to reverse the effects of chronic haloperidol. RESULTS: Continuous chronic infusions of haloperidol produced significant reductions in FR5 performance and a shift from lever pressing to chow intake in rats tested on FR5/chow feeding choice, with no evidence of tolerance over the 4-week infusion period. Behavior returned to baseline during the vehicle-infusion washout period. Istradefylline significantly reversed the effects of haloperidol, increasing lever pressing and decreasing chow intake in haloperidol-treated rats. CONCLUSIONS: These studies provide an important behavioral characterization of the effects of chronically infused haloperidol, and demonstrate that A2A antagonism reverses the effects of chronic haloperidol. This research could contribute to the understanding and treatment of motivational dysfunctions seen in schizophrenia, Parkinson's disease, and other disorders involving dopamine.

Environmental factors contributing to negative symptoms in youth at clinical high risk for psychosis and outpatients with schizophrenia.

BACKGROUND: A bioecosystem theory was recently proposed positing that negative symptoms of schizophrenia (SZ) are influenced by environmental factors. These environmental processes reflect sources of resource deprivation that manifest across multiple systems that impact individuals directly through microsystems and indirectly through the exosystem and macrosystem. As an initial test of this theory, the current study examined whether self-reported environmental resource deprivation was associated with anhedonia, avolition, and asociality. METHOD: Two samples were collected: (1) outpatients with schizophrenia or schizoaffective disorder (SZ: n = 38) and matched psychiatrically heathy controls (CN: n = 31); (2) youth at clinical high risk for psychosis (CHR: n = 34) and matched CN (n = 30). Measures of negative symptoms and environmental factors influencing the frequency of recreational, goal-directed, and social activities were collected. RESULTS: Negative symptoms were associated with environmental deprivation factors in the microsystem (number of social and activity settings) and exosystem (economy, mass media, politics/laws, neighborhood crime). These associations did not appear due to depression and were greater among those with SZ than CHR. CONCLUSIONS: These findings provide preliminary support for the bioecosystem theory and highlight an under-recognized role for environmental factors underlying negative symptoms across phases of psychotic illness. Environmental systems-focused treatment approaches may offer a novel means of treating negative symptoms, which could be promising when coupled with person-level pharmacological and psychosocial treatments.

Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features.

AIMS: Our study aimed to develop a machine learning ensemble to distinguish "at-risk mental states for psychosis" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings. METHODS: 58 non-help-seeking medication-naïve ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and "Subject's Overview" section was filmed (5-10 min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used. RESULTS: Final model reached 83 % of mean F1-score, and balanced accuracy of 85 %. Mean area under the curve for the receiver operator curve classifier was 93 %. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item). CONCLUSION: Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.

Environmental context predicts state fluctuations in negative symptoms in youth at clinical high risk for psychosis.

BACKGROUND: Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants. METHODS: CHR youth (n = 116) and CN (n = 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts. RESULTS: Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home. CONCLUSIONS: Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.

Turning the Spotlight on Apathy: Identification and Treatment in Schizophrenia Spectrum Disorders.

Among negative symptoms, apathy is central to the impairments in real-life functioning in schizophrenia spectrum disorders (SSD). Thus, optimizing treatment for apathy appears key to improve outcomes. In treatment research, however, negative symptoms are typically studied as a unifactorial construct. We, therefore, aim to shed necessary light on the status of apathy identification and treatment in SSD.

Negative Symptom Inventory-Self-Report (NSI-SR): Initial development and validation.

