Impairment in non‐word repetition: a marker for language impairment or reading impairment?

Aim A deficit in non‐word repetition (NWR), a measure of short‐term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language impairment and assessed any differential impairment of NWR, compared with two other tests of verbal memory in children with language impairment with and without reading impairment. Method Our sample comprised children aged 6–16y 11mo participating in a study of the genetics of language impairment: 78 children from 68 families (53 males, 25 females) with current language impairment (C‐LI), compared with their 74 siblings: 25 children (18 males, seven females) with a past history of language impairment and 49 children (27 males, 22 females) who had never had a language impairment. The tests used were the Clinical Evaluation of Language Fundamentals (CELF III), the Children’s Test of Non‐word Repetition (CN‐Rep), the Wide Range Assessment of Memory and Learning (WRAML) verbal memory index, the Wechsler Intelligence Scale for Children‐III (WISC‐III) digit span, and the Wechsler Objective Reading Dimensions (WORD^UK). Results Reading impairment was present in two‐thirds of the children with current language impairment. NWR deficits were significantly worse in children with language impairment who had reading impairment in reading decoding (p=0.007 and 0.004 – average group compared with borderline and definitely impaired groups respectively) or spelling (p=0.002 and 0.005 – average group compared with borderline and severely impaired groups respectively) (not correlated with severity of language impairment) but not comprehension impairment. In contrast, WISC digit span and WRAML verbal memory were impaired in all children with language impairment and did not differentiate those who also had reading impairment. Interpretation We suggest that current NWR ability may be a marker of a process specifically underlying language impairment, co‐occurring with reading impairment involving reading decoding and spelling, rather than a generic correlate of language impairment. Other verbal memory deficits appear to be pervasive in children with language impairment.     

Understanding aberrant white matter development in schizophrenia: an avenue for therapy?

Although historically gray matter changes have been the focus of neuropathological and neuroradiological studies in schizophrenia, in recent years an increasing body of research has implicated white matter structures and its constituent components (axons, their myelin sheaths and supporting oligodendrocytes). This article summarizes this body of literature, examining neuropathological, neurogenetic and neuroradiological evidence for white matter pathology in schizophrenia. We then look at the possible role that antipsychotic medication may play in these studies, examining both its role as a potential confounder in studies examining neuronal density and brain volume, but also the possible role that these medications may play in promoting myelination through their effects on oligodendrocytes. Finally, the role of potential novel therapies is discussed.     

Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia?

OBJECTIVE: Evidence from many different lines of research supports the hypothesis that schizophrenia is a disorder of development with etiological factors implicated as early as the second trimester in utero. We suggest that low maternal folate, acting to increase homocysteine levels, may provide a functional link between many of the identified prenatal risk factors and the hypothesized mechanisms whereby neurodevelopmental patterning deviates toward a schizophrenic potential. METHODS: PubMed was searched from the present back to 1963, when elevated homocysteine was identified as a pathogen in homocystinuria as first described by Carson and colleagues (Arch Dis Child 1963;38:425-36). All articles for homocystinuria, homocysteine, folate, and development with schizophrenia were evaluated. RESULTS: The findings from this review support the hypothesis that maternal low folate and high homocysteine levels may provide a potential teratogenic mechanism that increases the risk for developing schizophrenia. CONCLUSION: The potential role of maternal folate deficiency and hyperhomocystinemia in the genesis of schizophrenia would extend the range of their known teratogenic effects. Given the potential for preventive treatment offered by this hypothesis, we believe further investigation into this mechanism is warranted.     

Theory of mind impairment: a distinct trait‐marker for schizophrenia spectrum disorders and bipolar disorder?

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait‐marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high‐risk (HR) for psychosis and first‐degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait‐marker.     

Self‐reported psychotic experiences in the general population: a valid screening tool for DSM‐III‐R psychotic disorders?

OBJECTIVE: To examine the diagnostic value of self-reported psychotic-like experiences for DSM-III-R psychotic disorders. METHOD: A general population sample of 7076 subjects aged 18-64 years was interviewed with the Composite International Diagnostic Interview (CIDI) and, if there was evidence of psychotic experiences, the Structured Clinical Interview for DSM-III-R. RESULTS: The probability of having a psychotic disorder increased in a dose-response fashion with the level of self-reported psychotic experiences, but individual CIDI psychotic experience ratings had relatively low post-test probabilities (PPs) (range: 5.1-26.5%). However, limiting the sample to individuals who had been in contact with mental health services substantially improved PPs (range: 13.3-43.1%). CONCLUSION: Screening for psychosis in the population carries a high risk of stigmatization in false-positive cases and violation of the right 'not to know' in true-positive cases. However, in mental health care users, self-reported psychotic experiences may be a useful screening tool in individuals who have already developed help-seeking.     

Sexual dimorphism in schizophrenia: is there a need for gender-based protocols?

Gender differences have been reported in various aspects of schizophrenia, including its epidemiology, clinical course and the response to antipsychotic medications. Over the past few years the authors have been investigating sex differences in brain function in individuals with schizophrenia and have found an intriguing disturbance of normal sexual dimorphism during emotional and cognitive processing. These results can be partly accounted for by altered levels of sex steroid hormones (i.e., estrogen and testosterone) in patients. A handful of clinical research groups have tried low doses of estrogen, testosterone or their precursors as adjunct therapies to the currently available antipsychotic medications in women and men with schizophrenia. The results have been promising, but further investigation is warranted. In the future, new more specific steroidal compounds will be developed and we will see more studies examining sex differences in the brain, behavior and mental health problems. This research will help to identify individuals who may benefit greatest from adjunct hormonal therapies and will further our understanding of the etiology of schizophrenia and other psychiatric disorders.     

