In contrast to the validated scales for face-to-face assessment of negative symptoms, no widely accepted tools currently exist for remote monitoring of negative symptoms. Remote assessment of negative symptoms can be broadly divided into 3 categories: (1) remote administration of an existing negative-symptom scale by a clinician, in real time, using videoconference technology to communicate with the patient; (2) direct inference of negative symptoms through detection and analysis of the patient\'s voice, appearance, or activity by way of the patient\'s smartphone or other device; and (3) ecological momentary assessment, in which the patient self-reports their condition upon receipt of periodic prompts from a smartphone or other device during their daily routine. These modalities vary in cost, technological complexity, and applicability to the different negative-symptom domains. Each modality has unique strengths, weaknesses, and issues with validation. As a result, an optimal solution may be more likely to employ several techniques than to use a single tool. For remote assessment of negative symptoms to be adopted as primary or secondary endpoints in regulated clinical trials, appropriate psychometric standards will need to be met. Standards for substituting 1 set of measures for another, as well as what constitutes a \"gold\" reference standard, will need to be precisely defined and a process for defining them developed. Despite over 4 decades of progress toward this goal, significant work remains to be done before clinical trials addressing negative symptoms can utilize remotely assessed secondary or primary outcome measures.

OBJECTIVE: To analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP).
METHODS: We measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex.
RESULTS: Prolactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline.
CONCLUSIONS: Prolactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

OBJECTIVE: Despite the clinical relevance of negative symptoms in schizophrenia, our understanding of negative symptoms remains limited. Although various courses and stages of schizophrenia have been identified, variations in the negative symptom networks between distinct stages of schizophrenia remain unexplored.
METHODS: We examined 405 patients with early schizophrenia (ES) and 330 patients with chronic schizophrenia (CS) using the Scale for the Assessment of Negative Symptoms. Network analysis and exploratory graph analysis were used to identify and compare the network structures and community memberships of negative symptoms between the two groups. Further, associations between communities and social functioning were evaluated. The potential influences of other symptom domains and confounding factors were also examined.
RESULTS: Multidimensional differences were found in the networks of negative symptoms between ES and CS. The global connectivity strength was higher in the network of ES than in the network of CS. In ES, central symptoms were mainly related to expressive deficits, whereas in CS they were distributed across negative symptom domains. A three-community structure was suggested across stages but with different memberships and associations with social functioning. Potential confounding factors and symptom domains, including mood, positive, disorganization, and excitement symptoms, did not affect the network structures.
CONCLUSIONS: Our findings revealed the presence of stage-specific network structures of negative symptoms in schizophrenia, with negative symptom communities having differential significance for social functioning. These findings provide implications for the future development of tailored interventions to alleviate negative symptoms and improve functionality across stages.

Social anhedonia is a hallmark symptom of schizophrenia. Discrepancies in anticipated versus consummatory pleasure for non-social stimuli are well-documented. Thus, a similar emotional paradox may underlie social anhedonia. If so, our understanding of social anhedonia-including how to treat it in schizophrenia-could be enhanced. This project used a 5-day experience sampling method (ESM) to measure discrepancies between anticipated and consummatory pleasure for real-world social activities in people with schizophrenia and healthy controls (n = 30/group). ESM results were compared to laboratory assessments of negative symptoms and neurocognition. The schizophrenia group exhibited similar levels of anticipated and consummatory social pleasure as controls throughout daily life, and both groups were accurate in their short-term predictions of pleasure. Clinical interviews revealed those with schizophrenia showed significant deficits in long-term social pleasure prediction (i.e., a 1-week timeframe). Thus, people with schizophrenia may exhibit differences in ability to predict pleasure in the short-term versus the long-term. Negative symptoms and neurocognition were related to anticipated, but not consummatory, social pleasure, suggesting anhedonia is driven by deficits in thinking about pleasure, rather than inability to experience pleasure. Clinical implications include focusing on building upon short-term ability to predict pleasure in therapy to increase social motivation in schizophrenia.

Schizophrenia is associated with changes in white matter (WM) integrity and with reduced life expectancy, in part because of the cardiometabolic side effects of antipsychotics. Physical activity (PA) has emerged as a candidate lifestyle intervention that is safe and effective. The study aimed to assess how an adapted PA program delivered remotely by web (e-APA) improved WM integrity in patients with schizophrenia (SZPs) and healthy controls (HCs) and to evaluate associations among WM integrity, cardiorespiratory fitness, and symptom severity. This longitudinal study was conducted over 16 weeks with 31 participants (18 SZPs and 13 HCs). Diffusion tensor imaging and tract-based spatial statistics were employed to assess WM integrity. Cardiorespiratory fitness was measured by maximal oxygen uptake (VO2max), and assessments for clinical symptoms included the Positive and Negative Syndrome Scale, Self-evaluation of Negative Symptoms and the Brief Negative Syndrome Scale (BNSS). Only the SZPs had significantly increased WM integrity after the e-APA program, with increased fractional anisotropy and decreased radial diffusivity in fasciculi involved in motor functions and language process. Furthermore, decreased negative symptoms assessed with BNSS were associated with greater WM integrity following the program. These findings suggest that e-APA may improve WM integrity abnormalities and support e-APA as a promising therapeutic strategy.

