Short-term functional outcome in psychotic patients: results of the Turku early psychosis study (TEPS).

BACKGROUND: Functional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N). METHODS: Altogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA. RESULTS: During follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning. CONCLUSIONS: In patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis.

Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function.

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [11C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (VT) of [11C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

Korsakoff Syndrome in Non-alcoholic Psychiatric Patients. Variable Cognitive Presentation and Impaired Frontotemporal Connectivity.

Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate fasciculus, may be a feature of non-alcoholic Korsakoff syndrome in psychiatric patients.

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy.