Highlights from the 2014 Schizophrenia International Research Society Conference April 5-9, 2014.

The 2014 Schizophrenia International Research Society (SIRS) Conference, held in Florence, Italy, attracted more than 1,700 attendees from over 55 countries to the stately Firenze Fiera Conference Center from April 5-9, 2014. Providing plenary sessions, special sessions, symposia, workshops, oral presentations and poster presentations, this 4th Biennial SIRS Conference was jointly sponsored by Vanderbilt University School of Medicine, Department of Psychiatry and SIRS. In conjunction with the Schizophrenia Research Forum, a Web project of the Brain and Behavior Research Foundation, and with our thanks to the SIRS organizers and staff, we bring you the following report on the meeting's discussions concerning drug therapy developments for schizophrenia.

Highlights from the Biennial International Congress on Schizophrenia Research (ICOSR), April 21-25, 2013.

The 2013 International Congress on Schizophrenia Research, held in Orlando Grande Lakes, Florida, attracted over 1,000 attendees to the JW Marriott Hotel from 21-25 April 2013, not to mention the satellite meetings on cognition and the schizophrenia prodrome. With thanks to the Schizophrenia Research Forum (www.schizophreniaforum.

Role of glutamic acid decarboxylase 67 in regulating cortical parvalbumin and GABA membrane transporter 1 expression: implications for schizophrenia.

Markers of GABA neurotransmission are altered in multiple regions of the neocortex in individuals with schizophrenia. Lower levels of glutamic acid decarboxylase 67 (GAD67) mRNA and protein, which is responsible for most cortical GABA synthesis, are accompanied by lower levels of GABA membrane transporter 1 (GAT1) mRNA. These alterations are thought to be most prominent in the parvalbumin (PV)-containing subclass of interneurons, which also contain lower levels of PV mRNA.

Cortical basket cell dysfunction in schizophrenia.

Schizophrenia, a debilitating illness affecting 0.5-1% of the world's population, is characterized by positive, negative and cognitive symptoms. The latter are the best predictor of functional outcome, though largely untreated by current pharmacotherapy; thus a better understanding of the mechanisms underlying cognitive deficits in schizophrenia is crucial.

Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia.

Deficits in cognitive control, a core disturbance of schizophrenia, appear to emerge from impaired prefrontal gamma oscillations. Cortical gamma oscillations require strong inhibitory inputs to pyramidal neurons from the parvalbumin basket cell (PVBC) class of GABAergic neurons. Recent findings indicate that schizophrenia is associated with multiple pre- and postsynaptic abnormalities in PVBCs, each of which weakens their inhibitory control of pyramidal cells.

Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features.

Objective: Cognitive deficits in schizophrenia are associated with altered activity of the dorsolateral prefrontal cortex, which has been attributed to lower expression of the 67 kDa isoform of glutamic acid decarboxylase (GAD67), the major γ-aminobutyric acid (GABA)-synthesizing enzyme. However, little is known about the relationship of prefrontal GAD67 mRNA levels and illness severity, translation of the transcript into protein, and protein levels in axon terminals, the key site of GABA production and function.

Method: Quantitative polymerase chain reaction was used to measure GAD67 mRNA levels in postmortem specimens of dorsolateral prefrontal cortex from subjects with schizophrenia and matched comparison subjects with no known history of psychiatric or neurological disorders (N=42 pairs).

Phosphorylation of the homer-binding domain of group I metabotropic glutamate receptors by cyclin-dependent kinase 5.

Phosphorylation of neurotransmitter receptors can modify their activity and regulate neuronal excitability. Cyclin-dependent kinase 5 (cdk5) is a proline-directed serine/threonine kinase involved not only in neuronal development, but also in synaptic function and plasticity. Here we demonstrate that group I metabotropic glutamate receptors (mGluRs), which modulate post-synaptic signaling by coupling to intracellular signal transduction pathways, are phosphorylated by cdk5.

Altered markers of tonic inhibition in the dorsolateral prefrontal cortex of subjects with schizophrenia.

Objective: Cognitive impairments in schizophrenia are associated with lower expression of markers of gamma-aminobutyric acid (GABA) synthesis in the prefrontal cortex. The effects of GABA are mediated by GABA(A) receptors that mediate either phasic or tonic inhibition. The authors assessed the expression of GABA(A) receptor alpha4 and delta subunits, which coassemble to form receptors mediating tonic inhibition, in schizophrenia.