Patient Intake

• 39-year-old army sergeant

• Complains of:

• – Dizziness

• – Frequent severe headaches

• – Memory loss

• – Nervousness

• – Habitual stammering

• – Flashbacks and recurrences of images from the war

• – Being emotionally distant from others

• – Nighttime awakenings from nightmares

• – Bilateral knee pain

• – Low back pain

Patient Intake

• 34-year-old man with a chief complaint of “paranoia”

• Parents, who asked for the appointment and with whom the patient lives, are approaching their own retirement and concerned about the patient's ability to ever live on his own and what will happen to all of them after their money runs out, or to him, after their deaths

Patient Intake

• 72-year-old female

• Chief complaint: anxiety

Patient Intake

• 33-year-old woman with a chief complaint of “extreme anxiety”

Patient Intake

• 62-year-old male

• Chief complaint: “feeling drugged and lethargic”

Patient Intake

• 21-year-old man who states he has no chief complaint but is here because his parents made him come

• The chief complaint of the parents is that their son is not transitioning successfully into independent adult life (i.e., failure to launch)

Patient Intake

• 32-year-old man

• Chief complaint by the patient: parents will not leave him alone

• Chief complaint by the parents: son will not take care of his hygiene or his room, and is not on a trajectory towards ever living on his own

Patient Intake

• 24-year-old male

• Chief complaint: crippling depression

Patient Intake

• 48-year-old man diagnosed with paranoid schizophrenia and alcohol dependence (now in a controlled environment) with a 23-year history of alcohol abuse and relapse, and a 16-year history of psychotic illness

• Referred by his treating psychiatrist for expert psychopharmacological consultation because the patient continues to have symptoms despite heroic treatment with antipsychotics

• Multiple prior psychiatric hospitalizations with history of poor compliance

• Predominant symptoms are persecutory ideation, ideas of reference, auditory hallucinations, and disorganized thinking with history of suicide attempts

• History of thrombocytopenia, considered a contraindication for clozapine by medical consultants

• History of alcohol and marijuana abuse

• At least one first degree relative with a psychotic illness

• Current hospitalization resulted from an incident in which the patient believed that his family was being abused via the internet and thus he needed to burn down his house to stop it, which he did, plus dousing himself with gasoline intending to commit suicide but was unable to successfully light himself on fire

• Arrested and convicted of the acts but found not criminally responsible by reason of insanity and admitted to a forensic facility

Patient Intake

• 27-year-old woman with a chief complaint of depression

Patient Intake

• 30-year-old man with a chief complaint of anxiety and depression

Patient Intake

• 45-year-old woman with a chief complaint “feeling sick all the time” by which she means being tired, seeing things, hearing things, inability to drive, and problems with daily living

• Her husband states that she has bouts of depression with confusion and that is the main problem

• Her psychiatrist is referring her for recommendations now that many medications including clozapine, as well as ECT have not been adequately effective

Patient Intake

• 65-year-old man with a psychotic disorder since age 26 currently diagnosed as paranoid schizophrenia, with multiple hospitalizations for auditory hallucinations, ideas of reference, persecutory delusions, disorganization of thinking and aggressive behavior

• He has exhibited episodes of psychomotor agitation and aggressive behavior but has never met full criteria for either mania or major depression, but has carried the diagnosis of schizoaffective disorder at times in the past

• About 18 years ago stabbed the manager of his board and residential care facility during an argument and was convicted of attempted murder but found not criminally responsible by reason of insanity and admitted to a forensic facility

• Now developing deficits in cognition and short term memory consistent with early Alzheimer's disease and confirmed on neuropsychological testing

Patient Intake

• 28-year-old man

Patient Intake

• 21-year-old male with a three-year history of psychotic illness arrives with his mother and sister

• Chief complaint: “I’ve been misdiagnosed as schizophrenia”

• He believes that medications do not help and that they cause movement disorders

Patient Intake

• 60-year-old man

• Chief complaint is “being unstable”

• Patient estimates that he has spent about two thirds of the time over the past year being in a mixed dysphoric state and about one third as depressed, but waxing and waning every few days, or even every few hours

Dramatic scientific and technological advances in the field of drug discovery have been made over the past decade, without a corresponding improvement in the success rate of compounds in clinical development. In response, translational research was developed as a research discipline with the aim of improving the correspondence between preclinical and clinical success of therapeutic treatments by identifying novel disease biomarkers, drug targets, and mechanisms of action for compounds of interest. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have been widely used to reveal the neurobiological underpinnings of human cognition and emotion. The knowledge gained from such studies is currently being employed in the clinical setting to better diagnose and develop treatments for mood disorders. Many of the imaging techniques established in humans are now feasible in animal models (rodents and non-human primates), allowing closer alignment of imaging biomarkers across species and improved congruency between the laboratory and clinical setting. In this review, we explore the use of neuroimaging biomarkers as a translational technique to pave the way to improved clinical success through greater psychiatric disease understanding.

Prevalence of depression has increased progressively over the last decades. Besides the impact on human quality of life, the pharmaco-economical impact of this syndrome requires ongoing development of newer, more powerful antidepressants. While optimizing existing therapeutic compounds, multiple approaches can be taken to generate superiority over these compounds. The delay in onset of action of antidepressants is of relevance as the presence of side effects during the initial absence of clinical effects causes low therapy compliance. Obviously, a decrease in onset of action would overcome this problem. Current therapy still induces considerable side effects depending on the class of antidepressants used. Reducing these has multiple advantages, such as it will increase compliance but also facilitate the rapid and safe initiation of drug treatment. In line with safety requirements is the notion that new antidepressants should not be prone to hazardous effects in overdose, nor should they induce dangerous interactions by interfering with other treatment. Finally, it is currently recognized that depression is a cluster of symptoms rather than a concise disease. To this end, it is recognized that more tailored treatments might be required in the future. Arguably targeting subsymptoms and comorbid features such as anxiety are of high relevance. Attempts to improve antidepressants have been made into monoamine-related strategies, but also more recently in non-monoamine strategies. The effectiveness of monoamine-targeted selective, dual- and triple-uptake inhibitors and augmented uptake inhibitors is discussed. In addition, new strategies such as monoamine non-uptake inhibitor drugs or non-monoamine drugs exerting effects on Glu, gamma-aminobutyric acid (GABA), Substance P, and acetylcholine are discussed, as are more miscellaneous approaches.