Clinical insight among persons with schizophrenia spectrum disorders treated with amisulpride, aripiprazole or olanzapine: a semi-randomised trial.

BACKGROUND: Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement. METHODS: Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight. RESULTS: Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics. CONCLUSIONS: Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011.

A combined individual and group-based stabilization and skill training intervention versus treatment as usual for patients with long lasting posttraumatic reactions receiving outpatient treatment in specialized mental health care - a study protocol for a randomized controlled trial.

BACKGROUND: Suffering linked to previous interpersonal trauma is common among patients in mental health care. Diagnostic labels may vary, but the clinical picture is often characterized by long-lasting and complex psychological and somatic symptoms, subjective distress and reduced quality of health and life. A substantial proportion of patients do not recover after individual treatment in ordinary specialized mental healthcare settings, despite the proven usefulness of individual trauma-specific treatments. The therapeutic factors that arise in group settings, such as normalization, shame reduction and corrective relational experiences, may be particularly useful for trauma survivors. However, evidence in support of group treatment for trauma survivors is scarce. This study aims to test whether combining a novel group intervention to individual treatment is superior to conventional individual out-patient treatment in an ordinary community mental health hospital. METHODS: In a single-site, non-blinded, randomized controlled trial (RCT), the effect of a combined group-based stabilization and skill-training (SST) intervention added to individual treatment will be compared to conventional treatment (treatment as usual, TAU) alone. Participants (N = 160) with ongoing and long-lasting reactions related to known adverse life events from the past will be recruited among patients at general outpatient clinics in a community mental health centre at St. Olav's University Hospital, Trondheim, Norway. Following baseline assessment and randomization, participants will complete follow-up measures at 4, 8, 13 and 19 months post-baseline. The primary outcome is personal recovery (The questionnaire about the process of recovery , QPR). Secondary outcomes include (1) self-reported symptoms of posttraumatic stress, general mental and somatic health symptoms, well-being, functional impairment and client satisfaction, (2) immunological and endocrine response measured in blood samples and (3) national registry data on occupational status, use of mental health services and pharmacological treatment. Additionally, mechanisms of change via posttraumatic cognitions will be examined. DISCUSSION: The addition of a group-based intervention to individual treatment for trauma survivors might prove to be an efficient way to meet the need of long-lasting high-intensity treatment in a large group of patients in mental health care, thereby reducing their suffering and increasing their psychosocial functioning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03887559. Registered on 25 March 2019.

Aerobic interval training in standard treatment of out-patients with schizophrenia: a randomized controlled trial.

OBJECTIVE: To evaluate the feasibility and effects of integrating aerobic interval training (AIT) in standard care of out-patients with schizophrenia on aerobic capacity and conventional cardiovascular disease (CVD) risk factors. METHODS: Out-patients with schizophrenia spectrum disorder were randomized to the following: 1) a training group (TG), performing AIT 2 day/week at the clinic with adherence support from municipal services; or 2) a control group (CG), given two AIT sessions and encouraged to exercise on their own. Feasibility was assessed through retention/adherence. V˙O2peak was measured directly along with conventional CVD risk factors before and after 12 weeks. RESULTS: Of 48 out-patients, 16/25 and 18/23 completed the TG and CG respectively. After 12 weeks, V˙O2peak was higher (2.7 ± 4.8 ml/kg/min, P < 0.01) in the TG compared with the CG. The TG improved V˙O2peak by 3.1 ± 3.7 ml/kg/min (P < 0.01), while no change in the CG was observed. No intergroup difference in weight, body mass index (BMI), waist circumference, blood pressure, lipids, or glucose at posttest was observed. Weight (1.9 ± 4.0 kg, P < 0.05) and BMI (0.5 ± 1.1 kg/m2 , P < 0.05) increased in the CG, with no change in the TG. CONCLUSION: AIT, combined with adherence support, of out-patients with schizophrenia was feasible, improved V˙O2peak , and may be integrated in standard care. (ClinicalTrials.gov identifier: NCT02743143).

Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care.

BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in 7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic acid decarboxylase-65 (GAD65) antibodies in 1.9%, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich glioma-inactivated protein-1 (LGI1) and γ-aminobutyric acid B (GABAB) receptor antibodies were not detected. NMDAR antibodies of class IgG were present in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally prevalent in patients with and without psychosis. There were no significant differences in antibody prevalence in the different diagnostic categories, except for a higher odds ratio of being NMDAR antibody positive for patients without a specific psychiatric diagnosis. CONCLUSIONS: NMDAR IgG autoantibodies, which are known to be strongly associated with anti-NMDAR encephalitis, were rarely found. CASPR2 and GAD65 antibodies were more frequently encountered in the present study than previously reported. Further research on the clinical significance of anti-neuronal autoantibodies in patients with acute psychiatric symptoms is needed.

The primary IgM antibody repertoire: a source of potent idiotype immunogens.

A widely held view is that, to elicit adaptive immune responses, most protein antigens must be given with adjuvants that activate the innate immune system. It has also been proposed that the immune system is tolerant to idiotypes (Id) of the syngeneic primary antibody (Ab) repertoire. We now show that among 73 purified noncomplexed secretory IgM monoclonal antibodies (mAb), 4 (5.5%) elicited high levels of IgG Ab against the Id even though no adjuvant was added. The responses were controlled by H2-linked immune response genes. IgG1, but no IgG2a or IgG2b, anti-Id Ab were detected, indicating involvement of T helper type 2 (Th2) cells. All 4 IgM mAb are likely germ-line gene-encoded, and 1 was shown to represent a recurrent Id. After endotoxin depletion the most potent immunogen of the 4 still provoked robust humoral anti-Id responses. The results suggest that a natural protein of the primary IgM Ab repertoire can be immunogenic without an adjuvant.

A syngeneic idiotype is immunogenic when borne by IgM but tolerogenic when joined to IgG.

Some syngeneic monoclonal antibodies (mAb) elicit immune responses like conventional T-dependent antigens. To find out whether the heavy chain class (isotype) plays a role for the immunogenicity of an idiotype (Id), we isolated rare subclones of an IgM mAb (termed Id3) in which the variable region of the heavy chain (VH) is associated with a new constant region (CH). The VH-Id3 gene is a member of the murine 36-60 family and probably has three replacement mutations. The light chain V gene is germ-line V lambda 2. IgM, IgG1, IgG2a and IgG2b variants of Id3 were purified from protein-free medium and injected without adjuvant into BALB/c mice. The parental 19S IgM mAb given subcutaneously (s.c.) elicited a vigorous humoral response against Id3; in comparison, monomeric 8S IgM was a much weaker immunogen. Unlike IgM, multiple challenges with the IgG switch variants failed to induce anti-Id3 Ab. IgG variants gained immunogenicity if they were purified from medium containing fetal calf serum, mixed with complete Freund's adjuvant or injected into mice primed with IgM-Id3. Pretreatment with 100 micrograms s.c. + 50 micrograms of the IgG2a variant extinguished the Ab response to parental IgM, but the response to adjuvant-free bovine serum albumin was intact. Therefore, the tolerance induced by the IgG2a switch variant is antigen-specific and not due to toxicity. Significant inhibition of the Ab response to parental IgM was observed after treatment with 4 micrograms of the IgG2a switch variant. Administration of the IgG1 and IgG2b switch variants also inhibited this response significantly. Thus, the outcome of an encounter with Id3 is strongly influenced by the CH isotype to which the Id is joined. This suggests novel ways to minimize unwanted Ab responses against Id of human therapeutic mAb. In the context of the theory of Id networks, we suggest that dominant B cell clones can preempt anti-Id Ab responses against themselves by early switching from IgM to IgG secretion, before immunogenic IgM Ab have had time to activate anti-Id B cells.