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BACKGROUND: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic-pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. METHODS: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). RESULTS: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose-response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. CONCLUSION: Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality.

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INTRODUCTION: People with personality disorders (PDs) have an elevated suicide risk. However, correlates of suicidal ideation (SI) and suicide attempts (SA) remain largely unknown in this population. A growing body of literature highlights the contribution of the Big Five personality traits in suicide-outcomes. Therefore, the present study investigates the association between the Big Five personality traits and SI and SA in people with PDs while applying the ideation-to-action framework. METHOD: Data were obtained from 105 treatment-seeking individuals diagnosed with PDs participating in the Trauma tO Personality Spectrum Study (TOPSS). Multinomial logistic regression analyses were used to analyze the association between the NEO Five-Factor Inventory and the three category suicide-outcome: non-suicidal, SI, and SA. RESULTS: After controlling for age, gender, a comorbid depressive disorder, the severity of borderline manifestations, and other personality traits from the Big Five taxonomy, significantly lower levels of extraversion were observed in participants with SI compared to non-suicidal participants (OR = 0.27, 95% CI 0.10-0.72) but not in SA participants. In contrast, higher levels of extraversion were associated with SA when compared to SI (OR = 3.52, 95% CI 1.33-9.32). Other Big Five traits were not independently associated with suicide-outcomes. CONCLUSIONS: Of the Big Five traits, the introversion-extraversion dimension most clearly distinguishes individuals with SI from non-suicidal individuals, as well as those with a SA in the past from those with SI only. Prospective studies are required to investigate if this personality trait can predict the progression from being non-suicidal to having SI and from having SI to performing an attempt.

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BACKGROUND: Depressive and anxiety disorders are often associated with suicide ideation (SI) and attempt (SA). However, analyses of prevalence, course, and more specific risk mechanisms are needed to improve knowledge and detection of high risk individuals with depressive and anxiety disorders. Previous studies often lacked statistical power, assessment of detailed determinants and follow-up measurements. METHODS: The Netherlands Study of Depression and Anxiety (NESDA), a large cohort study, overcomes some earlier limitations. Scale for Suicide Ideation and Compositive Interview Diagnostic Instrument data were analyzed to report on prevalence of SI and SA. Additionally, important sociodemographic, clinical, psychological, environmental, and neurobiological determinants and course of SI and SA identified in depressive and/or anxiety disorder respondents in 16 NESDA articles were summarized. RESULTS: Within respondents with 12-month diagnosis (n=1,783), SI and 12-month SA prevalence ranged from 17.1-20.1% and 0.8-3.0% respectively across 5 waves during 9-year follow-up and SI was highly recurrent. Both SI and SA were especially associated with comorbid depression and anxiety, higher clinical severity, sleep dysfunctions, higher aggression and hopelessness, and childhood trauma. In the (neuro)biological domain, SI was linked with immune dysregulation and SA with abnormal brain activity during emotion processing and genetic risk. LIMITATIONS: Most articles were cross-sectional in nature, preventing causal inferences and no conclusions could be drawn about the overall magnitude of results. CONCLUSION: SI and SA are multifactorial phenomena and especially prevalent amongst comorbid depressive and anxiety respondents. Considering many overlapping SI and SA determinants, more neurobiological determinants and use of innovative methodological techniques are desirable.

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OBJECTIVE: Individuals with a depressive and/or anxiety disorder are known to have an elevated risk of suicide. However, these diagnoses alone are insufficient at differentiating patients with suicide ideation that attempt suicide from those that do not. Few studies examined such differences in an ideation-to-action framework. Using this framework, extensive multivariate testing was performed to examine differences between suicidal patients with and without a suicide attempt. METHOD: Data were from 1576 respondents with a depressive and/or anxiety disorder, participating in the Netherlands Study of Depression and Anxiety. Logistic regression analyses were used to analyze associations between sociodemographic, clinical, personality, and psychosocial risk factors and suicide ideation and attempt. RESULTS: Patients with suicide ideation could be uniquely distinguished from non-suicidal patients by more years of education, presence of a depressive disorder (vs anxiety disorder) and higher introversion. Patients with suicide ideation and a past suicide attempt could be uniquely distinguished from non-suicidal patients by a younger age of onset, a lifetime alcohol use disorder, more external locus of control and lower levels of social support. Within the group of patients with suicide ideation, patients with a suicide attempt were more likely to have childhood trauma and lower education, and be of non-Western descent than patients with suicide ideation and no past attempt. CONCLUSION: This study found that although various clinical, personality and psychosocial characteristics distinguish patients with suicide ideation from non-suicidal patients, many of these often-cited factors do not distinguish patients with a suicide attempt from those who only think about suicide. However, childhood trauma, lower education and non-Western descent could aid in detecting suicide attempt risk among patients with suicide ideation.