Gastrointestinal distress to serotonergic challenge: a risk marker for emotional disorder?

OBJECTIVE: Serotonin is an important mediator of gut sensation and motility. The authors' aim was to determine whether inadvertent gastrointestinal (GI) distress to serotonergic challenge predicted future major depressive and/or anxiety disorders in exposed children. METHOD: l-5-hydroxytryptophan was administered to 119 prepubertal children free of psychiatric disorder as part of a psychobiological cohort study initially designed to examine familial loading for mood disorder as the exposure of interest. Subjects were followed longitudinally with standardized psychiatric interviews to identify new-onset mood and anxiety disorders over 90.3 +/- 29.2 months, with the average assessment interval being 16.6 +/- 6.2 months. Reports of GI distress in a subgroup during serotonergic challenge led the authors to examine GI distress to infusion as an exposure post hoc and to perform survival analysis using major depressive and/or anxiety disorders as the outcomes of interest. RESULTS: GI distress to serotonergic challenge was experienced by 23 subjects, with 7 (30.4%) developing an emotional disorder during follow-up in comparison to 12 (10.4%) of 96 nondistressed subjects. The distressed group was at significantly greater risk of subsequent major depression and/or anxiety (p =.026), even after controlling for family history of psychiatric disorder. CONCLUSIONS: GI distress to serotonergic challenge in childhood is associated with heightened risk for subsequent major depressive and/or anxiety disorders. Studies of serotonergic neurotransmission may aid our understanding of nonrandom associations between functional GI symptoms and emotional symptoms and disorders.     

APOE ε4 and risk for Alzheimer's disease: Do regionally distributed white matter hyperintensities play a role?

BackgroundWe previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume.MethodsParticipants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis.ResultsIn WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH.ConclusionsAPOE ε4 is associated with increased parietal lobe WMH.     

Comparison of severe life stress in depressed mothers and non‐mothers: Do children matter?

Given the high rates of maladjustment among children of depressed mothers, parenting is likely to cause significant life stress in this population, potentially worsening the course of mothers' depression. The present study is a comparison of severe life stress in 38 mothers and 62 non-mothers receiving treatment for recurrent major depression. Life stress was assessed using the Life Events and Difficulties Schedule [Brown and Harris, 1978a]. We hypothesized that mothers would evidence a greater number of severe life events and marked difficulties both in the year prior to the onset of their depressive index episode and in the time period following the onset of their current depressive episode. Prior to depression onset, mothers reported a significantly greater number of entrapping difficulties, but not marked difficulties, severe events, entrapping events, or humiliating events. However, following the onset of depression, mothers experienced a significantly greater number of severe events, entrapping events, marked difficulties, and entrapping difficulties, but not humiliating events. Mothers' elevated levels of stress were attributable to child-related stress, predominantly related to children's psychological and behavioral problems. Our findings suggest that comprehensive treatment for mothers with major depression needs to address their parenting style and any psychological problems experienced by their children.     

Auditory stimulation enhances thalamic somatosensory high‐frequency oscillations in healthy humans: a neurophysiological marker of cross‐sensory sensitization?

Electrical stimulation of upper limb nerves evokes a train of high‐frequency wavelets (high‐frequency oscillations, HFOs) on the human scalp. These HFOs are related to the influence of arousal‐promoting structures on somatosensory input processing, and are generated in the primary somatosensory cortex (post‐synaptic HFOs) and the terminal tracts of thalamocortical radiations (pre‐synaptic HFOs). We previously reported that HFOs do not undergo habituation to repeated stimulations; here, we verified whether HFOs could be modulated by external sensitizing stimuli. We recorded somatosensory evoked potentials (SSEPs) in 15 healthy volunteers before and after sensitization training with an auditory stimulus. Pre‐synaptic HFO amplitudes, reflecting somatosensory thalamic/thalamocortical activity, significantly increased after the sensitizing acoustic stimulation, whereas both the low‐frequency N20 SSEP component and post‐synaptic HFOs were unaffected. Cross‐talk between subcortical arousal‐related structures is a probable mechanism for the pre‐synaptic HFO effect observed in this study. We propose that part of the ascending somatosensory input encoded in HFOs is specifically able to convey sensitized inputs. This preferential involvement in sensitization mechanisms suggests that HFOs play a critical role in the detection of potentially relevant stimuli, and act at very early stages of somatosensory input processing.     

Pregabalin‐withdrawal encephalopathy and splenial edema: A link to high‐altitude illness?

A postherpetic-neuralgia patient abruptly discontinued pregabalin. Thirty hours later, unexplained nausea, headache, and ataxia developed, progressing to delirium 8 days later. Magnetic resonance imaging indicated T2-hyperintense lesions of her splenium. Similar magnetic resonance imaging abnormalities, interpreted as focal vasogenic edema, develop in some epileptic patients after rapid anticonvulsant withdrawal. Patients with high-altitude cerebral edema have similar splenial-predominant magnetic resonance imaging abnormalities that accompany these same neurological symptoms. This case is the first to associate anticonvulsant-withdrawal splenial abnormalities with neurological symptoms, with gabapentin-type anticonvulsants, and is among the first in nonepileptic patients, suggesting that sudden anticonvulsant withdrawal alone, unaccompanied by seizures, can initiate symptomatic focal brain edema. The similarity of this syndrome to high-altitude cerebral edema suggests a possible common pathophysiology and offers potential therapies.     

Correction to: Cortical activation abnormalities in bipolar and schizophrenia patients in a combined oddball–incongruence paradigm

European Archives of Psychiatry and Clinical Neuroscience - A correction to this paper has been published: https://doi.org/10.1007/s00406-021-01276-6