Prevalence, correlates, and clinical features of delayed-onset posttraumatic stress disorder in a nationally representative military sample

Purpose

Since its inclusion in the Diagnostic and Statistical Manual of Mental Disorders, there has been skepticism over the validity of delayed-onset posttraumatic stress disorder (PTSD). Paucity of research on the correlates and the clinical consequences of delayed-onset PTSD have historically added to this skepticism. The objective of this study was to address an important gap in the literature by examining the prevalence, the correlates, and the clinical consequences of delayed-onset PTSD using data from a large epidemiological survey.

Methods

Data were drawn from the Canadian Community Health Survey-Canadian Forces Supplement (N?=?8,441), a cross-sectional epidemiological survey of mental health in the Canadian Forces. Logistic regressions were used to identify correlates of delayed onset. Cox regressions were used to examine the impact of delayed onset on symptom duration.

Results

The prevalence of delayed-onset PTSD in this Canadian population was less than 1%. Delayed-onset cases accounted for 8.5% of all PTSD cases. Experiencing trauma in early childhood, experiencing a repeated trauma, and serving in the land troops were all associated with greater likelihood of developing delayed-onset PTSD. Delayed onset, after controlling for important sociodemographic, military, and clinical variables, was associated with greater symptom duration.

Conclusions

The phenomenon of delayed-onset PTSD, albeit uncommon, does exist. Certain trauma characteristics may increase the risk for developing delayed-onset PTSD. Delayed onset may be associated with more chronic forms of this disorder.     

Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations

Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditions, the endogenous excitability regulator neuropeptide Y (NPY) has been shown to modulate afferent inputs onto dentate gyrus CCK-basket cells, providing a possible novel mechanism for excitability control in the hippocampus. Using GAD65-GFP mice for CCK-basket cell identification, and whole-cell patch-clamp recordings, we explored whether the effect of NPY on afferent synapses to CCK-basket cells is modified in the hyper-excitable dentate gyrus. To induce a hyper-excitable state, recurrent seizures were evoked by electrical stimulation of the hippocampus using the well-characterized rapid kindling protocol. The frequency of spontaneous and miniature excitatory and inhibitory post-synaptic currents recorded in CCK-basket cells was decreased by NPY. The excitatory post-synaptic currents evoked in CCK-basket cells by optogenetic activation of principal neurons were also decreased in amplitude. Interestingly, we observed an increased proportion of spontaneous inhibitory post-synaptic currents with slower rise times, indicating that NPY may inhibit gamma aminobutyric acid release preferentially in peri-somatic synapses. These findings indicate that increased levels and release of NPY observed after seizures can modulate afferent inputs to CCK-basket cells, and therefore alter their impact on the oscillatory network activity and excitability in the hippocampus.     

Characterization of a rat model of Huntington's disease based on targeted expression of mutant huntingtin in the forebrain using adeno-associated viral vectors

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (htt) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant htt is ubiquitously expressed, it has not been possible to establish clear structure‐to‐function relationships for the clinical aspects. In the present study, we have injected recombinant adeno‐associated viral vectors of serotype 5 (rAAV5) expressing an 853‐amino‐acid fragment of htt with either 79 (mutant) or 18 (wild‐type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of htt in the forebrain. Rats were followed for 6 months and compared with control rats. Neuropathological assessment showed long‐term expression of the green fluorescent protein (GFP) transgene (used as a marker protein) and accumulation of htt inclusions in the cerebral cortex with the rAAV5‐htt‐79Q vectors. We estimated that around 10% of NeuN‐positive cells in the cerebral cortex and 2% of DARPP‐32 neurons in the striatum were targeted with the GFP‐expressing vector. Formation of intracellular htt inclusions was not associated with neuronal loss, gliosis or microglia activation and did not lead to altered motor activity or changes in body weight. However, the same mutant htt vector caused orexin loss in the hypothalamus – another area known to be affected in HD. In conclusion, our results demonstrate that widespread forebrain expression of mutant htt can be achieved using rAAV5‐vectors and suggest that this technique can be further explored to study region‐specific effects of mutant htt or other disease‐causing genes in the brain.     

Are dopa-responsive dystonia and Parkinson’s disease related disorders? A case report

Objectivel-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinson’s disease. In classical DRD no changes in the dopaminergic uptake have been observed.MethodsA 65-year old woman presented with clinically remarkably slowly progressing Parkinson’s disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [¹²³I] FP-CIT-SPECT (DaTSCAN?) in order to elucidate a striatal dopaminergic deficit.ResultsWe found a reduced uptake in the [¹²³I] FP-CIT-SPECT (DaTSCAN?) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene.ConclusionsPatients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [¹²³I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.     

Comparison of bupivacaine alone and in combination with sufentanil in patients undergoing arthroscopic knee surgery

Purpose  

One disadvantage of spinal anesthesia using bupivacaine is the relatively short duration of action. Combining it with opioids can increase its analgesic effects. It was aimed to analyze the effectiveness and the side effects of bupivacaine alone and in combination with sufentanil in arthroscopic knee surgery during unilateral spinal anesthesia.