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Experiencing self-agency over one's own action outcomes is essential for social functioning. Recent research revealed that patients with schizophrenia do not use implicitly available information about their action-outcomes (i.e., prime-based agency inference) to arrive at self-agency experiences. Here, we examined whether this is related to symptoms and/or familial risk to develop the disease. Fifty-four patients, 54 controls, and 19 unaffected (and unrelated) siblings performed an agency inference task, in which experienced agency was measured over action-outcomes that matched or mismatched outcome-primes that were presented before action performance. The Positive and Negative Syndrome Scale (PANSS) and Comprehensive Assessment of Symptoms and History (CASH) were administered to assess psychopathology. Impairments in prime-based inferences did not differ between patients with symptoms of over- and underattribution. However, patients with agency underattribution symptoms reported significantly lower overall self-agency experiences. Siblings displayed stronger prime-based agency inferences than patients, but weaker prime-based inferences than healthy controls. However, these differences were not statistically significant. Findings suggest that impairments in prime-based agency inferences may be a trait characteristic of schizophrenia. Moreover, this study may stimulate further research on the familial basis and the clinical relevance of impairments in implicit agency inferences.

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The proneness-persistence-impairment (PPI) model states that psychotic experiences are more likely to lead to impairment if their expression becomes persistent. Higher genetic risk for psychosis is known to affect proneness and persistence of subclinical positive symptoms. Less is known about potential effects of genetic risk on the course of subclinical negative symptoms, impairment, and their subsequent associations. The current study examined these issues in a large sample (n=1131), consisting of individuals with higher genetic risk (siblings of patients with psychotic disorders, n=703) and lower genetic risk (controls without a family member with lifetime psychosis, n=428). Psychotic experiences were assessed with the CAPE questionnaire, at two time points three years apart. Participants were allocated to one of four groups representing developmental course: stable low, decreasing, increasing or persisting subclinical positive/negative symptoms. Lifetime clinical psychosis was an exclusion criterion at baseline. Higher genetic risk status was found to be associated with a persisting course of both subclinical positive and negative symptoms, symptom-related distress and functional impairment. There is no evidence for an effect of genetic risk status on the association between developmental course and impairment. The results of the current study underline the importance of assessing psychotic experiences in the context of genetic risk, multidimensional and over time. Additionally, the current findings both underscore and contribute to the PPI model: psychotic experiences are more likely to lead to impairment if their expression becomes persistent, both in individuals with higher and lower genetic risk for psychosis.

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There have been suggestions that a sense of self emerges through social interaction, which requires an intact capability to distinguish self from others. Here we investigated the contribution of first rank delusions and hallucinations, i.e. symptom expressions of a disturbed sense of self, to social functioning in patients with a psychotic disorder. Life-time and present-state positive symptom clusters (e.g. first rank delusions and hallucinations) and present-state negative symptoms were submitted to hierarchical multiple-regression analyses with (different domains of) social functioning as dependent variable. In addition to negative symptoms (ß=-0.48), the life-time presence of first rank delusions is significantly negative associated with level of social functioning, in particular with the quality of interpersonal interactions, with a modest standardized regression coefficient (ß=-0.14). We reconfirmed the well-established relationship between negative symptoms and social functioning, but the life-time presence of first rank delusions may also have an subtle ongoing effect on the quality of the interaction with others. We propose that the experience of first rank delusions may be an expression of enduring self-disturbances, leaving patients unsure on how to behave in social interactions.

