Long-term Changes in Personal Recovery and Quality of Life Among Patients With Schizophrenia Spectrum Disorders and Different Durations of Illness: A Meta-analysis.

BACKGROUND AND HYPOTHESIS: In schizophrenia spectrum disorders (SSD) personal recovery and subjective quality of life (S-QOL) are crucial and show conceptual overlap. There is limited knowledge about how these outcomes change over time. Therefore, we investigated changes in personal recovery or S-QOL for patients with SSD. We specifically focused on the influence of the patients' durations of illness (DOI) on changes in personal recovery and S-QOL. STUDY DESIGN: We included 46 studies investigating longitudinal changes in quantitative assessments of personal recovery or S-QOL for patients with SSD. Outcomes were categorized in overall personal recovery, overall S-QOL connectedness, hope and optimism, identity, meaning in life, and empowerment. We evaluated effect sizes of change between baseline and follow-up assessments. We also evaluated potential moderating effects, including DOI on these changes in outcomes. STUDY RESULTS: We found small improvements of overall personal recovery and S-QOL, but marginal or no improvement over time in the other more specific outcome domains. Patients without a schizophrenia diagnosis, a younger age, and more recent publications positively influenced these changes. We found no significant influence of DOI on the changes in any outcome domain. CONCLUSIONS: Improvement in personal recovery or S-QOL of people with SSD is modest at best. However, these studies did not fully capture the personal narratives or nonlinear process of recovery of an individual. Future research should focus on how to shift from a clinical to more person-oriented approach in clinical practice to support patients in improving their personal process of recovery. REVIEW PROTOCOL REGISTRATION: CRD42022377100.

Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine.

BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.

Modulation of brain activation during executive functioning in autism with citalopram.

Adults with autism spectrum disorder (ASD) are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). However, there is limited evidence to support this practice. Therefore, it is crucial to understand the impact of SSRIs on brain function abnormalities in ASD. It has been suggested that some core symptoms in ASD are underpinned by deficits in executive functioning (EF). Hence, we investigated the role of the SSRI citalopram on EF networks in 19 right-handed adult males with ASD and 19 controls who did not differ in gender, age, IQ or handedness. We performed pharmacological functional magnetic resonance imaging to compare brain activity during two EF tasks (of response inhibition and sustained attention) after an acute dose of 20 mg citalopram or placebo using a randomised, double-blind, crossover design. Under placebo condition, individuals with ASD had abnormal brain activation in response inhibition regions, including inferior frontal, precentral and postcentral cortices and cerebellum. During sustained attention, individuals with ASD had abnormal brain activation in middle temporal cortex and (pre)cuneus. After citalopram administration, abnormal brain activation in inferior frontal cortex was 'normalised' and most of the other brain functional differences were 'abolished'. Also, within ASD, the degree of responsivity in inferior frontal and postcentral cortices to SSRI challenge was related to plasma serotonin levels. These findings suggest that citalopram can 'normalise' atypical brain activation during EF in ASD. Future trials should investigate whether this shift in the biology of ASD is maintained after prolonged citalopram treatment, and if peripheral measures of serotonin predict treatment response.