Schizophrenia is a chronic psychiatric disorder severely affecting patients\' functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness\'s prognosis. Cognitive remediation (CR) interventions have been applied to target these symptoms. Brain stimulation also provides promising yet preliminary results in reducing negative symptoms, whereas its effect on cognitive impairment remains heterogeneous. Here, we combined intermittent theta burst stimulation (iTBS) with CR to improve negative symptoms and cognitive impairment in schizophrenia spectrum patients. One hundred eligible patients were invited, and twenty-one participated. We randomized them into four groups, manipulating the stimulation condition (real vs. sham) and CR (no training vs. training). We delivered fifteen iTBS sessions over the left dorsolateral prefrontal cortex for three weeks, followed (or not) by 50 min of training. Consensus-based clinical and cognitive assessment was administered at baseline and after the treatment, plus at three follow-ups occurring one, three, and six months after the intervention. Mixed-model analyses were run on cognitive and negative symptom scores. The preliminary findings highlighted a marginal modulation of iTBS on negative symptoms, whereas CR improved isolated cognitive functions. We herein discuss the limitations and strengths of the methodological approach.

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.

BACKGROUND: The existing research has mainly focused on exploring how the duration of untreated psychosis effects the further course of the disease. By contrast, the duration of an untreated illness (DUI) in youth depression and its impact on the further course of the disease has remained scarcely investigated.
OBJECTIVE: The current study aims to determine how the duration of untreated illness affects the severity of the symptoms during the first depressive episode and the degree to which the symptoms are reduced after treatment.
METHODS: Fifty-two young male patients (15-29 years old) were examined. First, they were hospitalized with a severe without psychotic symptoms (F32.2) and moderate (F32.1) depressive episode. The Hamilton Depression Rating Scale (HDRS), the Scale of Prodromal Symptoms (SOPS), and the Scale for Assessment of Negative Symptoms (SANS) were used to achieve the research goals. The examination was conducted twice at the time of patient admission to the hospital and before discharge. Our statistical analysis was carried out with the Statistica 12 software. The Mann-Whitney U test was used to compare the differences between two independent groups. The Spearman\'s rank correlation coefficient was used to uncover any correlation between how long the illness has remained untreated and the severity of its clinical symptoms.
RESULTS: All patients were hospitalized at the first depressive episode. The average duration of an untreated illness was 35.8±17.0 months. The patients were divided into two groups: the first group (59.6%, n=31), with a duration of the untreated illness of more than 36 months, and the second group (40.4%, n=21), with a duration of the untreated illness of less than 36 months. A cross-group comparison between the participants showed that the reduction of HDRS scores was significantly higher in the second group (p=0.019) at the time of discharge, with no differences in the severity of depressive symptoms (p=0.544) at the time of admission. Comorbidity was detected in 83.9% of the patients in the first group and in 42.9% of the patients in the second group. A greater therapy effectiveness was found to exist in the second group, as the depressive symptoms score on the HDRS scale (p=0.016; U=196.0) and prodromal symptoms score on the SOPS disorganization subscale (p=0.046; U=218.0) were found to have been reduced significantly.
CONCLUSIONS: The study showed that DUI has an impact on the reduction of depressive, negative symptoms and symptoms of disorganization in youth patients at the first depressive episode. A high level of comorbidity has been uncovered, confirming that a variety of non-psychotic and psychotic disorders in youth manifest themselves in depression at a prodromal stage, causing difficulties in establishing diagnoses and requiring subsequent verification. Future research might need to focus on exploring depressive symptoms as predictors of mental disorders in youth patients.
UNASSIGNED: В настоящее время большинство исследований сфокусированы на изучении влияния длительности нелеченого психоза на дальнейшее течение заболевания. В отношении длительности нелеченого заболевания при депрессии таких работ значительно меньше.
UNASSIGNED: Целью данного исследования является: установить влияние длительности нелеченого заболевания на тяжесть симптомов депрессии, на степень их редукции за время лечения.
UNASSIGNED: Обследованы 52 больных мужского пола 15–29 лет, впервые госпитализированных по поводу депрессивного эпизода тяжелой степени без психотических симптомов (F32.2) и средней степени тяжести (F32.1). Применялись Шкала оценки депрессивных симптомов (HDRS), Шкала оценки продромальных симптомов (SOPS) и Шкала оценки негативных симптомов (SANS). Обследование проводилось дважды: на момент поступления пациента в стационар и на этапе редукции психопатологических расстройств перед выпиской. Статистический анализ проводился с помощью программы Statistica 12. Для сравнения различий между двумя независимыми группами применялся непараметрический метод Манна — Уитни и ранговый коэффициент Спирмена для оценки взаимосвязей между длительностью нелеченного заболевания и тяжестью клинических симптомов.
UNASSIGNED: Выборка включала больных, впервые госпитализированных с диагнозом «Депрессивный эпизод», средняя длительность нелеченого заболевания составила 35.8±17.0 месяцев. Пациенты были разделены на две группы: 1 группа (59.6%, n=31) с длительностью нелеченого заболевания более 36 месяцев, 2 группа (40.4%, n=21) — менее 36 месяцев. Межгрупповые сравнения показали, что редукция баллов по шкале HDRS к моменту выписки была значительно выше во второй группе (р=0.019) при отсутствии различий по степени выраженности депрессии при поступлении (р=0.544). Коморбидность отмечалась у 83.9% пациентов первой группы и у 42.9% — у второй. Лучший эффект терапии был установлен у больных второй группы по степени выраженности депрессивных симптомов (p=0.016; U=196.0) и продромальных симптомов, оцененных по подшкале симптомов дезорганизации шкалы SOPS (p=0.046; U=218.0) при выписке.
UNASSIGNED: Исследование показало влияние длительности нелеченого заболевания на степень редукции депрессивных, негативных симптомов и симптомов дезорганизации у молодых людей с первым депрессивным эпизодом. Также была установлена большая степень коморбидности, подтверждающая, что различные непсихотические психические расстройства, а также психотические заболевания на продромальных стадиях могут проявляться депрессивной симптоматикой, что затрудняет диагностику юношеских депрессий и требует последующей верификации диагноза. Будущие исследования должны быть направлены на определение предикторной значимости юношеских депрессий в отношении развития психических расстройств в юношеском возрасте.

