Familial clustering of psychiatric disorders and low IQ.

BACKGROUND: Although the ICD and DSM differentiate between different psychiatric disorders, these often share symptoms, risk factors, and treatments. This was a population-based, case-control, sibling study examining familial clustering of all psychiatric disorders and low IQ, using data from the Israel Draft-Board Registry on all Jewish adolescents assessed between 1998 and 2014. METHODS: We identified all cases with autism spectrum disorder (ASD, N = 2128), severe intellectual disability (ID, N = 9572), attention-deficit hyperactive disorder (ADHD) (N = 3272), psychotic (N = 7902), mood (N = 9704), anxiety (N = 10 606), personality (N = 24 816), or substance/alcohol abuse (N = 791) disorders, and low IQ (⩾2 SDs below the population mean, N = 31 186). Non-CNS control disorders were adolescents with Type-1 diabetes (N = 2427), hernia (N = 29 558) or hematological malignancies (N = 931). Each case was matched with 10 age-matched controls selected at random from the Draft-Board Registry, with replacement, and for each case and matched controls, we ascertained all full siblings. The main outcome measure was the relative recurrence risk (RRR) of the sibling of a case having the same (within-disorder RRR) or a different (across-disorder RRR) disorder. RESULTS: Within-disorder RRRs were increased for all diagnostic categories, ranging from 11.53 [95% confidence interval (CI): 9.23-14.40] for ASD to 2.93 (95% CI: 2.80-3.07) for personality disorders. The median across-disorder RRR between any pair of psychiatric disorders was 2.16 (95% CI: 1.45-2.43); the median RRR between low IQ and any psychiatric disorder was 1.37 (95% CI: 0.93-1.98). There was no consistent increase in across-disorder RRRs between the non-CNS disorders and psychiatric disorders and/or low IQ. CONCLUSION: These large population-based study findings suggest shared etiologies among most psychiatric disorders, and low IQ.

Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: A preliminary study.

BACKGROUND: Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits. METHODS: Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. RESULTS: We found a significant improvement of the PANSS score (baseline 116.28+/-21.9 vs. 97.86+/-24.48 after six weeks, t=5.98, p<0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40+/-6.38 vs. 31.71+/-7.76 after six weeks, t=5.87, p<0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement. CONCLUSION: Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations.

Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder.

BACKGROUND: Persistent, intrusive re-experiencing in posttraumatic stress disorder (PTSD) is commonly construed as a failure of cingulate inhibition (i.e., extinction) over a hyperresponsive amygdala, based primarily on animal research of fear conditioning and the finding of cingulate hypoperfusion in PTSD. METHODS: We examined functional connectivity in patients with PTSD and healthy trauma survivors during repeated symptom provocation using H(2)O(15) positron emission tomography. RESULTS: Memory retrieval networks (right prefrontal cortex, hippocampus, and visual cortex) were common to both groups. Networks supporting autonomic and emotional control and preparatory motor action (amygdala, anterior cingulate, subcallosal gyrus, and premotor cortex) differed between the two groups and became progressively disparate with successive presentations of the traumatic script. Patterns of effective connectivity demonstrated the predominance of direct influences of the amygdala on visual cortex, subcallosal gyrus, and anterior cingulate in PTSD but not in control subjects. There was little evidence for failure of inhibition of cingulate or subcallosal cortex over the amygdala. CONCLUSIONS: These patterns might represent excessive influences of the amygdala over regions involved in autonomic, and higher-order visual memory processing in PTSD. The present data suggest that inferences of direct correspondence between animal studies and pathophysiology of PTSD should be made with caution.