Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

Normalization of increased retinal background noise after ADHD treatment: A neuronal correlate.

Inattention, distractibility, and problems inhibiting irrelevant information impose a large disease burden in attention deficit hyperactivity disorder (ADHD). Problems with cognitive function are found in many major psychiatric disorders, and our understanding of ADHD might add to our knowledge of other neuropsychiatric disorders. Despite the high impact of ADHD, the pathophysiology and the mechanism of treatment action remains poorly understood. Increasing evidence suggests that elevated neuronal and retinal background noise plays a prominent role in ADHD. However, the effect of treatment (e.g., methylphenidate) on noise remains unclear. For this study, retinal background noise was assessed with the pattern-electroretinogram (PERG) in 20 drug-naïve adults with ADHD before and after treatment with methylphenidate and in 21 control subjects. Background noise was identified using the Fourier magnitude at frequencies adjacent to the stimulus-response frequency of 12.5 Hz. At baseline, we found an elevated retinal background noise in ADHD patients (Mdn = 0.079 µV) compared to controls (Mdn = 0.062 µV; z = -2.79, p = 0.016, r = -0.44). The noise in the ADHD group decreased significantly at follow-up after treatment with methylphenidate (Mdn = 0.069 µV, z = -2.39, p = 0.035, r = -0.39) while there was no change in the control group. PERG-based retinal noise is increased in adult ADHD and normalizes along with clinical symptoms following treatment with methylphenidate. The retinal noise level might be a promising marker of ADHD in clinical and basic research and illustrates the biological match with nonhuman ADHD models.

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. METHODS: Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. RESULTS: We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks' lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). CONCLUSIONS: We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.

On the Effect of Sex on Prefrontal and Cerebellar Neurometabolites in Healthy Adults: An MRS Study.

In neuropsychiatric research, the aspects of sex have received increasing attention over the past decade. With regard to the neurometabolic differences in the prefrontal cortex and the cerebellum of both men and women, we performed a magnetic resonance spectroscopic (MRS) study of a large group of healthy subjects. For neurometabolic measurements, we used single-voxel proton MRS. The voxels of interest (VOI) were placed in the pregenual anterior cingulate cortex (pACC) and the left cerebellar hemisphere. Absolute quantification of creatine (Cre), total choline (t-Cho), glutamate and glutamine (Glx), N-acetylaspartate, and myo-inositol (mI) was performed. Thirty-three automatically matched ACCs and 31 cerebellar male-female pairs were statistically analyzed. We found no significant neurometabolic differences in the pACC region (Wilks' lambda: p = 0.657). In the left cerebellar region, we detected significant variations between the male and female groups (p = 0.001). Specifically, we detected significantly higher Cre (p = 0.005) and t-Cho (p = 0.000) levels in men. Additionally, males tended to have higher Glx and mI concentrations. This is the first study to report neurometabolic sex differences in the cerebellum. The effects of sexual hormones might have influenced our findings. Our data indicates the importance of adjusting for the confounding effects of sex in MRS studies.