The term “subjective response to antipsychotic” (SRA) refers to changes in the subjective state experienced due to antipsychotic (AP) exposition that is independent of the therapeutic or physical side effects of these drugs. This dimension of analysis has been extensively explored in schizophrenic disorders, finding that negative SRA is an early and independent predictor of compliance as well as a successful pathway to construct current theoretical frameworks of these disorders. There is an increasing use of AP in bipolar disorders’ treatment (BD) but no reviews on the topic have been published to date in this population. The aim of this work is to review published data of SRA in BD patients and to discuss their clinical and theoretical implications.

An extensive search in online databases was performed. Reports were reviewed and included if they described SRA in BD or included instruments aimed to assess it. Reports of cognitive, sexual, motor autonomic side effects were excluded. Findings were summarized in a narrative fashion.

Nine reports fulfilled the inclusion criteria and were included in the revision, reporting data from 1282 BD patients. Among these, three were prospective studies and three explored relations between SRA and treatment compliance.

There is an asymmetry between the increase in the use of antipsychotics in BD and the lack of data regarding the SRA. Phenomenologically, SRA in BD is similar to that found in schizophrenic subjects. Some of these symptoms may be misdiagnosed as depressive symptoms. The existing data show that SRA has a strong correlation with treatment compliance as well as a promising way to develop theoretical paradigms for these disorders.

The predictive accuracy of the Clinical High Risk criteria for Psychosis (CHR-P) regarding the future development of the disorder remains suboptimal. It is therefore necessary to incorporate refined risk estimation tools which can be applied at the individual subject level. The aim of the study was to develop an easy-to use, short refined risk estimation tool to predict the development of psychosis in a new CHR-P cohort recruited in European country with less established early detection services.

A cohort of 105 CHR-P individuals was assessed with the Comprehensive Assessment of At Risk Mental States12/2006, and then followed for a median period of 36 months (25th-75th percentile:10–59 months) for transition to psychosis. A multivariate Cox regression model predicting transition was generated with preselected clinical predictors and was internally validated with 1000 bootstrap resamples.

Speech disorganization and unusual thought content were selected as potential predictors of conversion on the basis of published literature. The prediction model was significant (p < 0.0001) and confirmed that both speech disorganization (HR = 1.69; 95%CI: 1.39–2.05) and unusual thought content (HR = 1.51; 95%CI: 1.27–1.80) were significantly associated with transition. The prognostic accuracy of the model was adequate (Harrell’s c- index = 0.79), even after optimism correction through internal validation procedures (Harrell’s c-index = 0.78).

The clinical prediction model developed, and internally validated, herein to predict transition from a CHR-P to psychosis may be a promising tool for use in clinical settings. It has been incorporated into an online tool available at: https://link.konsta.com.pl/psychosis. Future external replication studies are needed.

Negative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms.

Using post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227).

Change from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P <.05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P <.01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P <.05).

Since items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.

Patients with acute and transient psychotic disorders (ATPDs) are by definition remitting, but have a high risk of developing persistent psychoses, resembling a subgroup of individuals at Clinical High Risk for Psychosis (CHR-P). Their pathways to care, treatment offered and long-term clinical outcomes beyond risk to psychosis are unexplored. We conducted an electronic health record-based retrospective cohort study including patients with ATPDs within the SLaM NHS Trust and followed-up to 8 years.

A total of 2561 ATPDs were included in the study. A minority were detected (8%) and treated (18%) by Early Intervention services (EIS) and none by CHR-P services. Patients were offered a clinical follow-up of 350.40 ± 589.90 days. The cumulative incidence of discharges was 40% at 3 months, 60% at 1 year, 69% at 2 years, 77% at 4 years, and 82% at 8 years. Treatment was heterogeneous: the majority of patients received antipsychotics (up to 52%), only a tiny minority psychotherapy (up to 8%).

Over follow-up, 32.88% and 28.54% of ATPDS received at least one mental health hospitalization or one compulsory hospital admission under the Mental Health Act, respectively. The mean number of days spent in psychiatric hospital was 66.39 ± 239.44 days.

The majority of ATPDs are not detected/treated by EIS or CHR-P services, receive heterogeneous treatments and short-term clinical follow-up. ATPDs have a high risk of developing severe clinical outcomes beyond persistent psychotic disorders and unmet clinical needs that are not targeted by current mental health services.

Psychotic-like experiences (PLEs) often occur across different non-psychotic disorders in adolescent and young adult population and are related to early trauma. However, the mechanisms of how exposure to early trauma shapes the risk of PLEs are unclear. In our study, we investigated whether borderline personality features and further non-psychotic symptoms, i.e. factors related to both PLEs and childhood trauma, may mediate the relationship between childhood trauma and PLEs.

Two hundred inpatients aged 16–21 years who were treated due to non-psychotic disorders were included. PLEs were assessed with the Prodromal Questionnaire (PQ-16). Childhood Trauma was assessed with the Adverse Childhood Experience Questionnaire (ACE). Borderline personality features were assessed by using the Borderline-Symptom Checklist (BSL-23). Presence and frequency of depressive symptoms and anxiety were assessed by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Questionnaire (GAD-7).

Table 1Clinical characteristics (n = 200).

A significant relationship between childhood trauma (ACE total score) and PLEs was found (ß = 0.30, 95% CI 0.247--0.659). In particular, emotional neglect (r = 0.298, p < 0.001) and sexual abuse (r = 0.264, p < 0.001) were significantly associated with PLEs. Borderline personality features fully mediated the relationship of childhood trauma and PLEs (ß = 0.12, 95% CI: -0.019--0.370). Anxiety and Depression showed a significant, but partial mediation of the relationship.

Borderline personality features seem to be an important mediator of the relationship between childhood trauma and PLEs in adolescent patients with different non-psychotic psychiatric disorders. Theoretical and clinical implications are discussed.

Bipolar disorder (BD) and schizophrenia (SZ) are characterized by neurocognitive and functional deficits with marked heterogeneity. It has been suggested that BD with a history of psychotic symptoms (BD-P) could constitute a phenotypically homogeneous subtype characterized by greater neurocognitive and functional impairments, or by a distinct trajectory of such deficits. The aim of this study was to compare the neurocognitive and functional course of euthymic BD-P, euthymic BD patients without a history of psychosis (BD-NP), stabilized patients with schizophrenia and healthy subjects, during a five-year follow-up.

Neurocognitive and psychosocial function was examined in 100 euthymic patients with BD (50 BD-P, 50 BD-NP), 50 stabilized patients with schizophrenia (SZ), and 51 healthy controls (HC) at baseline (T1), and after a 5-year follow-up (T2).

The course of both neurocognitive performance and functional outcome of patients with SZ and BD (BD-P and BD-NP) is stable. The profile of neurocognitive impairment of patients with SZ or BD (BD-P and BD-NP), is similar, with only quantitative differences circumscribed to certain domains, such as working memory. The subgroup of patients with BD-NP does not show functional deterioration.

We have not found evidence of progression in the neurocognitive or psychosocial impairment in any of the three groups of patients, although it cannot be dismissed the possibility of a subset of patients with a progressive course. Other longitudinal studies with larger samples and longer duration are necessary to confirm these findings.