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OBJECTIVE: It has been suggested that specific psychotic symptom clusters may be explained by patterns of biological abnormalities. The presence of first rank symptoms (FRS) has been associated with cognitive abnormalities, e.g., deficits in self-monitoring or in the experience of agency, suggesting that a specific network of neural abnormalities might underlie FRS. Here, we investigate differences in cortical and subcortical brain volume between patients with and without FRS. METHODS: Three independent patient samples (referred to as A, B, and C) with different mean ages and in different illness stages were included, leading to a total of 348 patients within the schizophrenia-spectrum. All underwent magnetic resonance imaging of the brain. In addition, the presence of FRS was established using a diagnostic interview. Patients with (FRS+, A: n = 63, B: n = 129, and C: n = 96) and without FRS (FRS-, A: n = 35, B: n = 17, and C: n = 8) were compared on global and local cortical volumes as well as subcortical volumes, using a whole brain (cerebrum) approach. RESULTS: Nucleus accumbens volume was significantly smaller in FRS+ as compared with FRS- in sample A (p < 0.005). Furthermore, FRS+ showed a smaller volume of the pars-opercularis relative to FRS- in sample B (p < 0.001). No further significant differences were found in cortical and subcortical volumes between FRS+ and FRS- in either one of the three samples after correction for multiple comparison. CONCLUSION: Brain volume differences between patients with and without FRS are, when present, subtle, and not consistent between three independent samples. Brain abnormalities related to FRS may be too subtle to become visible through structural brain imaging.

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BACKGROUND: The Remission in Schizophrenia Working Group (RSWG) has proposed remission criteria for schizophrenia, which were shown to be valid in terms of functional and clinical outcomes. However, studies investigating the association between dynamics in remission status in relation to longitudinal functional and clinical outcome are scarce. METHODS: A total of 648 patients were allocated to four change-in-remission groups, i.e. remission/remission, remission/no-remission, no-remission/remission, and no-remission/no-remission. Remission status was based on PANSS ratings. Multilevel linear modelling techniques were used to investigate whether enduring remission was associated with more improvement in functional outcome at follow-up. Further, change in functional and clinical outcome at follow-up measurement was assessed for each remission category separately. RESULTS: Both at baseline and at follow-up, remission status was associated with better functioning. At baseline, patients who subsequently moved out of remission status could be characterized by more severe psychopathology, disabilities, unmet needs and worse quality of life (QoL) compared with patients who continued to be in remission. The stable in-remission group was characterized by significantly better functioning and QoL, both at baseline and follow-up compared with all other remission groups. Nevertheless, QoL increased in all four patient categories. CONCLUSIONS: In a large sample of patients with a non-affective psychotic disorder, stable remission or moving into remission over time, based on the RSWG criteria, was associated with a favourable functional outcome and QoL, providing further support for the clinical validity of the RSWG remission criteria. The findings also suggest growing adaptation and self-management over time, despite ongoing difficulties.

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A phenomenological approach explains the apparently unintelligible experiences of patients with schizophrenia as a disruption of the normal self-perception. Patients with schizophrenia suffer from a decline of "me," the background core of their experiences. Normally tacit experiences intrude into the forefront of their attention, and the sense that inner-world experiences are private diminishes. These patients lose the sense that they are the origin of their thoughts and actions; their self-evident network of meanings and a solid foundation of life disintegrate. Subsequently, their experiential world is transformed, alienated, intruded, and fragmented. In this article, a phenomenological investigation of the self-experiences and actions of 4 patients with schizophrenia is presented.

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Kurt Schneider defined 'first rank symptoms' (FRS) of psychosis. Previous research found two clusters of FRS: 'loss of ego bound' symptoms (e.g., delusions of external control) and auditory hallucinations (e.g, commenting voices). In patients with a psychosis we investigated whether FRS are a separate cluster within the group of positive symptoms, consisting of two underlying factors that are stable over time. We conducted a principal axis factor analysis (PAF) at baseline (n = 857) and a confirmative factor analysis (CFA) at three-year follow-up (n = 414) on (FRS) symptom score. Also, we investigated the stability of the two-factor structure of FRS over the interval. PAF on 16 items representing positive symptoms at baseline revealed two factors with eigenvalues > 1. FRS-delusional self experience (thought withdrawal, thought broadcasting, thought insertion, and beliefs that impulses and/or actions are controlled by an outside force) clustered in one factor and FRS-auditory hallucinations (auditory hallucinations, conversational voices, and voices commenting on one's actions) in the second factor. Furthermore, CFA on the FRS-items at follow-up confirmed the two-factor structure of FRS. FRS delusional self experience and FRS-auditory hallucinations at baseline were significantly associated with the same factors at three-year follow-up (FRS-delusional self experience: r = 0.38; FRS-auditory hallucinations r = 0.47). Hence, our findings confirm a two-factor structure of first rank symptoms, i.e. FRS-delusional self experience and FRS-auditory hallucinations, with a moderate to large internal coherence within each factor and relative stability over time. Future studies on self-processes may contribute to our understanding of the pathophysiology of first rank symptoms.

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