Psychiatric symptoms of patients with primary mitochondrial DNA disorders

<p>Abstract</p> <p>Background</p> <p>The aim of our study was to assess psychiatric symptoms in patients with genetically proven primary mutation of the mitochondrial DNA.</p> <p>Methods</p> <p>19 adults with known mitochondrial mutation (MT) have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI), the Symptom Check List-90-Revised (SCL-90-R), the Beck Depression Inventory-Short Form (BDI-SF), the Hamilton Depression Rating Scale (HDRS) and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II) As control, 10 patients with hereditary sensorimotor neuropathy (HN), harboring the peripheral myelin protein-22 (PMP22) mutation were examined with the same tools.</p> <p>Results</p> <p>The two groups did not differ significantly in gender, age or education. Mean HAQ-DI score was 0.82 in the MT (range: 0-1.625) and 0.71 in the HN group (range: 0-1.625). Level of disability between the two groups did not differ significantly (<it>p </it>= 0.6076). MT patients scored significantly higher on the BDI-SF and HDRS than HN patients (12.85 versus 4.40, <it>p </it>= 0.031, and 15.62 vs 7.30, <it>p </it>= 0.043, respectively). The Global Severity Index (GSI) of SCL-90-R also showed significant difference (1.44 vs 0.46, <it>p </it>= 0.013) as well as the subscales except for somatization. SCID-I interview yielded a variety of mood disorders in both groups. Eight MT patient (42%) had past, 6 (31%) had current, 5 (26%) had both past and current psychiatric diagnosis, yielding a lifetime prevalence of 9/19 (47%) in the MT group. In the HN group, 3 patients had both past and current diagnosis showing a lifetime prevalence of 3/10 (30%) in this group. SCID-II detected personality disorder in 8 MT cases (42%), yielding 3 avoidant, 2 obsessive-compulsive and 3 personality disorder not otherwise specified (NOS) diagnosis. No personality disorder was identified in the HN group.</p> <p>Conclusions</p> <p>Clinicians should be aware of the high prevalence of psychiatric symptoms in patients with mitochondrial mutation which has both etiologic and therapeutic relevance.</p

Genes Linking Mitochondrial Function, Cognitive Impairment and Depression are Associated with Endophenotypes Serving Precision Medicine

Mitochondria densely populate cells in central nervous system providing essential energy for neurons and influencing synaptic plasticity. Harm to these organelles can impair cognitive performance through damaged neurotransmission and altered Ca2+ homeostasis. Impaired cognition could be one underlying factor which can characterize major depressive disorder, a huge burden for society marked by depressed mood and anhedonia. A growing body of evidence binds mitochondrial dysfunctions with the disease. Cognitive disturbances with different severity are also observable in several patients, suggesting that damage or inherited alterations of mitochondria may have an important role in depression. Since several different biological and environmental factors can lead to depression, mitochondrial changes may represent a significant subgroup of depressive patients although cognitive correlates can remain undiscovered without a specific focus. Hypothesis driven studies instead of GWAS can pinpoint targets relevant only in a subset of depressed population. This review highlights results mainly from candidate gene studies on nuclear DNA of mitochondrion-related proteins, including TOMM40, MTHFD1L, ATP6V1B2 and MAO genes, also implicated in Alzheimer's disease, and alterations in the mitochondrial genome to argue for endophenotypes where impaired mitochondrial function may be the leading cause for depressive symptomatology and parallel cognitive dysfunction

Kannabiszhasználat mellett kialakuló szkizofréniaspektrumzavar klinikai jellegzetességeinek vizsgálata [Clinical characteristics of cannabis-induced schizophrenia spectrum disorder]

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia

THE MODIFYING EFFECT A PMP22 DELETION IN A FAMILY WITH CHARCOT-MARIE-TOOTH TYPE 1 NEUROPATHY DUE TO AN EGR2 MUTATION

Background Mutations of both the PMP22 and EGR2 genes cause Charcot-Marie-Tooth (CMT) disease type 1. Deletion of the PM P22 gene, results in hereditary neuropathy with liability to pressure palsies. More publications exist about the interaction of PMP22 duplication and other CMT-causing gene mutations. In these cases the intrafamiliar discordant phenotypes draw the attention to the possible role of modifying genes. The gene-gene interactions between the PMP22 and EGR2 genes are not well understood. Case report We report two brothers with late onset CMT1 due to a c. 1142 G\u3eA (Arg381His) heterozygous substitution in the EGR2 gene. Additionally, the older brother with the less severe symptoms harbored the PMP22 gene deletion also. Conclusion The coexistence of the two genetic alterations did not aggravate the clinical symptoms. Moreover, the PMP22 deletion appeared to have a beneficial modifying effect, thus implying potential gene-gene interaction of PMP22 and EGR2. PMP22 deletion may increase Schwann cells proliferation and compensate the dominant-negative effect of the Arg381His substitution in the EGR2 gene

Mitochondrial DNA Mutations and Cognition: A Case-Series Report

Mutations in the mitochondrial genome can impair normal metabolic function in the central nervous system (CNS) where cellular energy demand is high. Primary mitochondrial DNA (mtDNA) mutations have been linked to several mitochondrial disorders that have comorbid psychiatric, neurologic, and cognitive sequelae. Here, we present a series of cases with primary mtDNA mutations who were genotyped and evaluated across a common neuropsychological battery. Nineteen patients with mtDNA mutations were genotyped and clinically and cognitively evaluated. Pronounced deficits in nonverbal/visuoperceptual reasoning, verbal recall, semantic word generativity, and processing speed were evident and consistent with a mitochondrial dementia that has been posited. However, variation in cognitive performance was noteworthy, suggesting that the phenotypic landscape of cognition linked to primary mtDNA mutations is heterogeneous. Our patients with mtDNA mutations evidenced cognitive deficits quite similar to those commonly seen in Alzheimer\u27s disease and could have clinical relevance to the evaluation of dementia