Paranoid ideation is a transdiagnostic construct that is associated with social impairment and often occurs in psychotic spectrum disorders. Little research has examined how paranoid ideation is related to social behaviors that underlie social impairment and may ultimately lead to social rejection. It is important to consider that negative symptoms and sleep problems also contribute to social impairment. No research has assessed the unique and combined influence of paranoid ideation, negative symptoms, and sleep problems on social impairment. Therefore, the current study examined how paranoid ideation, negative symptoms, and sleep problems contribute to poorer social skills and social rejection in a transdiagnostic sample of persons with psychosis and community members (N = 112). Assessments included diagnostic and symptom interviews, questionnaires, behavioral ratings of social skill and facial displays of affect, and naive observer reactions utilizing thin-slice methodology. Greater paranoid ideation, negative symptoms, and sleep problems were each related to poorer social skill and more negative reactions from observers. When considered in path analyses, negative symptoms were associated with observer reports of less willingness to interact with participants through poorer social skill. These findings demonstrate the symptom correlates of social rejection and how interpersonal behavior may contribute to social exclusion.

OBJECTIVE: Suicidal thoughts are common among patients with first episode psychosis (FEP). The impact of symptoms\' severity and social cognition on suicidal risk should be a focus of attention. This study aimed at assessment of the severity of suicidal ideation in patients with FEP and its potential association with the theory of mind (ToM) impairment and symptoms\' severity.
METHODS: Ninety-six participants were recruited consecutively and subdivided into three equal groups: FEP, schizophrenia, and healthy controls (HC). The symptoms\' severity was assessed using Positive and Negative Syndrome Scale (PANSS) and Beck Depression Inventory (BDI). Suicidal ideation was evaluated using Beck Scale for Suicidal Ideation (BSSI). Reading the Mind in the Eyes revised version (RMET) was used to assess ToM.
RESULTS: Suicidal ideation was significantly higher only in FEP compared to HC (p = 0.001). Both FEP and schizophrenia had substantially lower performance than HC on RMET (p < 0.001). Higher depression (β = 0.452, p = 0.007) and negative symptoms (β = 0.433, p = 0.027) appeared to be significantly associated with increased suicidal ideation severity in FEP while RMET did not.
CONCLUSIONS: Patients with FEP and chronic schizophrenia have comparable deficits in theory of mind dimension of social cognition. The severity of negative and depressive symptoms potentially contributes to the increased risk of suicide in FEP.