Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort.

BACKGROUND: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. METHODS: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. RESULTS: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (Δ15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (Δ2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. CONCLUSIONS: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

No progression of the alterations in the cortical thickness of individuals with schizophrenia-spectrum disorder: a three-year longitudinal magnetic resonance imaging study of first-episode patients.

BACKGROUND: Cortical thickness measurement offers an index of brain development processes. In healthy individuals, cortical thickness is reduced with increasing age and is related to cognitive decline. Cortical thinning has been reported in schizophrenia. Whether cortical thickness changes differently over time in patients and its impact on outcome remain unanswered. METHOD: Data were examined from 109 patients and 76 healthy controls drawn from the Santander Longitudinal Study of first-episode schizophrenia for whom adequate structural magnetic resonance imaging (MRI) data were available (n = 555 scans). Clinical and cognitive assessments and MRIs were acquired at three regular time points during a 3-year follow-up period. We investigated likely progressive cortical thickness changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The effects of cortical thickness changes on cognitive and clinical variables were also examined along with the impact of potential confounding factors. RESULTS: There were significant diagnoses × scan time interaction main effects for total cortical thickness (F 1,309.1 = 4.60, p = 0.033) and frontal cortical thickness (F 1,310.6 = 5.30, p = 0.022), reflecting a lesser thinning over time in patients. Clinical and cognitive outcome was not associated with progressive cortical changes during the early years of the illness. CONCLUSIONS: Cortical thickness abnormalities do not unswervingly progress, at least throughout the first years of the illness. Previous studies have suggested that modifiable factors may partly account for cortical thickness abnormalities. Therefore, the importance of implementing practical actions that may modify those factors and improve them over the course of the illness should be highlighted.

Three-year longitudinal population-based volumetric MRI study in first-episode schizophrenia spectrum patients.

BACKGROUND: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate. METHOD: The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors. RESULTS: Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F 1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness. CONCLUSIONS: Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.

Global and regional cortical thinning in first-episode psychosis patients: relationships with clinical and cognitive features.

BACKGROUND: The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features. METHOD: We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated. RESULTS: Patients showed a significant total cortical thinning (F=17.55, d=-0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=-0.24, p=0.021) and parietal cortical thickness (r=-0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls. CONCLUSIONS: Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.