Schizophrenia (SZ) is a debilitating psychiatric disorder where patients experience cognitive decline. Antipsychotic drugs alleviate positive symptoms but do not improve cognitive performance. We previously demonstrated that Toll-like receptors (TLRs), involved in cytokine production, can predict cognitive deficits in SZ patients. In this study, we aim to investigate the potential moderating effects of antipsychotic drugs on the associations between cytokines, TLRs, and cognition.

In total, 280 participants (201 controls and 79 cases of SZ) were recruited in Ireland. Venous blood from the participants was stimulated with TLR ligands. Levels of cytokines were measured from plasma and post-blood stimulation. The participants were administered a battery of cognitive tasks using the Cambridge Neuropsychological Test Automated Battery and Wechsler Adult Intelligence Scale-IIIR. Olanzapine equivalents were calculated using the defined daily dose method.

The results indicate that antipsychotic drug dose does not predict TLR activity or cognition, indicating that antipsychotic drug dose does not have a direct effect on cognition or TLR activity. However, the relationship between TLR4 activity and visual learning and memory is moderated by the antipsychotic drug dose (B = −0.065; p < 0.001), where increasing doses have a decreasing impact on their relationship.

Our data indicate that the dose of antipsychotic drugs alone cannot predict changes in cognitive performance and TLR4-activity. It also suggests that antipsychotic drug doses significantly affect TLR activity and its relationship with cognition. These effects are more pronounced on some domains than others. These findings open up new avenues for understanding the complex interplay between antipsychotic drugs, TLRs, and cognitive deficits in SZ.

Adolescent mental health has worsened, and prevention efforts have become increasingly important. The purpose of this study was to examine longitudinal symptom trajectories of depression and anxiety throughout adolescence, in a contemporary sample. The stress–diathesis model was used to inform potential vulnerability factors and stressors associated with these trajectories.

Symptoms of depression and generalized anxiety were assessed in a school-based population sample of N = 6102 adolescents (aged 13–14 at baseline). Growth mixture models across four time points were used to model longitudinal trajectories of symptoms. Multinomial regression was used to examine factors associated with each trajectory class.

Of the full sample, 49.5% were female, 45.9% were male, and 4.6% were gender diverse. Four discrete classes for both depression and anxiety trajectories were identified, which comprised consistently low symptoms (‘low’; 72.5% depression; 66.9% anxiety), consistently high symptoms (‘high’; 11.5% depression; 18.4% anxiety), elevated symptoms that reduced over time (‘decreasing’; 8.3% depression; 6.9% anxiety), and low-moderate symptoms that increased over time (‘increasing’; 7.7% depression; 7.8% anxiety). Factors associated with poorer trajectories were being female or gender diverse, lower socioeconomic status, higher levels of neuroticism and lower levels of conscientiousness, greater adverse childhood experiences, higher levels of peer problems, bullying victimization, and negative family interactions.

A range of background vulnerabilities and specific stressors were associated with poorer depression and anxiety trajectories over a 3-year period. Prevention approaches may require policy and practice changes that promote more supportive family, school, and societal environments from childhood to adolescence.