Autism and epilepsy: cause, consequence, comorbidity, or coincidence?

Autism is associated with epilepsy in early childhood, with evidence suggesting that individuals with both autism and more severe cognitive impairment are at higher risk. However, the incidence of an abnormal electroencephalogram and/or epilepsy in the full range of pervasive developmental disorders (PDDs) is not well defined. This naturalistic study addresses the incidence of epilepsy and electroencephalographic abnormalities in children with PDDs. The clinical history and electroencephalograms of 56 children diagnosed with PDD-not otherwise specified, autism, or Asperger syndrome were retrospectively reviewed. Forty percent of children with autism were diagnosed with epilepsy. Abnormal electroencephalograms and epilepsy occurred at significantly higher rates in children in the more impaired range of the autism spectrum (P<0.05). These findings suggest that the use of neurological investigative techniques such as electroencephalography should be a consequence of careful clinical evaluation and should be considered routinely during evaluation of more impaired individuals.     

Autism,macrocrania and epilepsy: how are they linked?

To evaluate the possible association of autistic disorder (AD), macrocrania and epilepsy, we performed a retrospective study comparing epileptic and non-epileptic AD patients with macrocrania, and AD patients with macrocrania to age- and sex-matched AD controls without macrocrania. We found macrocrania in 17.3% of 121 patients with AD. Epilepsy was not significantly more frequent in AD patients with macrocrania than in those without macrocrania. There were no significant differences in the other clinical characteristics studied except for epileptiform EEG abnormalities which were more often found in AD patients with epilepsy. AD with macrocrania and epilepsy is not a syndrome but may be a marker for a group of subjects with AD. A role for familial macrocrania needs further assessment.     

Autism and ADHD across the life span. Differential diagnoses or comorbidity?

Exclusion criteria of the DSM-IV-TR and ICD-10 do prevent dual diagnoses of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). However, inattention, impulsivity and hyperactivity are amongst the most frequent associated symptoms of ASD. Psychopathological, neuropsychological, brain imaging and genetic studies suggest possible pathophysiological links between ASD and ADHD. Thus, standard diagnostic procedures for both disorders should assess the presence of potential comorbid symptoms of the other disorder. Treatment strategies for ADHD symptoms in the context of ASD overlap with those for patients with ADHD, but lower dosages and slower titration might be recommendable.     

Neuroinflammation and cytokine abnormality in major depression: Cause or consequence in that illness?

Depression results from changes in the central nervous system (CNS) that may result from immunological abnormalities. The immune system affects the CNS through cytokines, which regulate brain activities and emotions. Cytokines affect two biological systems that are most associated with the pathophysiology of depression: The hypothalamic-pituitary-adrenal axis and the catecholamine/sympathetic nervous system. Neuroinflammation and cytokines affect the brain signal patterns involved in the psychopathology of depression and the mechanisms of antidepressants, and they are associated with neurogenesis and neural plasticity. These observations suggest that neuroinflammation and cytokines might cause and/or maintain depression, and that they might be useful in the diagnosis and prognosis of depression. This psychoneuroimmunologic perspective might compensate for some of the limitations of the monoamine theory by suggesting that depression is a result of a failure to adapt to stress and that inflammatory responses and cytokines are involved in this process. In this review, the interactions of cytokines with the CNS, neuroendocrine system, neurotransmitters, neurodegeneration/neurogenesis, and antidepressants are discussed. The roles of cytokines in the etiology and psychopathology of depression are examined. The use of cytokine inhibitors or anti-inflammatory drugs in depression treatment is explored. Finally, the significance and limitations of the cytokine hypothesis are discussed.     

Depression and stroke: cause or consequence?

Depression after stroke is common. Although different opinions exist about the definition, diagnosis, and measurement of outcomes related to depression after stroke, there is little debate about the prevalence of depression symptoms and their impact on stroke survivors and their families. Depression after stroke has long been recognized as a common condition with many negative effects in the poststroke period, but more recently depression has also been identified as an independent stroke risk factor. Given that there are at least 500,000 new ischemic strokes yearly in the United States, a conservative estimate is that 150,000 U.S. stroke survivors develop poststroke depression each year. Because effective treatments exist but are likely underutilized for depression, this is an important example of an evidence-practice gap to which increased efforts to improve care should be made. Such efforts would likely improve not only patient symptoms but may also decrease stroke risk, influence stroke functional recovery, decrease mortality, and reduce poststroke health care utilization. This article provides an overview of depression diagnosis in stroke, reviews the epidemiology of poststroke depression and its associated morbidity and mortality, and reviews existing evidence on the treatment and prevention of poststroke depression.     

Depression and Alzheimer's disease: symptom or comorbidity?

Alzheimer's disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer's disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimer's disease.     

Fabry's disease and psychosis: causality or coincidence?

A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.     

Stroke and sleep apnoea: cause or consequence?

The relationships between obstructive sleep apnoea syndrome (OSAS) and stroke are still under discussion, but increasing evidence demonstrates that the OSAS is an independent risk factor for stroke. However, in rare cases, OSAS could be a consequence of strokes, especially if located in the brainstem. Many recent studies have found a 70 to 95% frequency of OSAS (defined by an apnoea/hypopnoea index >10) in patients with acute stroke. Age, body mass index, diabetes, and severity of stroke have been identified as independent predictors of stroke. Furthermore, the presence of OSAS in stroke patients could lead to a poor outcome. The potential mechanisms linking OSAS and stroke are probably multiple (arterial hypertension, cardiac arrhythmia, increased atherogenesis, coagulation disorders, and cerebral haemodynamic changes). Despite numerous uncertainties, OSAS should be systematically screened at the moment it is clinically suspected in patients with acute stroke. However, the optimal timing (early or differed) for treatment with nasal continuous positive airway pressure remains to be determined.     

Autism and ADHD: how far have we come in the comorbidity debate?

The potential for the coexistence of the developmental disorders autism and attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a long time been a contentious issue. While from a neurobiological perspective it is possible, and even highly likely, that ADHD and autism might clinically co-exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10) currently preclude such a dual-diagnosis. The aim of the current review is to summarise current diagnostic criteria and treatment strategies for the two disorders, relevant theories of developmental dysfunction, and update the state of the debate regarding comorbidity. Evidence from clinical, neuroimaging and neuropsychological domains is considered, and similarities and differences between the two disorders are identified. Suggestions for future research into the comorbid profiles of these disorders are proposed, with a strong emphasis placed on the neuropsychological assessment of executive functioning as a potentially useful tool for both identifying similarities, and differentiating the disorders.     

Impaired language performance as a precursor or consequence of Rolandic epilepsy?

Loss of function mutations of the CACNA1A gene, coding for the α1A subunit of P/Q type voltage-gated calcium channel (Ca(V)2.1), are responsible for Episodic Ataxia type 2 (EA2), an autosomal dominant disorder. A dominant negative effect of the EA2 mutated protein, rather than a haploinsufficiency mechanism, has been hypothesised both for protein-truncating and missense mutations. We analysed the cacna1a mRNA expression in leaner mice carrying a cacna1a mutation leading to a premature stop codon. The results showed a very low mutant mRNA expression compared to the wild type allele. Although the mutant mRNA slightly increases with age, its low level is likely due to degradation by nonsense mediated decay, a quality control mechanism that selectively degrades mRNA harbouring premature stop codons. These data have implications for EA2 in humans, suggesting a haploinsufficiency mechanism at least for some of the CACNA1A mutations leading to a premature stop codon.