Negative symptoms (i.e., anhedonia, avolition, asociality, blunted affect, alogia) are frequently observed in the schizophrenia-spectrum (SZ) and associated with functional disability. While semi-structured interviews of negative symptoms represent a gold-standard approach, they require specialized training and may be vulnerable to rater biases. Thus, brief self-report questionnaires measuring negative symptoms may be useful. Existing negative symptom questionnaires demonstrate that this approach may be promising in schizophrenia, but no measure has been devised for use across stages of psychotic illness. The present study reports initial psychometric validation of the Negative Symptom Inventory-Self-Report (NSI-SR), the self-report counterpart of the Negative Symptom Inventory-Psychosis Risk clinical interview. The NSI-SR is a novel transphasic negative symptoms measure assessing the domains of anhedonia, avolition, and asociality. The NSI-SR and related measures were administered to two samples: 1) undergraduates (n = 335), 2) community participants, including: SZ (n = 32), clinical-high risk for psychosis (CHR, n = 25), and healthy controls matched to SZ (n = 31) and CHR (n = 30). The psychometrically trimmed 11-item NSI-SR showed good internal consistency and a three-factor solution reflecting avolition, asociality, and anhedonia. The NSI-SR demonstrated convergent validity via moderate to large correlations with clinician-rated negative symptoms and related constructs in both samples. Discriminant validity was supported by lower correlations with positive symptoms in both samples; however, correlations with positive symptoms were still significant. These initial psychometric findings suggest that the NSI-SR is a reliable and valid brief questionnaire capable of measuring negative symptoms across phases of psychotic illness.

Initiative apathy trait underlies individual differences in the ability to anticipate and expend cognitive effort in cost-benefit decision-making tasks.

Initiative apathy is the most disabling form of apathy, prevalent both in neuropsychiatric pathologies and in the healthy population. This apathy has been specifically associated with functional abnormalities of the anterior cingulate cortex, a key structure underlying Effort-based Decision-Making (EDM). The main aim of the present study was to explore, for the first time, the cognitive and neural effort mechanisms of initiative apathy, by distinguishing the steps of effort anticipation and effort expenditure and the potential modulating effect of motivation. We conducted an EEG study in 23 subjects with specific subclinical initiative apathy and 24 healthy subjects with no apathy. The subjects had to complete two effort tasks. The analysis of behavioral choices, CNV, and mPFC theta power highlighted that initiative apathy is associated with effort avoidance and impairments of effort anticipation and effort expenditure that suggest EDM deficits. Better knowledge of these impairments should aid the development of new, more targeted therapeutic interventions necessary for reducing the debilitating consequences of initiative apathy.

Negative symptoms in schizophrenia differ across environmental contexts in daily life.

A recent environmental theory of negative symptoms posits that environmental contexts (e.g., location, social partner) play a significant-yet often unaccounted for-role in negative symptoms of schizophrenia (SZ). "Gold-standard" clinical rating scales offer limited precision for evaluating how contexts impact symptoms. To overcome some of these limitations, Ecological Momentary Assessment (EMA) was used to determine whether there were state fluctuations in experiential negative symptoms (anhedonia, avolition, and asociality) in SZ across contexts (locations, activities, social interaction partner, social interaction method). Outpatients with SZ (n = 52) and healthy controls (CN: n = 55) completed 8 daily EMA surveys for 6 days assessing negative symptom domains (anhedonia, avolition, and asociality) and contexts. Multilevel modeling demonstrated that negative symptoms varied across location, activity, social interaction partner, and social interaction method. For the majority of contexts, SZ and CN did not report significantly different levels of negative symptoms, with SZ only reporting higher negative symptoms than CN while eating, resting, interacting with a significant other, or being at home. Further, there were several contexts where negative symptoms were similarly reduced (e.g., recreation, most social interactions) or elevated (e.g., using the computer, working, running errands) in each group. Results demonstrate that experiential negative symptoms dynamically change across contexts in SZ. Some contexts may "normalize" experiential negative symptoms in SZ, while other contexts, notably some used to promote functional recovery, may increase experiential negative symptoms.

Negative symptoms of schizophrenia: Trying to answer unanswered research questions.

My research has focused on unmet needs in caring for people with schizophrenia. In particular, I focused on negative symptoms, a complex psychopathological dimension of the disorder, with a significant impact on the disease outcome, and not effectively addressed by existing treatments. In the present commentary, I summarize the trajectory of my research activity. I start with the description of my initial attempts to define the role of the dorsolateral prefrontal cortex in the pathogenesis of broadly defined negative symptoms. Then, I report on the evidence that led me to realize that no progress in research on schizophrenia negative symptoms could occur without considering the heterogeneity and complexity of the construct. Finally, I illustrate my attempts to succeed in this direction and the most pressing unsolved issues in this research field.